clinical medicine insights. received 5 may 2021 | revised 10 june 2021 | accepted 15 july 2021 | published online 27 july 2021 doi: https://doi.org/xx.xxx/xxx.xx cmi 2 (3), 150−154 (2021) issn (o) 2694-4626 research article trend and pattern of antibiotic practice in paediatric surgery in bangladesh mohammad mahabubul alam1 mohammad saiful islam2 shamsuzzaman khan3 mafia afsin laz4 1assistant professor, department of pediatric surgery, cumilla medical college, cumilla, bangladesh 2professor, department of pediatric surgery, bangabondhu sheikh mujib medical university, dhaka, bangladesh 3assistant professor, department of pediatric surgery, shaheed suhrawardi medical college, dhaka, bangladesh 4assistant professor, department of pediatric surgery, sir salimullah medical college & mitford hospital, dhaka, bangladesh abstract introduction: antibiotics are frequently over prescribed, misused or inappropriately used both in developed or developing countries. the extent and pattern of inappropriate use is well documented in developed countries but such studies are few in developing countries like bangladesh. objective: to find out trend and pattern of antibiotic practice in paediatric surgery in bangladesh methodology: this cross sectional descriptive study was carried out on 260 paediatric patients of 0-15 years age range, to find out the pattern of antibiotic practice in pediatric practicing hospital and different clinic of cumilla, bangladesh. all the patients were studied after categorization into i) clean ii) cleancontaminated iii) contaminated and iv) dirty wounds according to their potentiality of post-operative wound infection. total period of antibiotic practice was divided into a. pre-operative (up to the day before operation) b. per-operative (during or just before operation) c. post-operative (days after operation) and d. post-discharge stage for the convenience of this study. antibiotic practice in all categories during all periods mentioned were compared and evaluated. results: more than two antibiotics were given in a single patient in 48.1% of clean and 51.9% of contaminated patients in a combination or sequentially. more than 3 antibiotics were used in a single patient. on the average total number (mean) of antibiotic use was more than two (2.64 +1.09). the highest number (mean) of antibiotics was used in contaminated category (3.29) with range of (0-7). overall total duration (mean) of antibiotic used was 17.40 days. keywords: antibiotic practice, paediatric surgery, preoperative, postoperative copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). cmi 2 (3), 150−154 meerp ltd 150 https://creativecommons.org/licenses/by-nc-nd/4.0/ 1 introduction antibiotics are frequently over prescribed, misused or inappropriately used both in developed or developing countries1. this is not only unnecessary and wastes of resources but also increases the risk of adverse clinical consequences in a situation where objective benefits are doubtful2. studies conducted in general and teaching hospitals showed that about 28% of our patients and 52%of the inpatient of a general hospital and 60.36% of the patients in a teaching hospital received antibiotic therapy that was not appropriate3. irrational use of antibiotic was also wide spread seen in several studies conducted in china4,5, indonesia and sudan6 and thailand.7 antibiotic misuse is also commonly seen at discharge after operation. this abuse of antibiotic prophylaxis leads to excessive surgical wound infection rates and strongly contributes to the emergence of bacterial resistance8. the number of this antibiotic resistance strains has been correlated with the number of kilograms of antibiotic used in any given hospital. the cost of such irrational drugs is enormous in terms of our scarce resources9.it has been observed that even after obtaining adequate asepsis surgical site infections are still one of the most important causes of postoperative morbidity and mortality10. antibiotics have a key role to play in minimizing these unwanted consequences11. the risk of postoperative wound infection has been reported to a range from 0% to 40% depending upon the surgical procedure performed. most surgeons tend to use antibiotic in almost all cases of surgery irrespective of their categories in order to have an infection free record12. common errors in antibiotic prophylaxis includes selection of wrong antibiotic, administering first dose too early or too late of making incision, failure to repeat doses during prolong procedures, excessive duration of prophylaxis and inappropriate use of broad spectrum agents. the reasons behind this over use may be lack of confidence regarding sterilization status of operation theatre and instruments, inadequate information about sensitivity pattern of local infecting agents, over reliance on newer antibiotics, preference of daily dosing to multiple dosing, affluent patients preference of costly drugs and above all aggressive sales promotion by pharmaceutical companies13. although the extent and pattern of inappropriate antibiotic uses are extensively documented in the developed world14, such types of studies are now few and limited in developing countries like bangladesh. this study will therefore be undertaken to find out the extent and pattern of antibiotic use in our paediatric surgery to identify the prescribing trend to emphasize the issue of rational usage. 2 methodology this cross sectional descriptive study was carried out on 260 paediatric patients of 0-15 years age range, to find out the pattern of antibiotic practice in pediatric practicing hospital and different clinic of cumilla, bangladesh. all the patients were studied after categorization into i) clean ii) clean-contaminated iii) contaminated and iv) dirty wounds according to their potentiality of post-operative wound infection. total period of antibiotic practice was divided into a. pre-operative (up to the day before operation) b. per-operative (during or just before operation) c. post-operative (days after operation) and d. postdischarge stage for the convenience of this study. antibiotic practice in all categories during all periods mentioned were compared and evaluated. table 1: classification of surgical wounds. supplementary information the online version of this article (https://doi.org/xx.xxx/xxx.xx) contains supplementary material, which is available to authorized users. cmi 2 (3), 150−154 meerp ltd 151 meerp ltd alam et al. 3 results on the average total number (mean) of antibiotic use was more than two (2.64 +1.09). the highest number (mean) of antibiotics was used in contaminated category (3.29) with range of (0-7). the lowest number of antibiotics was used in clean category (2.19 sd+1.06) (table-2). the difference in the number of total antibiotics used is not significant (p>.05) between clean-contaminated and dirty category. overall total duration (mean) of antibiotic used was 17.40 days. the duration of total antibiotic used in clean and dirty categories was around 16 days. maximum total duration (20 days) of antibiotic use was found in clean-contaminated category (table-3). the difference between group a, group c and group d was not significant revealed byanova (p>.05ns).mean duration of postoperative antibiotics use was found highest in clean-contaminated category (15.07 days), lowest in dirty category (12.75 days). the duration is significantly higher in group a, group b and group c than group d revealed by anova test. table 2: total number of antibiotic used in each patient (n=260) figure 2: table 3: frequency of use of antibiotic at different stages (n=260) figure 3: overall 68.0% patient received pre-operative antibiotics. minimum (49.6%) use seen in clean and maximum (76.6%) in dirty category. on the average 79.6% patients received per-operative antibiotics. maximum (74.4%) per-operative use was seen in clean and minimum (40.0%) in dirty category. overall 95.7% of patients received post-operative antibiotics including all the patients of clean-contaminated category. more than 80% patients in each group received antibiotic after discharge. no significant difference is found in postoperative and post-discharge antibiotics use among the groups (p>0.1ns). 4 discussion this high frequency of pre-operative antibiotic usage was perhaps due to prolonged pre-operative hospital stay. antibiotic prophylaxis has been extensively substantiated by controlled clinical trials15. nevertheless much concern has been voiced in the last few decades about indiscriminate use of antimicrobials, including broad-spectrum agents threatening emergence of multiple drug resistance16. it was apprehended that indiscriminate use is ubiquitous, as such is also prevalent in our working situation. this trend of antibiotic use increases the risk of drug reaction but also diminishes their effectiveness, promote drug resistance and increases the overall treatment cost 17. the total duration of antibiotic usage during pre and postoperative periods was found unduly prolonged (17.4 days) and had no significant difference in between clean and clean contaminated categories of wounds18 had also observed prolonged postoperative antibiotic use where most of the antibiotics were given for more than five days. postoperative antibiotics were also found to be used for prolong period (13 days) which exceeds the recommended limit of surgical prophylaxis of (24-48 hours) after operation15,19. it has been found that the critical period of antibiotic action for effective postoperative bacterial killing in clean or contaminated operation was up to 36 hours of operation20 and prolong postoperative antibiotic use has no added advantage or therapeutic benefit 17,21. it was found that most of the patients (98%) belonging to all categories received antibiotics at least at one of four stages of treatment irrespective of their nature of surgical disease and category of wounds. such practice of generalized use of antibiotic has no rational basis as it has been meerp ltd cmi 2 (3), 150−154 (2021) 152 “trend and pattern of antibiotic practice in paediatric surgery in bangladesh” observed in studies that antibiotics were generally not needed in “clean surgery” at any stage of treatment 22,23 if not indicated otherwise. it was also found that about two thirds (66.5%) of all patients including about half (50.0%) of those in the clean wound category received pre-operative antibiotics. however it has been found that the length of preoperative hospital stay is not associated with increased risk of post-operative wound infection 24. almost all patients received post-operative antibiotics and virtually no significant difference was observed in the frequency of antibiotic usage between different categories of the patients in respect to the nature of wounds. all of the prophylactic antibiotic usage was continued beyond 48 hours of operation. the period of continuance after the recommended 48 hours 25was also much higher than the finding of kass18 where he observed 65% of antibiotic prophylaxis was exceeded this limit in comparison to this study where the limit was exceeded by 100%. the trend of antibiotic usage after discharge in respect to the frequency and duration of their use was found similar in the different categories of surgical wounds and virtually had no significant difference between clean and dirty category. the practice of antibiotic termination also appeared similar among different cmi 2 (3), 150−154 (2021) meerp ltd 153 groups. antibiotic use was found generous in all the patients of surgical diseases irrespective of their surgical wound categories. no distinct pattern of choice of antibiotic was used in different categories of patients. postoperative antibiotics were used in a similar frequency in all the categories. antibiotic use was continued for more than 48 hours after operation in all categories of surgical illness. present trend of antibiotic practice in paediatric surgery. 5 conclusion antibiotic overuse is generalized and not categorized according to the categories of surgical wounds. a consensus and collaborated effort is crucial to minimize this widespread indiscriminate antibiotic use. 2. momen a, choudhury sar, anwar nakm. extent and pattern of antibiotics used in the management of clinically diagnosed case of common cold and fever in some government and private hospitals. bang j of physiol and pharmacol. 1999; 15(2): 67-9. 3. rashid hu, chowdhury sar, islam n. pattern of antibiotic use in two teaching hospitals. tropical doctor. 1986; 16:152-54. 4. yang yh, fu fg, peng h. abuse of antibiotics in china and its potential interference in determining the etiology of paediatric bacterial disease. paed inf dis.1993; 12: 988 89. 5. world health organization (who), antibiotics: the resistant problem. who features. 1994; 89:107-10. 6. arustyono. promoting rational use of drugs at the community health centres in indonesia. [online] 1999. [cited: 0505 -2005] sep 9; available from http://www.dec2.bumc.bu.edu/ prdu/otherdocuments/arus-indonesia prdu/ htm. 7. aswapokee n, veithayapichet s, richard fh. pattern of antibiotic use in medical wards of university hospital, bangkok, thailand. rev inf dis j.1990; 12(no.1):136-41. 8. ali l, chowdhury s.a.r. study of drug utilization pattern at a teaching hospital. bang. j. physiol. phalmacol.1993; 9 (no.1): 27 8. 9. cobb pj, scheneig r, hurt tk, mandy lm. infection and inflammation and antibiotics. in: current surgical diagnosis and treatment. lawrence w w, gerard m d (eds), 11th ed. mc grew hill, new york, 2003, pp 120 51. 10. nichols rl. postoperative infections in the age of drug-resistant gram positive bacteria. am j med.1998;104: 11s-16s. 11. williams jd. antibiotic policy. scand j infect dis suppl. 1986; 49:175-81. 12. peter je, foord r. epidemiology of wound infection; a 10-years prospective study of 62,939 wounds symposium on surgical infections. surgical clinics of north america. 1980; 60 (no.1): 27-40. 13. islam ms. prophylactic use of antibiotics in caesarean section; effects of intervention on cost effectiveness [ms thesis] bsmmu, dhaka; 2003;1-98. references 1. ramsey le. bridging the gap between clinical pharmacology and rational drug prescribing, br j clin pharmacol. 1993; 35: 575 76. how to cite this article: alam m.m., saiful islam m., khan s., laz m.a. “trend and pattern of antibiotic practice in paediatric surgery in bangladesh”. clinical medicine insights.. 2021;150−154. https://doi.org/xx.xxx/xxx.xx 14. niher rb, biswas rs, pal ps, jain sk, malhotra sp, gupta a. pattern of drug use in two tertiary hospital in delhi. indian j physiol pharmacol. 2000; 44 (no.1): 109-12. 15. stone hh, hanry bb, kolb ld, geheber ce, hooper ca, katholi re et al. prophylactic and preventive antibiotic therapy: timing duration and economical. ann surg. virginia. 1979; 189(no.6): 691-99. 16. raveh dy, levy y, schlesinger a, greenburg, rudensky, yinnon a m. longitudinal surveillance of antibiotic use in the albeny regional hospital. q j med. 2001; 94:14152. 17. davis a, kiblbar c. prevention of infection in surgical practice. in: clinical surgery in general, rcs manual course. kirk km, mensfield (eds), 3rd ed. churchill livingstone, philadelphia, 1999, pp 211-19. 18. kass eh. antimicrobial usages in general hospital in pensylvania. ann of int med. 1978; 89(no. 2): 800 01. 19. davenport m, doig cm. wound infection in paediatric surgery; a study in 1094 neonates. j paediatr surg. 1993; 28(no.1): 26-30. cmi 2 (3), 150−154 (2021) 154 alam et al. meerp ltd 20. geircksky ke, fuglesang, cristiansen e, rossen b. short term chemotherapeutic prophylaxis in gastrointestinal operation. surgery & gynaecology & obstetrics. 1980; 151: 349 52. 21. griffith da, shorey ba, simpson ra, williams nb. 1976. single dose antibiotic prophylaxis in gastrointestinal surgery. the lancet. 1976; 14:325 28. 22. bhattacharyya n, kosloske na. postoperative wound infection in pediatric surgical patients: a study of 676 infants and children. j pediatr surg. 1990; 25 (no.1):125 29. 23. rahman ms. comparison among no antibiotic: single antibiotic and multiple dose antibiotic prophylaxis [ms thesis], 2003; 43 24. ehrenkranz nj. surgical wound infection occurrence in clean operations; risk stratification for interhospital comparisons. am j med. 1981; 70: 909-14. 25. antibiotic guideline. antibiotie prophylaxis in surgery. bangabandhu sheikh mujib medical university, dhaka. 2005; 72 9. meerp ltd introduction methodology results discussion conclusion blank page clinical medicine insights received 10 dec 2020 | revised 15 jan 2021 | accepted 20 feb 2021 | published online 30 mar 2021 doi: https://doi.org/xx.xxx/xxx.xx cmi 2 (1), 59−64 (2021) issn (o) 2694-4626 if:1.6 research article biostatistical analysis of the risks of spatial spread during the covid-19 pandemic bin zhao 1∗ xia jiang 2 jinming cao 3 1school of science, hubei university of technology, wuhan, hubei, china. 2hospital, hubei university of technology, wuhan, hubei, china. 3school of information and mathematics, yangtze university, jingzhou, hubei, china. abstract with the spread of the new coronavirus around the world, governments of various countries have begun to use the mathematical modeling method to construct some virus transmission models assessing the risks of spatial spread of the new coronavirus covid-19, while carrying out epidemic prevention work, and then calculate the inflection point for better prevention and control of epidemic transmission. this work analyzes the spread of the new coronavirus in china, italy, germany, spain, and france, and explores the quantitative relationship between the growth rate of the number of new coronavirus infections and time. background: in december 2019 , the first chinese patients with pneumonia of unknown cause is china admitted to hospital in wuhan, hubei jinyintan , since then, covid-19 in the rapid expansion of china wuhan, hubei, in a few months time, covid-19 is soon it spread to a total of 34 provincial-level administrative regions in china and neighboring countries, and hubei province immediately became the hardest hit by the new coro-navirus. in an emergency situation, we strive to establish an accurate infectious disease retardation growth model to predict the development and propagation of covid-19, and on this basis, make some short-term effective predictions. the construction of this model has relevant departments are helpful for the prevention and monitoring of the new coronavirus, and also strive for more time for the clinical trials of chinese researchers and the research on vaccines against the virus to eliminate the new corona virus as soon as possible. methods: collect and compare and integrate the spread of covid19 in china, italy, france, spain and germany, record the virus trans-mission trend among people in each country and the protest measures of relevant government departments. according to the original data change law, establish a logistic growth model. findings: based on the analysis results of the logistic model model, the logistic model has a good fitting effect on the actual cumulative number of confirmed cases, which can bring a better effect to the prediction of the epidemic situation and the prevention and control of the epidemic situation. interpretation: in the early stage of the epidemic, due to inadequate anti-epidemic measures in various countries, the epidemic situation in various countries spread rapidly. however, with the gradual understanding of covi d -19, the epidemic situation began to be gradually controlled, thereby retarding growth. mrerp ltd controlled, thereby retarding growth. keywords: new coronavirus, logistic growth model, infection prediction and prevention copyright : © 2021 the authors. published by mrerp ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). cmi 2 (1), 59−64 59 https://creativecommons.org/licenses/by-nc-nd/4.0/ 1 introduction after the outbreak of covid-19 in china, covid-19 has also erupted in other countries in the world. among the countries where new pneumonia outbreaks, spain, italy, france and germany are more serious1. as of april 27, spain, italy, france and germany have each accumulated diagnosed 229842 cases, 199414 cases, 165,842 cases, 158758 cases, the new crown pneumonia spread and various measures of everyday life and people’s social normal operation had not estimated impact2. in fact, there are some urgent problems to be solved regarding the spread of covid -19 . can existing interventions effectively control covid-19? can you elaborate on the changes and development characteristics of each epidemic situation? can you combine the conclusions found in the comparison of the city / region, actual national population, medical level, traffic conditions, geographic location, customs and culture, and anti-epidemic measures ? what mathematical model can we build to solve the problem? covid-19 is a new coronavirus discovered in december 2019. the epidemic data is not sufficient, and clinical methods such as clinical trials are still in the exploration stage. so far, the epidemic situation data is difficult to apply directly to the existing mathematical model. the problems to be solved are: how effective the existing emergency response is and how to invest medical resources more scientifically in the future. on this basis, this article aims to study the shortcomings of this part3-5. 2 methods 2.1 data we obtained epidemiological data from the aminer website, the people’s republic of china from january 22 to april 3, and spain, italy, france, germany fromfebruary 15 toapril 27. this includes data such as cumulative confirmed cases, cumulative deaths, newly diagnosed cases per day, cumulative number of cured cases, and existing confirmed cases. the relevant input is shown in the figure: figure 1: cumula vely confirmed cases figure 2: cumula vely cured cases figure 3: daily new cases figure 4: cumula ve deaths figure 5: exis ng confirmed cases supplementary information the online version of this article (https://doi.org/xx.xxx/xxx.xx) contains supplementary material, which is available to authorized users. corresponding author: bin zhao school of science, hubei university of technology, wuhan, hubei, china. cmi 2 (1), 59−64 mrerp ltd 60 biostatistical analysis of the risks of spatial spread during the covid-19 pandemic 2.2 the model based on the collected epidemic data, we tried to find the propagation law of covid-19 and proposed effective prevention and control methods. there are generally three methods for systematically studying the spread of infectious diseases. one is to establish a dynamic model of infectious diseases. the second is statistical modeling using statistical methods such as random processes and time series analysis. the third is to use data mining technology to obtain information in the data and discover the epidemic law of infectious diseases. using the collected data from various countries, this article mainly uses the third method. in this paper, the growth model of covid-19 transmission is established , and the prediction effect of the mathematical model on the spread of covid-19 epidemic is compared. 2.3 based on logistic estimated square law the traditional seir model can not describe the different developments of the epidemic well. after analyzing the actual situation and the existing data, we have established a more effective infectious disease transmission model. according to the actual situation of the epidemic, we will analyze the relevant data indicators of the five countries (cumulatively diagnosed cases, cumulative deaths, newly diagnosed cases per day, cumulative number of cured cases, existing confirmed cases) to adapt to the current situation of the new coronary pneumonia epidemic in the world propagation. as can be seen from the data graph, the change in cumulative death toll in italy over time is a nonlinear process. considering the shape of the scatter plot and the model generally involving the logistic curve model, here we use the logistic curve model for fitting. the basic form of the logistic curve model is: y = 1 / (a + be ^ (-t)) therefore, we need to transform this nonlinear process into a linear model after data processing. take x0 = e ^ (-t), y0 = 1 / y; then the original model is converted to a linear model y0 = a + bx0. 2.4 simulation since covid-19 has been developing in italy for a long period of time, and the cumulative number of confirmed cases is relatively large, the data is more convincing, so here we take the cumulative number of confirmed cases in italy from february 15th to may 3rd the nonlinear model becomes a linear model, andmatlab is used for fitting linear regression analysis. matlab source code is as follows6-9: x = [1: 1: 27]; y = [3,3,21,229,655,1701,3089,5883,10149, 17660,27980, 41035,59138,74386,92472,105792,119827,132547,1436 26,156363,165155,175925,183957,192994,199414,2054 36 , 210717]; plot (x, y, ’r *’); xlabel (’time’) ylabel (’population’) x0 = exp (-x); y0 = 1. / y; f = polyfit (x0, y0,1); y_fit = 1 ./ (f (1). * exp (-0.338. * x) + f (2)); plot (x, y_fit * 1000); hold on plot (x, y, ’r *’); xlabel (’time’) ylabel (’population’) 3 results 1.1 logistic model estimates on the basis of the cumulative number of confirmed cases in italy from february 15th to may 3rd, we used matlab to establish a logistic model and performed linear regression analysis. using the above processing, we can get the predicted cumulative number of confirmed cases in italy as shown in figure 6. as shown in figure 6, we can conclude that the logistic model has a good fitting effect on the actual cumulative number of confirmed cases, thus providing reference value for departments and hospitals at all levels to effectively intervene and prevent the spread of new coronavirus in the next few days. 4 discussion the spread of covid-19 is affected by many complex factors. in the early stage of the transmission cmi 2 (1), 59−64(2021) mrerp ltd 61 mrerp ltd bin zhao, xia jiang and jinming cao figure 6: the significance of each parameter under theconstruc on of logis c model figure 7: : comparison of actual cumula ve confirmed cases and simulatedcumula ve confirmed cases of covid-19, it is difficult to establish a logistic model and parameter estimation and obtain a fairly accurate simulation result, but the initial estimated parameters such as the growth rate of the confirmed cases and the possible cumulative maximum confirmed cases can be obtained through existing data. it is helpful to solve important parameters such as infection rate and recovery rate, which will help us to grasp the transmission trend of covid-19 more accurately. 5 limitations 1. promotion of the model: the seirmodel based on 2019-ncov can be established. the seir model is superior to the logistic model in trend prediction, but due to the many parameters to be considered, the calculation error is greater than the logistic model 2. a dynamic growth rate model based on 2019ncov can be established. the dynamic growth rate model has a good fitting effect, but has a certain 3. you 4. after the turning point of the epidemic situation, that is, the fitting effect of the reducer and the saturation period is poor, and even a large error occurs conflict of interest we have no conflict of interests to disclose and the manuscript has been read and approved by all named authors. acknowledgement this work was supported by the philosophical and social sciences research project of hubei education department (19y049), and the staring research foundation for the ph.d. of hubei university of technology (bsqd2019054), hubei province, china. mrerp ltd cmi 2 (1), 59−64 (2021) 62 biostatistical analysis of the risks of spatial 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caused by an hku2-related coronavirus of bat origin[j]. nature, 2018, 556: 255258. how to cite this article: b.z., x.j., j.c. biostatistical analysis of the risks of spatial spread during the covid-19 pandemic. clinical medicine insights. 2021;59−64. https://doi.org/xx.xxx/xxx.xx mrerp ltd cmi 2 (1), 59−64 (2021) 64 introduction methods results discussion limitations references clinical medicine insights received 15 apr 2021 | revised 25 may 2021 | accepted 30 june 2021 | published online 19 july 2021 doi: https://doi.org/xx.xxx/xxx.xx cmi 2 (3), 144−149 (2021) issn (o) 2694-4626 research article clinical perception, demographic profile with pc among adolescents with substance use disorder niaz mohammad khan 1∗ , msi mullick 2 sharmin hussain 3 1associate professor of psychiatry, national institute of mental health, dhaka, bangladesh 2professor of child and adolescent psychiatry, bangabandhu sheikh mujib medical university, dhaka 3junior consultant, pediatrics, and fcps trainee of pediatric neurology, national institute of neurosciences (nins), shere bangla nagar, dhaka, bangladesh abstract background: substance use disorder (sud) in adolescents, is a condition in which the use of one or more substances leads to clinically significant impairment or distress. it is a significant public health problem globally with a higher burden in low and middle-income countries. objective: to find out the clinical perception, demo-graphic profile with pc among adolescents with substance use disorder. methods and materials: this descriptive and observational study was conducted in the department of psychiatry, bangabandhu sheikh mujib medical university (bsmmu), dhaka, bangladesh from march 2016 to september 2018. participants 75 (seventy five) psychiatric comorbidity among adolescents with substance use disorder patients included in the study. data collection of central drug addiction treat-ment centre (cdc), tejgaon, dhaka and ashoktipunorbashonnibash (apon), singair, manikganj, bangladesh. adolescents with substance use disorder aged between 11 to 17 years. only male patients were taken as the sample because the above-mentioned treatment facilities do not provide service for the female adolescents. there are two groups of substance-related disorders: substance use disorders and substance-induced disorders. results: the present study aimed at assessing the presence of comorbid psychiatric disorders among adolescents with substance use disorder (sud) included a total of 70 adolescents. over half (60%) of the respondents were <15 years old, and 40% of the respondents were >15 years age. the mean age of the respondents was 13.2 ± 2.1years, and the range was 11-17 years. more than three-quarters (81.4%) of the respondents were muslim and 14.2% hindus. most of the patients (45.7%) had more than one psychiatric disorder diagnosed. regarding the specific disorder diagnosed conduct disorder was 31.4% and different socio-demographic features were collected like age, education level, family income, religion, family type, and family members and their relationships with the presence of psychiatric disorders was calculated. none showed a significant relationship. conclusion: based on the findings of the study, it can be concluded that clinical perception, demographic profile of adolescents with sud have a high rate of other comorbid psychiatric disorders. understanding the relationship in etiological perspective and variables which influences the problem will help to provide intervention services for adolescents affected by sud. further epidemiological studies are needed to get a more representative result. keywords: adolescence, substance use disorder, psychiatric disor-der, clinical aspect. copyright : © 2021 the authors. published by medical editor and educational research publishers ltd.. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). cmi 2 (3), 144−149 meerp ltd 144 https://creativecommons.org/licenses/by-nc-nd/4.0/ 1 introduction substance-related disorders are psychiatric disturbances developing during or following substance use, and attributable to it. the drugs that most often produce substance-related disorders include tobacco, alcohol, cannabis, stimulants and other hallucinogens. numerous other substances, including nitrous oxide, amyl-or butyl-nitrite, or anabolic steroids also may produce these disorders (1) . there are substantial geographic variations in drug use prevalence among the adolescents, with higher rates in higher-income countries (although data from lower-income countries often are lacking). a study was done in west bengal, india, out of 416 students, 52 (12.5%) used or abused any one of the substances irrespective of time and frequency in the lifetime; 26 (15.1%) were among the urban students and 26 (10.7%) were among their rural counterparts. more than two-thirds (73.07%) of the respondents expressed a desire to quit substance use and 57.69% had tried to stop. ‘easy availability’ and ‘relief from tension’ were the most frequent reasons for the continuation of substance use (2) . comorbid mental disorder among adolescents with substance abuse include depression, anxiety, conduct disorder, and attention-deficit/hyperactivity disorder (adhd) (3) . a study conducted by shantna. k. et al., (4) show that the most prevalent comorbid disorders in substance dependence patients and substance abusers were depressive disorders. they also conclude that the majority of substance dependence patients suffered from comorbid mental disorders. the community-based prevalence study of psychiatric disorder among children of bangladesh has not yet been studied. according to the analytical predictions, prevalence would be roughly 10-20% among children and adolescents as like as the prevalence findings of the reports of the developing countries. a study of psychiatric outpatient attendance at the institute of mental health and research in dhaka, revealed that 8.6% of cases were children or adolescents (5) . in a different analysis of psychiatric morbidity among the institute outpatients, emotional disorder was found to be the largest group with 32.5%, followed by conduct disorder 18.8%; mental retardation comprised 16.2%, psychoses and allied conditions 11.2%, epilepsy with behavioral problems 12.5% and the rest 8.5% comprised of other groups of disorders, according to icd-9 criteria (6) . in a survey among the children in a child guidance clinic at the bangladesh institute of child health and dhaka childrens’ hospital, rabbani and quamaruzzaman et al., (7) assessed psychiatric morbidity by using the rutter multiaxial diagnostic system. their findings revealed that conduct disorder was 8.9%, somatoform disorders 7.1%, attention deficit hyperactivity disorder 68%, autism 6%, and other emotional disorder 15.28% of the cases. specific delays in development were found to be 10%, andmental retardation was 17.8% of the cases. substance-induced depression occurs during periods of substance use but exceeding the expected effects of intoxication or withdrawal from the substance used. primary or independent major depression is defined as either predicting substance use entirely or occurring during periods of sustained abstinence (8) . another investigatedadolescent admissions to residential substance abuse programme and reported theprevalence of psychiatric disorders comorbidity in 64% of the 91 adolescents; depression (24%), conduct disorder (cd) (24%) and attention deficit hyperactivity disorder (adhd–11%)were themost common conditions (9) . in one study, alcoholics with independent major depression were found to be more likely to attempt suicide than those with substance-induced depression [8]. in a systematic review made in bangladesh reports the prevalence of mental disorders in children. earliest report among urban primary school children revealed 13.4% had some behavioral disorder, with boys being twice more affected than girls (20.4 vs. 9.9%). however, a study among socially disadvantaged (urban slum) children, reported 22.9% had some form of psychiatric disorder with a slightly lower prevalence in boys than girls (20.0% in boys and 25.5% in girls). another study found 14.6% of children with behavioral problems as reported by the parents in rural bangladesh (6) . another more recent community-based study reported the prevalence of mental disorder among 18.4% of the children (10) . the study was intended to find out the different type of sud our adolescents are suffering from in two different treatment centers and their magnitude and pattern of comorbid sud. the expected outcome of cmi 2 (3), 144−149 meerp ltd 145 clinical perception, demographic profile with pc among adolescents with substance use disorder the study is to help in the field of the adolescent sud and its comorbidity’s proper assessment, diagnosis, and formulation of an effective management plan. 2 materials and methods this descriptive and observational study was conducted in the department of psychiatry, bangabandhu sheikh mujib medical university (bsmmu), dhaka, bangladesh from march 2016 to september 2018. participants 75 (seventy five) psychiatric comorbidity among adolescents with substance use disorder patients included in the study. data collection of central drug addiction treatment centre (cdc), tejgaon, dhaka and ashoktipunorbashonnibash (apon), singair, manikganj, bangladesh. adolescents with substanceusedisorder aged between 11 to 17 years. only male patients were taken as the sample because the above-mentioned treatment facilities do not provide service for the female adolescents. there are two groups of substance-related disorders: substance use disorders and substance-induced disorders. the diagnostic criteria are given in appendix iii. collected data was processed, cleaned and entered into a windows pc. data were analyzed using statistical software spss version 22.0. 3 results the present study aimed at assessing the presence of comorbid psychiatric disorders among adolescents with substance use disorder (sud) included a total of 70 adolescents. over half (60%) of the respondents were <15 years old, and 40% of the respondents were >15 years age. themean age of the respondents was 13.2± 2.1 years, and the range was supplementary information the online version of this article (https://doi.org/xx.xxx/xxx.xx) contains supplementary material, which is available to authorized users. corresponding author: niaz mohammad khan associate professor of psychiatry, national institute of mental health, dhaka, bangladesh 11-17 years. more than three-quarters (81.4%) of the respondents were muslim and 14.2% hindus. most of the patients (45.7%) hadmore than one psychiatric disorder diagnosed. regarding the specific disorder diagnosed conduct disorder was 31.4% and different socio-demographic features were collected like age, education level, family income, religion, family type, and family members and their relationships with the presence of psychiatric disorders was calculated. none showed a significant relationship.type and frequency of psychiatric disorder diagnosed: most of the patients (45.7%) had more than one psychiatric disorder diagnosed. regarding the specific disorder diagnosed conduct disorder was 31.4%, adhd in 21.4%, odd in 18.5%, mdd in 17.1%, both specific and social phobia in 10%, gad in 7.1%, ocd in 5.7% (table: 1-3). the family history of mental illness and family history of substance use shows no significant relationships. significant differences were found between the adolescents with andwithout any history or trouble with law enforcing agency. table-1: demographic features and presence of psychiatric disorders (n=70) table-2: other pertinent information and presence of psychiatric disorders (n=70) cmi 2 (3), 144−149 (2021) meerp ltd 146 meerp ltd niaz mohammad khan, , msi mullick and sharmin hussain 4 discussion the present study aimed to determine the pattern of comorbid psychiatric disorders among the admitted adolescents of two institutions namely central drug addiction treatment center (cdc), tejgaon, dhaka, and the ashoktipunorbashonnibash (apon) in singair, manikganj, bangladesh. the authority of the two institutions was helpful regarding the data collection. over half (60%) of the respondents were <15 years old, and 40% of the respondents were >15 years age. the mean age of the respondents was 13.2 ± 2.1 years with a range of 11-17 years. only male patients were taken as the sample because the above-mentioned treatment facilities do not provide service for the female adolescents. more than threequarters (81.4%) of the respondents were muslim, and nearly 60% had a monthly family income of less than taka 30000, around 66% of the respondents had in the primary level of education, and 15.7% had secondary, and 12.8% were illiterate, and 5.7% had non-formal education. regarding the type of family, 80% were from a joint family with 20% having 5 – 6 family members. regarding the pattern of sud among the adolescents most common was the tobacco use disorder (51.4%), followed by cannabis use disorder (47.1%), sedative, hypnotic, or anxiolytic use disorder (22.8%), amphetamine-type substance (20.0%), inhalant use disorder (17.1%), opioid use disorder (15.7%), alcohol use disorder (12.8%), >1 substance use disorder (87.1%). there were no cases of hallucinogen use disorder. data from the monitoring the future (mtf) study in the us, a national school-based survey, show that adolescent substance use is relatively common by the end of the high school years. cannabis was the most frequently used illegal drug, with 31.5% of 12th graders reporting some lifetime use (11) . alcohol and tobacco are even more common, with 73% of today ’ s students have consumed alcohol by the end of high school and 45% of high school seniors reporting drinking in the past month (12) . forty-seven percent of high school seniors report some experience with cigarette smoking, and 22% were current smokers in 2006 (13) . the use of different drugs is highly interrelated in both epidemiological and clinical samples of adolescents (14) . a study was done among the street children in mumbai, india shows the prevalence of substance use disorder is around 90%. nicotine was the most frequent substance of abuse, used by 104 (63.8%) adolescent street children. seventy-eight (48%) adolescents were using inhalants. sixty (37%) were using alcohol, and 42 (26%) were using sedatives and stimulants. thirtyone (19%) were found to be using cannabis and opioids (14) . according to the analytical predictions, prevalence would be roughly 10-20% among children and adolescents as like as the prevalence findings of the reports of the developing countries. a study of psychiatric outpatient attendance at the institute of mental health and research in dhaka, revealed that 8.6% of cases were children or adolescents (10) . in a different analysis of psychiatric morbidity among the institute outpatients, emotional disorder was found to be the largest group with 32.5%, followed by conduct disorder 18.8%; mental retardation comprised 16.2%, psychoses and allied conditions 11.2%, epilepsy with behavioral problems 12.5% and the rest 8.5% comprised of other meerp ltd cmi 2 (3), 144−149 (2021) 147 table-3: pattern of psychiatric disorder diagnosed (n=54) clinical perception, demographic profile with pc among adolescents with substance use disorder groups of disorders, according to icd-9 criteria (6) . a multicentric exploratory study to assess the prevalence of psychiatric disorders among 5-10-year-olds in rural, urban and slum areas in bangladesh by mullick and goodman found the overall prevalence is 15.2% [6]. rabbani et al., (7) shows the prevalence of mental disorders among children adolescents aged 5-17 years is 18.4%. so it is evident that the burden of the comorbid psychiatric disorder is found very high among adolescents with sud. most common disorder found was conduct disorder (cd) 31.4%, attention-deficit/hyperactivity disorder (adhd) 21.4%, oppositional defiant disorder (odd) 18.5%, major depressive disorder (mdd) 17.1%, social phobia 10%, specific phobia 10%, panic disorder 7.1%, generalized anxiety disorder (gad) 7.1%, obsessive compulsive disorder (ocd) 5.7%, post traumatic stress disorder (ptsd), and separation anxiety disorder 2.8%. methods for the epidemiology of child and adolescent mental disorders (meca) study found 29.8% for anxiety disorders, 7.9% for mood disorders, 18.7% for disruptive behaviors. the study also showed that among adolescents with current sud, 76.0% (70.0% of females, 80.0 % of males) also had anxiety, mood, or disruptive behavior disorder compared with 24.5% of adolescents without current sud, (15) described several possible relationships between adolescent substance abuse and affective disorders, conduct disorder and antisocial personality, anxiety disorders, attention-deficit hyperactivity disorder, schizophrenia and psychotic symptoms, and eating disorders. another investigated adolescent admissions to residential substance abuse program and reported the prevalence of psychiatric disorders comorbidity in 64% of the 91 adolescents; depression (24%), conduct disorder (cd) (24%) and attention deficit hyperactivity disorder (adhd – 11%) were the most common conditions [9]. further, literature review estimate rates of psychiatric comorbidity among adolescents receiving treatments for substance abuse at 50–90% (16) . the high levels of psychiatric comorbidity among adolescents with sud suggest dual diagnosis is ‘the rule rather than the exception’ (17) . adolescents with sud have higher rates of both mood disorders and cd (16) ], attention deficit hyperactivity disorder, cd and substance use often co-exist and are associated with poorer treatment outcomes, (9) those with cd are more likely to have an earlier onset of substance use (17) , timely intervention of co-occurring psychiatric and suds is associated with better engagement with treatment (18) . 5 conclusions based on the findings of the study, it can be concluded that clinical perception, demographic profile of adolescents with sud have a high rate of other comorbid psychiatric disorders. understanding the relationship in etiological perspective and variables which influences the problemwill help to provide intervention services for adolescents affected by sud. further epidemiological studies are needed to get a more representative result. references 1. thapar a, taylor e, snowling m, scott s, leckman j, pine d. rutter’s child and adolescent psychiatry. malden, ma: wiley-blackwell; 2015. 2. pal r, dasgupta a, tsering d. substance use among adolescent high school students in india: a survey of knowledge, attitude, and opinion. journal of pharmacy and bioallied sciences. 2010;2(2):137–137. available from: https://dx. doi.org/10.4103/0975-7406.67005. doi:10.4103 /0975-7406.67005. 3. griswold ks, aronoff h, kernan jb, kahn ls. adolescent substance use and abuse: recognition and management. am fam physician. 2008;77(3):331–336. 4. shantna k, chaudhury s, verma an, singh ar. comorbid psychiatric disorders in substance dependence patients: a control study. industrial psychiatry journal. 2009;18(2):84– 84. available from: https://dx.doi.org/10.4103/ 0972-6748.62265. doi:10.4103/0972-6748.622 65. cmi 2 (3), 144−149 (2021) meerp ltd 148 https://dx.doi.org/10.4103/0975-7406.67005 https://dx.doi.org/10.4103/0975-7406.67005 http://dx.doi.org/10.4103/0975-7406.67005 http://dx.doi.org/10.4103/0975-7406.67005 https://dx.doi.org/10.4103/0972-6748.62265 https://dx.doi.org/10.4103/0972-6748.62265 http://dx.doi.org/10.4103/0972-6748.62265 http://dx.doi.org/10.4103/0972-6748.62265 meerp ltd niaz mohammad khan, , msi mullick and sharmin hussain 5. mullick msi, khanam m, islam h. psychiatric morbidity of outpatient 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clinical medicine insights. 2021;144−149. ht tps://doi.org/xx.xxx/xxx.xx meerp ltd cmi 2 (3), 144−149 (2021) 149 https://dx.doi.org/10.1097/yco.0b013e3282f32408 https://dx.doi.org/10.1097/yco.0b013e3282f32408 http://dx.doi.org/10.1097/yco.0b013e3282f32408 http://dx.doi.org/10.1097/yco.0b013e3282f32408 https://dx.doi.org/10.1016/s0740-5472(01)00193-3 https://dx.doi.org/10.1016/s0740-5472(01)00193-3 http://dx.doi.org/10.1016/s0740-5472(01)00193-3 http://dx.doi.org/10.1016/s0740-5472(01)00193-3 https://dx.doi.org/10.1080/17450120701843166 https://dx.doi.org/10.1080/17450120701843166 http://dx.doi.org/10.1080/17450120701843166 http://dx.doi.org/10.1080/17450120701843166 https://dx.doi.org/10.1016/s1056-4993(03)00068-3 https://dx.doi.org/10.1016/s1056-4993(03)00068-3 http://dx.doi.org/10.1016/s1056-4993(03)00068-3 https://dx.doi.org/10.4088/jcp.0706e02 https://dx.doi.org/10.4088/jcp.0706e02 http://dx.doi.org/10.4088/jcp.0706e02 https://dx.doi.org/10.1080/10550490601006022 https://dx.doi.org/10.1080/10550490601006022 http://dx.doi.org/10.1080/10550490601006022 http://dx.doi.org/10.1080/10550490601006022 introduction materials and methods results discussion conclusions cmi 03 (04), 363−371 cmi journal 363 clinical medicine insights doi: https://doi.org/10.52845/cmi/2023-4-1-1 cmi 04 (01), 363-371 (2023) issn (o) 2694-4626 research article identification the hub genes in hl-60 leukemia cells on decitabine through bioinformatics analysis fuxue meng*, lonakuan li, qin zheng medical experiment center, the third affiliated hospital of guizhou medical university, duyun 558000, guizhou province, china. corresponding author: fuxue meng introduction acute myeloid leukemia (aml) is a malignant clonal proliferative disease derived from hematopoietic stem cells, and its 5-year survival rate is very low. in the past few decades, the development of sequencing technology has resulted in the accumulation of a large number of omics data for various complex diseases. the subsequent development of bioinformatics revealed to us more rapid and intuitive multiple gene expression patterns [1;2] . decitabine, as a specific inhibitor of dna methyltransferase (dnmt), can be incorporated into dna during the replication process, irreversibly or covalently bound to dnmt, depleting the storage of dnmt in the cell, and making dna progressive demethylation. decitabine can also enhance the body's anti-tumor immunity through non-methylated anti-tumor effects, stimulate the expression of tumor-associated antigens, or change the cellular immune status by regulating regulatory t cells; it can be mediated by p53 damage repair pathway promotes apoptosis of leukemia cells [3;4] . study [5] have shown that compared with the abstract objective: aims to identification the hub genes in hl-60 acute myeloid leukemia cells treated with decitabine, provide meaningful insights into the pathogenesis of aml. methods: the gene expression profile of gse24224 was obtained from geo database, go and pathway enrichment were performed though david, established a ppi network from the string database and was displayed through the weight network diagram of omicshare tools. mirna targets and rbp targets prediction were carried out to further unravel the functions of hub genes identified. results: 1558 differentially expressed genes were identified. go and pathway analyses mainly involved citrulline metabolic process, positive regulation of neutrophil extravasation, positive regulation of cell adhesion molecule production, phospholipase a2 inhibitor activity, hematopoietic cell lineage, tgf-β signaling pathway, p53 signaling pathway. the mirna and rbp targets prediction hinted that the 10 hub genes identified plays an important role in prognosis of aml. conclusion: this study intimated that hub genes c3, c3ar1, fpr2, gna11, ptafr, itgam, anxa1, lpar1 cxcr4 and fpr1 identified predictively targeted hsa-mir-520d-5p, hsa-mir-362-5p, hsa-mir-224-5p, hsa-mir-1913, hsa-mir-196b-5, hsa-mir-188-5p, hsa-mir-130a-5p, hsa-mir-204-5p, hsa-mir-211-5p, hsa-mir-671-5p, hsa-mir-296-3p and hsa-mir-23b-3p and adar1, dgcr8, dkc1, elavl1, fbl, fus, hnrnpc, igf2bp2, nop58, taf15, u2af2 and upf1 proteins may regulate the occurrence and development of aml. this study provides meaningful insights and ideas for further understanding the pathogenesis of aml. key words: acute myeloid leukemia; hub genes; hl-60; bioinformatics analysis; decitabine copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/lic enses/bync-nd/4.0/). https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ cmi 03 (04), 363−371 cmi journal 364 cmi journal fuxue meng et al. simulated control group, there are significant differences in gene expression in the hl-60 cells group treated with decitabine, which plays a key role in the function of hl-60 cells, but the specific mechanism is still unclear. therefore, this study utilized bioinformatics analysis methods to analyze the hl-60 cell gene chip that was acted by decitabine, in order to discover biomarkers related to the disease, and provide a theoretical basis for revealing the molecular mechanism of the occurrence and development of aml. methods microarray data collection and deg screening the publicly accessible data gse24224 was obtained from the gene expression omnibus (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc =gse24224) that deposited by fabiani et al [5] . containing six samples (three decitabine treated hl-60 cells and three mock treated hl-60 cells) were utilized in the present study. gene expression profiling (gep) was performed using the affymetrix u133 plus 2.0 expression array. all hybridization reactions were performed using genechip fluidics station 450, and genechips were scanned using the affymetrix genechip scanner 3000 (affymetrix, usa). the raw data of gse24224 was processed using the affy package pair in r, using correction, normalization and log2 conversion [6] . the differentially expressed genes (degs) in decitabine treated hl-60 cells compared with mock treated hl-60 cells were determined using limma package [7;8] . degs were screened with a false discovery rate (fdr) corrected p<0.05 and |log fold-change (fc)|>1, then were confirmed using the geo2r application from geo. functional enrichment analysis investigation into the functions of enriched degs may improve understanding of their involvement in aml. in the present study, functional enrichment analysis of degs based on david (https://david.ncifcrf.gov/tools.jsp), a widely used web-based genomic functional annotation tool. degs were subjected to molecular function and pathway studies by gene ontology (go) analysis and kyoto encyclopedia of genes and genomes (kegg) pathway analysis. p < 0.05 was set as cutoff values. protein-protein interaction (ppi) network construction and hub genes identification genes are likely to function together rather than alone in complex diseases. hub nodes in the network may represent key role. in the present study, protein-protein interaction (ppi) network analysis was performed to investigate the degs based on the string online database (https://string-db.org/cgi/input.pl). the minimum required interaction score was set as medium confidence > 0.8. in addition, the network was constructed through the weight network diagram of omicshare tools (https://www.omicshare.com/tools/index.php/) to confirm the hub genes and the genes with top-ten highestweight nodes were defined as hub genes. mirna target prediction in this study, the targets of the hub genes were predicted using four databases: mirwalk (http://mirwalk.umm.uni-heidelberg.de/), targetscan (http://www. targetscan.org), mirmap (https://mirmap.ezlab.org) and starbase v2.0 (http://starbase.sysu.edu.cn/). the screening criterion was that the mirna target exists in the four databases concurrently. the venny 2.1 online tool (https://bioinfogp.cnb.csic.es/tools/venny/) was used to find overlapping genes between degs and predictive genes of dems. the mirna-gene regulatory network was depicted and visualized using cytoscape 3.7.1 (https://cytoscape.org/). rna binding protein (rbp) target prediction as the core position of the post-transcriptional regulatory network, rna binding protein (rbp) participates in multiple processes of rna processing, including alternative splicing, rna transport and stability maintenance, rna localization, and mrna translation [9] . in order to further understand the function of the hub gene, we used the rbp-mrna module on the starbase v2.0 software to performed rbp prediction. results differentially expressed gene acquisition by the cutoff of a 1-fold change and p < 0.05, 1592 differentially expressed were identified filtered out. after removing the genes without gene symbol, 1558 differentially expressed genes remain, of which 1368 were up-regulated genes and 190 were down-regulated genes. the heatmap with clustering of differentially cmi 03 (04), 363−371 cmi journal 365 cmi journal fuxue meng et al. expressed gene were illustrated, and volcano plots were generated to demonstrate the distribution of the differentially expressed gene ( figure 1 ). figure 1 heatmap and volcano plots showing the difffferential expression genes between decitabine treated hl-60 cells and group. a: the heatmap of difffferential expression genes; b: the volcano plots difffferential expression genes (|log 2 foldchange| ≧ 1 and p value < 0.05). go and pathway analysis the go functional enrichment resulted in degs mapped to 198 go terms. with p<0.05 as the significant enrichment criterion, top ten of significant enriched functional clusters were screened. of them, the degs go enrichment mainly involved citrulline metabolic process, positive regulation of neutrophil extravasation, positive regulation of cell adhesion molecule production, phospholipase a2 inhibitor activity, mrf binding, phagolysosome, synaptonemal complex. kegg enrichment analysis with p<0.05 was used as an enrichment screening standard, involved such as staphylococcus aureus infection, hematopoietic cell lineage, tgf-beta signaling pathway, p53 signaling pathway ( figure 2 ) . figure 2 go and kegg analysis of degs. a: kegg enrichment histogram analysis of degs ; b: kegg enrichment bubble chart of degs; c: go enrichment histogram analysis of degs; d: go enrichment bubble chart of deg (p<0.05). ppi network analysis to screen and identification the hub genes in hl60 cells, we established a ppi network from the string database with scores of > 0.8. then, the network was constructed through the weight cmi 03 (04), 363−371 cmi journal 366 cmi journal fuxue meng et al. network diagram of omicshare tools to confirm the hub genes and the genes with top-ten highestweight node of degs such as c3, c3ar1, fpr2, gna11, ptafr, itgam, anxa1, lpar1 cxcr4 and fpr1 were defined as hub genes ( figure 3 ). figure 3 ppi network construction and hub genes determination. b: ppi network of degs; a,c,d: the weight network of degs, c3, c3ar1, fpr2, gna11, ptafr, itgam, anxa1, lpar1 cxcr4 and fpr1 identified as the hub genes (scores > 0.8 ). mirna target prediction for further understand the functions of the hub genes, the mirna target prediction were carried out through four databases: mirwalk, targetscan, mirmap and starbase v2.0. the c3 and frp1 genes only have overlapping mirna targets in three of the databases, and the remaining eight hub genes existed overlapping mirna targets in the four databases, as the figure 4 shows. cmi 03 (04), 363−371 cmi journal 367 cmi journal fuxue meng et al. figure 4 mirna target prediction of hub genes. a, b: predict mirna targets the wenn map of c3 and frp1 in three databases that predict mirna targets; c: eight hub genes for predicted mirna targets network; d: network of 7 hub genes with overlapping mirna targets. rna binding protein (rbp) target prediction rna in the cell interacts with rbp to form a ribonucleoprotein (rnp) complex, which plays an important role in rna synthesis, transport, stability, translation, and cellular localization. in order to further understand the function of hub genes, we carried out the rbp prediction. the results show that the top 10 rbp targets predicted by the 8 hub genes with the strongest weight were elavl1, fus, dkc1, hnrnpc, adar, igf2bp2, nop58, taf15, upf1, u2af2 (figure 5). figure 5 rbp targets prediction of hub genes. a, b: the networks of rbp targets. the larger point, darker the color, indicating the stronger the correlation and the greater the frequency of action; c: screening of rbp targets with strong correlation. discussion this study obtained gene expression profiles of hl-60 cells that decitabine induced and mock control group gse24224 from geo database and carried out degs screening, to understand the biological functions biological and the enrichment pathways involved through go and kegg analysis. hereafter, ppi and weighted network analysis were conducted to identify the hub genes that play a key regulatory role in hl-60 cells. further performed mirna targets prediction and rbp targets prediction to clarify the possible mechanism of the hub gene for aml. in this study, we screened 1558 degs, of which 1368 were up-regulated and 190 were downregulated. based on go enrichment analyses, it was found that degs mainly involved molecular functions including hematopoietic cell lineage, tgf-β signaling pathway, p53 signaling pathway. the tgf-β signaling pathway plays a negative role in the regulation of cell proliferation and differentiation in the hematopoietic system. when zfyve16 is overexpressed, the negative regulation of the tgf-β signaling pathway is enhanced, which may inhibit the malignant proliferation activated by flt3 [10] . in addition, tgf-β stimulates the tumor pre-osteolytic and osteolytic factor production , thereby stimulating further bone absorption [11;12] . this classifies tgfβ as as an important factor responsible for the feedforward vicious circle that drives tumor growth in the bones. in addition, abnormal reactivation of tgf-β usually leads to carcinogenic behavior [13;14] . their role in tumorigenesis usually reflects their role in embryonic development, but also extends to other features often observed in cancer, such as cachexia and bone loss [15] . in the stage of prostate tumorigenesis, increased tgf-β production leads to the degradation of extracellular matrix, immunosuppression and angiogenesis, all of which lead to escape cell death and increase cell survival rate, which is conducive to the reproduction of cancer cells [16] . the regulation of p53 gene activity is mainly at the posttranscriptional level. after phosphorylation of p53 protein is activated, it becomes p-p53, which then cmi 03 (04), 363−371 cmi journal 368 cmi journal fuxue meng et al. acts by inducing cell cycle arrest and inducing apoptosis to inhibit tumor cell proliferation [17;18] . after the above research and analysis, ppi networks were constructed by string, and from the intersection, 10 hub genes were obtained, which were verified and show with weighted network analysis. the analytic results of c3, c3ar1, fpr2, gna11, ptafr, itgam, anxa1, lpar1 cxcr4 and fpr1 were statistically significant, which suggested that these ten genes possibly play a key regulatory role in aml. in order to further understand the functions of ten hub genes, we performed mirna targets prediction and rbp targets prediction. mirna is an endogenous single-stranded small rna with a length of 21-25 bases, which can regulate the expression of target genes by specifically binding to mrna to degrade or inhibit protein translation of mrna. studies have shown that mirnas are often located in tumorigenesis-related regions or fragile sites, amplification regions, heterozygous loss regions or breakpoint regions. the specificity of mirna expression in tumor cells is specific to tumor occurrence, development, invasion, metastasis, and metastasis. it plays an important role in the prognosis and other processes, providing potential therapeutic targets or new strategies [19;20] . in this study, we selected 7 hub genes whose mirna prediction targets were hsamir-520d-5p, hsa-mir-362-5p, hsa-mir-224-5p, hsa-mir-1913, hsa-mir-196b-5，hsa-mir-1885p, hsa-mir-130a-5p, hsa-mir-204-5p, hsa-mir211-5p, hsa-mir-671-5p, hsa-mir-296-3p and hsa-mir-23b-3p. li [21] showed that hsa-mir-3623p was highly expressed as a marker in aml, and suggesting that it is related to the poor prognosis of aml patients. the prediction result of hsamir-1913 in aml is consistent with the result of wang [22] . rbp refers to the general term for proteins that directly bind to rna. rna in cells interacts with rbp to form a ribonucleoprotein (rnp) complex, which plays an important role in rna synthesis, transport, stability, translation, and cell positioning [23] . in the current study, the hub genes c3, gna11, ptafr, itgam, anxa1, lpar1 and cxcr4 were predicted to be strongly associated with proteins adar1, dgcr8, dkc1, elavl1, fbl, fus, hnrnpc, igf2bp2, nop58, taf15, u2af2 and upf1. interestingly, xiao [24] and peng [25] reported that adar1 plays an important role in acute myeloid leukemia. among them, xiao’s study demonstrate that adar1 may be involved in the regulation of the proliferation of aml cells partially via regulation of the wnt signaling pathway [24] . he et al reported that igf2bp2 overexpression indicates poor survival in patients with aml, igf2bp2 may serve as a biomarker to predict the prognosis of aml and as a potential target in aml [26] . conclusion in conclusion, the present study identified a panel of 10 genes in aml hl-60 cells. gene function and pathway investigation indicated that these genes were mainly engaged in citrulline metabolic process, positive regulation of neutrophil extravasation, positive regulation of cell adhesion molecule production, phospholipase a2 inhibitor activity, hematopoietic cell lineage, tgf-β signaling pathway, p53 signaling pathway. moreover, the mirna and rbp targets prediction hinted that the 10 hub genes identified plays an important role in prognosis of aml. hub genes c3, c3ar1, fpr2, gna11, ptafr, itgam, anxa1, lpar1 cxcr4 and fpr1 predictively targeted hsa-mir-520d-5p, hsa-mir-362-5p, hsamir-224-5p, hsa-mir-1913, hsa-mir-196b-5, hsa-mir-188-5p, hsa-mir-130a-5p, hsa-mir-2045p, hsa-mir-211-5p, hsa-mir-671-5p, hsa-mir296-3p and hsa-mir-23b-3p and adar1, dgcr8, dkc1, elavl1, fbl, fus, hnrnpc, igf2bp2, nop58, taf15, u2af2 and upf1 proteins may regulate the occurrence and development of aml, but further verification is needed. in short, this study provides meaningful insights and ideas for further understanding the pathogenesis of aml. abbreviation aml acute myeloid leukemia dnmt dna methyltransferase degs differentially expressed genes rbp rna binding protein c3ar1 complement component 3a receptor 1 fpr2 formyl peptide receptor 1 cmi 03 (04), 363−371 cmi journal 369 cmi journal fuxue meng et al. gna11 g protein subunit alpha 11 ptafr platelet activating factor receptor itgam integrin subunit alpha m anxa1 annexin a1 lpar1 lysophosphatidic acid receptor 1 cxcr4 c-x-c motif chemokine receptor 4 fpr1 formyl peptide receptor 1 elavl1 elav like rna binding protein 1 fus fus rna binding protein dkc1 dyskerin pseudouridine synthase 1 hnrnpc heterogeneous nuclear ribonucleoprotein c adar adenosine deaminase, rna specific igf2bp2 insulin like growth factor 2 mrna binding protein 2 nop58 nop58 ribonucleoprotein taf15 tata-box binding protein associated factor 15 upf1 upf1, rna helicase and atpase u2af2 u2 small nuclear rna auxiliary factor 2 acknowledgements we acknowledge geo database for providing their platforms and contributors for uploading their meaningful datasets. simultaneously, we also appreciate to the omicshare tool that online data analysis platform. authors contributions the design, study conduct, and financial support for this research were provided by meng fx, li lk and zheng q participated in the interpretation of data, review, and approval of the publication. funding this study was supported by the guizhou provincial health commission science and technology project (gzwjkj2019-2-006) and the qiannan prefecture science and technology project (qiannankeheshezi 2018 (36)). availability of data and materials the original data of this research come from the third platform geo database (gse24224), and bioinformatics analysis was carried out through relevant analysis tools. ethics approval and consent to participate not applicable. consent for publication not applicable. competing interests the authors declare that they have no competing interests. references 1. pelcovits a, niroula r. acute myeloid leukemia: a review. r i med j. 2020, 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abstract : methicillin-resistant staphylococcus aureus (mrsa) is a common and important cause of nosocomial infections not found in hospitals and health care facilities where people are poorly protected, mrsa is commonly spread in hospitals by patients as a primary reserve, health care workers (hcws), surrounding environments, and sometimes airborne, mrsa possesses a number of toxicity factors that play an important role in the spread and resistance of bacteria, including a super-antigen encoded by the tst gene toxic shock syndrome-1 ( tss-1) infectious complications are secondary forms of invasive bacterial diseases such as pneumonia, lung disorders, urinary tract infections, food poisoning, arthritis, endocarditis, meningitis, arthritis, toxic shock syndrome, sepsis and m. the study found the presence of methicillinresistant staphylococcal bacteria (mrsa), 39/46 (85%), the tst gene was absent in most isolates, only 6/39 (15.4%) of the tst gene. key words: staphylococcus aureus (mrsa), genê tst introduction staph aureus is one of the most common pathogenic bacteria, as its pathology is dependent on a group of virulence factors that affect the host and cause the disease. (hoseini alfatemi et al. 2014)it is also one of the "eskape" organisms, can cause many serious infections so it is considered a serious and growing threat worldwide that can affect various groups and can cause serious nosocomial infections. (liang et al. 2019) staph aureus can avoids further clearance by the immunity through the expression of surface-linked proteins and polysaccharide capsules that prevent opsono-phagocytic killing. staphylococcus protein a (spa) is a membrane-bound protein that binds with fc region in igg, thereby avoiding recognition of macrophages (walton 2013) the success of staph aureus a pathogen is explained by it ability to express: (1) its ability to invade and inflammate. this includes a number of mechanisms including colonization, synthesis of extracellular structure of molecules that facilitate adherence and help them avoid host defenses. (2) its ability to produce toxins. (zhu 2010) and(haghkhah 2003) neutrophils are the decisive defense of the body in controlling the colonization and spread of staph aureus despite the behavior of staphylococcus for many evasion strategies.one of these strategies is the induction of neutrophil cell death, which causes inflammations and tissue damage and increased disease severity. (yang et al. 2019) in addition to evading strategies, staph aureus produces many virulence factors, which include enzymes and toxins, in addition to its ability to produce septic shock by activating and interacting with the immune system and coagulation (rigby and deleo 2012) and (gordon and lowy 2008) . staph aureus produces a wide variety of exotoxins, among the numerous toxins of including enterotoxins, the enterotoxins super antigens have already been assigned to the pyrogenic toxin super antigen family based on their biological activity and structural similarity, toxic shock toxin-1 (tsst-1) that induces super antigenic activity, and exfoliative toxins (ets), these toxins are responsible for specific acute clinical syndromes such as toxic shock syndromes (tss) , food poisoning due to staphylococcus enterotoxins and staphylococcal scarlet fever (a mild form of tss), all these toxins share in their structural and biological properties, and this indicates that they are derived from a common ancestor. (zhu 2010) and (thomas et al. 2006) . another class of genetic characteristics of staphylococci is a super-antigen that encoded by tst gene, that carried on proliferation of tst genes in methicillin-resistant staphylococcus aureus (mrsa clinical medicine insights page 2 mobile genetic elements (mge) named (sapis.), nearly 15 kb genomic regions that significantly denote a number of virulence genes, (sapis) linked to specific staph aureus genetic families, known as lineages (sharma et al. 2018) and (shien 2014) toxic shock syndrome-1 (tss-1) secondary inflammatory complications include invasive forms of bacterial diseases such as inflammation of the lungs, lung abscesses, urinary tract infections, food poisoning, osteoarthritis, endocarditis, meningitis, arthritis, toxic shock syndrome, septicemia, death (bocskay 2016) materials and methods sampling a total of 484 samples collected from patients (skin swab, nasal swab and wound swab), health care workers (skin swab and nasal swab), hospital words (orthopedic and surgical words) and operation theater (various places of operation theater before and after sterilization). samples were collected in the period between november 2018 and august 2019, from two locations, al-basrah teaching hospital and al-saddr teaching hospital. each swab was transferred in to enrichment medium (brain heart infusion broth (bhib)) for 2-4 hour at 37 o c. (nicholas p. vitko and anthony r. richardson 2014) culture and identity staphylococcus grows easily on most routine media at aerobic or micro-aerophilic conditions. it was quickly grows at (37°c), and the ideal temperature in which the pigment is formed is 20-25°c staph aureus usually forms grey to golden yellow colonies due to carotenoids, produces β-haemolysis on horse, sheep or human blood agar plates (suzuki et al. 2012) and (gillet et al. 2002) the bacterial morphology was observed microscopically as gram-positive cocci arranged in grape-like irregular clusters (gillet et al. 2002) all staph aureus strains produce coagulase enzyme. staph aureus are catalase positive and oxidase negative (suzuki et al. 2012) staph aureus express a clumping factor (fibrinogen affinity factor) (reddy, srirama, and dirisala 2017) staphylococcus can grow in a medium with a high salt concentration, so they can grow easily in msa. the acidity of the medium changes as the bacteria ferments mannitol and turn phenol red phindicator; staph aureus changes color of msa from the alkaline (red)to the acidic(yellow), while the rest of the staphylococcus will grow without changing the color of the medium. (gillet et al. 2002) detection of mrsa • cefoxitin disc diffusion, significant method to detect mrsa, by testing mrsa resistance to the cefoxitin disc, culture was done on mha plate , incubation temperatures at 35-36 0 c and times of 18-24 hour strains of staph aureus having zone of inhibition less than 19mm defined as mrsa. (brown et al. 2005) • pcr methods, strains of staph aureus harboring meca gene defined as mrsa (brown et al. 2005) genomic dna extraction as the instruction of manufacturer (promega company) polymerase chain reaction (pcr) according to the manufacturer's instructions, the dna were detected by gel electrophoresis, the samples were loaded in 0.8% agarose gel 1×tbe (54 g tris-base, 0.5m edta, 1-l distilled water, ph=8 and diluted with 400 ml of distilled water) and electrophoresed at 60 v for 30 min. polymerase chain reaction technique pcr is a very effective method to amplify a particular dna as many copies of a specific dna (bartlett 2003), all mrsa isolates were assayed for the presence of the tst gene by pcr using previously described primers, for pcr used diluted forward and reverse primers to reach (100 pmol/μl) concentration as stock solution, distilled water was used as the negative control. statistical analysis statistical analysis was done using spss (statistical package for social sience) program v. 20, experimental data were presented in terms of observed numbers and percentage frequencies, and then analyzed by using chi-square (χ2) test to determine the relationship between the variables, p value ≤ 0.05 proliferation of tst genes in methicillin-resistant staphylococcus aureus (mrsa clinical medicine insights page 3 was considered statistically significant. results identification of bacterial isolates samples were collected in the period between november 2018 and august 2019 from two locations, albasrah teaching hospital and al-sadder teaching hospital. out of 485 samples only 46 (9.48 %) were identified as coagulase positive staphylococci, as shown in table (3-1) pcr product was electrophoresed in 1.5 % agarose gel, stained with ethidium bromide, , 7 μl of pcr products and promega dna ladder (501000bp) carefully loaded in the wells and electric current was matched (65 volt for 45 h). the gel was then observed under a uv light and compare with ladder (50-1000bp). detection of mrsa isolate cefoxitin resistance staph aureus isolate harboring meca gene (mrsa) was detected in 39from 46(85%) s. aureus isolates. 10(90%) isolates of mrsa were from wound samples, 6 (75%) from patient skin swab and 5 (83%) from patient noses, 4(80%) from hospital wards, 4(80%) from health care workers hands, 7(100%) from health care workers noses and 3 (75%) from hospitals theaters samples. meca gene detactions staphylococcus meca gene presence in all mrsa isolates, to detect staph aureus isolates with meca gene, it was subjected to pcr technique, meca gene band detected at 147bp region. tst gene detection tst gene detected only in 15.4% of mrsa isolate. after amplification by pcr technique. genes were detected by gel electrophoresis of amplified pcr products of tst genes (326bp) of staph aureus isolates in pcr techniqerror! reference source not found. sequencing for tst gene query isolate (our isolate) begin from (9-291) bp when compared with subject isolate (stander isolate) begin from (455638-455356) bp, where the compatibility occur between the two isolates for identification query isolate, identities was 98%, there was a mismatch at seven places. discussion the study showed that these bacteria isolated from the hospital environment (operating rooms and patients' rooms) and hands and noses of workers and patients may be causes wound infection, there is increasing concern about mrsa contamination and infections in the hospital words meanly in post-operative wound, in our study isolation showed high prevalence range of mrsa strains 85% (39/46) of the total staph aureus isolated from various samples, higher rate of mrsa isolations from h.c.w nasal swabs 100% (7/7), followed by wound swabs 90.9% (10/11), nasal swab from patient 83% (5/6), h.c.ws hand swabs and hospital words 80% (4/5) for each, lowest rate were recorded for the patient skin swab (6/8) and operative rooms (3/4) 75% each. the finding about high prevelance of mrsa is not surprising and is also in line with several studies carried out in iraq. (al-azawi et al. 2016) ; (al-dahbi and al-mathkhury 2013) and (almaliki 2009) the ratio of mrsa was relatively low in a study conducted in kurdistan region of iraq, in 2015 where the mrsa prevalence was 53% (hussein et al. 2015) in another study in iran was 69% (jahanshahi, zeighami, and haghi 2018) while in a study conducted in india, the percentage was much lower 16.6% (goud et al. 2011) mrsa prevalence 51.4% at the korean hospital from the staph aureus collected from blood and nasal colonizers (peck et al. 2009) in general mrsa was highly prevalent in asian countries (hussain et al. 2019) in the german study there was a decrease in mrsa rate (schubert, kämpf, wahl, et al., 2019b) in turkey 2017, high rates of staph aureus high resiste to penicillin and ampicillin (yılmaz and aslantaş 2017) a study in isfahan, iran, in 2018 showed a nasal carriage of mrsa 51.9% among patient and 16% among health workers (moshtagheian et al. 2018) mrsa prevalence in wounds was high, and this is consistent with previous studies, 76.9% (khanal and jha 2010); 44% (tyagi, kapil, and singh 2008); 60.1% (orrett and land 2006); 34.8% (hafeez, chughtai, and aslam 2004) the presence of mrsa in wounds delays healing (solomkin 2001). in other study the average of mrsa rate for wound infections after cardiothoracic surgery was 54% in a three-year period from 2007 to 2010 (walsh, greene, proliferation of tst genes in methicillin-resistant staphylococcus aureus (mrsa clinical medicine insights page 4 and kirshner 2011) during the present study, mrsa isolate from hcws noses was (19.4%) which corresponds to previous studies (caceres 2011); (shittu et al. 2011) and (munoz et al. 2008); 12.7% (shibabaw, abebe, and mihret 2013) 12% in (ibarra et al. 2008); 14.3% (radhakrishna et al. 2013), mrsa rate was low in other studies; only 5.3% in iran study (askarian et al. 2009); and it was 0% in kenya (omuse, kariuki, and revathi 2012) with increasing of mrsa colonization rate, there is greater risk in developing drug-resistant wound infections. therefore, it is necessary to avoid infection as much as possible. previous reserchs have shown a large infections rate due to cross-contamination by hands of health staff (rotter and koller 1991) all mrsa isolate in our study harboring meca gene. this result agreed with many other studies that showed all mrsa isolate harboring meca gene (yang et al. 2020); (mussa and almathkhury 2018); (karmakar, dua, and ghosh 2016)(al-charrakh, al-hassnawi, and al-khafaji 2015); (dağı et al. 2015) other studies considered that methicillin resistance can be happen in meca absence, mrsa could have other mechanism(s) for resistance; e.g., altered target site or may be reduced drug accumulation. meca gene absence may also due to a technical error upon detection. (mahdi et al. 2016); (carpaij et al. 2011) and (wielders et al. 2002) the tsst coded by tst gene (dinges, orwin, and schlievert 2000) the tst gene was detected in (15.4%) mrsa isolates in our study, the percentage was close to these studies (ezeamagu et al. 2018) and (hoseini alfatemi et al. 2014) (14%,11.6%) respectively.in other studies, the tst gene ratio was slightly higher, tst gene was detected in (26.31%) (costa et al. 2018) (27.9%) (megevand,et,al,2010), other studies recorded highly prevalent tst gene (72.2%) in mrsa isolates from blood (peck et al. 2009) whereas in another study, tst genes were non-detected (motallebi et al. 2019) references 1. al-azawi, noor, k. mohammed ali, alaa alwan, s. b. i. al-rifai, and a. al-bayati. 2016. “antibiotic resistance pattern of ha-mrsa strains isolated from leukemia patients in baghdad, iraq.” international journal of infectious diseases 45:81–82. 2. al-charrakh, alaa h., huda h. al-hassnawi, and jawad k. al-khafaji. 2015. “molecular characteristics of community-associated methicillin-resistant staphylococcus aureus (ca-mrsa) isolates from clinical specimens in iraq.” british microbiology research journal 5(3):227. 3. al-dahbi, ali m. and harith j. al-mathkhury. 2013. “distribution of methicillin resistant staphylococcus aureus in iraqi patients and healthcare workers.” iraqui journal of science 54(2):293–300. 4. al-maliki, a. a. a. 2009. “a study of some methicillin-resistant staphylococci (mrsa) and (mrse) isolated from baghdad hospital patients.” 5. alkharsah, khaled r., suriya rehman, fatimah alkhamis, amani alnimr, asim diab, and amein k. al-ali. 2018. “comparative and molecular analysis of mrsa isolates from infection sites and carrier colonization sites.” annals of clinical microbiology and antimicrobials 17(1):1–11. 6. bartlett, john m. s. and david stirling. 2003. pcr protocols. vol. 226. 7. biglari, haniyeh, ali mojtahedi, morovat taheri kalani, ali ashraf, and maryam shakiba. 2019. “investigation of vancomycin susceptibility and toxic shock syndrome toxin 1 gene among staphylococcus aureus strains isolated from patients and icu staff in the north of iran.” gene reports 14(december 2018):138–41. 8. bocskay, ildiko. 2016. “methicillin-resistant staphylococcus aureus infections in the eight service planning areas of los angeles county.” walden dissertations and doctoral studies. 9. brown, derek f. j., david i. edwards, peter m. hawkey, donald morrison, geoffrey l. ridgway, kevin j. towner, and michael w. d. wren. 2005. “guidelines for the laboratory diagnosis and susceptibility testing of methicillin-resistant staphylococcus aureus (mrsa).” journal of antimicrobial chemotherapy 56(6):1000–1018. 10. caceres, mercedes. 2011. “frequency of nasal carriers of methicillin-resistant staphylococcus aureus among health workers in nicaraguan hospitals.” revista panamericana de salud publica= pan american journal of public health 30(6):610–14. 11. carpaij, neeltje, rob j. l. willems, thomas w. rice, robert a. weinstein, jason hinds, adam a. witney, jodi a. lindsay, marc j. m. bonten, and ad c. fluit. 2011. “genetic variation in spatiotemporal confined usa300 community-associated mrsa isolates: a shift from clonal dispersion to genetic evolution?” plos one 6(2). proliferation of tst genes in methicillin-resistant staphylococcus aureus (mrsa clinical medicine insights page 5 12. costa, f. n., n. o. belo, e. a. costa, g. i. andrade, l. s. pereira, i. a. carvalho, and r. l. santos. 2018. “frequency of enterotoxins, toxic shock syndrome toxin-1, and biofilm formation genes in staphylococcus aureus isolates from cows with mastitis in the northeast of brazil.” tropical animal health and production 50(5):1089–97. 13. dağı, hatice türk, duygu fındık, gamze demirel, and uğur arslan. 2015. “detection of methicillin resistance and various virulence factors in staphylococcus aureus strains isolated from nasal carriers.” balkan medical journal 32(2):171–75. 14. dinges, martin m., paul m. orwin, and patrick m. schlievert. 2000. “exotoxins of staphylococcus aureus.” clinical microbiology reviews 13(1):16–34. 15. ezeamagu, cajethan, irene imanatue, margaret dosunmu, adebola odeseye, glory baysah, daniel aina, foluke odutayo, and grace mensah-agyei. 2018. “detection of methicillin resistant and toxin-associated genes in staphylococcus aureus.” beni-suef university journal of basic and applied sciences 7(1):92–97. 16. garazi, michele, barbara edwards, donna caccavale, charles auerbach, and gisele wolf-klein. 2009. “nursing homes as reservoirs of mrsa: myth or reality?” journal of the american medical directors association 10(6):414–18. 17. gillet, yves, bertrand issartel, philippe vanhems, jean christophe fournet, gerard lina, michèle bes, françois vandenesch, yves piémont, nicole brousse, daniel floret, and jerome etienne. 2002. “association between staphylococcus aureus strains carrying gene for panton-valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients.” lancet 359(9308):753–59. 18. goud, rajendra, soham gupta, ujjwal neogi, deepali agarwal, kesava naidu, raju chalannavar, and gaddad subhaschandra. 2011. “community prevalence of methicillin and vancomycin resistant staphylococcus aureus in and around bangalore, southern india.” revista da sociedade brasileira de medicina tropical 44(3):309–12. 19. hafeez, rubeena, a. s. chughtai, and m. aslam. 2004. “prevalence and antimicrobial susceptibility of methicillin resistant staphylococcus aureus (mrsa).” int j pathol 2(1):10–15. 20. hoseini alfatemi, seyedeh mahsan, mohammad motamedifar, nahal hadi, and hadi sedigh ebrahim saraie. 2014. “analysis of virulence genes among methicillin resistant staphylococcus aureus (mrsa) strains.” jundishapur journal of microbiology 7(6):1–10. 21. hussain, muhammad shahbaz, abbas naqvi, and muhammad sharaz. 2019. “methicillin resistant staphylococcus aureus (mrsa).” the professional medical journal 26(01):122–27. 22. hussein, nawfal r., ahmed alyas, marwan majeed, and mahde s. assafi. 2015. “prevalence rate and prevalent genotypes of ca-mrsa in kurdistan region: first report from iraq.” international journal of pure and applied sciences and technology 27(1):44. 23. ibarra, maria, tristan flatt, diane van maele, aisha ahmed, jaime fergie, and kevin purcell. 2008. “prevalence of methicillin-resistant staphylococcus aureus nasal carriage in healthcare workers.” the pediatric infectious disease journal 27(12):1109–11. 24. jahanshahi, aidin, habib zeighami, and fakhri haghi. 2018. “molecular characterization of methicillin and vancomycin resistant staphylococcus aureus strains isolated from hospitalized patients.” microbial drug resistance 24(10):1529–36. clinical medicine insights received 15 apr 2021 | revised 30 apr 2021 | accepted 15 june 2021 | published online 30 june 2021 doi: https://doi.org/xx.xxx/xxx.xx cmi 2 (2), 104−109 (2021) issn (o) 2694-4626 if:1.6 research article desarda repair no mesh and lichtenstein repair for inguinal hernia (a study of 2793 patients) dr. pedro rolando lòpez rodrìguez 1∗ dr. eduardo garcia castillo 2 dra. olga caridad leòn gonzàlez 3 dr. jorge agustin satorre rocha 4 dr. luis marrero quiala 5 dra. lais angèlica ceruto ortiz 6 1specialist of i degree and ii degree in general surgery, axiliary professor, consulting professor and auxiliary researcher. 2specialist of i degree in general surgery . assistant professor. 3specialist of i degree in general surgery ,auxiliary professor and auxiliary researcher. 4specialist of i degree in general surgery and auxiliary professor 5specialist of i degree in general surgery and assistent professor. 6third year resident in general surgery abstract introduction: the objective of this study is to compare the outcomes of desarda repair no mesh and lichtenstein repair for inguinal hernia. patients and methods: this is a prospective randomized controlled trial study of 2793 patients having 2936 hernias operated from january 2002 to december 2020.1434 patients were operated using lichtenstein repair and 1359 using desarda repair. the variables like age, sex, location, type of hernia, tolerance to local anesthesia, duration of surgery, pain on the first, third and fifth day, hospital stay, complications, re-explorations, morbidity and time to return to normal activities were analyzed. follow up period was from 1-10 years (median 6.5 years). results: there were no significant differences regarding age, sex, location, type of hernia, and pain in both the groups. the operation time was 53 minutes in desarda group and 43 minutes in the lichtenstein group that is significant (p<0.05).the recurrence was 0.4 % in desarda group and 0.4 % in lichtenstein group. but, there were 14 cases of infection to the polypropylene mesh in the lichtenstein group, 7 of this required re-exploration. the morbidity was also significantly more in lichtenstein group (5,1 %) as compared to desarda group (3.1 %). the mean time to return to work in the desarda group was 8.26 days while a mean of 12.58 days was in the lichtenstein group. the mean hospital stay was 29 hrs. in desarda group while it was 49 hours in the lichtenstein group in those patients who were hospitalized. conclusions: desarda repair scores significantly over the lichtenstein repair in all respects including re-explorations and morbidity. desarda repair is a better choice as compared with lichtenstein repair. keywords: lichtenstein repair, desarda repair, inguinal hernia, randomized trial. copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). cmi 2 (2), 104−109 meerp ltd 104 https://orcid.org/0000-0001-5646-1699 https://orcid.org/0000.0002-7560-3581 https://orcid.org/0000-0001-9437-3091 https://orcid.org/0000-0002-7976-8869 https://orcid.org/0000-0002-4705-4714 https://orcid.org/0000-0003-4650-9040 https://creativecommons.org/licenses/by-nc-nd/4.0/ https://medicineinsights.info/index.php/cmi/index 1 introduction the surgeons use different techniques in cuba for inguinal hernia repair like bassini or shouldice and its modifications or different types ofmesh repairs. the standardmesh is not available at many places and it is expensive also. hernia treatment has become a health problem because of its social, economic and labor implications due to its high incidence in our population (1). until recently, the only parameters to be evaluated were recurrence, complication rates etc. today, other parameters like cost, postsurgerywellbeing and quality of life have gained importance. the demand of general surgeons is to identify operations that are simple to perform without the need for complicated dissection and with low complication and recurrence rates. avoidance of use of foreign material where possible is a basic surgical principal.the authors read about the desarda repair which seems be simple in concept, avoids the use of mesh and gives the desired results. this repair is based on the concept of providing a strong and physiologically dynamic posterior wall to the inguinal canal. an undetached strip of the aponeurosis of the external oblique muscle replaces the absent aponeurotic element in the posterior wall and the weakened conjoint muscle receives additional strength from the external oblique muscle to keep it physiologically dynamic (2).there are still many controversies to answer. which is the best technique for repair? (3) is hernioplasty better than herniorrhaphy? which is the best technique for hernioplasty or herniorrhaphy?does laparoscopic surgery have a better cost-efficiency than open surgery? is mesh necessary in all inguinal hernia repairs?the objective of this study is to re-evaluate the lichtenstein mesh repair and compare it with the novel and “no mesh, physiological repair” described by desarda. methods a prospective randomized controlled trial was carried out in 2793 patients having 2936 hernias operated from january 2002 to december 2020. 1434 patients having 1536 hernias were in the lichtenstein group and 1359 patients having 1406 hernias in the desarda group. all the patients from both sexes older than 16 years with primary and recurrent inguinal hernias were included. patients operated on emergency basis were excluded. the diagnosis of inguinal hernia and its typewasmade by clinical examination. information was given to the patients as regards the anesthetic procedures. the patient chose type of anaesthesia after discussion with the surgeon. the randomization was performed using a consecutively numbered, sealed envelope, which was opened, in theatre and all patients having an even number were operated by the lichtenstein and uneven numbers by the desarda technique. the operating surgeon completed a data sheet. the operating surgeon was at consultant level for all operations. the evaluator was also a surgeon of consultant level. all patients signed a written informed consent. approval of the local ethical committee was given prior to the onset of the study. desarda repair was performed according to the surgical technique described by dr. desarda and mesh prosthesis repair was undertaken as described in the textbooks. prophylactic antibiotic was administered in the operating room before surgery (cefazoline 1g.) in the lichtenstein group only. all patients were discharged as soon as their post-surgical recovery allowed and all patients were instructed to do daily, routine, non-strenuous work after discharge.a non-steroidal anti-inflammatory (diclofanac) analgesic was prescribed for a period of 5 days and continued if required. the consultants followed all the patients at 8 days, 1 month, 6 months and then yearly thereafter.a data sheet was completed by the operating surgeon including type of hernia (nyhus classification) (4), anaesthesia, technical details and intra operative complications. at discharge, further data was added including any early post-operative complications. patients were asked to complete a pain score on the first, third and fifth day after surgery using a linear analogue scale (5, 6). at first follow up, one month after surgery, further data supplementary information the online version of this article (https://doi.org/xx.xxx/xxx.xx) contains supplementary material, which is available to authorized users. corresponding author: dr. pedro rolando lòpez rodrìguez specialist of i degree and ii degree in general surgery, axiliary professor, consulting professor and auxiliary researcher. email: pedro.rolando.lopez42@gmail.com cmi 2 (2), 104−109 meerp ltd 105 mailto:pedro.rolando.lopez42@gmail.com meerp ltd dr. pedro rolando lòpez rodrìguez et al. were collected including time to return to normal activities. the student t test was used to compare the independent measures and the mann whitneyu test for nonparametric data. the chi-squared test and fisher’s exact test were used to measure the association between quality variables. 2 results table 1: age,sex, location and type of hernia. therewas no significant difference in relation to sex, age, location and type of inguinal hernia in both the groups. table1 local anesthesia was used in 612 patients in licht-enstein group and 865 patients in the desarda group. all those 1477 (53.0%) patients were operated on as outpatient basis without hospitalization. in the re-mainder short term of 1207 patients who were treated as in-patients,the mean hospital stay was 28 hours in desarda group and 48 hours in the lichtenstein group (p<0.05) (table 2). all those 707(53.0%) patients were operated on as outpatient basis without hospitalization. in the re-mainder of 635 patients who were treated as in-patients,the mean hospital stay was 27 hours in de-sarda group and 47 hours in the lichtenstein group (p<0.05) (table 2). table 3: o. 3 dura on of surgery and pain. tolerance to local anesthesia was good during surgery in 52,0 % and 58,5 % respectively (ns). the mean duration of surgery was 40 minutes for licht-enstein and 51 minutes for desarda group (p<0.05). analysis of pain scores from day one to day 5 showed no significant difference (table 3). there was no incidence of severe pain in either group. meerp ltd cmi 2 (2), 104−109 (2021) 106 table 2: o. 2 anesthesia and hospital stay table 4: o. 4. recurrence and re-explora on. desarda repair no mesh and lichtenstein repair for inguinal hernia (a study of 2793 patients) the recurrence rate was 0.44% in the desarda group, and 0.41 % in the lichtenstein group (ns). seven patients in the lichtenstein group required reexploration and mesh removal for the sepsis. thus 0.5 % of patients in the lichtenstein group required a further surgical intervention for either recurrence or sepsis which was significantly higher than the desarda group (p<0.05) (table 4). table 5: o. 5 morbidity . the seroma was the complication that most frequently occurred with 27 patients in both groups (1.0%). 74 (5,3 %) patients developed post-operative complications in the lichtenstein group and 43 (3.1 %) patients showed complications in the desarda group, the recurrence in both groups ( 0,4) (p<0.05) (table 5). 69,5 % patients returned to work within 8-15 days in the desarda group with a mean of 13,4days while table 6: o. 6 return to work. 56,0 % patients returned to work within 8-15 days with a mean of 14.5 days in the lichtenstein group , that is significant because in the lichtenstein group the morbidity is higher than in the desarda group (p<0.05) (table 6). there was no case of chronic groin pain lasting for more than 6 months in either of the groups. follow up was complete in over 97% at 1 year, 92% at 2 years,89% at 3 years, 83% at 4 years,80% at 5 years, 80% at 6 years, 76% at 7 years, 73% at 8 years, 72% at 9 years and 70% at 10 years with no significant difference between the two operation groups. lichtenstein group : mean: 1-7 days : 6,8 days , 8-15 days : 14,5 days , 16-30 days : 21,3 days. desarda group : mean :1-7 days : 5-7 days , 8-15 days : 13,4 days, 16-30 days : 18,4 days. 3 discussion mesh repair is now widely used in the developed world and is often referred to as the gold standard despite a relative paucity of clinical trials comparing mesh with suture repair. the cost of surgery (7) and the post-operative morbidity affecting the quality of life are important considerations in the inguinal hernia surgery. there are no clear scientific evidences to prove that the mesh prosthetic repair is superior to the non-prosthetic repair in this respect (8). there are advantages and disadvantages associated with all types of open inguinal hernia repairs. existing non-prosthetic repair (bassini/shouldice) is blamed causing tissue tension and mesh prosthetic repair is blamed for known complications of a foreign body. dr. desarda sutures an undetached strip of the external oblique aponeurosis between the muscmi 2 (2), 104−109 (2021) meerp ltd 107 meerp ltd dr. pedro rolando lòpez rodrìguez et al. cle arch and the inguinal ligament to give a strong and physiologically dynamic posterior wall (9). this results in a tension free repair without the use of any foreign body. being simple to perform it eliminates disadvantage of technical difficulty seen with shouldice repair. different studies have tried to give an answer as to which of the existing operation is best for inguinal hernia repair (10, 11). the eu hernia trialist collaboration (12) made a systematic revision of the randomized prospective studies and the analysis of the results of these different studies. it showed that the duration of surgery was less in hernioplasty in six studies, longer in three and equal in the remaining six. in our group, there was a significant but slight increase in operating time with the desarda operation. postoperative pain after mesh prosthetic repair may be less than after shouldice repair because of reduced tension (12, 13). our results have shown that there are no significant differences between the two groups for pain on the first to fifth day after surgery. we found no significant difference in analgesic requirements between the techniques. overall morbidity was 5.0%, which is similar to the rates described in other studies (712%) (14). the morbidity rate was higher after the lichtenstein repair (53 cases, 7.5% versus 26, 3.4% in the desarda group). there were 8 mesh infections after surgery in the lichtenstein group. two cases required partial excision of the mesh and in one case, it was associated with recurrence. desarda technique has lower morbidity as compared to mesh hernioplasty. we believe that the four cases of recurrences seen in desarda group were due to failure of proper lateralization of the cord and insufficient narrowing of the internal ring as advised by desarda. this was evident at re-exploration in those cases that needed only narrowing of the internal ring with few more stitches. in patients admitted to hospital, post-operative stay and the period required to return to normal work after surgery was also significantly in favour of the desarda group. 62 patients from lichtenstein group required more than 3 days in the hospital due to local wound complications or for some other reasons compared to only 5 patients from thedesarda group, a significant difference.we noted a marked difference in the type of anaesthetic used 39% v 72% for local, 54% v 25% for spinal and 7% v 2% for general anaesthetic in lichtenstein v desarda group. this could affect the statistics of hospital stay of the patients who required hospitalization. the external oblique muscle technique satisfies all criteria of modern hernia surgery. it is simple and easy to do. it does not require risky or complicated dissection. there is minimal tension in the suture line. it does not require any foreign material and it does not use weak muscle or fascia transversalis for repair. it does not use mesh prosthesis so it is more economical. no foreign body is required in the desarda repair thus avoiding morbidity associated with foreign bodies including rejection, infection and chronic groin pain. jacek szopinski et al. (15) stated in their randomized controlled trial (rct) that the “desarda technique has the potential to enlarge the number of tissue based methods available to treat groin hernias. themost evident indications for use of the desarda technique include use in young patients, in contaminated surgical fifields, in the presence of fifinancial constraints, or if a patient disagrees with the use of mesh.”situma et al. (16) compared desarda technique with the modified bassini technique in their rct and concluded that there is no difference in short-term outcome between desarda and modified bassini inguinal hernia repair as regards resumption of normal gait and patterns of pain. manyilirah (17) concluded in their rct that the efficacy of the desarda technique in respect of the early clinical outcomes of hernia repair is similar to that of lichtenstein method. however the operator in this study showed that the desarda repair takes a significantly shorter operative time (18–20). the authors therefore conclude that thedesarda repair for inguinal hernia gives the same or better results when compared with the lichtenstein mesh repair with shorter hospital stay, more rapid recovery and avoidance of specific mesh related complications whilst also reducing the cost of surgery. it is technically simpler than the shouldice repair and we recommend that surgeons become acquainted with this technique [21,22,23,34] (21–23). conclusion .desarda repair scores significantly over the lichtenstein repair in all respects including reexplorations andmorbidity. desarda repair is a better choice as compared with lichtenstein repair. meerp ltd cmi 2 (2), 104−109 (2021) 108 desarda repair no mesh and lichtenstein repair for inguinal hernia (a study of 2793 patients) 4 conflicts of interestthe authors do not declare conflicts of interest. references 1. rutkow mi. epidemiologic, economic and sociologic aspects of hernia surgery in the united states in the 1900s. surg north am. 1998;78(6):941–951. 2. poojary hs, prasanna pg, mulki s. desarda technique versus lichtenstein repair for inguinal hernia in tertiary care centre: a prospective study. international surgery journal. 2020;7(3):680–680. available from: https://dx. doi.org/10.18203/2349-2902.isj20200543. doi: 10.18203/2349-2902.isj20200543. 3. porrero jl, bonachía o, lópez-buenadicha a, sanjuanbenito a, sánchez-cabezudo c. reparación de la hernia inguinal primaria: lichtenstein frente a shouldice. estudio prospectivo y aleatorizado sobre el dolor y los costes hospitalarios. cirugía española. 2005;77(2):75– 78. available from: https://dx.doi.org/10.1016/ s0009-739x(05)70811-3. doi:10.1016/s0009-73 9x(05)70811-3. 4. aragon fj; 2001. 5. price dd, bush fm, long s, harkins sw. a comparison of pain measurement characteristics of mechanical visual analogue and simple numerical rating scales. pain. 1994;56(2):217– 226. available from: https://dx.doi.org/10.1016/ 0304-3959(94)90097-3. doi:10.1016/0304-395 9(94)90097-3. 6. porrerojl, sanchez-cabezudo c, lee p. study of unilateral post-herniorrhaphy analgesia with local anaesthetic and monitored anaesthesia care. ambulatory surg. 1998;6:211–214. 7. hospitalarios c; 2005. 8. porrero jl. el cambio de la cirugía de la hernia en la última década. fundamentos de la hernioplastia sin tensión madrid: fundación jiménez díaz. 1999;p. 9–11. 9. desarda mp. surgical physiology of inguinal hernia repair a study of 200 cases. bmc surgery. 2003;3(1):1–9. available from: https: //dx.doi.org/10.1186/1471-2482-3-2. doi:10.11 86/1471-2482-3-2. 10. simonsmp, kleijnen j, van geldere d, hoitsma hfw, obertop h. role of the should ice technique in inguinal hernia repair: a systematic review of controlled trials and a meta-analysis. british journal of surgery. 2005;83(6):734–738. available from: https://dx.doi.org/10.1002/bjs. 1800830606. doi:10.1002/bjs.1800830606. 11. mcgillicuddy je. prospective randomized comparison of the shouldice and lichtenstein hernia repair procedures. archives of surgery. 1998;133(9):974–974. available from: https: //dx.doi.org/10.1001/archsurg.133.9.974. doi:1 0.1001/archsurg.133.9.974. 12. mesh compared with non-mesh methods of open groin hernia repair: systematic review of randomized controlled trials. br j surg. 2000;87(7):854–859. 13. kingsnorth an, porter cs, bennett dh, walker aj, hylandme, sodergren s. lichtenstein patch or perfix plug-and-patch in inguinal 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https://dx.doi.org/10.1016/s0009-739x(05)70811-3 http://dx.doi.org/10.1016/s0009-739x(05)70811-3 http://dx.doi.org/10.1016/s0009-739x(05)70811-3 https://dx.doi.org/10.1016/0304-3959(94)90097-3 https://dx.doi.org/10.1016/0304-3959(94)90097-3 http://dx.doi.org/10.1016/0304-3959(94)90097-3 http://dx.doi.org/10.1016/0304-3959(94)90097-3 https://dx.doi.org/10.1186/1471-2482-3-2 https://dx.doi.org/10.1186/1471-2482-3-2 http://dx.doi.org/10.1186/1471-2482-3-2 http://dx.doi.org/10.1186/1471-2482-3-2 https://dx.doi.org/10.1002/bjs.1800830606 https://dx.doi.org/10.1002/bjs.1800830606 http://dx.doi.org/10.1002/bjs.1800830606 https://dx.doi.org/10.1001/archsurg.133.9.974 https://dx.doi.org/10.1001/archsurg.133.9.974 http://dx.doi.org/10.1001/archsurg.133.9.974 http://dx.doi.org/10.1001/archsurg.133.9.974 https://dx.doi.org/10.1067/msy.2000.104124 https://dx.doi.org/10.1067/msy.2000.104124 http://dx.doi.org/10.1067/msy.2000.104124 http://dx.doi.org/10.1067/msy.2000.104124 https://dx.doi.org/10.1007/s00268-012-1508-1 https://dx.doi.org/10.1007/s00268-012-1508-1 http://dx.doi.org/10.1007/s00268-012-1508-1 http://dx.doi.org/10.1007/s00268-012-1508-1 meerp ltd dr. pedro rolando lòpez rodrìguez et al. 16. situma s, kaggwa, masiira, mutumba s. comparison of desarda versus modified bassini inguinal hernia repair: a randomized controlled trial. east cent afr j surg. 2009;14(2):70–76. 17. manyilirah w, kijjambu s, upoki a, kiryabwire j. comparison of non-mesh (desarda) and mesh (lichtenstein) methods for inguinal hernia repair among black african patients: a short-term double-blind rct. hernia. 2012;16(2):133–144. available from: https: //dx.doi.org/10.1007/s10029-011-0883-0. doi: 10.1007/s10029-011-0883-0. 18. yousset t, el-alfy k, farid m. randomized clinical trial of primary inguinal hernia. int j surg. 2015;20:28–34. 19. dieng m, cisse m, seek m, diallo fk, tourè ad. cure des hernies inguinales simples de l’ adulte pastie avec l’ aponèurose du grand oblique: technique de desarda. e-mèmoires de l’acadèmie nationale de. chirurgie. 2012;11(2):69–074. 20. pachauri a, kumar a. outcome of desarda repair in incarcerated inguinal hernia repair: experience in university hospital. international surgery journal. 2019;6(6):2084–2084. available from: https://dx.doi.org/10.18203/23492902.isj20192371. doi:10.18203/2349-2902.is j20192371. 21. jianxin z, dong jw, zhiyong z. desarda inguinal hernia repair and synthetic patch (open vs tep) hernia repair comparative study. j chinese her and abdominal surg. 2013;7(6):559– 563. 22. roduìguez prl, herrera p, g p, gonzàlez l, c o, alonso c, et al. a randomized trial comparing lichtenstein repair and no mesh desarda repair for inguinal hernia: a study of 1382 patients. east cent afr j surg. 2013;. 23. fardhus md, sharfuzzaman am, dewan n, hossain a, sami-al-hassam a, rabj z. lichtenstein versus desarda’s technique of hernia repair. j of surg bscien. 2018;22(2):99–103. how to cite this article: d.p.r.l.r., d.e.g.c., d.o.c.l.g., d.j.a.s.r., d.l.m.q., d.l.a.c.o. desarda repair no mesh and lichtenstein repair for inguinal hernia (a study of 2793 patients) . clinical medicine insights. 2021;104−109. https:/ /doi.org/xx.xxx/xxx.xx meerp ltd cmi 2 (2), 104−109 (2021) 109 https://dx.doi.org/10.1007/s10029-011-0883-0 https://dx.doi.org/10.1007/s10029-011-0883-0 http://dx.doi.org/10.1007/s10029-011-0883-0 http://dx.doi.org/10.1007/s10029-011-0883-0 https://dx.doi.org/10.18203/2349-2902.isj20192371 https://dx.doi.org/10.18203/2349-2902.isj20192371 http://dx.doi.org/10.18203/2349-2902.isj20192371 http://dx.doi.org/10.18203/2349-2902.isj20192371 introduction results discussion conflicts of interestthe authors do not declare conflicts of interest. clinical medicine insights received 15 may 2021 | revised 20 june 2021 | accepted 30 july 2021 | published online 9 aug 2021 doi: https://doi.org/xx.xxx/xxx.xx cmi journal 2 (3), 163−168 (2021) issn (o) 2694-4626 case study benign cystic mesothelioma: unknown cause of abdominal mass n.benjelloun 1∗ m.salihoun 1 i.serraj 1 m.acharki 1 s.sassi 2 k. znati 2 y. bakali 3 | f. sabbah3 | n. kabbaj 1 1department of gastroenterology ``efd-hge'', university hospital ibn sina rabat, morocco 2department of pathology, university hospital ibn sina, rabat 3surgery unit "clinique chirurgical c", university hospital ibn sina, rabat. abstract benign cystic mesothelioma (bcm) is a rare and benign disease that arises from the peritoneal mesothelium. it occurs predominantly in young to middle-aged women. the majority of cases were associated with a history of abdominal or pelvic operation, an endometriosis, and pelvic inflammatory disease. the etiopathogenesis is still unclear. malignant transformation is extremely rarewith only two cases reported in the literature. like the etiology, the name of this entity is also controversial. some authors prefer the term “peritoneal inclusion cyst” instead of “benign multicystic mesothelioma” and argue that the term mesothelioma should only be used when there is evidence of atypia. most cases of bcm are discovered incidentally. others reflect sequela of tumor mass effect. it appears intra-operatively as large, multifocal, cystic lesions in the peritoneal and pelvic cavity. diagnosis is achieved through surgical sampling with histopathological examination. immunobiologically, bcm exhibits multiple small cystic spaces with flattened lining containing calretinin positive cells without atypical features, mitotic figures, or tissue invasion. treatment includes cytoreductive surgery. we report on a 38-yearold woman who presented an abdominal mass discovered incidentally. laparoscopic exploration revealed two cystic masses. the whole tumor was successfully excised and histopathology revealed benign cystic peritoneal mesothelioma. keywords: cystic peritoneal mesothelioma, abdominal mass, laparoscopy copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). cmi journal 2 (3), 163−168 meerp ltd 163 https://creativecommons.org/licenses/by-nc-nd/4.0/ 1 introduction benign cystic peritoneal mesothelioma (bcm), a rare tumor, occurs mainly in women in their reproductive age. the pathogenesis of bcm is unclear and a controversy regarding its neoplastic and reactive nature exists. bcm is generally considered a benign process; however, given the high rate of recurrence and possible malignant transformation, close followup is important. we would like to report a new case of bcm associated with celiac disease. 2 case report we report the case of a 38-years-old women followed in our unit for celiac disease. she was asymptomatic and the systematic clinical examination showed an isolated abdominal painless mass in the left flank, measured approximately 20*30mm, fixed at the profond plane. the blood analysis showed normal findings, leukocytes 5800/mm3, hemoglobin’s 13,2 g/dl, and platelets 354.000/mm3. the biochemical test results were as follows: c-reactive protein negative, creatinine 0.83 mg/dl, with normal liver function. the tumor marker tests; cea and ca 19-9 were negative. abdominal ultrasonography showed two well-limited rounded hypoechoic masses, measuring 2.54 * 3.20cm and 0.79 * 1.07cm in the left flank. abdominal computed tomography (ct) scan revealed amesenteric lesion on the left flank, oval, well limited, heterogeneous tissue and fluid, measuring 40 * 26mm (figure 1), evoking a carcinoid tumor or a gastrointestinal stromal tumor. ct scan guided biopsy wasn’t done to avoide the dissemination of malignant cells. an exploratory laparoscopy which confirmed the presence of two masses measuring 4 cm and 2 cm next to the superior mesenteric axis. the intervention was converted to open laparotomy in order to resect those masses (figure 2). figure 2: operatory piece of mesenteric mass. supplementary information the online version of this article (https://doi.org/xx.xxx/xxx.xx) contains supplementary material, which is available to authorized users. corresponding author: n.benjelloun department of gastroenterology ``efd-hge'', university hospital ibn sina rabat, morocco cmi journal 2 (3), 163−168 meerp ltd 164 the postoperative outcome was uneventful and the patient was discharged after 2 days without compli-cations. macroscopic examination revealed 8 formations, which one of them was a cystic mass of 4,5 cm in major axis with a fleshy yellow wall, and the others correspond to a fibrosis tissues. microscopic examination showed cystic mass bordered by a sim-ple cubic coating, deprived of atypia and resting on a fibrous wall with few cells and crossed by a fine capillary network (figure 3). figure 1: ct images: sagi al and axial views of the mesenteric lesion. benign cystic mesothelioma: unknown cause of abdominal mass figure 3: histopathology results: cysts lined by cuboidal mesothelial cells. at immunohistochemistry the tumor cells were reactive for calretinin (figure 4), and non-reactive for ber-ep4 (figure 5), consistent with benignmulticystic peritoneal mesothelioma. figure 4: immunohistochemically reac on for calre nin 3 discussion bcm, also known as multilocular peritoneal inclu-sion cysts, is an uncommon lesion arising from the peritoneal mesothelium that covers the serous cavity [1]. it is a rare disease that occurs most often in young women with an average age of 37 years and is associated with a history of prior abdominal surgery, endometriosis or inflammatory pelvic disease [1,2]. until 2019, there are less than 200 documented cases worldwide, and it accounts for approximately 3-5% of the peritoneal mesotheliomas and the estimated incidence is 2 for 1,000,000 per year [2]. this tumor was originally described by plaut in 1928 as a cyst of the pelvis after being discovered by accident during a surgery of uterine leiomyomas. in 1979,mennemeyer and smith first defined the lesion as a « multicystic peritoneal mesothelioma » in a 27year-old female with multicystic diffuse lesion involving omentum, peritoneum, and pelvic viscera [3]. the pathogenesis of bcm is controversial due to its association with pelvic inflammatory disease (pid), endometriosis, leiomyoma, and a history of previous surgery, some authors believe that it has a possible reactive etiology. one of the hypotheses states that chronic peritoneal inflammation triggers the proliferation and migration of peripheral mesothelial cells and associated connective tissue, giving rise to these cysts. some authors have proposed a neoplastic origin based on a slow but progressive growth of the lesions, a tendency to recur after surgical resection, and high disease related mortality in advanced stages [4,5]. a genetic and familial association of bcm has been reported by a few studies [4]. cmi journal 2 (3), 163−168 (2021) meerp ltd 165 figure 5: immunohistochemically reac on for berep4. meerp ltd n.benjelloun et al. in addition, some studies suggest that female sex hormones play a role in its pathogenesis. this hypothesis is supported by the fact that bcm occurs mainly in females of reproductive age [2]. it has a strong predilection mostly for the surface of the pelvic viscera and serosal surfaces of the intestine and omentum or in the retroperitoneal space, spleen, and liver [3]. malignant transformation is extremely rare, with only two cases reported in the literature, despite the potential recurrence [3,4]. mostly, bcm is asymptomatic and is often discovered incidentally on imaging or during laparotomy for other indication [4,6]. typical symptoms include abdominal distention, abdominal tenderness, ascites, nausea, and constipation, urinary symptoms, and dyspareunia [5,7].when it reaches large sizes, it may present as a painful abdominal mass. in addition, its presentation in the form of acute abdomen had been reported [6]. abdominal tenderness, abdominal distention, and palpable abdominal or pelvic mass may be present on physical examination [4]. on ultrasound bcm typically appears as a multicystic, vascular mass without calcifications (figure 6). this aspect is named « spider in the web » [5,7]. ct scan typically shows a multicystic lesion with density similar to blood (figure 7). it is used to evaluate the location and the extent of the cystic mass, where lesion appears as a low-density, multiloculated, and thin-walled multicystic mass. however, the results obtained by us and ct scans do not differentiate bcm from other cystic mass [2]. the definitive diagnosis is histopathological. the electron microscopy or immunohistochemistry can assist diagnosis. serum tumor markers such as ca125, cea, ca-15.3, ca-19.9, ferritin, 2microglobulin are usually normals with one case reported, with elevated ca-19.9 with regression after surgical treatment [10,11]. the management protocol isn’t consensual. while fine-needle aspiration could be used as a diagnostic tool, in most cases this method is not informative. laparoscopy is the most accurate diagnostic method since it allows visualization, biopsies of the suspected tissue with intraoperative frozen section if possible, though an invasive procedure [3,6]. the bcm is characterized by solitary or multiple cysts, with fine septa, multiloculated and filled with serous fluid or blood. the size of lesions is few millimeters to 30 centimeters. themicroscopy shows up multiple cystic spaces lined by cuboidal epithelium, there is no atypia or mitosis, cysts are separated by fibrous septa with areas of chronic inflammation and proliferation stromal cells [9]. there have been rare reports of transformation to low-grade malignant mesothelioma, but it is generally classified as a benign process [ 6,7]. the immunohistochemically study is important to exclude possible mimic neoplasms cystic. generally positive markers include calretinin, d2-40, ck5/6 and wt-1, mesodermal markers present in epithelia, especially the mesothelium. markers moc-31, pax8, bg8, ber-ep4, b72.3, cea, and cdx-2 are frequently negative. most often used an epithelial marker (cytokeratin), and cd34, an endothelial marker that can also be used to exclude lymphangioma or other suspected vascular neoplasms [9,7]. the differential diagnosis of bcm includes benign and malignant cystic or multicystic abdominal tumors such as cystic lymphangioma, endometriosis, cystic forms of endosalpingiosis, cystic adenomatoïd tumor, pseudomyxoma peritonei, malignant peritoneal mesothelioma. this last is a major differential in the diagnosis of bcm, and distinguishing benign and malignant mesothelioma is very crucial to patient care [4,10]. due to its rarity, bcm treatment options remain an area of controversy and there is no streamlined treatment plan. currently aggressive surgical resection is the mainstay [10]. alternative treatments such as hormonal therapy, sclerotherapy, and potassium-titanylphosphate laser vaporization have been proposed in the recent studies. hormonal therapy with anti-estrogen drugs like tamoxifen and gnrh agonist can be an alternative to surgery in selected patients with estrogen-dependent neoplasm, as they were showed to be associated with a decrease in cyst volume. laser vaporization with potassium titanyl-phosphate laser were shown to have a significant efficiency at penetrating the tumor, but its therapeutic efficacy is still unknown. sclerotherapy consists of injecting povidone–iodine meerp ltd cmi journal 2 (3), 163−168 (2021) 166 benign cystic mesothelioma: unknown cause of abdominal mass or ethanol through a catheter directly into the cyst [2,11]. the treatment of choice for multicystic mesothelioma is total surgical excision. chemotherapy and radiation therapy are generally not indicated, because benign nature of this process. some authors have proposed heated intraperitoneal chemotherapy as a possible treatment option, but there is inadequate evidencebased research on this topic [11,12]. although bcm is associated with a favorable prognosis in a short term, because it is a completely benign condition; in long term it has been described about 50% after a period of 3 to 27 months (mean 32 months). there is a 40–55% recurrence rate in female patients and a 33% recurrence rate in male patients. no risk factors predicting the recurrence of bcm have been identified yet [5,7,9]. there is evidence that malignant transformation could occur. there are two cases described of malign processing [7]. a long follow-up period is always necessary, although there is still no consensus on when and what additional tests should be ordered. some authors suggest that ct should be done every 3 months for the first year after resection and then annually for the next 5 years [4]. 4 conclusions bcm is a rare benign neoplasm that is associated with no well-defined symptoms, typical clinical, or imaging data. the diagnosis remains unclear and the definitive diagnosis requires histology and immunohistochemistry. bcm has a high risk of recurrence and a significant potential of malignant transformation. 5 references [1] ahmed el geidie, hosam hamed, ahmed shehta. laparoscopic excision of benign multicystic peritoneal mesothelioma. the egyptian journal of surgery 2014, 33:277–280. [2] barbara noiret, florence renaud, guillaume piessen and clarisse eveno. multicystic peritoneal mesothelioma: a systematic review of the literature. pleura peritoneum. 2019 sep 1; 4(3): 20190024. [3] soundappan somasundaram, monty khajanchi, tejas vaja, bhushan jajoo, and amit kumar dey. benign multicystic peritoneal mesothelioma: a rare tumour of the abdomen. hindawi publishing corporation; case reports in surgery volume 2015, article id 613148, 3 pages. [4] momal tara chanda, jacob edensb, tayson linc, ian andersonb, richard berri. benign multicystic peritoneal mesothelioma: literature review and update. autopsy and case reports 2020;10(3): e2020159. [5] claire baezaa, camille coppolaa, muriel vialatrentinib, nicolas bourgona, jean-jacques terzibachianc, didier riethmullera. mésothéliome kystique péritonéal, à propos d’un cas et revue de la littérature. imagerie de la femme (2014). [6] hyun deok shin suk bae kim. benign cystic mesothelioma misdiagnosed as peritoneal carcinomatosis. case reports in gastroenterol 2016;10:115–120. [7] mazdak momeni, elena pereira, gennadiy grigoryan, and konstantin zakashansky. multicystic benign cystic mesothelioma presenting as a pelvic mass. hindawi publishing corporation; case reports in obstetrics and gynecology, volume 2014, article id 852583, 3 pages. [8] s. gussago1, p. spina, and a. guerra1. benign multicystic peritoneal mesothelioma (bmpm) as a rare cause of abdominal pain in a young male: case report and review of the literature. journal of surgical case reports, 2019;3, 1–4 doi: 10.1093. [9] agnaldo viana pereira neto, nathanael de freitas pinheiro júnior, renata campos simões cabral, isabelle torres, hilton pina, antônio carlos travessa and milena bastos brito. benign multicystic peritoneal mesothelioma: case report. general medicine: open access 2016, 4:3, issn: 2327-5146 [10] justin a snyder, robert carman jr, allison a aggon, joseph p cardinale. benign multicystic peritoneal mesothelioma: a rare case presenting as pneumoperitoneum and pneumotosis intestinalis. journal cmi journal 2 (3), 163−168 (2021) meerp ltd 167 meerp ltd n.benjelloun et al. of gastrointestinal oncology, vol 2, no 1, march 2011. [11] ruri lee, angela tong, boaz kurtis, anthony g. gilet. benign multicystic peritoneal mesothelioma. radiographics 2016; 36:407–411. [12] hicham elbouhaddouti, abdesslam bouassria, ouadii mouaqit, el bachir benjelloun, abdelmalek ousadden, khalid mazaz,and khalid ait taleb. benign cystic mesothelioma of the peritoneum: a case report and literature review. world j emerg surg. 2013; 8: 43; how to cite this article: n.b., m.s., i.s., m.a., s.s., k.z., y.b., f.s., n.k. benign cystic mesothelioma: unknown cause of abdominal mass. clinical medicine insights. 2021;163−168. https://doi.org/ xx.xxx/xxx.xx meerp ltd cmi journal 2 (3), 163−168 (2021) 168 introduction case report discussion conclusions references clinical medicine insight received: 21-07-2020 | accepted: 10-09-2020 | published: 19-09-2020 pages: 24-26 clinical medicine insights page 24 aquaintance of sample collection -must for patient care kaorey nivedita n introduction: pre-analytical procedures are a common source of error in laboratory diagnoses that arise during patient preparation, sample collection, sample transfer, and sample storage. although it has been reported that the pre-analytical phase is error-prone, it has recently been shown that a lot of errors occur in the „pre-analytical phase‟ where the initial procedures of the testing process are performed by health care professionals in outside the direct control of a clinical laboratory that is a phlebotomist who collects blood from patients. in the current scenario the continuity of quality in laboratory medicine is their emphasis on the performance and effectiveness of the analysis processes [1]. although recent evidence suggests that many errors are actually found outside the analytical stage which is the forward and post-analytical stage. these stages are found to be more subtle than the risk of error [2]. therefore our learning needs to be updated for all pre-analytic variables. commonly reported types of pre-analytical error are missing sample or test request, incorrect or missing identification, infusion contamination, hemolyzed samples, saturated and inadequate containers, unsuitable containers, unsuitable blood rate for anticoagulant and unstable carcass condition. and storage [3] the new update of clsi guidelines for venous specimen collection focuses on further details of patient identification, specimen labeling, patient posture, collection from mastectomy patients, managerial use, adverse reactions, needle transplantation, anterior venous and anterior presentation. prevention of iatrogenic anemia. preffered venipuncture sites include the antecubital fossa and the back of the hand. prioritization for the antecubital veins are as follows a. veins in the median aspect center of the arm b. veins in the lateral aspect outer thumb side that is cephalic vein c. veins in the medial aspect inner little finger side that is basilic vein. tourniquet application must not exceed one minute before accessing the vein to prevent hemoconcentration . because of the prevalence of methicillin resistant staphylococcus aureus and other pathogens on previously used tourniquets, single-use tourniquets are recommended to prevent the spread of healthcare-acquire infections.while 70% isopropyl alcohol is still the recommended antiseptic of choice, the procedure that has to follow is “cleanse the site with friction” not using concentric circles from inside to outside. studies suggest that the friction scrub with movement back and forth is superior to concentric circular cleaning. the site must be allowed to air dry before performing the venipuncture. once the site is cleaned, if it is necessary to repalpate the site, the gloved finger must also be cleaned with alcohol in order to not contaminate the site. the needle insertion is the site one inches below, not above the insertion site to reduce the risk of an accidental needlestick. the order of draw is to be aquaintance of sample collection -must for patient care clinical medicine insights page 25 maintained whether the specimens are collected by evacuated tube method or by syringe and is also the same for plastic or glass tubes. order of draw is recommended due to the carryover from one tube to another. a. blood culture tube (yellow with sps) or blood culture bottles b. sodium citrate tubes (light blue) c. serum tubes non additive and additive tubes and gels (red,sst) d. heparin tubes with or without gel (light green or dark green) e. edta tubes with or without gel (lavender, pearl white or pink) f. sodium fluoride or potassium oxalate with antiglycolytic inhibitor (gray). only blood cultures, glass non additive tubes or plastic tubes without clot activator may be collected before the coagulation tube light blue .syringes must not be used for trace element collections that include testing for cobalt and chromium because the plunger tip contributes such elements to the specimen blood collection devices and their components like tube stoppers, tube walls, surfactants, clot activators, and separator gels may interfere with the endogenous analytes, extraneous materials, or bind blood components result in erroneous measurements of the elements[4]. differences in posture standing, sitting, supine cause changes in plasma volume resulting in hemoconcentration from supine to sitting to standing, thereby increased analyte levels [5]. using a too-thin needle may result in hemolysis, distorting results for hematological cell counts and potassium concentrations [6]. prolonged use of a tourniquet results in hemoconcentration and changes in analyte concentrations [7]. although mixing is recommended by manufacturers of collection tubes, a recent study showed that lack of mixing did not lead to clinically significant differences in analytes compared to mixing [8]. hemolysis, icterus, and lipemia may result in spurious test results [9]. inadequate filling will decrease blood to additive ratio, which may lead to inaccurate results [10]. thus with awareness and the introduction of strategies to recognize preanalytical errors the goal of achieving total laboratory quality is finally within our grasp. hence laboratory physician and all laboratory personnel should be aware that spurious interferences may be present and that each laboratory is ultimately responsible for evaluating equipment and developing normal reference ranges. careful evaluation of how specimens are collected, centrifuged, stored, and transported should be considered. further, open communication between laboratory staff, laboratory physician,clinician should be pursued to ensure best patient outcomes, minimize unnecessary costs, limit the need to redraw patients, improve laboratory productivity, and decrease testing turnaround time. references 1. barth jh. clinical quality indicators in laboratory medicine. ann clin biochem. 2012;49:9–16. [pubmed] 2. plebani m. the detection and prevention of errors in laboratory medicine. ann clin biochem. 2010;47:101–10. [pubmed] 3. carraro p, plebani m. errors in a stat laboratory: types and frequency 10 years later. clin chem. 2007;53:1338–42. [pubmed] 4. bowen ra, remaley at. interferences from blood collection tube components on clinical chemistry assays. biochem med (zagreb) 2014;24:31-44. https://www.ncbi.nlm.nih.gov/pubmed/22042979 https://www.ncbi.nlm.nih.gov/pubmed/19952034 https://www.ncbi.nlm.nih.gov/pubmed/17525103 aquaintance of sample collection -must for patient care clinical medicine insights page 26 5. lippi g, salvagno gl, lima-oliveira g, brocco g, danese e, guidi gc postural change during venous blood collection is a major source of bias in clinical chemistry testing. clin chim acta 2014;440:164–8. 6. lippi g, salvagno gl, montagnana m, brocco g, cesare gg. influence of the needle bore size used for collecting venous blood samples on routine clinical chemistry testing. clin chem lab med 2006;44:1009-14 7. lippi g, salvagno glmontagnana m, lima-oliveira g guidi gc, favaloro ej quality standards for sample collection in coagulation testing. semin thromb hemost 2012;38:565–75 8. lima-oliveira g.lippi g, salvagno gl, brocco g, gaino s, dima f, et al.processing of diagnostic blood specimens: is it really necessary to mix primary blood tubes after collection with evacuated tube system? biopreserv biobank2014;12:53–9. 9. lippi g, plebani m, favaloro ej. interference in coagulation testing: focus on spurious hemolysis, icterus, and lipemia. semin thromb hemost 2013;39:258–66. 10. clsi. collection, transport, and processing of blood specimens for coagulation testing and general performance of coagulation assays: approved guideline. wayne (pa): clsi; 2008. clsi document h21–a5. clinical medicine insight 80-6pages: 0 2020-09-2020 | published: 19-90-52020 | accepted: 1-80-01received: clinical medicine insights page 6 rituximab treatment for chronic idiopathic urticaria with recurrent angioedema dr. vikola yigovski dept. of medicine, faculty of medicine, china abstract : we report on 4 patients with severe chronic urticaria and idiopathic recurrence with angioedema attacks. initially, they initially respond to high-dose corticosteroids but still recur on a high-protection dose. next, test the use of steroid-sparking drugs i.e.. internal immunoglobulin then mycophenolate mofetil with hydroxychloroquine and tacrolimus could not sustain a quench. therefore, rituximab was given. one month after rituximab infections, the prednisone dose was successfully discontinued and discontinued. subsequently, all patients remained in complete rest for 10-18 months. key words: angioedema, prednisone, rituximab, urticaria. introduction : urticaria is a common dermatological condition which typically presents with intensively pruritic, wellcircumscribed, raised wheels ranging from several millimeters to several centimeters or larger size. urticaria can occur with angioedema, which is localized non-pitting edema of the subcutaneous tissue that can be painful and obstructs the air way. chronic urticaria (cu) is defined as urticaria persisting almost daily for more than six weeks [1]. it generally lasts 1 to 5 years, but can have a prolonged course beyond 5 years in roughly 14% of patients [2]. the latter is considered a major health burden since the persistent pruritis impairs daily functions, disturbs sleep and hence the quality of life [3]. in general population the prevalence of cu is 0.5-5% [4]. according to the grade system, the mainstay of treatment of urticaria is avoidance of identified triggers, second-generation h1 antihistamines, leukotriene antagonists, short course corticosteroids and omalizumab if severe with or without angioedema [1]. in the present article, we describe our experience with treatment of systemic and idiopathic cu with rituximab in patients who had failed multiple corticosteroid-sparing agents. patients and methods: inclusion criteria: all patients, with generalized purpuric wheals with surrounding erythema which persisted for > 6 weeks, were seen in the past 2 years. all patients had the following criteria: (a) high ige levels with/without previous history of atopy and/or bronchial asthma. (b) none had secondary cause for allergy viz. malignancy, infections and parasitic infestations (c) no evidence of physical cause for their illness (heat, cold, solar, vibration, delayed-pressure, dermatographism, aquagenic and cholinergic induced urticaria) which was confirmed with skin testing. the latter included; wet cloth, hot bath, prick/patch tests (d) no clinical evidence of food-association (e) no evidence of new drug addition especially acei, arb, oral contraceptives and all drugs were tested by a 2-weeks discontinuation period. (f) skin biopsy that did not show vasculitis (g) normal tsh, crp, iga level, hepatitis b & c serology, helicobacter antibodies, antimicrosomal antibodies, serum protein electrophoresis, ra, anca, ana, and serum complements. treatment protocol: all patients were treated with prednisone 1 mg/kg for a minimum of 1 month. subsequently, the dose was decreased by 5 mg/week. if fails to maintain a remission for > 2 weeks; intravenous immunoglobulin (ivig) is used. if the latter fails, another 2-weeks trial of mycophenolate mofetil with hydroxychloroquine and tacrolimus is used. if fails again; rituximab infusions are to be given. rituximab treatment for chronic idiopathic urticaria with recurrent angioedema clinical medicine insights page 7 rituximab infusions: the patients were treated with four weekly infusions of 500 mg of rituximab (mabthera). the patient was pre-medicated with two 500 mg paracetamol and one piriton tablets followed by an infusion of 125 mg of solumedrol in 50 ml of d5w over 30 minutes before infusions. the 500 mg of rituximab was diluted in 450 ml of ns leading to a concentration of 1 mg/ml. the first infusion rate was 20 ml/h for the first 30 minutes followed by 20 ml increments/hour every 30 minutes till the total dose is achieved. the second infusion was a rate was started at 40 ml/hour, the third at 80 ml/hour and the fourth at 120 ml/hour. flow cytometry showed that her cd19 lymphocytes dropped to zero after one week of therapy and remained < 0.5% for 8 months. interestingly, the patient is asymptomatic and up to 12 months after normalization of her cd19 i.e. total of 20 months following the start of rituximab therapy. results a total of 4 patients fullfiled the inclusion criteria and hence were included in the study). all patients were adults (26-50 years) and had cu for > 6-8 months prior to inclusion in the study all patients had recurrent attacks of angioneurotic oedema that had required multiple hospital admissions. efficacy of rituximab: the drug was tolerable on such dosage despite 4-6 hour infusion time. there were no post-infusion immediate reactions and there was no report of delayed side effect. one month after the last dose of rituximab; prednisone dose was tapered down and the drug was discontinued without relapse of their urticaria. duration of follow up: the patients were followed up for > 14 months in the last patient and up to 24 months in the first patient. discussion urticaria is not a single disease but a reaction pattern that represents cutaneous mast cell degranulation. the latter results in extravasation of plasma into the dermis, forming the characteristic hives which are edematous pruritic pink wheals of variable size and shape. the lesions may be associated with angioedema which is a swelling deeper than wheals and may affect mucosal surfaces with typical sites of predilection that include the eyelids, lips, and tongue [5]. urticaria being defined as chronic if lesions recur for longer than 6 weeks. cu includes physical urticaria, idiopathic urticaria, and urticarial vasculitis [1]. in our study, we included patients with idiopathic type of cu and excluded those with physical and vasculitic ones [6, 7]. idiopathic cu is the most common type, comprising up to 90% of all cases of cu. it has been estimated that idiopathic cu affects between 0.6% to 5% of the population during their lifetime [8]. over half of all cases of idiopathic cu are thought to be caused by an autoimmune mechanism. this is supported by the observation that 60% of patients with idiopathic cu will have a wheal and flare reaction to intradermal autologous serum injections in the autologous serum skin test (asst) [9]. approximately 50% of patients with idiopathic cu have igg antibodies that are specific for the high affinity ige receptor (fcεri) [10, 11]. these autoantibodies activate mast cells in the skin, circulating basophils, and the complement system [9]. additional immunological causes in cu include igg antibodies directed against ige antibodies and the low affinity ige receptor (fcεrii), antiendothelial antibodies, and complement c8 alpha-gamma (c8α-γ) deficiency [12]. our patients had severe and persistent idiopathic cu and were hardly controlled with highdose corticosteroids. the latter has significant long-term side effects viz. osteoporosis, hypertension, glucose intolerance, obesity, stria, cushinoid appearance, growth retardation, decreased immunity, poor wound healing [13]. to avoid corticosteroids-toxicity, multiple drugs were proposed for such condition viz. intravenous immunoglobulin, mycophenolate mofetil, hydroxychloroquine, and tacrolimus [1]. all those drugs were tried in our patients and, had failed to be even steroid-sparing agents. since cu is a disease of the mature b producing excessive amounts of autoantibodies [vida supra], we elected to use rituximab in such drug-refractory patients. rituximab is a murine antibody that destroys both normal and malignant b cells b that have cd20 on their surfaces and is therefore used to treat diseases which are characterized by having too many b cells, overactive b cells, or dysfunctional b cells. the following effects have been found: (a) the fc portion of rituximab mediates antibody-dependent cellular cytotoxicity (adcc) and rituximab treatment for chronic idiopathic urticaria with recurrent angioedema clinical medicine insights page 8 complement-dependent cytotoxicity (cdc. (b) rituximab has a general regulatory effect on the cell cycle. (c) it increases mhc ii and adhesion molecules lfa-1 and lfa-3 (lymphocyte function-associated antigen). (d) it elicits shedding of cd23. (e) it down regulates the b cell receptors (f) it induces apoptosis of the cd20+ cells [14]. the latter may be the basis of maintenance of long-term remission via generation of new cells without memory ones [15]. in conclusion; our results are promising for a new hope in treatment of drug-refractory cu with rituximabtreatment. the latter is safe and is able to produce a long-lasting remission of a disabling disease. references: 1bernstein ja, lang dm, md, khan da. the diagnosis and management of acute and chronic urticaria: 2014 update. j allergy clin immunol 2014; 133: 1271-1277. 2toubi e, kessel a, avshovich n, et al. clinical and laboratory parameters in predicting chronic urticaria duration: a prospective study of 139 patients. allergy. 2004 aug;59(8):869-873. 3o'donnell bf, lawlor f, simpson j, morgan m, greaves mw. the impact of chronic urticaria on quality of life. br j dermatol. 1997;136:197–201. 4hellgren l. the prevalence of urtecaria in the total population. acta allergol 1972; 27: 236-240. 5kaplan ap, greaves m. pathogenesis of chronic urticaria. clin exp allergy. 2009;39:777–87. 6dice jp. physical urticaria. immunol allergy clin north am. 2004 may; 24(2):225-46. 7chang s, carr w. urticarial vasculitis. allergy asthma proc. 2007 jan-feb; 28(1):97-100. 8champion rh, roberts so, carpenter rg, et al. urticaria and angio-oedema. a review of 554 patients. br j dermatol. 1969 aug;81(8):588-597. 9sabroe ra, grattan ce, francis dm, et al. the autologous serum skin test: a screening test for autoantibodies in chronic idiopathic urticaria. br j dermatol. 1999 mar;140(3):446-52. 10kaplan ap. chronic urticaria: pathogenesis and treatment. j allergy clin immunol. 2004 sep;114(3):465-474. 11hide m, francis dm, grattan ce, et al. autoantibodies against the high-affinity ige receptor as a cause of histamine release in chronic urticaria. n engl j med. 1993 jun 3;328(22):1599-1604. 12puccetti a, bason c, simeoni s, et al. in chronic idiopathic urticaria autoantibodies against fc epsilonrii/cd23 induce histamine release via eosinophil activation. clin exp allergy. 2005 dec;35(12):1599-1607. 13bosch x, ramos-casals m, khamashta ma. drugs targeting b-cells in autoimmune diseases. springer science & business media; 2013: 1-4. 14shaw t, quan j, totoritis m. b cell therapy for rheumatoid arthritis: the rituximab (anti-cd20) experience. ann rheum dis 2003; 62 (suppl 2): ii55-ii59. clinical medicine insights received 25 june 2021 | revised 22 july 2021 | accepted 18 aug 2021 | published online 31 aug 2021 doi: https://doi.org/10.52845/cmi/2021-2-3-5 cmi journal 2 (3), 169−184 (2021) issn (o) 2694-4626 review article alcohol and noncommunicable diseases: part i cardiovascular diseases, obesity, respiratory diseases, depression, liver diseases shashi k. agarwal, md ∗ 12227 us highway 1, #309 north brunswick, nj 08902 usa abstract alcohol is a popular drink and is consumed globally. it has received considerable scrutiny in its effect on health. although its relationship with most cardiovascular diseases is j/u shaped, in general, alcohol intake can increase the risk of several diseases. heavy intake may induce weight gain. although no definite relationship has been noted with copd, asthma, and lung cancer, it does appear to increase the propensity for the development of pneumonia. its use is strongly related to chronic liver disorders. its relationship with depression is bidirectional, and deleterious for both conditions. in general, alcohol intake of 2 drinks per day for men and 1 drink per day for women appears to be relatively safe. keywords: alcohol, non-communicable diseases, cardiovascular diseases, respiratory diseases, copd, obesity, depression, liver diseases copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). 1 introduction non-communicable diseases (ncd) are chronic andmay lead to prolonged disability and premature death1,2. it is estimated that ncds are responsible for over 70% of total global deaths each year3. the majority of these occur in lowand middle-income countries4 and a severe financial burden5. the sustainable development goals hope to reduce by 2030 (relative to 2015 levels) premature mortality from ncds by one third6. the effects of alcohol on health can vary depending on the amount and pattern of intake7−9. in the united states, a standard drink contains 12–15 g of pure ethanol and this is present in 100–125 ml of wine, 240–300 ml of beer, and 30–37.5 ml of spirits10. moderate alcohol intake is considered as two standard drinks a day for men and one standard drink a day for women11,12. heavy drinking is defined as, high-dose intake, of >60 g/day in men and >40 g/day in women, usually taken over long term13. binge drinking is considered as 4 or more drinks for women and 5 or more drinks for men over a 2-hours or in cmi journal 2 (3), 169−184 meerp ltd 169 open access journal https://doi.org/10.52845/cmi/2021-2-3-8 https://orcid.org/0000-0003-0007-5582 https://creativecommons.org/licenses/by-nc-nd/4.0/ https://medicineinsights.info/ alcohol and noncommunicable diseases: part i cardiovascular diseases, obesity, respiratory diseases, depression, liver diseases one sitting14,15. compulsive excessive alcohol intake may lead to alcohol use disorder (aud)16. the national institute on alcohol abuse and alcoholism defines aud as “a chronic relapsing brain disease characterized by an impaired ability to stop or control etoh use despite adverse social, occupational, or health consequences”17. although low to moderate alcohol intake may have some beneficial effects, alcohol consumption, in general, is associated with several negative health consequences18. besides its impact on diseases mentioned in this manuscript, alcohol intake can cause cancers of the breast, mouth, throat, esophagus, liver, and colon19, learning and memory difficulties (including dementia)20,21, and mental health disorders, such as depression and anxiety20,22. alcoholics tend to be more prone to trauma20,23 and more likely to be involved in homicide, suicide, sexual assault, and violence24−27. drinking alcohol during pregnancy can be extremely dangerous, and can increase the risk of miscarriage, stillbirth, or fetal alcohol disorder28−30. alcohol poisoning is a medical emergency and is associated with extremely high blood alcohol levels31. the world health organization estimated that, in 2018, around 5% of global deaths were attributable to alcohol consumption32. the health effects of alcohol on ncds are discussed in this two-part manuscript. part i discusses the relationship between alcohol intake and cardiovascular diseases (cvd), chronic obstructive pulmonary disease (copd), depression, and liver diseases. part ii discusses its impact on cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, and arthritis. supplementary information the online version of this article (10.52845/cmi/2021-2-3-5) contains supplementary material, which is available to authorized users. corresponding author: shashi k. agarwal, md shashi k. agarwal, md 2227 us highway 1, #309 north brunswick, nj 08902 usa email: usacardiologist@gmail.com 2 discussion cardiovascular diseases (cvds) are an array of diseases that affect the cardiovascular system33. they include hypertension (htn), coronary heart disease (chd), stroke, heart failure (hf), cardiac arrhythmias, congenital heart disease, peripheral artery disease (pad), vasculogenic erectile dysfunction (ed), and venous thromboembolism (vte)33. they cause considerable morbidity and are the number one cause of mortality worldwide34,35. almost one-third of all worldwide deaths are attributable to cvds36. in 2016, chronic respiratory diseases were responsible for 7% of all global deaths37,38. communityacquired bacterial pneumonia, although not an ncd, is strongly associated with alcoholism39. pulmonary tuberculosis is also deleteriously affected by alcoholism40. overweight refers to a bmi of 25– 29.9 kg/m2 while obesity exists when the bmi is ≥30 kg/m2.41. obesity affected 42.4% of the us population in 2017–201842. obesity is associated with several ncds43,44, especially type 2 diabetes mellitus (dm) and cvds45. depression is a common cause of emotional suffering46. it is closely associated with anxiety47, dementia48, dm49, chd50, parkinson’s disease51, epilepsy52, pain53, several cancers54, osteoporosis55, and irritable bowel syndrome56. chronic liver pathologies are also common57. themajor chronic diseases affecting the liver are hepatitis b virus (hbv)58 and hepatitis c virus (hcv) 59infections, steatohepatitis due to non-alcoholic fatty liver disease60, alcoholic liver disease61, hepatic cirrhosis62, and primary hepatocellular carcinoma63. the development and progression of ncds are dependent on several modifiable and non-modifiable risk factors. non-modifiable risk factors include heredity, age, race, and gender. socioeconomic, cultural, political, and environmental factors may also play a role. the major modifiable factors include diet, obesity, physical activity, and non-smoking. alcohol consumption is also a modifiable factor that impacts ncds and is discussed in this manuscript. cmi journal 2 (3), 169−184 (2021) meerp ltd 170 mailto:usacardiologist@gmail.com meerp ltd shashi k. agarwal, md 2.1 cardiovascular diseases light to moderate alcohol intake has been associated with a lower risk of cardiovascular disease64. heavy consumption has been associated with deleterious cv outcomes including increased mortality65. studies have established that alcohol consumption and cvd have a jor u-shaped relationship66. harmful cvd effects are also noted with binge drinking67 and alcohol use disorder68. about 5% to 24% of hypertension cases are associated with ethanol consumption69,70. it is estimated that intake of 3 to 4 drinks per day raises the prevalence of hypertension by 50%, when compared with nondrinkers, while an intake of 6 to 7 drinks per day, increases the prevalence by 100%71. binge drinking, in the short term, raises the blood pressure from 4 to 7 mmhg systolic and 4 to 6 mmhg diastolic72−74. reduction in alcohol intake to <2 alcoholic drinks per day helps reduce the blood pressure in a doseresponse manner75. most studies indicate that alcohol consumption between 2.5 g/day and 30 to 60 g/day (mild to moderate drinking) is cardioprotective for both cv mortality and chd mortality76. in a meta-analysis done by bagnardi and colleagues, the risk of chd was higher in binge and heavy drinkers, when compared with non-drinkers77. a similar pattern has been noted between alcohol intake and stroke78. larsson et al in a systemic review and meta-analysis of 27 prospective studies concluded that light to moderate alcohol consumption (1-2 drinks/day) was associated with a lower risk of ischemic stroke, whereas heavy drinking (>2-4 drinks/day) was associatedwith an increased risk, especially of hemorrhagic stroke78. hf also appears to be less in individuals consuming <7 drinks/week79. wannamethee et al. found that heavier drinking (≥5 drinks/day or ≥35 drinks/week) significantly increased the risk for hf80. heavy alcohol intake may also induce alcoholic cardiomyopathy81. the causal relationship between alcohol intake and atrial fibrillation has also been known for a long time82. in a recently published study of 107,485 subjects followed for nearly 14 years, csengeri et al. found that alcohol increased the risk of developing atrial fibrillation by16%, irrespective of the type of beverage consumed83. according to koskinen and group, 5%-10% of all new episodes of atrial fibrillation are related to alcohol use84. alcohol also plays a significant role in sudden cardiac death (scd)85. in a study of the finnish population, 4 of 10 victims of unexpected scd exhibited evidence of alcohol intake before the fatal event86. drinking during pregnancy is also harmful to the offspring, who may be born with congenital anomalies such as aberrant great vessels, atrial septal defects, and ventricular septal defects87,88. high levels of alcohol intake are also associated with an increased risk of pad89. wang et al, in ametanalysis, determined that light tomoderate alcohol intake (<21 drinks/week) correlated with a decreased risk of erectile dysfunction90. alcohol is also associated with many other cvd risk factors, such as sleep disorders91, chronic kidney disease92, weight gain93, depression94, and smoking95. the beneficial effects of alcohol are related to several actions96−104. alcohol intake has an inverse associationwith t2dm (low tomoderate intake)96 and tends to increase hdl-c and apolipoprotein a-i97−99 – these effects are cvd protective. alcohol helps alter the atherosclerotic plaque composition and provides stabilization100. alcohol also exerts several effects on factors involved in hemostasis, such as inhibition of platelet aggregation101, lowering of fibrinogen levels102 and plasma viscosity103, as well as increasing levels of tissue plasminogen activator104. 2.2 obesity the relationship between alcohol intake and obesity has been well studied105,106. several studies have however produced conflicting findings105,107. since alcohol provides extra calories (1 gram of alcohol provides 7.1 kcal (29 kj), its intakewith a regular diet may lead to a positive energy balance, and weight gain108. it is estimated that in the us, 16% of adult drinkers’ total energy intake comes from alcohol109. however, alcohol’s relationship with obesity is not that simple110−112. several studies show that lightto-moderate alcohol intake is not associated with weight gain105,108. moderate drinkers are more likely to follow healthier lifestyles, such as exercising regularly and eating fruits and vegetables, which tends to prevent weight gain107,113. heavy drinking does tend to be associated with an increased risk of obesity107. meerp ltd cmi journal 2 (3), 169−184 (2021) 171 alcohol and noncommunicable diseases: part i cardiovascular diseases, obesity, respiratory diseases, depression, liver diseases a recent study confirmed that high alcohol consumption, especially binge drinking, was associated with higher risks of obesity in korean men114. the increased tendency for men to gain weight with excessive alcohol drinking may be because they tend to drink about three times the amount of alcohol consumed by women and are more likely to drink beer and spirits115. beer is rich in carbohydrates and may provide more calories108,116. women tend to drink more wine, which is more likely to protect against weight gain105. many other factors like socioeconomic status117, behavioral changes118, metabolic effects119, etc. may also play a role. the available data, however, does not conclusively confirm a positive association between alcohol consumption and weight gain105,120. 2.3 respiratory diseases there is no definitive association between alcohol intake and copd, or lung cancer121−123. the association between alcohol abuse and pneumonia is, however, strong124−126. although not an ncd, this association will be briefly discussed. aud individuals are often affected by bacterial pneumonia with streptococcus pneumoniae and klebsiella pneumoniae127,128. these patients are more prone to bacteremia, sepsis, septic shock126,129, and adult respiratory distress syndrome (ards)130. ards is almost four times more likely to occur in aud patients than nonalcoholic patients131,132. its presence is associated with poorer outcomes, including persistent hospitalization and death133. abusers of alcohol are not only less likely to receive preventive antipneumococcal vaccination134 but may also experience a less protective response135. individuals with aud are also more likely to develop tuberculosis (tb)136 and respiratory syncytial virus infection137. acute lung injury is also seen more commonly in alcoholics after major trauma, such as a motor vehicle accident, gunshot wound, or burns138,139. excessive alcohol consumption increases susceptibility to pneumonia through multiple mechanisms140−143. these include a reduced immunity140, altered microbial composition in the lung passages and alveoli141, and an increased risk of aspiration142. several other factors are also known to play a deleterious role143. 2.4 depression alcohol misuse and depression commonly cooccur144,145. aud individuals are many times more likely to have suffered from major depressive disorder146,147. depression may also lead to alcohol abuse in some individuals148. the alcohol–depression relationship appears to be curvilinear, with alcohol abstinence and heavy drinking both being associated with a higher risk of depression149,150. both conditions are interlinked and co-existence results in greater severity and a worse prognosis for both disorders than either condition independently151−154. data indicates that men usually develop aud before depression, while women develop depression and then progress on to aud155,156. patients who abuse alcohol may also exhibit more depression and tend to be not adherent to treatment157. alcohol abstinence appears to significantly improve depressive symptoms in depressed individuals158. antidepressants may be useful for the treatment of depression, alcohol dependence, or both, concurrently. behavioral treatments are also effective in both159−161. 2.5 liver diseases alcohol-related hepatoxicity appears to be the “oldest form of liver injury known to humankind”162,163. alcohol-related damage to the liver is broadly called alcoholic liver disease (ald) and includes alcoholic fatty liver, alcoholic hepatitis, and alcoholic cirrhosis164. about 90% of alcoholics develop alcoholic fatty liver (steatosis), about 25% develop alcoholic hepatitis, about 15% develop alcoholic cirrhosis, and about 10% develop hepatocellular carcinoma (hcc)165−168. continued alcohol consumption usually leads to progression from alcoholic fatty liver to hepatitis and then on to cirrhosis. alcoholic steatosis is usually asymptomatic (although some nausea, anorexia, and vomiting may be present)169 and these patients exhibit mild elevations of gamma-glutamyl transpeptidase (ggt), aspartate aminotransferase (ast), and alanine aminotransferase (alt) levels170. there is no abnormality of the serum bilirubin, international normalized ratio (inr), or albumin level. on liver biopsy, there cmi journal 2 (3), 169−184 (2021) meerp ltd 172 meerp ltd shashi k. agarwal, md is microvesicular and macrovesicular fat accumulation within hepatocytes, minimal inflammatory reaction, and no hepatic fibrosis171. abstinence will often revert these changes172. patients with alcoholic hepatitis may have jaundice, pyrexia, unintentional weight loss, malnutrition, and an enlarged, tender liver173. there are moderate elevations in ggt, ast, and serum bilirubin174. typically, the ast:alt ratio is ≥ 2:1 in these patients175. the liver biopsy usually shows neutrophilic infiltration, hepatocyte necrosis, steatosis, and the presence of mallory bodies176. patients with alcoholic cirrhosis may also exhibit gynecomastia, palmar erythema, spider angiomata, testicular atrophy, parotid gland enlargement; signs of portal hypertension, and dupuytren’s contracture177. laboratory findings often include hypoalbuminemia, hyperbilirubinemia, thrombocytopenia, and prolonged prothrombin time, and increased inr173. the liver biopsy usually reveals bridging fibrosis and regenerating nodules, and these are uniformly sized and micronodular178. in western countries, alcohol is responsible for up to 50% of end-stage liver disease179. it is estimated that almost 50% of all deaths from cirrhosis in the world are related to ald180. potentiating factors for ald include metabolic syndrome181, diabetes182, smoking183, obesity184, iron overload185, and chronic viral hepatitis b or c186,187. genetic factors may also play a role188. although abstinence markedly reducesmortality189, the only definitive treatment for ald remains liver transplantation190−193. alcohol abuse in patients with hepatitis b or hcv infection will often hasten the development of cirrhosis and its complications including hcc194. alcohol abuse is reported to be responsible for approximately 15%– 30% of hcc195,196. 3 conclusion alcohol drinking is popular all over the world. this manuscript focuses on the relationship between alcohol intake and cardiovascular diseases, obesity, respiratory diseases, depression, and liver disorders. alcohol consumption is generally safe, provided the consumption is in low to moderate amounts. it appears to be beneficial in these amounts for cvds. however higher levels of alcohol consumption are harmful. alcohol intake of more than 3 drinks per day in men and more than 2 drinks in women, should be avoided. acknowledgment: none funding: none 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cmi journal 2 (2), 98−103 (2021) issn (o) 2694-4626 research article frequency and relationship between changes in some blood factors and acute radiation-induced skin complications among head and neck cancer patients in sanandaj in 2017 ” kamel abdi 1∗ shahla naeemi 2 kajal mohammadi 3 mohsen habibi 4 jamil abdolmohammadi 5 nayer seyfizadeh 6 fardin gharibi 7 farideh elahimanesh 8 1nursing department, faculty of medicine, komar university of science and technology, kurdistan region, iraq 2msc of radiobiology, kurdistan university of medical sciences, sanandaj, iran 3msc of biomedical engineering, kurdistan of university of medical science, sanandaj, iran 4department of radiotherapy, faculty of paramedical science, tehran university of medical science, tehran, iran 5department of radiology, faculty of paramedical, kurdistan of university of medical science, sanandaj, iran 6neuroscience research center, tabriz university of medical science, tabriz, iran 7msph health management, vice chancellor for resource management affairs, kurdisan university of medical science, sanandaj, iran 8department of radiology, faculty of paramedical, kurdistan of university of medical science, sanandaj, iran abstract background: head and neck cancers account for 2 to 5% of body cancers and radiotherapy is one of the treatments for these conditions. destroying cancer cells without damaging healthy cells around the tumor is very difficult. cancer cells eventually die after repeated injuries by radiation in various treatment sessions, but unlike cancer cells, repair and replacement of normal cells happens between treatment sessions. in these patients, the most important complications are skin and blood complications. the occurrence of these complications may cause interruption of treatment by physicians’ order or patients’ request. discontinuation of treatment may result in disturbance of tumor cells destruction that is the main purpose of radiotherapy. the high prevalence of head and neck cancer that are candidate for radiotherapy, and the increase use of electron beam therapy have made the occurrence of acute skin reactions and reduction of blood factors inevitable. in this cross-sectional study, we evaluated 60 patients include 22 female and 38 male patients who underwent neck and head radiotherapy from march 2017 to march 2018 in sanandaj, west of iran. for this purpose, by assessing the weekly blood tests, we evaluated blood cells changes. the rate and intensity of acute skin complications were recorded according to the rtog ( radiation therapy oncology group) scoring system. then, the collected data were entered into spss version 20 and anova test was used for analysis. p-value<0.05 was considered statistically significant. results: the evaluation of 60 patients' tests revealed that blood factor changes happen during radiotherapy. mitotic catastrophes occur in blood cells and bone marrow suppression happens concurrently and without replacement. regarding the radiation-induced skin complication, there is not a notable complication in the first weeks (first and second weeks), but from the late third week, these complications begin to manifest and continue to the tenth week, then the intensity mitigate and acute complications recover and became mild. in this study, the intensity of complications depends on the total and fractional delivery schedule doses. conclusion: skin complications and blood factor changes occur during radiotherapy frequently. the changes of different blood factors are not the same and some of them can undergo decrease whereas increment happens in others. keywords: skin complications, blood cells, radiotherapy, head, and neck cancer copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). cmi journal 2 (2), 98−103 meerp ltd 98 https://creativecommons.org/licenses/by-nc-nd/4.0/ 1 background: head and neck cancer account for 2 to 5 percent of all body cancers and include cancers in the upper gastrointestinal (gi) and respiratory system. for example, paranasal sinuses, nasal and oral cavity, oropharynx, hypopharynx, larynx, and upper esophagus. radiotherapy is an integral part of therapy for cancer patients that is used alone or in combination with other therapies like surgery or chemotherapy. half of the cancer patients, experience radiotherapy as a part of their treatment. the effect of radiation on normal cells causes the complications of radiotherapy. [1] cancerous and normal cells react differently to radiation, but eradicating cancerous cells without damaging normal cells around the tumor is very difficult. the damages of repeated radiation would kill the cancerous cells eventually but recovery and replacement of normal cells, unlike cancerous cells; occur between therapeutic sessions.[2] although cancer patients do not feel any of these intracellular changes, the radiation effects on cancerous and normal cells would increase gradually that can even cause cessation of the treatment.[3] the intensity of the skin complications correlates with different factors like total radiation dose, technique, and place, the volume of irradiated tissue, chemotherapy, chronic disease, dose parameters, time, and fractional doses.[4] different scoring systems are used for determining the extent of radiation-induced skin complications (risc). scoring skin complications according to clinical manifestation and patient’s expression is classified into 45 grades. these complications vary from mild erythema to dry desquamation and moist desquamation. [5] the high prevalence of head and neck cancer candidates for radiotherapy, and using low depth electrons are inevitable reasons for acute skin complications. the occurrence of these complications may persuade physicians or patients to cease the treatment. the cessation of treatment may disturb the destruction of the tumor that is the main purpose of radiotherapy. [6] bonemarrow cells are the main hematogenous tissue in the body are the most sensitive tissue against radiation. pelvis and vertebra bones account for about 60% of blood-producing tissues, and ribs, skull, sternum, scapula, proximal femur, and humerus bone account for the 40% remaining. damaging the hematogenous tissues reduces blood cells number and changes the hemoglobin and hematocrit. [7]different blood cells have a different sensitivity to radiation, and the first lymphopenia, then granulopenia, thrombocytopenia, and anemia lastly occur. the extent of damages depends on different factors like the amount of received radiation, radiation time, the number of sessions, and the volume of irradiated tissue. [8] the level of hemoglobin and white blood cells can affect the response to radiotherapy, radiotherapy in patients with a high level of hemoglobin and hematocrits is more effective in comparison to patients with anemia. [9] the high prevalence of acute skin complications and utilizing low depth electrons, reduction of blood cells and risc is inevitable that cause cessation of treatment. this cessation may disturb the eradicating of the tumor that is the main purpose of radiotherapy. [2] given the acute skin complications and reduction of blood cells caused by radiotherapy that affect the treatment and patient’s quality of life, the present study aimed at evaluating the frequency and relationship between these complications among head and neck cancer patients. 2 methods: in this cross-sectional study, 67 patients include 42 male and 25 female patients were study from march 2017 to march 2018. this study was conducted on patients who underwent radiotherapy on the head and neck. for this purpose, by evaluating the patients’ blood test, blood cell changes were identified. for each patient, the blood cell test was performed and recorded in the patients’ files during therapy. the supplementary information the online version of this article (https://doi.org/xx.xxx/xxx.xx) contains supplementary material, which is available to authorized users. corresponding author: kamel abdi nursing department, faculty of medicine, komar university of science and technology, kurdistan region, iraq cmi journal 2 (2), 98−103 meerp ltd 99 meerp ltd kamel abdi et al. extent and intensity of the acute skin complications were scored according to the rtog system. this evaluation started from the first day and up to the thirteenth week of treatment. finally, after analyzing the data, the frequency and intensity of complications were evaluated. for evaluating blood cell changes, blood cell counting was performed before, during, and up to the end of radiotherapy using formula. in this evaluation, in addition to red blood cells (rbc), white blood cell (wbc), platelet, and hemoglobin, partial and complete lymphocytes and neutrophils were evaluated too. this evaluation was performed for all the weekly tests. other information like demographic information, cancer type, treatment type and place, dose, the number of sessions, and duration of treatment were recorded. finally, the spss version 20 was used for analyzing obtained data; an independent t-test was used for analyzing descriptive data. p-value<0.5 was considered statistically significant. ethical consideration : the study protocol was approved and funded by kurdistan university ofmedical science.written informed consent for participation was obtained from each participant after full disclosure of the aim of the study. 3 results: out of 67 eligible patients, four male patients (iraqi patients) and three female patients (death during the study) were excluded from the study and 60 cases (38 male and 22 female) remained. the patients’ ages range from 24 to 85 years with a median of 57 years. treatment period range from 29 to 64 days. the cumulative dose varies from 31.9 to 75.2 gy (table 1). regarding the cancer type, 46 cases of carcinoma, 4 cases of sarcoma, and 10 cases of lymphoma comprise the patients. out of this number, 25 patients underwent surgery, and 35 cases did not undergo surgery. also, 13 patients received chemotherapy before radiotherapy, 47 patients did not receive it, and 31 patients received radiotherapy and chemotherapy concurrently. radiotherapy type was on fraction schedule and the daily doses were 180, 180-200, and 200 cgy for 30,20, and 10 cases respectively. the skin complications were evaluated according to the rtog system weekly for 13 weeks (table 2). most of the skin complications in these patients were observed in grades two and three (figure 1, table2). patients’ blood cells including leukocytes, erythrocytes, platelets, neutrophils, and lymphocytes before and after treatment were measured based on the pearson correlation coefficient. according to this analysis, there was a significant relationship between these blood factor changes and radiotherapy (table3). in the first week, the number of white blood cells decreased, which stimulated the bone marrow, and in the second week, the number of lymphocytes increased, but in the third and fourth weeks, it decreased due to bone marrow intense suppression (figure 2). the rate of decrease in red blood cells during treatment was gradual (figure 3). the platelet size was constant in the first and second weeks and decreased in the third and fourth weeks due to platelet loss after mitotic death due to radiation (figure 4). neutrophils increased during irradiation (figure5). lymphocytes decreased between the first and second week and remain constant in the third week, and decreased again in the last week (figure 6). 4 discussion: one of the common therapies for head and neck cancers is radiotherapy. in this method, a radiation source (internal or external) is used for irradiation of the tumor-bearing tissues. in radiotherapy, especially the external one, in addition to tumor, the normal cells around the tumor-bearing tissue are irradiated too. radiation would damage the cells that eventually kill them. the more multipliable, the more sensitive to radiation. [8] radiation would affect bone marrow that is the hematogenous tissue in the body. blood cells have different sensitivity to radiation in a way that first lymphocyte, then granulocytes, thrombocytes, and lastly anemia occurs. the cumulative dose, the number of sessions, the dose, and the volume of irradiated tissue are among the factors that influence the blood cell changes.[7] in a study meerp ltd cmi journal 2 (2), 98−103 (2021) 100 frequency and relationship between changes in some blood factors and acute radiation-induced skin complications among head and neck cancer patients in sanandaj in 2017” entitled thei impact of white blood cell count and hemoglobin level on the response to radiotherapy in patients with colorectal cancer “, chiao and colleagues revealed that patients with a high level of wbc and hemoglobin respond better to radiotherapy.[9] in line with our study, faraji and colleagues reported that the decline of wbc correlates with the cumulative dose of radiation, and the decline of hemoglobin and platelet correlates with the length of the radiation period.[10] the intensity of skin reactions depend on factors like radiation type, therapeutic technique, irradiated tissue position, dose, and period length. according to clinical manifestation and patient’s description, radiation-induced skin reactions are classified into 4 to 5 grades. these complications vary from mild dry desquamation to moist desquamation[5] that may persuade the physician or patient to cease the treatment, and disturb the purposeful therapy.[6] the result of a study conducted by yungjing wang on 47 anaplastic thyroid carcinoma patients in 2002 revealed that patients who received higher fractional dose manifest acute dermatitis grade iii whilst patients who received palliative care and lower dose did not manifest dermatitis that is in line with our report.[11] the result of another study by tejpal and colleagues on 264 patients inflicted with advanced squamous cell carcinoma of the head and neck that treated with cisplatin and radiotherapy (crt) concurrently showed that the mean age was 54 years, and dermatitis grade iii (rtog-3) occurred in 35 percent of patients.[12] in a systemic review by langendijk and colleagues on the efficacy of radiotherapy and cetuximab (crt) on head and neck squamous cell carcinoma patients revealed that skin reactions correlate with radiation dose and therapeutic technique, and response-dose relationship applied for the occurrence of risc.[13] in this report, we concluded that blood cells undergo changes during therapy. during radiation, the wbc would reduce at the first week that triggers bone marrow that causes lymphocytosis at the second week, but at the third and fourth weeks of radiation, due to suppression of bone marrow, a large reduction of lymphocyte would occur. regarding rbc, there was a gradual reduction in its number that can be explained by the longer lifespan of a red blood cell. the size of the platelet remained unchanged during the first and second weeks, but from the third and fourth weeks, it would decline that is due to the destruction of platelets and mitosis death due to radiation. radiation has a different effect on neutrophils, and a growing trend was observed during therapy. regarding risr, no notable complication was noted at the first and second weeks, but gradually from the late third week, the skin complications would start to manifest as dry desquamation and sweat reduction. this trend would continue until the tenth week. the intensity of reactions varies from a mild reaction to moist desquamation and generalized moderate edema, and even wound, bleeding, and necrosis was observed in four patients. from the tenth week on, the intensity of complications decreased, and the acute ones recovered and became mild. in this study, the intensity of complications correlates with the cumulative and fractional scheduled doses. it worthmentioning that for preventing these complications during radiotherapy, from the first week until the thirteen weeks we evaluate the skin complications and refer patients to dermatologist weekly. arranging these appointments made some difficulties, especially for patients from other cities that made us exclude foreign patients. the limitation of our study was the low number of participants. it is recommended to perform this study on a larger number of patients to obtain more accurate results. 5 conclusion: skin complications and blood factor changes are the most frequent complications of radiotherapy. our study revealed the different blood factor changes and its relationship with the stage of the radiotherapy. declaration: ethical approval and consent to participate: this study was approved and funded by deputy of research of kurdistan university of medical science (ir.muk.rec.1395/324), the written consent was taken from the patients before participating in the study. consent for publication: he written informed consent was obtained from all research participants after a full explanation of the study. cmi journal 2 (2), 98−103 (2021) meerp ltd 101 meerp ltd kamel abdi et al. availability of data and materials: all of the data and materials are available for sharing. competing interest: the authors declare no conflict of interest. funding: this research was supported by grants from the kurdistan university of medical sciences. the funding bodies played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. authors’ contributions: all authors (ka, shn, km, mh, ja, ns, fgh, and fe) participated in the design of the study and helped to draft or revise the manuscript. ja, km and shn participated in the acquisition of data. fe and ns performed the statistical analyses. ka and fgh profred the final version of the manuscript. all authors have read and approved the final manuscript acknowledgment: herby, the researchers would like to thank the deputy of research and technology of kurdistan university of medical science for funding this study (ir.muk.rec.1395/324), our colleagues in the radiotherapy center in tohid hospital, and all of the patients in this study for their cooperation. abbreviations: rtog: radiation therapy oncology group anova: analysis of variance risc: radiation-induced skin complications gi: gastrointestinal wbc: white blood cell crt: cisplatin and radiotherapy cgy: centi-gray 6 reference [1] bhide sa, newbold kl, harrington kj, nutting cm. clinical evaluation of intensity-modulated radiotherapy for head and neck cancers the british journal of radiology 2012;85:487–94. https://doi.o rg/10.1259/ bjr/859421 36 [2] macià i garau m, lucas calduch a, lópez ec. radiobiology of the acute radiation syndrome. rep pract oncol radiother 2011;16:123–30 . https:/ / doi.org/10.1016/j.rpor.2011.06.001 [3] emami b. tolerance of normal tissue to therapeutic radiation. rep radiother oncol 2013;1:123-7 . [4] scott a. involving patients in the monitoring of radiotherapy-induced skin rea reactions. journal of community nursing 2013; 27:16-23 . [5] xiao c ,hanlon a, zhang q, ang k, rosenthal di, nguyen-tan pf, et all. symptom clusters in patients with head and neck cancer receiving concurrent chemoradiotherapy. oral oncol 2012;49:360-6 . https://doi.org/10.1016/j.oraloncology.2012.10.004 [6] babin e, sigston e, hitier m, dehesdin d, marie jp, choussy o. quality of life in head and neck cancers patients: predictive factors, functional and psychosocial outcome. eur arch otorhinolaryngol 2008;265:265-70 . https://doi.org/10.1007/s00405-0 07-0561-0 [7] fajardo lg, felipe l. radiation pathology. 3th ed. philadelphia, new york: lippincott raven press; 1998. pp. 143-53. [8] hall eric j. radiobniology for radiologist. 5th ed. lippincottwilliams andwilkins press; 2000. pp. 347-9. [9] liu h-c, huang m-y, wang j-y, chang l-s, lin s-r. the impact of white blood cell count and hemoglobin level on the response to radiotherapy in patients with colorectal cancer. biomarkers and genomic medicine 2014;6:171-4 . https://doi.org/1 0.1016/j.bgm.2014.08.004 [10] faraji k, neamatzade s, saboori h. radiation effect on the number of circulating blood cells in patients receiving radiation therapy in tohid hospital. zanko journalofmedical sciences 2014;15:49-58 . [11] wang y, tsang r, asa s, dickson b, arenovich t, brierley j. clinical outcome of anaplastic thyroid carcinoma treated with radiotherapy of onceand twice-daily fractionation regimens. cancer 2006; 107:1786-92 . https://doi.org/10.1002/cncr.22 203 [12] gupta t, agarwal jp, ghosh-laskar s, parikh pm, d’cruz ak, dinshawka. radical radiotherapy with concurrent weekly cisplatin in loco-regionally advanced squamous cell carcinoma of the head and meerp ltd cmi journal 2 (2), 98−103 (2021) 102 frequency and relationship between changes in some blood factors and acute radiationinduced skin complications among head and neck cancer patients in sanandaj in 2017” how to cite this article: k.a., s.n., k.m., m.h., j.a., n.s., f.g., f.e. frequency and relationship between changes in some blood factors and acute radiation-induced skin complications among head and neck cancer patients in sanandaj in 2017 ”. clinical medicine insights. 2021;98−103. https://doi.org/xx.xxx/xxx.xx cmi journal 2 (2), 98−103 (2021) meerp ltd 103 neck: a single-institution experience. head neck oncol 2009;15:1-17. https://doi.org/10.118 6/1758 -3284-1-17 [13] langendijk ja, oosting sf. grading system and management guidelines for dermatitis induced by head and neck radiotherapy plus cetuximab: clinical validation required. ann oncol 2011;22:2157-9. https://doi.org/10.1093/annonc/ mdr410 background: methods: results: discussion: conclusion: reference clinical medicine insights received 20 jul 2021 | revised 22 aug 2021 | accepted 18 sep 2021 | published online 01 oct 2021 doi: https://doi.org/10.52845/cmi/2021-2-4-2 cmi journal 2 (4), 224−243 (2021) issn (o) 2694-4626 review article diet and non-communicable diseases: part ii cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, arthritis shashi k. agarwal, md ∗ 12227 us highway 1, #309 north brunswick, nj 08902 usa abstract several global studies have shown that diet plays an important role as a modifiable lifestyle factor in the development and progression of non-communicable diseases. a proper diet with a balanced percentage of macronutrients, viz. carbohydrates, proteins, and fats. it is also selective in the choice of macronutrients, preferring those that are plantbased, and avoiding refined carbohydrates, animal-based proteins, and saturated fats and trans-fats. it is also rich in needed micronutrients viz. vitamins and minerals, and adequate intake of water. this manuscript deals with the important role of a prudent diet in five major noncommunicable diseases. keywords: diet, non-communicable diseases, cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, arthritis copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). 1 introduction homo sapiens are natural omnivores1. our guts resemble those of gorillas and chimpanzees and are accustomed to handling a mostly plant-based diet with occasional meat intake2. in humans, the amount of caloric intake is important3. since overweight and obesity have a significant negative impact on chronic diseases, proper weight is an extremely important health issue4. an ideal body mass index (bmi) is calculated as the weight in kilograms divided by the height in meters squared and should be between 18.5 to 24.9 kg/m25. many other anthropometric measurements are often used, primarily because visceral or central obesity appears to be more hazardous than measurement of bmi alone6. these include waist circumference, waist to hip ratio, and waist to height ratio7. besides excess body weight, the quality of diet is also important for good health8−10. a healthy diet should provide appropriate proportions of macronutrients (carbohydrates, proteins, and fats) for the energy and physiologic needs8, sufficient micronutrients (vitamins and minerals) for normal growth, development, metabolism, and physiologic functioning9, and adequate water for hydration10. carbohydrates are cmi journal 2 (4), 224−243 meerp ltd 224 open access journal https://doi.org/10.52845/cmi/2021-2-3-8 https://orcid.org/0000-0003-0007-5582 https://creativecommons.org/licenses/by-nc-nd/4.0/ https://medicineinsights.info/index.php/cmi diet and non-communicable diseases: part ii cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, arthritis abundant in grains, fruits, vegetables, and legumes11. whole grains have a higher amount of fiber and micronutrients than processed grains and are therefore healthier12,13. legumes and nuts are also healthy14,15 – except that nuts are energy-dense and may increase body weight if not consumed judiciously16. fresh fruits and vegetables are good sources of phytochemicals (polyphenols, phytosterols, carotenoids), and dietary fiber – all healthy17−19. dietary proteins may be of animal origin (meat, dairy, fish, and eggs) or plant origin (legumes, soy products, grains, nuts, and seeds)20. proteins are good sources of energy and help maintain lean body mass21,22. animalbased sources of protein contain saturated fatty acids, which are unhealthy23,24. fats (or lipids), besides providing energy, also help make up the cellular membranes25. dietary fats may be monounsaturated fats, polyunsaturated fats, saturated fats, and trans fats26. unsaturated fats are found in a variety of foods, including fish, many plant-derived oils, nuts, and seeds, and are healthy27. monounsaturated fats (mufa) include oleic acid, canola oil, and olive oil and are heart healthy28. polyunsaturated fats (pufa) include omega 3 fatty acids (eicosapentaenoic acid or epa and docosahexaenoic acid or dha) and have positive health effects29−31. epa anddha are found primarily in oily fish32, whereas animal products (and some plant-derived oils) are rich in saturated fats and should be only consumed infrequently33−35. processed meats are carcinogenic (they are also low in micronutrients) and should be avoided36,37. trans fats found in foods are predominantly the result of processing vegetable oils but are also present in small quantities in animal products they are health harmful and should not be consumed32,38. micronutrients are required in trace amounts and include vitamins, sodium, potassium, magnesium, zinc, selenium, copper, and calcium39,40. these are low in processed and refined foods41. water is also a principal component of the body42. besides hydration, water also provides several micronutrients, including trace elements and electrolytes43,44. sugar-sweetened beverages, although water-based, are harmful, especially due to the high fructose content, and should be avoided45. coffee46, tea47, chocolate48, and olive oil49 are all plant-based and healthy. diabetics should watch their egg intake but in general, one egg a day14 and low dairy foods are safe50. dietary patterns and dietary ingredients strongly affect chronic noncommunicable diseases51. 2 discussion chronic noncommunicable diseases (ncd) are common conditions affecting humans52. according to the world health organization, in 2020, the common cases of cancer were related to the breast, lung, colon and rectum, prostate, skin (non-melanoma), and stomach53. cancer accounted for nearly 10 million deaths in 202053. it is on its way to replace cardiovascular diseases (cvd) as the number one killer in the world54. diabetes mellitus is approaching epidemic proportions worldwide55. according to the international diabetes federation, it affected 425 million people globally in 2017, and these numbers are expected to increase to 629 million by 204556. type 2 diabetes mellitus (t2dm) is responsible for 90% of all diabetes cases57 and is caused by a combination of defective insulin secretion by pancreatic βcells and/or the inability of insulin-sensitive tissues to respond to insulin58. t2dm results in considerable morbidity and mortality59. diabetics live approximately six years less than non-diabetics60. it is an expensive disease, with the economic burden being approximately 12% of global health expenditure61. chronic kidney disease (ckd) is defined as the presence of kidney damage or an estimated glomerular filtration rate (egfr) less than 60 ml/min/1.73 mt2, persisting for 3 months or more, irrespective of the cause62. it affects an estimated 10% to 15% of people around the world63. it is a progressive disease, and sufferers ultimately need dialysis or supplementary information the online version of this article (10.52845/cmi/2021-2-4-2) contains supplementary material, which is available to authorized users. corresponding author: shashi k. agarwal, md shashi k. agarwal, md 2227 us highway 1, #309 north brunswick, nj 08902,usa email: usacardiologist@gmail.com cmi journal 2 (4), 224−243 (2021) meerp ltd 225 mailto:usacardiologist@gmail.com meerp ltd shashi k. agarwal, md kidney transplantation64. ckd patients experience considerable cardiovascular complications65, poor cognitive function66, and a lower quality of life67. they also face an early death68. dementia is common globally69. a recent report estimated that 50 million people in the world are living with dementia, and this number is projected to increase to 82 million by 2030 and to 152 million by 205070. the most common cause is alzheimer’s disease (ad)71, which is characterized by amyloid plaques and neurofibrillary tangles in the brain72. symptoms include cognitive impairment and functional decline, loss of independence, poor quality of life, and premature institutionalization73,74. there is no cure for ad, and treatment remains symptomatic75. ad is also a major cause of death76. the main types of arthritis encountered in clinical practice are osteoarthritis (oa), rheumatoid arthritis (ra), and gout77. oa is characterized by progressive cartilage degradation, synovitis, osteophyte formation, and subchondral bone sclerosis78. treatment is largely symptom based79−81, and many patients may end up needing total joint replacement82. it is the fastestgrowing cause of disability worldwide83. rheumatoid arthritis is an autoimmune disease and presents as a symmetrical polyarthritis often with systemic manifestations84. gout is autoinflammatory joint arthritis and is associated with hyperuricemia85. it is induced by monosodium urate crystal deposition in joints and soft tissues86. 2.1 cancer a healthy diet is associated with lower cancer morbidity and mortality87−93. steinmetz et al. reviewed of 206 human epidemiologic studies and 22 animal studies and found that consumption of fruits and vegetables was protective for cancers of the stomach, esophagus, lung, oral cavity and pharynx, endometrium, pancreas, and colon94. islami et al reported that low fruit and vegetable consumption was associated with the development of 17.6% of oral cavity/pharyngeal cancers, 17.4% of laryngeal cancers, and 8.9% of lung cancers while low dietary fiber accounted for 10.3% of colorectal cancer cases95. red meat and processed meat are cancer provoking96,97. their consumption has been associated with an increased incidence of cancers of the breast, colon, stomach, and prostate95,98. a healthy diet improves cancer-related symptomology99, the efficacy of treatment100, and raises the quality of life101. cancer patients decrease their risk of getting a second primary tumor102 and improve their survival103,104. a healthy diet also helps mitigate against other chronic ailments like obesity, diabetes, osteoporosis, and cardiovascular disease, which are often present in cancer patients105−109.processed and red meat increases the exposure to carcinogens such as n-nitroso compounds, polycyclic aromatic hydrocarbons, and heterocyclic amines110−113. plantbased diets are rich in phytochemicals and fiber that diversify gut microbiomes, resulting in lower inflammation, decreased oxidative damage, better immunity, decreased tumorigenesis, and improved levels of circulating sex and growth hormones114−116. 2.2 diabetes mellitus the obesity epidemic is giving rise to an increased number of diabetics worldwide117. weight loss in individuals who are obese is effective in the prevention and management of t2dm118. a calorie restriction-induced weight loss of about 15 kg, can lead to remission of t2dm in about 80% of obese diabetics119. certain dietary ingredients also impact t2dm120−125. plant-based diets help reduce hba1c more when compared to hbaic in patients on a conventional diet120,121. high consumption of whole grains, low-fat dairy products, yogurt, olive oil, chocolate, fiber, magnesium, and flavonoid also significantly reduces the risk of t2dm122−125. intake of olive oil126 and coffee127 lowers the risk of t2dm. nut and legume intake does not appear to affect t2dm122. in contrast, a high consumption of red and processed meat, and sugar or sugarsweetened beverages significantly increases the risk of t2dm124,128,129. no association has been noted between fish intake and t2dm130. schwingshackl et al found that 1 serving/day of eggs (55 g/day) increases the risk of t2dm by threefold122. however, a recent review and meta-analysis of 82,750 women from the nurses’ health study, 89,636 women from the nhs ii, and 41,412 men from the health professionals follow-up study found no overall associmeerp ltd cmi journal 2 (4), 224−243 (2021) 226 diet and non-communicable diseases: part ii cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, arthritis ation between moderate egg consumption and risk of t2dm131. schwingshackl et al calculated that risk-decreasing foods are associated with a 42% reduction, while consumption of risk-increasing foods resulted in a threefold increase in t2dm risk, compared to non-consumption122. the mediterranean diet may result in a 30% relative risk reduction in type 2 diabetes over a 20-year period132. the dash diet, along with the alternate mediterranean diet index, healthy eating index 2010, and alternate healthy eating index 2010, has also shown an inverse association with t2dm133. a prudent diet is more effective in decreasing the risk of t2dm if it is combined with increased physical activity134. 2.3 kidney diseases diet plays an important role in ckd135. a proper diet, primarily plant-based, leads to a higher egfr and better serum albumin levels136. the prospective observational northern manhattan study with 900 participants found that plant-based diets resulted in a 12% lower risk of egfr decline when compared with meat-based diets137. a dietary pattern rich in whole grains, fruit, and low-fat dairy foods is associated with lower urinary albumin to creatinine ratio138. plant-based diets also are associated with decreased mortality in adults with ckd139. mortality is high is ckd, primarily from cardiovascular complications140,141. individual dietary components influence blood pressure, lipid levels, oxidative stress, insulin sensitivity, systemic inflammatory responses, pro-fibrotic processes, thrombosis risk, and endothelial function in these patients and thereby modify cvd and clinical outcomes142−144. ckd patients may be advised to reduce their fluid and salt intake145.a low protein diet is ckd friendly146. it helps delay the progression of ckd147. a diet rich in animal protein is potentially harmful and results in deleterious outcomes148. animal protein (red and processed meat), results in higher bp, vasodilation of afferent renal arterioles, glomerular hypertension, hyperfiltration, metabolic acidosis, mitochondrial oxidative stress, dna damage, and increased accumulation of the end-products of protein catabolism – all harmful to the kidneys149. a diet high in fruits and vegetables results in a slower ckd progression and reduces complications and is associated with decreased mortality146. patients adhering to a mediterranean diet for six years showed a 50% lower risk of developing ckd150. an analysis of several large rcts also showed that compliance with themediterranean diet reduced cvd in these patients151. dash diet is also ckd protective152−154. a recent german study also found that the dietary approaches to stop hypertension diet (dash) adherence was associated with better egfr numbers152. poor adherence to the dash diet results in a 16% higher risk of ckd (study of 15,000 atherosclerosis risk in communities participants)153. an inverse association between the dash diet and the risk of developing ckd can therefore be inferred154. healthy dietary patterns (higher in fruit and vegetables, fish, legumes, cereals, whole grains, and fiber, and lower in red meat, salt, and refined sugars also lead to better health quality of life in ckd patients144. 2.4 alzheimer's disease there appears to be no strong connection between diet and the risk or progression of dementia155. there is some suggestion that plant-based diets, especially rich in green leafy vegetables may reduce cognitive decline and dementia156. several studies have demonstrated that themediterranean diet may have a weak protective effect on cognition157−161. a slightly modified dash diet also appears to prevent cognitive decline162. the benefits may derive from the beneficial effects of healthy diets on the cardiovascular system163. some studies have noted that the intake of folate, b vitamins, vitamin c, d, e, and selenium,may beneficially modify cognitive impairment and dementia164−169. the lipididiet trial found that multi-nutrient supplementation slowed the decline of cognitive, functional, and structural aspects of dementia, and slowed disease progression, after a period of 36 months170. in this study, the authors did not find any difference between groups on the cumulative incidence of dementia nor the mean time to dementia diagnosis170. the world health organization does not recommend dietary supplements for the management of dementia171. cmi journal 2 (4), 224−243 (2021) meerp ltd 227 meerp ltd shashi k. agarwal, md 2.5 arthritis a weight losing diet resulting in weight loss shows a benefit on oa172−175. obesity increases strain on weight-bearing joints and aggravates oa172−176. an association of higher bmi with the development of hand oa has also been noted177. hyperglycemia affects the subchondral bone and is also a predictor of oa178−179. cholesterol has been found to accumulate in human oa cartilage180. higher intakes of total and saturated fat are associated with increased knee joint space-width loss, whereas higher intakes of monounsaturated fatty acids (mufas) and pufas are associated with reduced radiographic progression181. these can be modulated with dietary interventions. low levels of vitamin d and vitamin k have also been implicated in oa182, although benefit via supplemental remains unclear183,184. several diets have been studied in ra for their inflammation-reducing effects, including fasting185, the mediterranean diet186, the cretan mediterranean diet187, vegetarian diet188,189, and an anti-inflammatory diet190. fasting followed by a period of the mediterranean diet, the cretan mediterranean diet, a vegetarian diet or an anti-inflammatory diet have been shown to have a beneficial effect on ra191. a vegan diet is also useful192. several foods are pro-inflammatory, including highly refined flours, gluten, transand saturated fatty acids, dairy products, and red meat193−196. these may aggravate ra. some vegetables may worsen ra and include tomatoes, eggplants, and potatoes197. some micronutrients are anti-inflammatory and include long chain omega-3 polyunsaturated fatty acids monounsaturated fatty acids, antioxidants, phytochemicals, flavonoids, vitamin d, fruits with enzymatic proteins such as papain and bromelain, ginger, turmeric, black pepper, green tea, and legumes198−217. however, it is not clear if supplementation with these ingredients helps218−223. gout is related to hyperuricemia and dietary factors that increase the latter are harmful224. uric acid-raising foods like alcohol, fructose (fruit juices), meats, organ meats, and seafood, and sugar intake (including sugarsweetened beverages) should be reduced225−227. beneficial products in diet are low-fat dairy products, soy, and vitamin c228. coffee consumption may decrease the risk of gout229. both the dash diet230 and the mediterranean diet231 may help prevent gout or reduce gout attacks. 3 conclusion a healthy diet is rich in plant-based foods, including fresh fruits and vegetables, whole grains, legumes, seeds, and nuts, and lower in animal-based foods, particularly saturated fat-laden red meat, and processed meats. sugar-sweetened beverages are health harmful. coffee, tea, and olive oil are plant-based and healthy. alcohol is a double-edged sword and is harmful if consumed in more than moderate amounts. dietary and other lifestyle modifications are expected to reduce ncd-relatedmorality by 25% by the year 2025232. acknowledgment: none funding: none conflict of interest: none references 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(accessed 18 august 2018). available online: http://www.who.int/nmh/events/ncd_actio n_plan/en/. how to cite this article: agarwal s.k, md. diet and non-communicable diseases: part ii cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, arthritis. clinical medicine insights. 2021;224−243. https://doi.org/ 10.52845/cmi/2021-2-4-2 cmi journal 2 (4), 224−243 (2021) meerp ltd 243 227. shen, y., wang, y., chang, c. et al. prevalence and risk factors associated with hyperuricemia among working population at high altitudes: a cross-sectional study in western china. clin rheumatol 38, 1375–1384 (2019). https://doi.o rg/10.1007/s10067-018-4391-9. 231. stamostergiou j, theodoridis x, ganochoriti v, bogdanos dp, sakkas li. the role of the mediterranean diet in hyperuricemia and gout. mediterr j rheumatol. 2018 mar 19;29(1):21-25.doi: 10.31138/mjr.29.1.21. introduction discussion cancer diabetes mellitus kidney diseases alzheimer's disease arthritis conclusion cmi 03 (04), 372−377 cmi journal 372 clinical medicine insights doi:https://doi.org/10.52845/cmi/2023-4-1-2 cmi 04 (01), 372-377 (2023) issn (o) 2694-4626 research article inguinal hernias repair by laparascopy.(tep). olga caridad león gonzález 1 , pedro rolando lópez rodríguez2*, lais angélica ceruto ortiz 3 , jorge agustín satorre rocha 4 , eduardo garcía castillo 5 , luis marrero quiala 6 1 i degree specialist in general surgery. assistant professor and assistant researcher. 2 ii degree specialist in general surgery. consulting professor. assistant professor and assistant researcher. 3 resident of 3rd year in general surgery. instructor teacher. 4 first degree specialist in general surgery. assistant professor. 5 first degree specialist in general surgery. assistant teacher. 6 first degree specialist in general surgery.assistant professor corresponding author: pedro rolando lópez rodríguez introduction since the concept of endoscopic inguinal hernia repair was first described by ger in 1982, endoscopic techniques have been modified; it was a time when failures and complications coupled with high cost outweighed initial enthusiasm. (1) laparoscopic hernioplasty (lh) has gained popularity in the last decade and numerous controlled studies appear in the literature comparing laparoscopic techniques with conventional ones. (2) in recent years, hl, despite being one of the most controversial laparoscopic abstract introduction: the hernia affection is one of the processes that has been studied into much detail and whose treatment pursues excellence, although many controversies are still yet to be resolved. laparoscopy repair of inguinal hernia is a treatment method that improves the quality of management given to our patients. objective: to identify perioperative events, surgical complications and to evaluate the pain referred for the patients who have had inguinal hernia repair by the laparoscopic method. (tep). methods: a prospective and descriptive study was done on 80 patients who have had endoscopic (tep)repair of inguinal hernias between january 2013 and december 2020. results: we performed 100 hernioplastias by laparocoscopy in 80 patients. the male sex predominated in a 5:1 ratio and the surgical time average was, 53.5 minutes for unilateral hernias and 71.3 minutes for the bilateral ones. the most frequent complication in the transoperatory stage was ¨minor bleeding¨. at 15 days after surgery, 86.3% of the operated did not complain of pain, but social and laboral reintegration was at a 34% of the total. conclusions: laparoscopic inguinal hernioplasty is a good therapeutic option, mainly in patients with bilateral and reproduced inguinal hernias. keywords: laparoscopic hernioplasty, inguinal hernia, hernia recurrence. copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/lic enses/bync-nd/4.0/). https://doi.org/10.52845/cmi/2023-4-1-2 https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ cmi 03 (04), 372−377 cmi journal 373 cmi journal pedro rolando lópez rodríguez et al. procedures, has established itself as a therapeutic option to consider. the advantages of this method are demonstrated in bilateral, recurrent hernias and in the labor-active subject, who requires early return to work. (3) method between january 2013 and december 2020, a prospective, descriptive, longitudinal-cut study was carried out in 80 patients operated on by endoscopy (pet) with the diagnosis of inguinal hernia, at the general teaching hospital "enrique cabrera". all patients who agreed with the type of surgical intervention, the study and who gave their informed consent were included; patients older than 30 years classified asa i-iii, without anesthetic contraindications for laparoscopic intervention and patients classified as nyhus iii and iv. patients with previous surgical wounds in the inguinal region, to operate, not dependent on reproduced inguinal hernias and patients with complicated, irreducible or slipped inguinal hernias; they were excluded. the surgical techniques were: totally extraperitoneal laparoscopic inguinal hernioplasty (tep). the pet technique was performed with some variants such as: no use of the balloon trocar, the preperitoneal space was decolorized by means of the 0º laparoscope and the insufflation of co2 at 13 mmhg. in patients with large hernial rings, a polypropylene cone was placed in the hernial defect and subsequently a 15 x 12 cm polypropylene prosthesis. there was no need to fasten the meshes with clips. (4) in the immediate postoperative period, the visual pain scale analog scale (vas) was applied and a pain value was assigned by means of "little faces", which starts from very happy (i value) to very sad (x value). pain quantification was repeated in consultation 7 days, 15 days and one month after the operation. results 100 hernias were operated on in 80 patients (20 patients [25%] had bilateral hernias, 85 primary hernias, and 15 reproduced hernias). the average age was 55.6 years, the youngest patient was 30 years old and the oldest was 77 years old, but the majority (14 patients) belonged to the fifth decade of life. the male sex predominated in 84%, which represented a male / female ratio of 5: 1. 43% of the patients made great physical efforts on a regular basis. table 1. toxic habits and personal pathological history (app). toxic habits and (app) frequency % chronic cough 6 7,5 copd 4 5,0 constipation 7 8,7 heart disease 7 8,7 diabetes mellitus 7 8,7 smoking 36 45,0 alcohol consumption 17 21,2 n= 80 copd: chronic obstructive pulmonary disease table no 1 shows that 36 patients had the habit of smoking, which represents 45% of the total and 17 consumed alcohol for 21.2%. tabla 2. distributión according classificatión to the nyhus. (5) classificatión right left total frequency % frequency % iiia 19 33,1 16 34,7 35(35,0%) iiib 21 37,8 20 50,0 41(41,0%) iiic 6 14,1 3 10,8 9 (9,0%) iv 8 14,8 7 13,0 15(15,0%) total 54 54,0 46 46,0 100(100%)  thel total is 100 hernias operated on in 80 patients cmi 03 (04), 372−377 cmi journal 374 cmi journal pedro rolando lópez rodríguez et al. table 2 shows that right hernias were more frequent in 54.0% of the total; the indirect variety with great dilation of the annulus and destruction of the posterior wall (iiib) was the most frequent (41 hernias). nine femoral hernias and 15 recurrent hernias were operated on. the 100 surgeries were performed by pet technique (100.0%). two of the patients in whom a pet technique was started had to be converted to a conventional prosthetic technique due to accidental perforation of the peritoneum, passing co2 into the peritoneal cavity, and consequently, the loss of the preperitoneal surgical space, and another was the conversion of a failed pet technique. the mean surgical time for unilateral hernias was 53.5 min, with a minimum time of 25 min and a maximum of 120 min. in bilateral repairs, the average surgical time was 71.3 min, with a minimum of 40 min and a maximum of 110 minutes. the hospital stay was less than 24 hours in 70 patients (87.5%), in 5 patients it extended from 24 to 48 hours and in 5 patients it lasted more than 48 hours. tabla 3. complications. complications intraoperative complications 2 weeks after 1 month minor bleeding 22 (22%) accidental opening of the peritoneum 9 (9,0%) hematomas 13 ( 13,0% ) seromas 4 (4,0% ) recurrences 2 (2,0% ) table 3 shows minor bleeding as the most frequent complication in the intraoperative period, in 22 repairs (22.0%) that originated 13 hematomas (13.0%). no complications were observed after the second week, but two patients suffered recurrences (2.0%) more than two months after the operation. tabla 4. evaluatión of the visual analog scale (vas). (6) vas inmediate preoperative first day first week 15 days first month vas i 75 (93,7%) 19 (23,7%) 52 (65,0%) 69 (86,3%) 73 (91,3%) vas ii 54 (6,3%) 50 (62,5%) 15 (18,7%) 11 (13,7%) vas iii 7 (8,7%) 5 (6,3%) vas iv 4 (5,1%) 4 (5,0%) 7 (8,7%) vas v 4(5,0%) n = 80 table 4 shows the pain classification according to the vas scale. in the immediate postoperative period, after the patient recovered from anesthesia, 75 individuals (93.7%) were classified as vas i and 5 patients as vas ii. at 24 h after the operation, 19 patients (23.7%) were classified as vas i, 50 (62.5%) as vas ii, 7 patients as vas iii, and 4 as vas iv. in the first week postoperative consultation, 52 patients (65.0%) were classified as vas i and 15 as vas ii, and two patients with moderate pain (vas v) appeared in this period. at 15 days after surgery, 69 patients (86.3%) were vas i and at one month 73 (91.3%) were. the incorporation to the usual activities, including work, was of 3 patients (3.7%) a week after the operation, after 15 days there were 23 patients (28.7%) and at month 54 patients, for 67, 5% of the total. discussion currently, with the improvement of laparoscopic techniques, inguinal hernia surgery is emerging as safe, feasible and as a good therapeutic option, regardless of the age of the patient; however, the cmi 03 (04), 372−377 cmi journal 375 cmi journal pedro rolando lópez rodríguez et al. preoperative evaluation of the individual must be correct and thorough, specifically the cardiorespiratory function, since with the tep method a working space is created between the sheets of the transverse lamina, richly vascularized, so that the absorption and elimination of the co2 is greater than that produced in the peritoneal cavity during pneumoperitoneum. (7) although men predominated, there was a slight increase in women in the series with respect to other authors (8) in laparoscopic practice, the finding of hernial defects diagnosed during the intraoperative period is frequent, in men and women, the latter essentially with a history gynecological disorders. although the usefulness of hernia repairs in asymptomatic patients is questioned in some articles, the authors consider that it would be beneficial for the patient, if conditions permit, to repair the hernial defect by the tapp method. (9) the relationship between hernial disease and physical exertion has been classic since cooper's time. in the series, 68% of the patients performed physical activities that involved great and medium efforts and also analyzing the multifactorial nature in the pathogenesis of hernia disease, it is striking that approximately half of the operated patients were smokers, a factor that influences in collagen metabolism, significantly linked to hernia recurrences. (10) most of the repairs were by means of the tep technique and we consider, like other authors, that although the tapp technique brings us closer to the area from a perspective familiar to the surgeon (peritoneal cavity) and facilitates the so-called "learning curve"; hernia disease -because it is considered a parietal defectshould be given a solution from this same plane, to avoid the probability of serious complications of the intraabdominal organs and to leave the transperitoneal method as a tactical resource when the totally extraperitoneal method is unsuccessful. (eleven) average surgical time was similar to other series. (12) it is known that this tends to decrease when the surgical team gains in experience. the longest operating time recorded was in a patient, who started with a pet technique, but due to technical difficulties, he was converted to a conventional posterior repair. the main complications were related to minor intraoperative bleeding and postoperative hematomas. in 3 patients it was necessary to drain the hematoma due to the discomfort caused, however, in the rest of the patients with hematomas and seromas they were treated with conservative measures. in two patients, recurrence occurred 2 months after the operation, which was interpreted as a technical error. (13, 14) our results coincide with numerous studies that affirm less postoperative pain with the use of minimal access techniques, as well as a prompt socio-occupational reincorporation of patients. (1, 3, 9, 15) despite the fact that 70% and 93.3% of the patients at 1 week and 15 days after surgery, respectively, had no pain or minimal discomfort; only 18 individuals (30%) started their usual activities before 15 days. these results contrast with other studies that report a return to work and social activities between 10-15 days postoperatively, although it is likely that some sociocultural factors are influencing these results. (1, 16) in the series there were no major intraoperative or postoperative complications, only minor bleeding and bruising. in most of the patients, before 2 weeks postoperatively, the pain disappeared, however, the return to social work activities after 15 days was low. conclusions laparoscopic inguinal hernioplasty was an effective therapeutic option, especially for patients with bilateral and reproduced hernias. it provided benefits to patients and families, the former joining work and social activities early. conflicts of interest. the authors do not declare any conflicts of interest. authors' contributions pedro rolando lopez r odríguez: he reviewed medical records and searched bibliographies. he chose thesampling method by selecting the study population and analyzing and discussing thetable content. cmi 03 (04), 372−377 cmi journal 376 cmi journal pedro rolando lópez rodríguez et al. lais angelica ceruto ortiz: she stated the objectives of the study, selected and triangulated the variables and performed the translation into english and the final revision of themanuscript. olga caridad león gonzález: she helped in the review of medical records and search bibliography, performed statistical processing, calculated arithmetic mean and standard deviation of quantitative variables. jorge agustin satorre rocha: performed the statistical processing, calculated and interpreted the chi-square and associated variables according to duncan's test. eduardo garcia castillo: reviewed the literature on the subject looking for data epidemiological studies worldwide, designed the study methodology, classified the research, processed the information and narrowed the bibliographic references according to vancouver standards. he wrote the document. luis marrero quiala: reviewed the literature on the subject looking for data epidemiological studies worldwide, designed the study methodology, classified the research, processed the information and narrowed the bibliographic references according to vancouver standards. he wrote the document. referencias bibliográficas 1. ruiz-funes map, farell rj, marmolejo ca, sosa laj, cruz za. abordaje de hernias poco frecuentes por cirugía de mínimo acceso: serie de casos. rev mex cir endoscop. 2020; 21 (1): 6-14. https://dx.doi.org/10.35366/97607. 2. magnus h, anders b, westerdahl j. laparoscopic extraperitoneal inguinal hernia repair versus open mesh repair: long-term follow-up of a randomized controlled trial. surgery. 2008; 143(3):313-7. 3. bittner r, bain k, bansal vk, berrevoet f, bingener-casey j, chen d et al. update of guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias (international endo hernia society (iehs))part a. surg endosc. 2019; 33: 3069-3139. 4. cruz alonso jr. la endohernioplastia. detalles técnicos. arch cir gen dig [serie en internet]. 2007 [citado 10 de diciembre de 2010]. disponible en: http://www.cirugest. com/revista/2007/17/2007-09-03.htm 5. carbonell tatay f. hernia inguinocrural. valencia: ethicon; 2001.p. 141-142. 6. deloach lj, higgins ms, caplan ab, stiff jl. the visual analog scale in the immediate postoperative period: intrasubject variability and correlation with a numeric scale. anesth. 1998; 86:102-6. 7. halligan s, parker sg, plumb aa, windsor ac. imaging complex ventral hernias, their surgical repair, and their complications. eur radiol. 2018; 28: 3560-3569. 8. henriksen na, kaufmann r, simons mp et al. ehs and ahs guidelines for treatment of primary ventral hernias in rare locations or special circumstances. bjs open. 2020; 4: 342-353. 9. león gonzález oc, lópez rodríguez pr, danta fundora lm, satorre rocha ja, garcía castillo e, ceruto ortiz la. inguinal hernia repair by laparascopy. surg cas stud op acc j. 2019; vol3 (2): https://lupinepublishers .com/surgery_case_studiesjournal/pdf/sco. 10. bórquez mp, garrido ol, manterola dc, peña p, schlageter c, orellana j, et al. estudio de fibras colágenas y elásticas del tejido conjuntivo de pacientes con y sin hernia inguinal primaria. rev méd chile. 2003; 131(11):1273-9. 11. díaz martínez j, ramírez colin g. hernioplastia inguinal endoscópico total extraperitoneal (tep). experiencia de nuestros primeros 100 casos en el hospital de segundo nivel. cir endoscop. 2017 (acceso): 15 //2019; 18(2): 125-34. disponible en: http: //www.medigraphic.com/cgibin/new/rewsume n.cgi.id articulo=7338. 12. martin gómez m. cirugía laparoscópica de la hernia inguinal. tep. cir andal. 2018; vol 29 (2): 174-77: http: asa cirujanos. com/admin /upfiles/revista/2018/cir-andal_vol29_n2_ multi media 8. pdf. 13. palmisano em, martínez jd, garcía mm, gonzález jd. maniobras claves y trucos en tep. rev hispanoamerican hernia. 2018; vol 6(2): 86-90. http: //dx.doi.org/10.20960/rh. 14. hernia surge group. international guidelines for groin hernia management. hernia. 2018; 22: 1-165. 15. liu j, zhu y, shen y, liu s, wang m, zhao x et al. the feasibility of laparoscopic http://www.cirugest/ cmi 03 (04), 372−377 cmi journal 377 cmi journal pedro rolando lópez rodríguez et al. management of incarcerated obturator hernia. surg endosc. 2017; 31: 656-660 16. morera pérez m, roque gonzález r, gonzález león t, sánchez piñero ro, olivé gonzález jb. cirugía abdominal en el adulto mayor. rev cubana cir.2019; vol 58(1): (disponible en) http://scielo.sld.cu. file:///c:/users/dell/downloads/ru/cmi/vol%204%20iss%201/(disponible clinical medicine insight 23-9pages: 0 2020-09-2020 | published: 19-90-02020 | accepted: 1-70-21received: clinical medicine insights page 9 the people’s democratic movement (cpdm) and the renewal of its core organs: cameroon rmilija a, mandale j. 1,2 falna taubic, senior lecturer at the university of ngaoundere abstract : it depends on the strength of a leading or close party, depending on whether it can be called for intellectual reasons; and this was on the initiative of his national president who decided to open his headquarters and his specialized organizations from 1 august to 10 december 2015, a period of (03) three years after the official end of his term of office. his guides, renew. in this process a competition was identified in the search for new selection tasks. the task was not only the witch agreement but, and in some places also continued. what are the new socio-political foundations of the cpdm and its specialized bodies? what is the meaning and power that can streamline this process and maintain a socio-political perspective? here are some questions to consider in the current article. il will also be processed in the light of the database collections in the field, with a strategic analysis with the help of the dominant authoritarian theory. key words: renewal, elected task, political competition, reconciliation introduction : a political party founded in marche 24, 1985 in bamenda, the cpdm is a branch of a single party: the national union of cameroon. the party was set up remotely to have a policy-making committee set up by a central group to be appointed from among some of the members who have been appointed or elected. in addition, some specialized bodies such as the women of the people's democratic movement of cameroon (wcpdm) and the youth (ycpdm) complete this list. at the grass root level the party is represented by the section, sub-section, grassroot committee and a unit whose members are elected. the unit closely used to bear at a given moment the outlines of many subdivisions and, at a given time the realities of those subdivisions. a circular letter 1 signed by the national president had as main objective extending the existing branches but the right to vote was extend to all its active members who however, needed to clarify their as effective members through activities such as the purchase of their membership card and the payment of their subscriptions 2 . for the smooth running of the electoral process five (5) legal proceedings 3 were created. broadly speaking, how has this renewal process manifested itself through the political vitality of the grassroot actors and the authoritarianism of the ruling leader? that is the main question the present analysis will try to bring a plausible solution. it essentially leans on the ruling authoritarianism theory and the strategic analysis. the first one stipulates that the authorities have a tendency of influencing the rules put in 1 circular letter n° 001/cpdm/np of 27 july 2015 of the national party to the grassroot renewal and some specialized committees. 2 the purchase of the membership card was suspended following a press release signed by the communication secretary on november 10, 2015. 3 the authorities will be considered in subsequent development. the people’s democratic movement (cpdm) and the renewal of its core organs: cameroon clinical medicine insights page 10 place by politicians in their favour 4 and the second ones abides by the theory as people say: ...reflexion, in terms of strategy make people responsible for them to look into some organizational contexts the rationality of an actors to understand the organizational shape in the personal experiences of the actors (crozier, friedberg, 1982). in addition, the relation of power within the enterprise has as objective to integrate a coherent manner special logics in order to achieve global objectives it assigns to itself, but counting on its own resources, each peculiar group has to accept the behaviours (wether passives) adapted to the defense or to the promotion related to special preoccupations and not common objectives (crozier, friedberg, 1982:49). for this research work to be constructive, we proceeded with the empirical collection of data made up of some cpdm archives whose shortages were complemented with inquires in the field and investigations with some different political stakeholder. two political parties will be taken into consideration in this article. the first one consists in analyzing the sociopolitical foundations of the renewal and the second deals with sociopolitical reach. the mayo-kani and mayo-danay are the two main geographical areas for the study. ithe sociopolitical foundations of the cpdm grassroot renewal organs the picture below shows the cpdm grassroot renewal specialized organs in december, 2015. picture 1: global view on the cpdm, wcpdm, ycpdm sections in the mayo-kani et du mayo-danay sections 1the mayo-kani and mayo-danay cpdm sections : a geometric political variable representation before the creation of brand new sections the mayo-kani and mayo-danay divisions were respectively crammed with seven (7) sections and eleven (11) sub-divisions within which seven sections were subdivided. in fact, those divisions, within which seven (7) sections were subdivided. in fact, those divisions respectively had four (4) and three (3) sections. in the mayo-kani division were among others: the mayokani west with the kaélé and moutourwa subdivisions as headquarters, the mayo-kani south with the 4 it is the point on view sustained by authors like j.m. zambo belinga, “elections in cameroon: the contribution to explain how to take part in vote in localities known as acquired to the cameroon people’s democratic movement and the social democratic front” phd thesis in political sociology defended at the university of yaoundé i, 2004 with the theme: “quest of notability authoritative persistence and democratization in cameroon”, cahiers d’etudes africaines, xliii (3, 171,2003pp.573-589, j.a. njock, “political elections and democratization in sub-saharian africa: the case of the central african states, phd thesis in public law, defended at the university of sciences in lyon, 2001. 5 former president of the mayo-danay east section, elected candidate at the helm of the mayo-danay east i section (yagoua), makassia jean died in his native land yagoua on the16 august 2016 following a brief illness. département formers sections subdivisions président cpdm wcpdm ycpdm mayo-kani mayo-kani west kaélé,moutourwa sadjokoumaï mme.fah godjé emmanuel mayo-kani south mindif hamantchioutou madam baïbaï illiassa ousmana mayo-kany east guidiguistouloumdziguilao siddiki damdam houli mayo-kani north moulvoudaye adamamodi maïtchang delphine bachirou halilou mayodanay mayo-danay sud kalfou,tchatibalé , doukoula, datchéga djamaralourssandou mme. maïraossé djagué oumarou tambouctou mayo-danay east wina, gobo, guéré ,yagoua makassia jean5 manamourou épse silikam hinssou yetna mayo-danay north maga , guémé , kaï-kaï abba enock maïam mbarma adoum mbarma the people’s democratic movement (cpdm) and the renewal of its core organs: cameroon clinical medicine insights page 11 mindif subdivision as headquarters, the mayo-kani east with the guidiguis, touloum and dziguilao subdivisions as headquarters. in the mayo-danay division, the mayo-danay south had as section headquarters: the kalfou; tchatibali, doukoula and datcheka subdivisions respectively; as for the mayo-danay east section was made up of the wina, gobo, guéré and yagoua subdivisions as headquarters and lastly the mayo-danay north with maga, guémé and kaï-kaï as section headquarters. this division into sections was disproportionate with regard to subdivisional section cover. in the mayokani for instance, the mindif and moulvoudaye subdivisions are alone in sections whereas the kaélé and moutourwa as far at the guidiguis, touloum and dziguilao subdivisions are covered with two sections. consequently a question is raised to know why some sections only cover one subdivision while others cover many? what can be the sociopolitical reasons? the reason behind all this is the anteriority and existence of those subdivisions in comparison with those created in 1990, among others the moutourwa, guidigyuis, touloum and dziguilao subdivisions; hence, moutourwa was attacked to kaélé while guidiguis, touloum and dziguilao were attached to the former subdivision. but some time in 2015 and following a circular letter signed by the national cpdm president some new sections were created. 2some sociopolitical reasons in the creation of new sections the creation of new sections is shown as follow: picture 2: cpdm, wcpdm and the ycpdm new sections département former sections corresponding subdivisions new sections corresponding subdivisions mayo-kani mayo-kani west kaélé moutourwa mayo-kani west kaélé mayo-kani north -west moutourwa mayo-kani south mindif mayo-kani center mindif mayo-kani east guidiguis,touloum,, dziguilao mayo-kani east guidiguis mayo-kani northeast touloum mayo-kani south east dziguilao mayo-kani north moulvoudaye mayo-kani north moulvoudaye mayo-danay mayo-danay south kalfou,tchatibali,,doukoula,,datchéka mayo-danay center kalfou mayo-danay south -east i datchéka mayo-danay south west ii doukoula mayo-danay south west i tchatibali mayo-danay east wina, gobo, guéré ,yagoua mayo-danay south ii wina mayo-danay south east i gobo mayo-danay south east i guéré mayo-danay east i yagoua mayo-danay north maga,,kaï kaï,, guémé mayo-danay north maga mayo-danay north east kaïkaï mayo-danay east ii guémé athe new sections: an answer to grassroot political requirements the opportunity in opening new sections all over the national territory made in such away that the number of sections moved from seven (7) to eighteen (18) in our area of study. eleven (11) new sections were created: mayo-kani north west (kaélé ), mayo-kani north (moulvoudaye), mayo-kani north-west (moutourwa), mayo-kani center (mindif), mayo-kani east (guidiguis), mayo-kani north-east (touloum), mayo-kani south east (dziguilao). in the mayo-danay, eleven (11) sections were also created: mayodanay center (kalfou), mayo-danay south east i (datchéka), mayo-danay south west i (tchatibali), mayo-danay south west ii (doukoula), mayo-danay south ii (wina), mayo-danay south east i (guéré), mayo-danay east i (yagoua), mayo-danay north (maga), mayo-danay north east (kaïkaï) and mayodanay east ii (guémé). to every subdivision, henceforth corresponds a section. some subdivisions used to cover many others. this situation and in the opinion of many militants was frustrating. as an example, the militants of the dziguilao and touloum (mayo-kani east section) were considering themselves as underdogs of the the people’s democratic movement (cpdm) and the renewal of its core organs: cameroon clinical medicine insights page 12 guidiguis population. those in kaélé had difficulties in behaving that the president of the section could from moutourwa 6 whereas kaélé the headquater. this analysis is worthwhile for the population of tchatibali, datchaka and kalfou where the same situation prevailed. these subdivisions has as section headquarter doukoula 7 . the frustration was more considerable in that the section president was from doukoula. the creation of new sections abides by the answer to the population quest for independence, requirements and claims of the grassroot militants as well as the resolution of the question related to the otherness or the autochthony of the responsible grassroot people of the ruling party. the creation of these sections necessitated resource people for their effective functioning. blegal reasons for the renewal of cpdm basic organs in a circular signed by the cpdm national president, one can read: to equip our political party with good leaders who can enjoy renewed and strong legitimacy, it is high time we elected new members in view of choosing new bureau at the level of the basic organs of our political party and its specialized committees. actually and more than ever before, our party is in its specialized committees. actually and more than ever before, our party is in diehard need of honest men, women and youths, faithful, staunch and devoted with self-sacrifice in his service within the interest of the nation, qualified leaders ready to assume with conviction and to promote a new dynamism through the new impetus shared during the ordinary congress8. in fact, before 2015 the last renewal of the basic structures of the cpdm and its specialized organs took place from the 29 th to the 14 th march 2007. they had a mandate of five (5) years which was expected to expire in 2012. the extention of the mandates lasted after three (3) years. substantially, the elected president became illegal and that is why the national president strongly believes that: “time has come to renew or to reinforce the legitimacy of those leaders 9 ”. on the other hand, during that flexible mandate, some presidents proved their non-availability may be either because they resigned or died 10 . it was reasonable to provide them with ne human resources. that is why “the cpdm must adapt itself to the realities of other people around them 11 ”. he creation of new sections has a main objective bring the militants closer to the power and reinforce the capacity to supervise them. similarly, it is promoting the recruitment of new members and it is here that the recruitment according to the cpdm is materialized and on top of its regalia function as coordinator of electoral and parliamentarian games (schwatzenberg, 1974). therefore, the cpdm has put an end to simply being considered an elective party to become a party of active members. the expressive role played through the universal suffrage has extended. the involvement in elections being considered as the most visible aspect of activities related to political parties in a democratic system, the renewal of the basic organs of the cpdm encourages the coming into the party arena of a new political personal whose aim is to enhance and motivate polling days. iithe sociopolitical impact of the cpdm national president signed athe renewal process as such after creation of new sections the cpdm national president signed a circular letter 12 inviting his militants to massively register on the electoral lists. the circular letter sets modalities related to the conduct of the operations under the supervision of the central supervisory commission (csc).the dismantlings of that commission are found at the regional, divisional, communal and local levels. at the helm of each 6 the sociopolitical actors/leaders of the kaélé subdivision hardly believe that their political leadership cannot be shared with non indigenous people like the guiziga, toupouri… 7 doukoula is a 1st degree chiefdom and overpowers 2nd and 3rd degree chiefdoms like tchatibali and datcheka but the inhabitants of those chiefdoms has dispute on the political preeminence of doukoula over them. 8 circular letter no 001//cpdm/ np of 27 july 2015 of the national president related to the renewal of the basic organs and specialized organs. 9 idem. 10 the cpdm section of the mayo-kani east constituency, siddiki, was dead. 11 circular letter no 001//cpdm/ np, op. cit. 12 a circular letter no 001//np/, op.ct., sets modalities related to the holding of electoral operations which cover the period 1st to 10th december 2015. the people’s democratic movement (cpdm) and the renewal of its core organs: cameroon clinical medicine insights page 13 commission a president is found and assisted with two (2) vice-presidents some members and representatives. at the regional level the supervision is carried out by a regional follow up commission (rfc); at the divisional level, by a section electoral commission (sec) and at the local level by a renewal local committee (rlc). the operation was launched in the far north region by gregoire owona in maroua on 22 th october 2015, then, relayed by the authorities of the divisional commissions in kaélé and yagoua on 23 th october before reaching the section electoral commissions. this circular letter also sets electorate conditions whose main innovation lies at the level of all the militant voting right extensions, members of the cpdm or any of the specialized organs. the should be up to date in items of their subscription 13 . the other main innovation of the electoral process lies at the level of eligibility criteria: on top of residential conditions, political activism, commitment, efficiency, competence, morality, patriotism, experience, discipline and civic seniority. candidates postulating at the post of president must have at least occupied previously a post as a section bureau member or president, vice-president, secretary or political party subsection paymaster, expected are the members of the central committee, the wcpdm and ycpdm national board, parliamentarians and mayors 14 .the restriction which has considerably reduced the competition among the different actors finds expression in the will of the national president to professionalize the political activism (offerle, 1999) within the cpdm party. bthe constitution of the electorate 15 the constitution of the electorate was the work of the local renewal commission. made up of three members, that commission went on the field to register militants on the electoral list. the subscribing and contribution card we before hand put at the disposal of the different section authorities. they were bought by the active members of the party. in fact, they were endowed to a large extend with by some political figures among the external and internal elites 16 . the membership cards were also used as a tool to influence some local party authorities. the president section as well as their pay masters in possession of the cards could put them on the disposal of militants they trust. those who were suspected of playing the role of rivals faced difficulties in reaching their objectives. “my supporters did not succeed in buying their membership cards. i did everything possible as a parliamentarian to get them from yaoundé” 17 . cthe candidatures the cpdm partitioning is shown as follow: at the grassroot level there are cells; two (2) rank and file committees constitute one (1) sub-section most of which two (2) constitute one (1) sub-section most which two (2) others are representative of the section. the number of active members per call is established between twenty (20) and fifty (50). each grassroot rank and file structure must be adjusted with some specialized organizations such as the wcpdm and ycpdm. these different structures were refurbished but were not subjected to any form of competition as much as the section leaders of the cpdm, wcpdm and ycpdm. in this respect only the letters will be our focus as shown in the table below: picture 3: distributing of the different candidates at the section presidencies and specialized organs sections president rdpc ofrdpc ojrdpc 13following a press release signed by the cpdm communication secretary fame ndongo on 10th november 2015, militants were allowed to simply vote by showing their membership card. 14 circular letter no 001//cpdm/ np, op. cit. 15 it was punctuated with irregularities due to the lack of the mastery of basic texts of cpdm while the latter are mostly made up of women above 35. the reverse is however possible. a wcpdm must be registered among the member of the cpdm. and that is why the information shown in picture 1 has taken only into consideration votes legitimately expressed in favour of the different candidates. 16 the elite mentioned here is in most cases up of civil servants from different localities and some business people. 17 source: interview with danwé raïdandi, former parliamentarian and the president of the north-east section (touloum). the people’s democratic movement (cpdm) and the renewal of its core organs: cameroon clinical medicine insights page 14 mayo-kani center (mindif) haman tchiouto yane naïna sali haman mayo-kani east (guidiguis) banmou david aminatou toubogbé désiré boubatchaossala maïyanda julienne tchopwé emmanuel fatoing houlibélé mayo-kani north (moulvoudaye) manga abba maïtchang delphine manga abba mayo-kani nord-est (touloum) danwé raïdandi fanta jacqueline wangsso temwa maï doctor atiryang major mayo-kani nord-ouest (moutourwa) boulou nguizi joseph boulaï vagaï anisoudagaï kaélé malloum djanatou mayo-kani west (kaélé) waloubé jean mme. maïna hamadou sadjo danzabé gabriel mme. kidvou ousmanou mayo-kani south-east (dziguilao) maga ernest yanpelda kosga dieudonné gonra tchahtiga siddi dr.yingyang mayo-danay center (kalfou) kaossiri brekmo18 astadjam tamboutou oumarou youssafa blaowé martin maissiri jeannete dayang paul ladga dangnamou mayo-danay east i (yagoua) makassia jean manamourou épse silikam tapssou baïlopssou irassou justin foulta epse lawane ousman valla victor mayo-danay east ii (guémé) rodo marcel haïdamta cathérine ngayam pascal djafsia andré fanga odette pauline djia abdoulkarim wakna paul dimissia claire abdoulaye ndjidda mayo-danay north (maga) ibrahim boukar mdarma mariam margaza adogaye daïrou hamadou mayo-danay north -east (kaï-kaï) amrakaï martin kaltoumou ndjidda sali atchoufgaîni abba enock djara oumar nkono joêl b. mayo-dana y south-west ii (doukoula) kidmo mbraougué jacqueline maïkaoulari hourayang nestor djamara lourssandou woga madeleine ndi ndouwé jacques mayo-danay south i (datchéka) gaoussou martin bahané clarisse b.d. mando sadoulam marcel mayo-danay south ii (wina) toubakbé hinkaydoudi hélène mouroussou hira molgom maïgama kaogamla binyang rodrigue n. mayo-danay south-westi (tchatibali) hinma norbert gonwa sidonie djaowé kidari mando fourtoing konda delphine dan-ngah nkame roger mayo-danay south-east i (guéré) moussa guinitna david mounounda marie voudissou simon mayo-danay south-east ii (gobo) moussa lississou hapkansou agnès tchiouda badoumou haou djoubsia etienne altogether, ninety-seven (97) candidatures were recorded. thirty-seven (37) within the mayo-kani division and, sixty (60) for the mayo-danay division. no female candidature was recorded at the helm of the cpdm sections, but it is no peculiar to our study area 19 . the sections are like political structures whose prerogatives exclusively recorded for the mayokani and mayo-danay divisions against eleven (11) and twenty (20) for the wcpdm 20 , while the ycpdm registered respectively eleven (11) and nineteen (19). the mayo-kani cpdm sections east, west, south-east had a total of the great number of candidatures; a total of three (3) likewise of the mayo-danay center, east ii. those of the mayo-kani north-east, mayodanay east i, mayo-danay north, north east, south-west ii, south ii and south west i registered respectively two (2) candidatures while the others sections registered three (3) candidatures that is those of some ladies like maïna, kidvou and djanatou. two (2) candidacies were supposed to be registered. the third, that is madam kidvou’s was aroused and cheered by mrs zakiatou 21 who displayed the “winning strategy” by withdrawing from the competition was part and parcel of the electoral game. in fact, by 18waga martin, section general secretary, became president in replacement kaossiri brekmo who died and at the determinent of the vice-president who turned down the exigencies of the party texts. 19 this remark is valid i the whole national territory. 20 this figure would have reached twenty-one (21) if mrs tapita’s candidacy in the mayo-danay east i constituency had not been disqualified because of its sympathy to the renewal local committee. 21 source: field investigation done in kaélé in december 2015. the people’s democratic movement (cpdm) and the renewal of its core organs: cameroon clinical medicine insights page 15 arousing mrs kidvou’s candidacy, her objective was to reduce mrs maïna’s chances to win as she was considered as a political threat. candidate at the head of the wcpdm sections have a low-level in terms of scholarisation as compared to their male counterparts. most of them are either teachers or council workers. some of them have poor level of education. it is the case of maïtching delphine, a mayo-kani north wcpdm section candidate as far as yanpelda julienne and tchatiga who are candidates at the mayo-kani south east wcpdm section are illiterate. they can neither express themselves in french, nor english, and can neither read nor write the two official languages. this is a clear proof of the evidence of the disparity in terms of scholarisation between the men and women in our area of study. the women in those areas are politically marginalized at the determinant of the man and there is a kind of social exclusion which appears through scholarisation. all the former presidents manifested their will to once solicit the suffrage of the militant in view of being reelected with exception of people like adama modi (the former president of mayo-kani north section), temwa, haman tchiouto, fatoing houlibélé, boulou nguizi joseph, makassia jean, djamara lourssandou and abba enock. among those candidates, one has the impression that many have the tendancy to come back at the basis of the deposed political actors like danwé raîdandi (a former member of parliament (20072012) in the mayo-kani east electoral constituency; fatoing houlibélé, former mayor of the guidiguis council and former cpdm section president of the mayo-kani east constituency , permanent member of the cpdm central committee; ousmanou, former mayor of the kaélé council for 2007-2013 mandate, kaélé malloum, former mayor of the moutourwa council (1996-2002), blaowé martin former mayor of the kalfou council ( 2002-2007), banmou david former mayor of the guidiguis council (2002-2007), abba enock former mayor of the kaï-kaï council (207-2013), kidmo mbraougué former mayor of the doukoula council. in seeking to put it some strategies for the renewal of their respective mandates the various candidates put in place the reality that “… the interest for the power in place and the positioning seem to take control over practical behaviors of political leaders” (gaxie, 2003:94). that is absolutely true that the section in the cameroonian context has a certain political scale 22 for the straightforward reason that the president has a first-rate position in choice of candidates to run the different elective mandates (parliamentarians, municipal councilors). from this, emanates one of the roles played by any political party: the one that has to do with the selection of candidates at the local and national elections (braud, 1998: 378). it is more obvious that “the political parties set aside, as a whole, their best constituencies or the eligible for office positions on the lists intended and to those who are already full in exercise as far as their elective mandates are concerned” (gaxie, 2003:86). a flash-back attempt finds its way in a revenge position and gives, so as to say, the full meaning of the fight on the political arena a genuine field of battle to take up pierre bourdieu (2000) “the fight for a political 22 the observance of the cpdm scene shows that invested candidates to local elections (legislatives and municipal elections) emanate from the basic organs of the party. the people’s democratic movement (cpdm) and the renewal of its core organs: cameroon clinical medicine insights page 16 position is therefore is an essential element for any representation that can, at its level postulate to people willing to devote themselves for the various profits they expect to make” (gaxie, 2003:9). the cpdm is a real “political business (…) a competitive arena or, better to say, an arena of competitive arenas” (gaxie, 2003: 110). the candidates come from the different social and occupational categories and range from primary to university educational levels. they can be primary school teachers, secondary school teachers, universities lecturers, medical doctors and are devoted their best to be elected through electoral campaigns. 2electoral campaign elections in view of selecting the renewal of the cpdm basic organs and its specialized organs hold two (2) years after the legislative elections coupled with the municipal elections on 30 th september2013. the nomination of the candidates was carried out on the trick that the leaders of the political party agreed to vote by consensus to the detriment of the primaries which, in fact, are the “pointers of the putting in place of a partisan dictatorship leaned against discipline” (kaptchouang, 2016:39). generally, that way of investing was not appreciated by all. so, the election campaign took place in revenge and challenge atmosphere; a revenge for those who thought that their legitimacy was cheated and a challenge for those who were invested and elected. in the mayo-danay south west ii constituency, kidmo mbraogué called upon militant votes because for him it was high time to revise the defects orchestrated by the parliamentarian djamara lourssandou: “he did nothing and has failed, he hammered out” 23 during and interview granted to him. as for djamara lourssandou, his objective was to challenge those who were not for the investiture of his electoral roll on 30 september 2013. “they will see, i am back on top of the section” 24 . in the mayo-danay south ii constituency, it was a campaign whose objective to take revenge on toubakbé, former mayor (2007-2013) of the wina council against molgom, mayor on duties at the helm of that council; “let’s stand in the way of those impostors who have robbed our council” that is the slogan chanted by his partisans 25 appealed for the toupouri community mobilization 26 in view of benefiting from the political advantages. in the mayo-danay east i (yagoua) constituency, manipulation played a vital role in the structuring of the cdpm basis organs renewal process. in fact, unlikely to the obligations of the party which has entrusted the organization of the elections to the section electoral commission, makassia jean and manamourou elisabeth candidates appropriate to be elected at the helm of the cpdm and wcpdm respectively, have taken drastic measures to choose the presidents of the polling station on behalf of the people in char of the section commission. that interference 23 source: field investigation done in maroua, dcember 2015. 24 source: interview carried out in doukoula with the concerned on 3 november 2016. 25 source: interview carried out with dr kaïmangue mathias, a political actor in wina council in july 2017 in ngouandéré. 26toubakbé belongs to the majority ethnic group unlikely to the massa, an numerically one according to available statistics in the wina council archives. the people’s democratic movement (cpdm) and the renewal of its core organs: cameroon clinical medicine insights page 17 sparked off yaksia silina 27 reaction through a letter delivered to the divisional coordination commission 28 . as for the member of parliament manamourou she charged yetna for having knocked her off balance, and the latter on the other hand corroborate that she despised her by splitting on her; the fact remains that she subtly went into the yagoua regional hospital; a hospilasation at the end of which a legal medical certificate was issued to her. she ended up by lodging a complaint against yetna for committing violence and assaults on a political personality 29 . in the dziguilao constituency, the campaigns were conducted on a clan background. djaowé albert 30 invited his brothers 31 to vote for maga ernest who transformed his campaign into a fight against qualified civil servants described as in competent people and impostors 32 . according to the latter, the “politicaladministrative elite have shown their inability to conquer the dziguilao council. therefore, it is high time formers took the control of things hammered djaowé to militants while touring some villages during the electoral campaign. the mayo-kani west constituency (kaélé) witnessed the deployment of three (3) diametrically opposed groups: the first group working in favour of danzabé gabriel, a political protégé of tikela kemoné; the second one as leader waloubé jean, a new political actor dubbed by hélé pierre and the last group headed by the former mayor of the kaélé council ousmanou. elections in view of renewing the cpdm basic organs and its specialised organisations equally witnessed tense moments among the protagonist. in touloum, brawls between the former member of parliament danwé raïdandi and the current one temwa were rife. “i was attacked in bizili by the militants of my rival. they assaulted me tearing my clothes. during the assault i lost my phones” 33 . every campaign is “not only the matter of full showing off but a deaf-mute situation or not to say hidden agendas which, to be under a shadow are non-determinant factors” (wiessman, 1992: 6). the silent practices highlighted here focus on the circulation of money and whose objective is to bribe the militants. the case of maga ernest remains rampant. in fact, he was a candidate at the dziguilao section and disbursed in golonguini a village established to the benefit of the candidate gonra. some militants received some cashes from him 34 . nigh meetings were held at the residence of minister hélé pierre. here, the vote-catching politic prevailed (medard, 2000). actually, hélé pierre’s partisans are mostly constituted of civil-servants who 27 he is the member of the mayo-danay i (yagoua) section member of the electoral commission. 28 source: circular letter send to the coordination president of the divisional commission on the 2nd december 2015. 29 the matter is still pending at the level of the examining magistrate at the yagoua court. 30 he was elected deputy mayor on behalf of the mdr political party in 1996 and mayor of the same party in 2002 before joining the cpdm political party in 2009. 31 source: field investigation carried out in dziguilao in november 2015. the brothers here refer to ethnic clan gouyouri, large in number in a small village known is padé. 32 source: field investigation in dziguilao, november 2015. 33 source: interview with the person concerned, guidiguis 2015. 34 source: field investigation in golonghini, november and december 2015. the people’s democratic movement (cpdm) and the renewal of its core organs: cameroon clinical medicine insights page 18 have received benevolent services in the ministries he has managing, the ministry of tourism 35 , town planning and housing and the present ministry of environment, protection of nature and sustainable development. those customers had the responsibility to support the militants in view of insuring a victory over waloubé jean, the candidate of the minister. 3the renewal of the cpdm basic organs: the expression of democracy on the move, slow but reassuring the contribution to elections relating to the renewal of the cpdm basic organs and its specialized organisations led to some results 36 as the information in the picture below show. at the end of elections of the leaders presiding at the helm of the cpdm sections and the specialized organizations the following conclusions can be drawn: all the section presidents elected embraced on the reconquest of their position in power with diverse fortunes. it is the case of the members of parliament haman tchiouto in the mayo-kani center, boulou nguizi joseph in the mayo-kani north-west who succeeded to elect themselves contrary to temwa 37 who was defeated by danwé raïdandi in the mayo-kani north east constituency. on the other hand, banmou david, the former and current mayor of guidiguis council consolidated his posture after beating his rivals bouba tchaossala and fatoing houlibélé in the mayo-kani east constituency. the former president of the mayo-kani east constituency and permanent member of the cpdm central committee, fatoing houlibélé, has not succeeded his political come-back. the former mayor of the kaélé council, ousmanou also lost at the detriment of waloubé jean who rose in social status as well as maga ernest in the mayo-kani south east constituency in dziguilao. maga ernest won the elections visà-vis dr yinyang and gonra, candidate who rather received the anointing of the local political elites. in the same vain, djamara lourssandou lost to kidmo in the doukoula constituency. other political actors emerged victorious, for instance the former member of parliament and current senators amrakaï martin in the kaï-kaï constituency. but his candidacy was contested by the partisans of abba enock who had no doubt to assault his. the brawl between the two (2) protagonists let to the physical clash causing the judicial questioning of about fifteen (15) militants on each side. they were temporary remanded in custody at the yagoua prison. 38 rodo marcel also made his presence felt in front of djafsia andré in the guéré constituency. but, his election was qualified as “stolen and forced” 39 . in fact, the transcripts from the various polling stations established in his case were destroyed as well as the ballot boxes containing the ballot papers. the official report transcripts for questioning stipulate that: 35 this ministry changed its denomination and his known now as the ministry of tourism and leisure. that one of town, planning has changed into the ministry of habitat and urban development. 36 these results were published by sn no 004/en/cpdm/rbob/sg/pccs of 5 january 2016 published the results of the section bureau elections o cpdm, wcpdm, and ycpdm renewal of the basic organs. 37 the latter was installed at the detriment of pr danwé raïdandi for 2007 legislature and was elected in the mayo-kani south electoral constituency. 38 these freely appear in court. meanwhile the case remains unexamined with the judges of the yagoua court. 39 source: interview with djafia andré in yagoua 10 september 2018. the people’s democratic movement (cpdm) and the renewal of its core organs: cameroon clinical medicine insights page 19 that day and for non-founded reasons, the partisans of rodo marcel who, publicly, perpetrated acts of violence and vandalism on the scene burned three ballot boxes, tore two transcripts filled with voting papers, damaged a vehicle belonging to one of the members of the divisional supervision of election present and molested the president of the polling station of guéré, dapsia olivier, after destroying his transcripts and taking along with them his phone40. in maga, haman ndjidda was chosen at the detriment of daïrou hamadou who wanted to be elected in a consensual manner: “friendship played on may favour. i am a cpdm member since 1991, unlikely to my rival who is still young member of the party. that is why i was designated by the section electoral commission president” 41 . in wina, the mayor on duty and on the other hand the protégé of minister gounoko haounaye has lost in the duel opposing him to toubakbé whose list to run the municipal elections was rejected by communal commission” 42 . it was a political revenge on behalf of actors established for him, as reported by an investigator: “we wanted to show to molgom and his gang that they are imposters and we will defeat them” 43 . the revenge in question was materialized during the municipal elections on 30 th september 2013 where the partisans of toubakbé failed to sanction the cpdm by voting against it through substantial votes reaching 46% to the national union for democracy and progress (nudp) 44 . “officially, we campaigned for our party but unofficially, we asked our partisans to vote in favour of the nudp. moreover, we think that the nudp has won that election rigged by the cpdm” 45 . to the analysis above, it clearly appears that there are two (2) types power synopses in the cpdm: the absolute election through the competition among the different candidates and the consensus within the two (2) sides that are the authoritarianism consensus through a real concertation. the completion here refers to the participation of many candidates during the election. the authoritarianism consensus hangs on the electoral process and the influence here has an objective promoting the victory of their partisans. these political leaders are the image of what zambo qualifies of “electoral competition constructive elites” (zambo, 2004:157). one would have witnessed the distrust vis-à-vis the way political leaders are forcebly chosen. in fact, candidates invested to preside at the destiny of the mayo-kani south east, mayo-kani south east, mayodanay north east, mayo-dany west, mayo-danay south ii sections received political benediction of some cpdm resource personalities. however, the failed in their project and that failure can be interpreted through the disapproval and the political emancipation of the militants. if ion jacques (1997) asks himself about the death of militants we are rather thinking of their rebirth. it was a question of questioning the political leader’s crisis, the survival of monolithic era through the collapse of the consensus principle praised by the 40 source: official report containing questioning established by barrister soudebne benjamin, cherif bailiff at the 2nd notary’s office at the far north court of appeal and the yagoua court on the 10th september 2018. 41 source: interview with haman djidda in yagoua on 10th september 2018. 42 application for annulment with the list under the leadership of molgom was not successful. 43 source: interview with sobé in ngaoundéré on 30th may 2016. he is a political actor of that constituency and lives in ngaoundéré. 44 source: official report of municipal elections at the wina council, elecam regional delegation, far north, maroua. 45 the latter conscripted anonymity during the interview we granted him sometime in june 2016 in ngaoundéré. the people’s democratic movement (cpdm) and the renewal of its core organs: cameroon clinical medicine insights page 20 party leaders with the reason to maintain cohesion within the party. one witnesses, so to say the bird of democratic culture through troubles related to the rhetoric consensus. for all that, it appears illusory to believe i the end of the leaders authoritarianism. in mindif as far as in moulvoudaye the section presidents were elected through a consensual manner. in fact, “it was a kind of an electoral hold-up or a contested consensus 46 ” according to a political observer in mindif 47 . another one goes one step further qualifying the consensus process of “orchestrated” 48 deceit mentioning the election of the moulvoudaye president section as being the influence of adama modi, the former president of the mayokani north constituency. the electoral hold-up also punctuated the electoral process in guidiguis as far as the election of wcpdm section president is concerned aminatou. for maïgonwa who withdrew her candidacy: “the lamido of guidiguis threatened her using his position as a lamido to influence the election. in fact, she continues, aminatou did not win the election” 49 . it is the same viewpoint expressed by another candidate has-been: “we saw the lamido exercising the demonstration of power to favour the election of aminatou” 50 . this viewpoint goes in the same vain as that one of a member of the section electoral commission. he access: “the lamido used authoritarian methods. he unilaterally misplaced some polling stations” 51 . that situation was similar to that one in yagoua. the election of the cpdm president sections, makassia jean and manmourou elisabeth respectively was a result of an authoritarianism orchestrated by them as many people in charge of section electoral commission say 52 . whatever the case, the results were published. these results gave way to a litigious political ballet made up of applications for annulment at the level of the leading authorities of the party in the may-kani west constituency. in fact, the candidate has been, namely danzabé gabriel and the former mayor, with the help of tikela kemoné, in addition, the vice-president of the regional investiture commission and mrs maïna as far as the wcpdm is concerned complained to the investiture regional commission to cancel the elections. the elected candidate waloubé jean, as for him, wrote to the cpdm national president to uphold his election. “my opponents complained to the regional renewal commission to cancel my election. for me, i have directly upheld the national president of the party to confirm my election” 53 , he revealed it to us in kaélé in an interview granted to him. these practices “... relaunch the authoritative reality of the running of affairs by the state and the freedom eras in cameroon” (zambo, 2003:576) but above all “the need for political parties to be democratic as well as a greater rationalization part played the electoral systems” (vlachos, 1996: 245). conclusion 46 source: field inquiry carried out with a political actor who did not reveal his identity in maroua, september 2016. 47 source: investigation carried out on 28th july 2017 in maroua with a political actor who did not reveal his identity. 48 source: interview carried with dr fendjongué houli, political actor in moulvoudaye council, maroua, december 2015. 49 source: interview carried with maïgonwa in guidiguis, december 2015. 50 source: interview carried with bouba thaossala, guidiguis, december 2015. 51 source: interview carried with bouba wanribélé, guidiguis, member of the commission, october 2016. 52 source: field inquiry, october 2016. 53 source; interview with waloubé jean in kaélé, october 2016. the people’s democratic movement (cpdm) and the renewal of its core organs: cameroon clinical medicine insights page 21 as philippe braud (1997) believes, the eternal order of the fields was doubted. one would have noticed a closest association of the citizens to the decent management of their local affairs. local autonomy is the school to democracy. the merit of the cpdm basic organs and its specialized organizations will be the lesson we would have drawn that the local political field is a real counterbalance to possible authoritative drifts of the local and national political elite. that renewal process would have participated to the putting in an embrassing situation a local feudal system. one can conclude with zambo belinga that: the lack of democracy cameroonians are facing is founded on the difficulties distressing the leading categories to rebuild their behavioural universe so as to bind it to the principles and obligations of democracy (zambo, 2003:573). the creation of the permanent delegations 54 at the regional and divisional followed with the appointment of permanent delegate at the helm of its structures known under the terms the permanents of the party (denquin, 1985:330) contribute to a political will whose objective is to take control of the actions of those who, though, hold elective mandates. it is the result of partisan and immutable oligarchy (denquin, 1985: 282; michels, 1984 (inquisitive invention, the adjective permanent is a clear testimony). one witness, so to say, to the bureaucratization of the functioning of the party, though genuine. but the bureaucratization allies with authoritative planned economy which is a hindrance to a democracy which leans on the principle that people are ruling. it is in that vain of a governance attempt of the political arena that the leaders are appointed, not elected. the enlightened elite theory expanded by pareto bears its full meaning. the basic organ renewal and the specialized organizations without extincting the political dinosors would have encouraged and emerging new political elite at the basis. it would have also laid down the problem of the actors competence, id est the ability to have access to political discussion compared with the sociological profiles of the elected representatives. can one do politics once he-she is elected? in any case, the cpdm president, by initiating the renewal of the basic organs and its specialized organization through the election of the leaders by all the militants would have highlighted the election of the leaders by al the militants would have highlighted the election as a devolvement way of ensuring power and, beyond this, power and the role played by partisan organizations in the democratization process. this article on the cdpm renewal of the basic organs and the specialized organizations would have helped us to open reflexion ways on the political culture within the structures of the party as a change factor and the counter-change: to identify the stratification which are, at times, controversial among the militants from generation, to put together the among the militants from generation to generation, to put together the sociological setting up of the embers to the definition to the evolution of the program, to assess the influence of the way the party is organized to control the game the authorities are playing with the powers that be within the managing personnel (audiger, 2007:123-124). this renewal process has given the opportunities to the leaders to assess the enrollment of the members and the power of the cpdm, both at the local and national plan. one would have also noticed the politicization of ethnic groups and the ethnicisation of politics; a situation that needs to render the militants capable to of identifying legal and ideological resources. bibliographie audiger f. (2007), « le renouvellement de l’histoire des partis politiques », vingtième siècle, revue d’histoire, n° 96, pp.123-136. bourdieu, p. (2000), propos sur le champ politique, lyon, presses universitaire de lyon. braud, ph. (1997), science politique. la démocratie, éditions du seuil. braud, ph. (1998), sociologie politique, paris, lgdj. 54 decision no 001/cpdm/np/ of 19 may 2016 appointing the permanent members of the divisional delegations of the central committee of the cameroon people’s democratic movement. the people’s democratic movement (cpdm) and the renewal of its core organs: cameroon clinical medicine insights page 22 crozier. m. et friedberg, e. (1982), l’acteur et le système. les contraintes de l’action collective, paris, seuil. denquin, j-m. (1985), science politique, paris, puf, 5 ème édition. erhard, th. (2015), « des élections disputées ? découpage électoral et compétition électorale dans les circonscriptions législatives, en france, entre 1997 et 2012 », cevipol, n°2, pp.1-35. foulla damna, a. (2016), « les violences politiques à l’épreuve de la démocratie », revue africaine de parlementarisme et de démocratie, volume iii, n° 15, pp. 103-117. gaxie, d. (1980), « les logiques du recrutement politique », revue française de science politique, n° 1, pp. 5-45. gaxie, d. (2003), la démocratie représentative, paris, montchrestien. ion, j. (1997), la fin des militants ? paris, éditions de l’atelier. médard, j-f. (2000), « clientélisme politique et corruption », tiers-monde, n° 161, tome 41, pp.75-87. michels, r. (1984), les partis politiques. essai sur la tendance oligarchique des démocraties, paris, flammarion. njock, j-a. (2001), « élections politiques et démocratisation en afrique subsaharienne. le cas des etats de l’afrique centrale », thèse de doctorat en droit public, université des sciences sociales de lyon. nonna, m., perrineau, p. (1992), les comportements politiques, paris, armand collin. offerlé, m. (dir.) (1999), la profession politique, paris, belin. sawicki, f. (1996), « la science politique et l’étude des partis politiques », cahiers français « découverte de la science politique », n° 276, pp.51-59. schwartzenberg r-g. (1974), sociologie politique, paris, montchrestien. tchejip kaptchouang (2016), « la discipline du parti à l’épreuve de la pratique démocratique au cameroun », (1996-2014), revue africaine de parlementarisme et de démocratie, volume iii, n° 15, pp. 5770. vlachos, g. c. (1996), « vers un nouveau modèle de démocratie pluraliste », revue internationale de sciences politiques, vol 17, n°3, pp. 239-252. weissman, f., élection présidentielle au congo : entreprise politique et mobilisation électorale, cean, bordeaux. zambo belinga, j-m. (2003), « quête de notabilité sociale, rémanence autoritaire et démocratisation au cameroun », cahiers d’etudes africaines, xliii (3) 171, pp.573-589. zambo belinga, j-m. (2004), « les élections au cameroun : contribution à l’explication du vote dans les localités « dites acquises » au rassemblement démocratique du peuple camerounais et au social democratic front », thèse de doctorat d’etat en sociologie politique, université de yaoundé i. clinical medicine insights received 05 feb 2022 | revised 08 feb 2022 | accepted 14 feb 2022 | published online 16 feb 2022 doi: https://doi.org/10.52845/cmi/2022-3-1-3 cmi 03 (01), 256−261 (2022) issn (o) 2694-4626 if:1.6 research article environmental problem solution michael vladislavovich tyurin m.d., ph.d 1the ceo, executive chairman of microbial biocatalyst international, inc. and inorgcarbdiesel, inc. p. o. box 300230, houston, texas, the usa. abstract we describe herein our corporate experience of use of both carbon negative the gasoline replacement fuel isobutanol and the diesel fuel replacement fuel diacetyl alcohol in the engines of the sacrificed for this test corporate cars 2020 toyota camry and 2020 porshe cayenne turbo (gasoline replacement) and 2020 shevrolet silverado 1500 (diesel fuel replacement). gasoline fuel replacements were used for 20,000 miles and the diesel fuel replacement was used for 10,000 miles. the certified mechanics invited from the respective cars dealerships did not find no any deviations in said cars performance and no any gaskets leaks creating further problems in said cars. we suggest that our carbon negative gasoline and diesel fuel replacements will replace initially the gasoline and the diesel fuel nationwide and then world-wide. copyright : © 2022 the authors. published by publisher. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). 1 introduction we presently are in the desperate need to find the good our corporate investment opportunity to invest in our own gasoline stations to sell the fuel isobutanol and the fuel diactetyl alcohol as the replacements of the gasoline and the diesel fuel both originating from petroleum distillation, respectively. the refineries, 80 petroleum refineries in the continental us, producing a lot of air co2 as the mandatory byproduct of petroleum distillation, the petroleum distillation on the petroleum fractions with different content of the carbohydrate molecules c7 to c9 for the manufacture of gasoline and c10-c15 for the diesel fuel manufacture there is the now mandatory need to find the replacements of the gasoline and the diesel fuel from said petroleum distillation. with the petroleum-based gasoline and diesel fuel there is always the problem of polluting the environment during the petroleum distillation process, necessary to get the fractions of petroleum originated gasoline and petroleum originated diesel fuel, and more the air co2 contamination during burning of said gasoline and diesel fuel. even nasa in 2010 after bombarding the earth satellite moon and finding ice on the dark moon surface stated that the earth has passed the point of no return to the natural environmental conditions of the pre petroleum use era of the year 1900 [1]. using of gasoline or diesel fuel emits even more air co2. you remember the us families where each kid at the age 16 wants to cmi 02 (02), 256−261 manuscript central 256 https://doi.org/10.52845/cmi/2022-3-1-3 https://creativecommons.org/licenses/by-nc-nd/4.0/ manuscript central m.d., ph.d have their own car despite he or she has brothers or sisters. in 2010 nasa has claimed that our planet earth has reached the point of no return because the air co2 level has reached in 2010 the mark of 400 ppm. now it is above 450 ppm and growing above that. what specifically the air co2 does to the environment? the co2 is among the heaviest gases of the air blend, reaching its density of 1.997 g/m3. as such, the air co2 under no wind conditions spreads on the ground surface. co2 is known as the natural absorbent of the solar infrared energy. distributing over the ground co2 gets very hot due to the solar infra red energy adsorption and heats the ground. it has been noted, that in the southern us the ground temperature might exceed the water boiling temperature under the normal atmospheric pressure conditions. the ground is the main refuge for all the fresh water: water coming from rains and water coming from melting snow and ice. from the ground where it is collected the fresh water goes under the constant earth gravity to feel streams, rivers and lakes. if the fresh water gets boiled in the ground, then less fresh water goes to the rivers and lakes. not only boiling leads to the fresh water evaporation under the constant earth gravity force [1] this is the huge current environmental problem, identified by nasa in 2010 and noted by the author of this article in the year of 2000, when he worked at celanese chemicals dealing with the acetic action production by themicroorganismsactetogenswho are themajor air co2 absorbers to produce acetate via the acetylcoa pathway [1]. the fig. 1 shows the effect of air co2 on the earth environment. supplementary information the online version of this article (https://doi.org/xx.xxx/xxx.xx) contains supplementary material, which is available to authorized users. fig. 1. the negative environmental effect of the increased air co2 content [1]. evaporated fresh water gets in the earth atmosphere, and from the earth atmosphere comes to the space vacuum surrounding our planet. in 2010 nasa has found fresh water frozen as ice on the dark moon surface. we might need to remind the readers that moon is located in 220,000 miles away from earth surface. so, the universe vacuum sucks fresh water from earth indefinitely and the dark surface of the moon worked as the vacuum trap for said fresh water vapors from the earth. we on the earth produce the air co2, more and more every year, facilitating the loss of the fresh water to the outer space. the most advanced earth venture capitalists already have started testing of the new space travel technology intended for the search of the new planets for the relocation of the overcrowded earth population as the practical solution of the outlined above environmental problem earth faces currently. however, despite of the venture capitalist investments, the level of the technology used still does not allow the construction of the efficient outer space transportation vehicles. we are herein, on the planet earth, and we develop the carbon negative technologies of gasoline and diesel fuel manufacture from the concentrated air co2. we have already developed acetogensbiocatalysts for the efficient continuous fermentation of the gas blends composed from the concentrated air co2 and nitrogen, also present in the atmospheric air for above 70 %. the third component of said gas manuscript central cmi 02 (02), 256−261 (2022) 257 environmental problem solution blend is hydrogen, h2. we have postulated our environmentally free mission to produce the hydrogen by the sea water distillation using the free electricity obtained using the modern solar panels [5-7]. the equator area is the best for the solar energy collection using the solar panels. the level of solar irradiation at the equator area exceeding 11,000 miles around the earth, is 1,330 wt/m2 of solar panels/hour. basically, we are thinking of growing the separate line of the private investment to organize themanufacture of the solar panel boats, then distributed in the ocean around the equator. we are still in the process of determining how much that will cost to produce a particular solar panel boat, as it has to distill the sea water 24/7/365. said floating solar panel boats with the sea water distillation capability have to have the alkaline batteries currently available in the multitude at the disposing the used submarines shipyards in the usa. due to the restricted nature of said shipyards information, the process is somewhat complicated, but we are inspired by our direct desire and our corporate mission to establish the reliable network of floating sea water distillers, packing said distilled sea water in the regular water bottles for the selling to the earth customers. this is the second major solution of the environmental problem the overcrowded earth currently has, beyond the relocation of the humankind to the other planets. the relocation is great but has multiple problems not only related to the spacecraft creation but also to the potential danger of the new planets environment for the relocating people. we are working also in this direction trying to create de novo the ways to distribute the recombinant vaccine proteins in the human bodies [13]. unfortunately current technologies used by the gene transfer corporations do not allow the health safe systems for the recombinant protein distribution to the human bodies [2-4]. our publication shows this our intent acting in the form of the publication of the peer reviewed articles instead of filing the us patents due to the limits we do currently have with the investor funding [2-7]. if the author may come back to his fuel isobutanol as the carbon negative gasoline replacement, the network of the biochemical reactions leading from the atmospheric co2 and the atmospheric nitrogen to the fuel isobutanol is the following, as shown in fig. 2. we also have used the hydrogen obtained by the solar power distillation of the freely available sea water of the mexican gulf. the manufacturing cost of the fuel isobutanol in our hands was $0.35 per gallon of product. fig. 2. fuel isobutanol produced from the air with the addition of hydrogen obtained via solar panels powered electrolysis of the sea water [1]. let’s go to the fuels section of this article. isobutanol fuel as the carbon negative gasoline replacement was used in the gasoline engines of our corporation freely subjected to this fuel tests. since n-butanol became the fuel gasoline replacement of the future [12]. fuel isobutanol was also recommended as the part of the fuel mixture for the airjet turbines by the gevo inc. [8]. in the field of fuel butanol isomers our current competitors include only butamax (dupont enterprise). in the field of the existing gasoline market (over $1 trillion) or competitors are all international petroleum corporations like shell, bp, etc. we offer herein our carbon negative fuel isobutanol manufactured from the air co2 for only $0.35 per gallon. we describe in this article our corporate experience of use of both carbon negative the gasoline replacement fuel isobutanol and cmi 02 (02), 256−261 (2022) manuscript central 258 manuscript central m.d., ph.d the diesel fuel replacement fuel diacetyl alcohol in the engines of the sacrificed for this test corporate cars 2020 toyota camry and 2020 porshe cayenne turbo (gasoline replacement, 20,000 for each said vehicle) and the diesel fuel replacement fuel diactyl alcohol tested was the sacrificed by our corporations 2020 shevrolet silverado 1500 (10,000 miles for the last cartesting).. we are not in the position to disrupt the fuel market structure at this point of our corporate funding, and at the price ranks we facing currently we are not going to do so. to stay herein on the existing fuel market with our carbon negative gasoline replacement the fuel isoburanol we offer the free foods for the amount of the fuel isobutanol purchase to every customer at our future gasoline stations. this way we plan to be very profitable. remember, the author was almost killed for his intent to commercialize his fuel isobutanol manufacture technology at the international corporation ******, and after that, with the houston police report of not guilty for said the author’s corporate car totaling by the toyota tundra truck in houston texas, which has crossed the club creek drive where the author drove straight the author could not get any feedback from the houston fbi for the investigation of his attempted murder as it stands now in 2021, however the statute of limitations for the attempted murder in the usa is 20 years. the only drawback of the fuel isobutanol is the increase of its viscosity in the fuel line at negative surrounding air temperatures. to overcome this shortcoming of the fuel isobutanol for its use at the low temperatures we offer it not in the pure form as it has been suggested before [8], but as the mixture with the gasoline at the ratio 80% fuel isobutanol and 20% of gasoline. of course, in the southern states of the usa the 100% fuel isobutanol can and has to be used with no problems due to its higher viscosity at the low air temperatures almost around the year long: from february-march through the end of november. during short winter time we offer for sale the gasoline fuel isobutanol/gasoline mixture as described above. now, let’s go back to the carbon negative manufacture of the carbon negative diesel fuel manufacture. the author has invented and published in the peerreviewed journal and herein distributes his technology of the diesel fuel manufacture from the air co2 [8]. basically the biochemical network of the related to the carbon negative manufacture of the carbon negative diesel fuel is as shown in the fig. 3. fig. 3. shematic network of the biochemical reactions of the acetone production from air co2[10]. the produced acetone was condensed to the diacetyl alcohol per the us patent us1550792a [11]. the manufacturing cost of 1 gallon of the carbon negative fuel diactetyl alcohol is only $0.37 while shell, bp and other petroleum corporations spend over $1.70 per diesel fuel gallon manufacture at the petroleum refineries {1}. the author describes herein the results of his personal use of the fuel diacetyl alcohol solely in his corporate 2020 shevrolet silverado 1500 truck with no attempts to convey said personal experience on the other makes of the diesel fuel trucks and other diesel fuel engines. over the 10,000 miles run, the 2020 shevrolet silverado 1500 truck mileage was achieved on the highway at the average mileage ~35 mpg, and at ~24 mpg driving in the city. that was the new 2020 corporate shevrolet silverado 1500 truck with the diesel engine.with the older models of the diesel trucks these numbers will be most likely lower.we did not notice no side effect of using the diacetyl alcohol instead of the regular diesel fuel as the diesel truck engine and the truck was checked by the chevrolet mechanic, with the only exception that we had to keep in memory the need to feel the truck with the fuel only at the corporate territory, not at the regular gas station. probably, at this point we will offer the fuel diacetyl alcohol to the local gas stations as the fuel for the diesel manuscript central cmi 02 (02), 256−261 (2022) 259 environmental problem solution engines or will have our own carbon negative diesel fuel stations around the nation.. however, they will have to test all the safety parameters of storage of this fuel on the station and the details of its use by the customers if anything unusual comes up. if we are successful in all said tests, the satisfactory results will go for the national/world’s implementation of our new diesel fuel and to the new gasoline stations, selling only diacetyl alcohol to customers as the diesel fuel at the same sales cost, as there is no our intent to disrupt the fuel market by the sudden decrease of the fuel prices. again, in this case we will offer to the customers purchased our carbon negative diactetyl alcohol the food for the amount they spent on the diesel fuel. .ourmajor concern herein is related to the use of our gasoline and the diesel fuel replacements to help the air jet aviation to help to fight the air co2 production. we are not aware of any competition on the carbon negative diesel fuel market at this time, but the market competition will be with the major international petroleum corporations like shell, bp and others. 2 declarations: ethical approval and consent to participate. this article does not contain any section, requiring ethical approval. the only author of this article is complied this section with the consent to participate. consent to participate. the author complied with the consent to publish this article. consent to publish. the author complied with the consent to publish this original article. authors contribution. dr. michael v. tyurin has planned all the experimental work, conducted all the experiments, analyzed the experimental data, wrote this original manuscript, edited ot as appropriate and submitted for this publication the edited original manuscript. funding was done by the private investors, who declined to provide their names and their business affiliations. the investors noted, the author should decline any source of funding. competing interests. the author does not have any competing interests with any third party. the author declares his personal conflict of interests with the law firm in houston, tx hirsch andwestheimer, which has destroyed his corporate website http:syngasbiofuelsenergy.com, and with the major petroleum and gasoline/diesel fuel companies in houston (tx), with the houston police (city of houston) and with the houston fbi ignoring the author’s concern about his attempted murder committed by shell after the author has presented to shell his proprietary technology for gasoline manufacture from the air co2, not from petroleum (tyurin mv, et al. 2019) the attempted murder is of no interest for the corrupt by the major petroleum corporations in houston, tx houston fbi. the author has no intent to file the lawsuit against the houston fbi at any point, but he is inclined to make this case the public domain. houston fbi does not follow the established in the usa federal laws. availability of data and materials, all the data and materials are available if necessary from the author of this manuscript. authors’ information the author is the owner of his mentioned texas businesses microbial biocatalyst international, inc. and inorgcarbdiesel, inc. the work has been done at the corporate site with the usps address p. o. box 300230, houston, tx 77230. 3 references 1.http://syngasbiofuelsenergy.com 2.tyurin mv (2021) cure of the intestinal disorders (recombinant pancreatic lipase expression at intestinal bifidobacteria). medical & clinical research 6(12):788-794. 3.tyurin mv (2021) expression in situ of the recombinant human erythropoetin and recombinant in-sulin. j diabetes metab. 12:900. doi: 10.35248/2252-5211.21.12.900 4.tyurin mv (2021) successful treatment of diabetes ii in adult patient and new prospects of recombinant vaccine and recombinant proteins engineering in situ. j diabetes metab. 12:871-875. 5.tyurin mv 2021. gasoline replacement fuel diacetyl alcohol. international journal of automotive technology. submitted. 6.tyurin mv 2021. air co2 for the manufacture of the commodity fuels. atmospheric pollution cmi 02 (02), 256−261 (2022) manuscript central 260 manuscript central m.d., ph.d research, submitted october 2021. 7.tyurin mv 2021. diacetone alcohol as the diesel. energy efficiency. energy efficiency. ed.: dr. muhammad wakil shahzad. intechopen. rijeka: janeza trdine 9, 51000 rijeka, croatia. london: 5 princes gate court, london, sw7 2qj, uk. isbn 978-1-83969-828-6. 8.berzin v, kiriukhin m, tyurin m. (2012) selective production of acetone during continuous synthesis gas fermentation by engineered biocatalyst clostridium sp. macet113. letters of appl microbiol. 55(2):149-54. doi: 10.1111/j.1472765x.2012.03272.x. 9.glen johnston. alcohol to jet-isobutanol. pdf of the ppt presentation. expect for future development and production of aviation alternative fuel. 2017 icao seminal on alternative fuels. icao headquarters, montreal, 8-9 february 2017. 10.berzin v, kiriukhin m, tyurin m. (2012) selective production of acetone during continuous synthesis gas fermentation by engineered biocatalyst clostridium sp. macet113. letters of appl microbiol. 55(2):149-54. doi: 10.1111/j.1472765x.2012.03272.x. 11.us patent us1550792a. 12.tyurin mv, padda r, huang k-x, wardwell s, caprette d, bennett gn (2000) electrotransformation of clostridium acetobutylicum atcc 824 using high-voltage radio frequency modulated square pulses // j appl microbiol. 88(2):220-227. 13.tyurin mv. (2021) environmental problem solution. submitted for purlication. how to cite this article: m.d., ph.d m.v.t. environmental problem solution. clinical medicine insights. 2022;256−261. https://doi.or g/10.52845/cmi/2022-3-1-3 manuscript central cmi 02 (02), 256−261 (2022) 261 introduction declarations: references received 10 jan 2022 | revised 12 jan 2022 | accepted 16 jan 2022 | published online 19 jan 2022 doi: https://doi.org/10.52845/cmi/2022-3-1-2 cmi 03 (01), 250−256 (2022) issn (o) 2694-4626 if:1.6 research article the relationship between nutritional health services for pregnantwomen and the incidence of stunting in lhok bot, aceh jaya suriati 1 teungku nih farisni 1public health science study program, faculty of public health, teuku umar university, indonesia abstract health services are an effort provided by the public health center (puskesmas) to the community which includes planning, implementing, evaluating, recording, reporting, and pouring it into a system. stunting is a condition of failure to thrive in children under five as a result of chronic malnutrition so that children are too short for their age and period. growth will be stunted unlike normal-born children in general. pregnant women are a group that is vulnerable to nutritional problems. lack of nutrition for pregnant women has a very large impact on the child they are carrying. the purpose of this study is to determine if there is a relationship between maternal health services pregnant women with stunting and the relationship between nutrition of pregnant women who experience sez and stunting in the working area of the lageun public health center, setia bakti sub-district, aceh jaya regency. the method used is a quantitative method through a cross-sectional approach. the indicators used to assess health services for mothers pregnant women were anc, p-value = 0.095 (p>0.05), pregnant women received at least 90 fe pills (blood-enhancing tablets) p-value = 0.002 (p<0.05), pregnant women who attended counseling nutrition/class of pregnant women p-value = 0.246 (p>0.05), pregnant women got nutritional monitoring resulted p-value = 0.004 (p<0.05), households with pregnant women had family latrines with p-value = 0.435 (p>0.05), pregnant women who had access to safe drinking water resulted p-value = 0.590 (p>0.05), households with pregnant women had health insurance results p-value = 0.435 (p> 0.05). nutrition of pregnant women resulted p-value = 0.001 (p<0.05). the results of the study found that there was a relationship between nutritional health services for pregnant women and the incidence of stunting. the results were carried out with the chi-square test to obtain results from the relationship between health services for pregnant women and the incidence of stunting. keywords: health services, maternal nutrition, stunting copyright : © 2022 the authors. published by publisher. this is an (https://creativecommons.org/licenses/by-nc-nd/4.0/). cmi 03 (01), 250−256 open access article under the ccby-nc-nd license 250 clinical medicine insights https://doi.org/10.52845/cmi/2022-3-1-2 https://creativecommons.org/licenses/by-nc-nd/4.0/ 1 introduction health service is an effort provided by the public health center to the community which includes planning, implementing, evaluating, recording, reporting, and pouring in a system. health services are also the responsibility of the government in an effort to achieve community welfare. pregnant women, which is known as anc, pregnant women get aminimum of 90 fe pills (blood-boosting tablets), pregnant women who take nutritional counseling/pregnant women’s classes, pregnant women get nutritional monitoring. access to safe drinking water and households with pregnant women have health insurance. the problem in these services is the lack of health services for pregnant women and can result in stunting. stunting is a condition of failure to thrive in children under five as a result of chronic malnutrition so that children are too short for their age and their growth period will be stunted unlike normal children born in general. stunting condition is only seen after the baby is 2 years old. the definition of stunting according to the decision of the minister of health in 2010 is nutritional status based on the index of body length for age (pb/u) or height for age (tb/u) in the standard for assessing children’s nutritional status with measurement results that are in the standard value or z-score < -2 sd to -3 sd for short (stunted) and < -3 sd for very short (severely stunted). according to eko (2018), in the village pocket book, stunting is handled. stunting is a condition of failure to thrive in children under five due to chronic malnutrition so that children are too short for their age. stunting is caused by multi-dimensional factors. the most decisive intervention is at 1,000 hpk (1000 days) from the first birth. stunting is often described as a poor nutritional status and is chronic in development from early life. this condition is represented by a z-score for height for age (tb/u) less than -2 standard deviations (sd) based on growth standards according to who (who, 2010). factors for stunting or stunting are factors of social status, economy, food intake, infection, maternal nutritional status, infectious diseases and micronutrient deficiencies and the environment (who, 2018). many factors can cause stunting in toddlers including the nutritional status of mothers during pregnancy, so it is necessary to have adequate nutrition during pregnancy as needed to avoid the risk of stunting and as for other reasons, including a mother’s knowledge of the problem of balanced nutrition, which is very lacking, but sometimes the environment is also one of the causes because if sanitation and hygiene are poor it will affect nutrition. in 2017, more than half of children with stunting came from asia as much as 55%, africa is 39% and indonesia occupies the top 5 highest prevalence with stunting. in indonesia, stunting has the highest prevalence compared to other problems such as malnutrition, thinness, and obesity with stunting prevalence increased from 2016 which was 27.5% to 29.6% stunting in 2017, which tended to be static (moh, 2018). pregnant women are a group that is vulnerable to nutritional problems. lack of nutrition for pregnant women has a very large impact on the child they are carrying. if pregnant women experience nutritional problems, it will cause, among others: miscarriage, stillbirth, neonatal death, congenital defects, anemia in infants, and infants born with lbw. the nutrition obtained by pregnant women before and during pregnancy affects the growth and development of the baby in the womb. if the nutrients needed by pregnant women are fulfilled before and during pregnancy, they will give birth to healthy babies. a pregnant womanwill give birth to a healthy baby if the level of health and nutrition is in a good position, but until now there are still many pregnant women who experience nutritional problems, especiallymalnutrition such as chronic energy deficiency (kek) and nutritional anemia (depkes ri, 1996). the results of the 1996 skrt show that 41% of pregnant women suffer from ced and 51% who suffer from anemia have a tendency to give birth to babies with supplementary information the online version of this article (10.52845/cmi/2022-3-1-2) contains supplementary material, which is available to authorized users. cmi 03 (01), 250−256 manuscript central 250 manuscript central suriati and teungku nih farisni low birth weight (lbw). chronic energy deficiency (ced) is a state of malnutrition where the condition of the mother suffers from chronic food shortages which result in health problems for the mother in relative or absolute terms of one or more nutrients (helena, 2013). pregnant women who experience ced and anemia are at risk of experiencing greater pain, especially in the third trimester of pregnancy than mothers who are normal pregnant. babies who are born with low birth weight will have an effect on their growth and development period, so they will be at risk when they are adults. the risk of morbidity and mortality in infants is they will get susceptible to lower respiratory tract infections, learning disorders, behavioral problems, and so on (depkes ri, 1998). the nutritional needs of mothers during pregnancy are different, therefore who recommends an additional amount of 150 kcal a day in the first trimester, 350 kcal a day in the second and third trimesters. in canada, the addition for the first trimester is 100kcal and 300 kcal for the second and third trimesters. indonesia based on the widya karya national food and nutrition vi year 1998, the figure was determined to be 285 kcal per day during pregnancy. this figure certainly does not include additions due to changes in room temperature, physical activity, and growth. supervision issues for mothers during pregnancy are very necessary, because we have to monitor what foods are eaten by pregnant women so that their nutrition is fulfilled, through this supervision can be determined such as maternal health during pregnancy, how to make pregnant women aware of nutritional problems such as conducting education on nutrition for pregnant women. in aceh jaya, a nutrition house (rgg) has also been established to provide understanding to mothers who are pregnant and who have toddlers about nutritional problems. pregnant women need to maintain the food they assume during pregnancy, such as foods rich in protein, fat, calcium, calories which are often found in tempeh, tofu, vegetables, fruits, and nuts. 23.5cm while the kek lila is 23.5cm. the problem of supervision for mothers during pregnancy is very necessary, because we have to monitor what foods are eaten by pregnant women so that their nutrition is fulfilled. growth parameters continue to be a concern and are considered as parameters for assessing nutritional health status. the parameters that are often used are weight and height or body length (sediaoethema, 2012). births with low birth weight (lbw) represent more than 20 million births every year with an estimated 15% -20% of births worldwide which is still a global health problem (who, 2014). to prevent all of this from happening, efforts are made such as regulating food consumption in pregnant women, monitoring weight gain once a week or once a month, checking hb levels, and measuring lila before or during pregnancy. 2 method the method used is a quantitative method through a cross-sectional approach. according to arikunto (2006) quantitative method is a research approach that uses a lot of numbers ranging from data collection, interpretation of the data obtained, and exposure of the results of pregnancy and maternal characteristics during pregnancy on the incidence of stunting. cross-sectional research is a study to study the dynamics of the correlation between risk factors and effects, by approach, observation, or data collection. cross-sectional research only observes once and measurements are made on the subject variables at the time of the study (notoatmojo, 2010). the population in this study was 23 toddlers aged 24-60 years old in the working area of the lageun public health center, especially in the village of lhok bot. 3 research objective the purpose of this study was to determine whether there was a relationship between health services for pregnant women and the incidence of stunting and the relationship between maternal nutritional status during pregnancy and the incidence of stunting in the working area of the lageun public health center, setia bakti district, aceh jaya regency. manuscript central cmi 03 (01), 250−256 (2022) 251 the relationship between nutritional health services for pregnant women and the incidence of stunting in lhok bot, aceh jaya 4 results and discussion • general data • toddler age table 1. distribution of respondents by age under five in the work area of the lageun public health center. table 1 shows 9 toddlers aged 24-36 (39.13%), and 11 toddlers aged 36-48 (47.48%) and 3 (13.04%). 2.gender table 2 distribution of respondents based on gender of children under five in the lageun health center work area. table 2 shows that there are more male children under five than male children, namely 13 children under five (56.52%) and 10 female children under five (43.48%). • special data 1. maternal nutritional status during pregnancy table 3. distribution of respondents based on the nutritional status of mothers during pregnancy in the lageun health center work area. table 3. shows that mothers with lila (upper arm circumference) are 19 people (82.61%) while for mothers with kek (chronic energy deficiency) 4 people (17.39%) respondents who are at risk of giving birth to malnourished babies are 4 people while respondents who are not at risk of stunting are 19 people. however, there are also respondents who experience sez but when giving birth the baby is not stunted, because there are also mothers whose lila who is normal but she gave birth babies who are stunted, because we can see from the results of this study that only 4 mothers have sez while 5 stunted children, so there are stunting children but the mother’s lila is normal. normal lila >23.5cm. 2.stunting incident table 4. distribution of respondents based on the incidence of stunting in children under five in the working area of the lageun health center. cmi 03 (01), 250−256 (2022) manuscript central 252 manuscript central suriati and teungku nih farisni table 4 shows that the normal number of toddlers is 18 toddlers (27.78%) while the stunting toddlers are 5 toddlers (78.26%). there are 5 respondents who are at risk of stunting in lhok bot village, while 18 people are not at risk. 3.the relationship between maternal nutrition during pregnancy and the incidence of stunting in children under five in the work area of the lageun public health center. based on the table data above, this study used the chisquare test from the calculation, it got a p value of 0.001whichmeans (p <001), therefore there is a relationship between the nutritional status of the mother during pregnancy and the occurrence of stunting in infants/toddlers to be born. from the r value, it is known that 12,308 which means that the strength in the relationship is categorized as weak. the less nutrition of the mother during pregnancy, the greater the incidence of stunting in a child to be born. 4. relationship between health services for pregnant women and the incidence of stunting in the work area of the lageun public health center. based on the table data above, it is known that the results of the analysis using the chi-square test found the relationship between ante natal care and the incidence of stunting in toddlers, the p-value = 0.095 (p>0.05) therefore there was no relationship between anc and stunting. in infants/toddlers. meanwhile, the relationship between giving blood-added tablets and the incidence of stunting was found to be p-value = 0.002 (p<0.05), therefore there was a relationship between giving blood-added tablets (fe) and the incidence of stunting with the incidence of stunting, p-value = 0.246 (p>0.05) then there is no relationship between the class of pregnant women and the incidence of stunting. there is a relationship between nutritional monitoring and the incidence of stunting. the relationship between pregnant women who have latrines and the incidence of stunting obtained pvalue = 0.435 (p> 0.05), so there is no relationship between pregnant women who have latrines and the incidence of stunting. the relationship between pregnant women who have safe drinking water and the incidence of stunting is found to be p-value = 0.590 (p>0.05), so there is no relationship between pregnant women who have safe drinking water and the incidence of stunting. health insurance with stunting is obtained with a p-value = 0.435 (p>0.05), so there is no relationship between pregnant women who have health insurance and the incidence of stunting. anc services are preventive or preventive services to monitor maternal health and prevent complications for the mother and fetus. efforts must be made to ensure that pregnant women are healthy until delivery, if any physical or psychological abnormalities can be detected immediately, and pregnant women can giving birth without complications (bartini, 2012). ante natal care (anc) examination is very necessary which aims to optimize the mental, physical health of the mother and baby return of normal reproductive health (manuaba, 1998). the ministry of health recommends that pregnant women consume at least 90 iron tablets during pregnancy. however, the level of compliance of pregnant women in consuming fe tablets is still low. therefore, the incidence of stunting is related to pregnant women who do not take fe tablets. the class for pregnant women is one way that can be used to disseminate information related to nutrimanuscript central cmi 03 (01), 250−256 (2022) 253 the relationship between nutritional health services for pregnant women and the incidence of stunting in lhok bot, aceh jaya tion and health during pregnancy. from the results obtained, it can be concluded that there is no relationship between classes of pregnant women in lhok bot village and the incidence of stunting because there is no class of pregnant women in the village. nutrition monitoring is very influential on the occurrence of stunting, therefore it is necessary to monitor nutrition for pregnant women in order to prevent stunting. this nutrition monitoring can be through posyandu or other education. according to the association of indonesian environmental health experts (hakli) environmental health is an environmental condition that is able to support a dynamic ecological balance between humans and the environment to support the achievement of a healthy and happy quality of human life residents who have latrines. clean water is clean water used for daily needs whose quality meets health requirements and can be drunk when it has been cooked. there is no relationship between safe clean water and the incidence of stunting because almost all of these villages have safe water for consumption. several studies show that health insurance participation is able to improve nutritional problems. however, the results obtained through the chi-square test show that in lhok bot village there is no relationship with families who have health insurance with stunting. from 23 samples of pregnant women in the village of lhok bot loyal filial piety, several of them who suffered from constipation from the data obtained were 4 people (17.13%). a person’s background is one of the important elements that can affect health and nutrition because health problems often occur due to lack of knowledge or lack of information about health and good nutrition issues. pregnant women whose lila is sez will be vulnerable to giving birth to stunting babies, because of the lack of nutrition that they get when they are pregnant, so that they are not sufficient for the needs of the baby in their womb. in aceh province, the prevalence of sez risk for pregnant women aged 15-15 years who are pregnant is 20% while the prevalence of sez risk for women of childbearing age (not pregnant). nationally, the risk of sez in wus is 21% (aceh health profile, 2019) the occurrence of stunting is caused by a process of failure to achieve potential linear growth due to health status and nutritional status. linear growth or often called height is influenced by genetic factors, hygiene and sanitation factors and medical conditions, but there are also nutritional problems as mentioned above on. the implementation of health services is a shared responsibility between the government and the community, most of them can be carried out by public health center, none other than the lageun setia bakti puskesmas. one of the efforts to improve the performance of public health center services is by implementing health mss. 5 conclusion based on the results of research that has been carried out: 1) lack of health services for pregnant women can also cause stunting, 2) the risk that causes stunting in infants is greater due to mothers who experience sez during pregnancy because it is very closely related to stunting compared to normal mothers who experience seizures but do not give birth to stunting babies, 3) the status of pregnant women with sez in the lageun community health center working area is in themediumcategory 4) the health services can also be related to the incidence of stunting 6 suggestion based on the results of the research above, suggestions that can be conveyed to the public health center workers so that they can provide education to pregnant women/communities in lhok bot village to be able to improve health services for pregnant women and provide nutritious and balanced food to avoid stunting. cmi 03 (01), 250−256 (2022) manuscript central 254 manuscript central suriati and teungku nih farisni 7 references 1. purfika dwi lestari1), nikmatur rohmah2), resti utami3) (2012-2019), relationship of nutritional status of women while pregnant with stunting events in toddlers in the work area of puskesmas arjasa. things 1-9. http://repository.unmuhjember.ac.id/5047/ 11/k.%20artikel%20jurnal>pdf 2. zulhaida lubis (2003), the nutritional status of pregnant women and their effect on babies born.https:/ /scholar.google.co.id/citations?view_op=view _citation&hl=id&user=qd2n8ckaaaaj&cita tion_for_view=qd2n8ckaaaaj.zexyd9-uun ac. 3. ekayanthi niwayan dian1,suryani pudji2(2019), nutrition education in pregnant women prevent stunting in the class of mother hamil.no 3,vol 10,hal 312-319.https://www.ejurnal.poltekke s-tjk.ac.id/index.php/jk/article/download/1389 /1032 4. khoirun ni’mah1,siti rahayu nadhiroh2.factors related to stunting events on balita.no 1,vol 10,hal 13-19 .https://e-journal.unair.ac.id/index.php/mgi/ar ticle/dowload/3117/2264 5. yeni paramata* and marselia sandalayuk (2019) chronic lack of energy in women of childbearing age wiliyah limboto subdistrict, gorontalo.no regency 1,vol 2,p6. http s://jurnal.unigo.ac.id/index.php/gjph/article/do wload/390/330 6. rosdiana syakur1, musaidah2, jusman usman1, nurismala dewi1 (2020). factors that affect the incidence of chronic energy deficiency (kek) in pregnant women in the working area of maccinisombala health center makasar.no 2,vol 1,p9 https://uit.e-journal.id/jkkm/article/dow nload/621/450 7). katmini ”(2020), expectant mother’s health determinant for pregnancy alerts with minimal contact attainment four times over gestation (k4). no 1, vol 5 https://jurnalbidankestrad.com/index.php/jkk/aeticl e/view/137 8). nifar ruaida’. octovina soumoki (2018).you know,the whole pregnant and bblr thing with stunting incidents in toddlers in the tawiri county center ambon.peg 45-51 https://www,jurnalpoltekkesmaluku.com/indek.php/jkt/article/sownload/12/7 9). vita kartika mahira wati’ (2014) factors related to a chronic lack of energy (grandpa) in pregnant mothers are met weoning dam ang district, java east .vol 17,p10 http://media.neliti.com/media/publications/20898-i d-related-factors-of-chronic-energy-deficiency-at-p regnant-women-in-kamoning-and-t.pdf 10). fauziah faich carissa, fathurrohman, subowo ari (2012) monitoring bu and child services at the galan’s hospital sub-script. diponegoro school of science, tembalang semarang social and politics, universities 11). nurmayanti rika1),salimo harsono2),yuliana lanti retno dewi3) (2017) effects of maternal nutrition status,maternal education,maternal stres,and family income onbirthweight andbody lengt at birth in klaten,central java.hal 297-308 https://media.neliti.com/media/publications/235279 -effects-of-maternal-nutrition-status-mat-47213241. pdf 12). husna asmaul ”andika fauziah” rahmi nuzulul (2020) determination the occurrence of chronic energy deficiency (grandad to a pregnant mother in the library) hasan.vol 6 no.1. p608-615 https://jurnal.uui.ac.id/index.php/jhtm/article/dow nload/944/460 manuscript central cmi 03 (01), 250−256 (2022) 255 the relationship between nutritional health services for pregnant women and the incidence of stunting in lhok bot, aceh jaya 13.) hutasoit masta ’, utami khritina dias2, afriyiani nur fitri3, visits the ante christmas care is in touch with stunting events https://stikes-yogyakarta.e-journal.id/jksi/article/d ownload/13/7/ 14). bingan eline charla sabatina (2019) fe consumption relation with 12-24 month longevity, volume 15, number 2pages 115-120 http://ejurnal.poltekkestasikmalaya.ac.id/index.php/ bmi/article/download/415/238 15). ade irma suryani pane (2019) effects of environmental health on stunting riskonprefabricatedkids lang, faculty of nursing, north sumatra university,medan. 16). symbolon demsa (2014) influenceon the secure status of poor people to birth and birth status in bedouin indinesia (dataifls 1993-2007) volume 03, number 02 pages 55-65 https://jurnal.ugm.ac.id/jkki/article/doenload/36359 /21238 17.) lestari trimas ayu health care analyse of pregnant and childbirth mothers’ health care centers in the semarang city poned http://ejournal3.undip.ac.id/index.php/jppmr/article/ download/20115/18983 how to cite this article: s., t.n.f. the relationship between nutritional health services for pregnant women and the incidence of stunting in lhok bot, aceh jaya . clinical medicine insights. 2022;250−256. https://doi.org/ 10.52845/cmi/2022-3-1-2 cmi 03 (01), 250−256 (2022) manuscript central 256 introduction method research objective results and discussion conclusion suggestion references clinical medicine insights received 10 feb 2022 | revised 13 feb 2022 | accepted 18 feb 2022 | published online 20 feb 2022 doi: https://doi.org/10.52845/cmi/2022-3-1-4 cmi 02 (02), 262−267 (2022) issn (o) 2694-4626 if:1.6 research article vaccines against potential pathogens[vaccine against plague. ] dr.michael vladislavovich tyurin m.d., ph.d 1ceo, executive chairman, president of microbial biocatalyst international, inc. and inorgcarbdiesel, inc. dr. tyurin has gained two doctoral degrees in the former soviet union: m.d. in internal medicine (1986, saratov state medical university) and ph.d. in molecular biology, microbiology and molecular pharmacology (1990, the ussr research institute for antibiotics). dr. tyurin additionally has b. sci. in biological engineering (1984) and m. sci. in biology (1985) both from saratov state medical university. abstract we proposed human intestine as the gate for the delivery of the therapeutic recombinant proteins expressed inside of the human body. the normal intestinal microflora was used to express the selected genes of the pathogenic organism yersinia pestis the causative agent for plug in humans and animals. we have confirmed the production of the selected proteins by the pcr to their dnas expressed in intestinal bifidobacteria chosen. now it is the role of the immunologists to find the antibodies for the recombinant proteins expressed inside of the volunteer’s organism. keywords: expression of the recombinant proteins inside human’s body, bifidobacterium breve, use of genome tailoring technology to express the recombinant proteins inside of the volunteer’s body. copyright : © 2022 the authors. published by publisher. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). 1 introduction the author started his medical education at saratov state medical university after he spoke with his cousin galina about becoming the ph.d-scientist working with the yesrinia pestis the causative agent of plague and vibrio cholera the causative agent of cholera at the closed for the employment of the general public institution microbe in author’s native city saratov (now dissolved). said scientists had salaries substantially exceeding that of the regular former soviet society members, just like the author. for instance, the soviet academician was getting his salary of 1,000 russian rubles, while at the mentioned organization microbe senior ph.d. researcher was getting 2,600 rubles, etc. the author has made multiple friends among said ph.d-.level scientists from that closed for general public employment institution microbe. some contacts became very useful for dr. tyurin for making his scientific presentations at saratov state medical university during his course of studying. the most remarkable was the gift of the microbe institute medical advisor when she gave to dr. tyurin 5 kg of japanese agar-agar. the author could use that agar during his already scheduled ph.d. studies at the ussr research institute for antibiotics inmoscow, the former ussr, and for his future work as the ph.d-student in moscow, when dr. tyurin has gotten as a present those 5 kg of cmi 02 (02), 262−267 manuscript central 262 https://doi.org/10.52845/cmi/2022-3-1-4 https://creativecommons.org/licenses/by-nc-nd/4.0/ manuscript central m.d., ph.d the japanese agar-agar he later used in moscow for his ph.d-associated research and development (r & d). while studying at saratov state medical university and visiting the microbiology and immunology department of said university from early in 1981 till his graduation date in 1986 the author has learned that what he wanted to become after the graduation of saratov state medical university was not possible, complicated by his origin of the regular private person. he must note that his cousin galina was the daughter of the spcu (soviet communist party) second secretary of the saratov region spcu committee vladimir rodionov. that gave her the protected path to become the ph.d-scientist in said closed for the general public employment former soviet union institution microbe dealing with plaguecholera causative agents during the futile scientists attempts to create the new biological weapons of mass destruction with the tremendous destructive power and difficulty to cure. that mentioned closed system required mandatory thorough checking of the background by the kgb and the origination from families of the high ranked spcu-related people in the former soviet union, which was quite opposite to what the author had in his background. while learning about that in the course of study at saratov state medical university, the author continued to want to become the professional ph.d. level scientist working with microorganisms, and he was not any longer inspired by the levels of the respective salaries such noted secretly working on the weapons of the mass destruction ph.d.-scientists had in the former soviet union. on the second year of the author’s education (1982) at saratov state medical university the author has met professor boris shenderov, a person who just returned from zambia where he worked as the professor at the lusaca university. dr. shenderov worked for the kgb and that was the reason he was in zambia for his “work”. dr. shenderov visited saratov state medical university he graduated from as well. he has visited saratov state medical university in 1984 before moving to moscow, where the former soviet kgb gave dr. shenderov the rank of the colonel and the new work of the professor at the laboratory of the industrial hygiene at the ussr research institute for antibiotics, moscow, the former ussr. so, dr. shenderov used data the author has provided to him on the author’s studies of non-fermenting glucose gram negative organisms predominantly pseudomonas isolated from the hospital patients in the saratov region. said data gave the opportunity to publish them in the journal for dr. shenderov’s future moscow institution “antibiotics” in 1984 (the 1st publication dr, tyurin had in the former soviet union [1] while being a simple medical student). dr. shenderov invited dr. tyurin to continue the education in moscow to become his ph.d-student upon the graduation of the saratov state medical university, which the author did in 1986. upon the graduation of his phd.-studentship the author joined dr. shenderov at his another new work place, as dr. shenderov got the promotion from the kgb for his work in moscow since 1984, at gabrichevsky research institute for epidemiology and microbiology in 1990 where dr shenderov became the director. in 1992 the author has left dr. shenderov and his kgb-related work community and joined theauthor’s newwork acquired at vniigenetika (the adjinomoto-gniigenetika research institute), the author’s last place of work at the russian federation before moving permanently to the usa. the author has already described the known before place of entry to the human body bloodstream human intestine [2,3]. the author had specialization during his ph.d.-studentship years on the molecular biology, microbiology and molecular pharmacology of the normal intestinal microflora of humans and animals. the author has become the king of lactobacilli and substantially intensified his work with the human intestinal bifidobacteria at gniigenetika in 1992-1998, the predominant organisms in the intestine of many humans [4]. in this original research paper the author describes his personal experience with the volunteer he has successfully vaccinated by creating the recombinant strain of bifidobacteria isolated from the intestinal content of said volunteer as described in [2,3] and making said supplementary information the online version of this article (10.52845/cmi/2022-3-1-4) contains supplementary material, which is available to authorized users. manuscript central cmi 02 (02), 262−267 (2022) 263 vaccines against potential pathogens[vaccine against plague. ] volunteer to ingest the recombinant strain of his own intestinal bifidobacteria. as the target for the expression in the recombinant bifidobacterium breve 839 strain the author has chosen the dna with the known nucleic acid content originally isolated from the yersinia pestis strain. said strain was the causative agent for the human and animals plug [6]. the author’s choice for said proteins was dictated by the ethiological role of the yersinia pestis selected as the possible ethiologic agent of the emergent diseases the outer space travel crews might possibly face discovering other new planets similar to earth by the temperature and the atmosphere content in the coming future, the immediate projects of the environmental direction. . 2 materials and methods the isolation and investigation of intestinal bifidobacteria of the volunteer was performed as described [2,3]. using the described selective medium for the isolation of the intestinal bifidobacteria [2] the author has isolated bifidobacterium breve 839 strain from said volunteer’s freshly collected intestinal content (fresh feces). said strain was subjected to the reduction of its genome by removal of not essential for the vital functions of said strain natural genome genes at their positions 4346...4816 bp,10023...10574 bp, 16239...17477 bp, 19324...20316 bp, 20927...21592 bp,22486...23799 bp,237007...238836 bp, 24676...26007 bp, 31295...33502 bp,34410...36290 bp, 37707...39254 bp, 538583...541012 bp, 643441...645516 bp, 817368...820625 bp, 1476554...1481404 bp and 2258202...2261981 bp using the procedures described in [7-16]. total genomic dna from b. breve 839 was isolated by the procedure [4,18]. the primers for the pcr to check the presence of the recombinant pesticin and the hypothetical protein ypmt1.21c dna sequences were designed using the publically available tool [17]. the process of genetic modification of said b. breve 839 strain took less then 200 hours to ensure the strain regained the capability to adhere back to the intestinal wall of the volunteer as we have discussed before [2,3]. bifidobactrium breve 839 pesticin submission id 2526713. bifidobacterium breve 839 hypotetical protein ypmt1.21c submission id 2532183. 3 results development of the recombinant strain of b. breve 839 plug was performed as already described in [2,3]. said strain of intestinal human bifidobacteria of the volunteer has expressed both recombinant genes of pesticin and the hypothetical protein ypmt1.21c as that was shown by the pcr the author has performed with the total genomic dna isolated from b. breve 839 piug by the method described in [18] with the proper modifications of the procedure to isolate the total genomic dna. the pcr for the presence of the both recombinant genes of pesticin and the hypothetical protein ypmt1.21c ended up with the revealing of the proper dna fragments on the agarose gel for the pcr products [17]. upon said testing the 25ml of the 72-h broth culture of b. breve 839 plug grown in the liquid m3edium for the isolation of bifidobacteria with no antibiotics added were. ingested by the volunteer. in one hour he came back to his work and has ever worked as before the ingestion. now, it is the task for the immunologists to investigate the blood stream of said volunteer to recover the antibodies to the yersinia pestis pesticin and the hypotetical protein ypmt1.21c. 4 discussion we have discussed the prospects of our planet in the future at our corporate web site, and noted the coming in 10-20 years from now the shortage of the fresh water, leaving the earth to the outer space as described [2,3]. indeed, accumulated in the air co2 is one of the heaviest gasses in the air blend, reaching its density 1.97 g/cubic meter [3]. the co2 in the air gas mixture under the no wind environmental cmi 02 (02), 262−267 (2022) manuscript central 264 manuscript central m.d., ph.d conditions spreads on the ground surface and selectively absorbs all the infrared energy of the sun light, thus heating the ground significantly. that causes the extra evaporation of the fresh water from soil to the air. as you know, global warming presents itself in various forms, specifically with increased frequency of rainy weather, long rainy days, tornadoes, etc. but the earth gravity has been stable for the last few million years from now. therefore, under the constant gravity force applied, more fresh water vapors are in the air. the space, surrounding earth, as any space anywhere, has vacuum. that vacuum sucks fresh water vapors from earth air, and such fresh water vapors travel in the space in the unknown direction away from the earth. in 2010 nasa has bombarded the moon and found plenty of ice on its dark and very cold surface. the earth satellite moon is located 220,000 miles away from earth. one moon’s side is always dark and cold as it never gets sun light irradiation. it is very cold, as cold as the space vacuum, -273 o c. so nasa were guessing where said ice came from? moon worked as the cold trap for the fresh water vapors coming from earth in the space vacuum [http://syngasbio fuelsenergy.com]. what will happen next and the most important, when?wemight give the time frame for 10-20 or 10-50 years from now, based on the 2010 hasa discovery of ice on the moon and the nasa conclusion of their findings: earth as planet has passed the “point of no return” to the normal life. it is impossible to anticipate, that the fresh water loss to the outer space may be stopped at any time even if the earth population is suddenly decreased in its amount. the extra air co2 comes from the intensified petroleum use, and the use of its products for combustion, producing co2. people breath and produce co2 as well. it is anticipated the 14 billion people on earth by 2050. that increases more the air co2 content, leading to the increased freshwater loss as discussed. fig 1 shows our understanding of the fresh water loss process. fig, 1. fresh water loss to the space vacuum we have no any idea, what will happen soon, if no new planets, similar to earth, will be discovered and the overcrowded earth population will not start to move there. we do anticipate, that the reduction of the air co2 content is absolutely necessary and possible by the replacing of the existing economy based on the power generation suing the products of petroleum distillation on the petroleum refineries by the economy based on the energy generation using the discovered by the author carbon negative technologies of the fuels and chemicals production [2-16]. in this article, the author has shown that the expression of the recombinant proteins originated from yersinia pestis and expressed in the human intestinal bifidobacteria happens efficiently right in the body of the volunteer by the engineered strain of the intestinal bifidobacterium isolated and then returned back to the intestine of said volunteer. based on the described expression of the recombinant proteins, the author has concluded, that that will be possible to perform the immunization of the proposed coming soon manned crews of the outer space flights intended to discover new planets in the universe suitable for the relocation of the overcrowded earth. said immunization does require certain genetic manipulations which are possible on the board of said outer space travel vehicle(s) by the suing the described technologies of genome replacement in the intestinal microflora of the potential crew members of said vehicle. this circumstance closes the need for manuscript central cmi 02 (02), 262−267 (2022) 265 vaccines against potential pathogens[vaccine against plague. ] the special medical personnel on board of said outer space travel vehicle(s) to perform the immunization of the crew from the emergent infections reasonably anticipated for the existence in the new outer space locations. this approach may have crucial importance for the manned crews life during said long term outer space travel missions proposed. 5 declarations ethical approval and consent to participate. this article does not contain any section, requiring ethical approval. the only author is complied with the consent to participate. consent to participate. the author complied with the consent to publish this article. consent to publish. this original article has not been published anywhere or is under the consideration to publish anywhere else beside this journal. the author complied with the consent to publish this original article. authors contribution. dr. michael v. tyurin has planned all the experimental work, conducted all the experiments, analyzed the experimental data, wrote this original manuscript, edited ot as appropriate and submitted for this publication the edited original manuscript. funding was done by the private investors, who declined to provide their names and their business affiliations. the investors noted, the author should decline any source of funding. competing interests. the author declares his personal conflict of interests with the law firm in houston, tx hirsch and westheimer, which has destroyed his corporate website http:syngasbiofuelsenergy.com, and with the major petroleum and gasoline/diesel fuel companies in houston (tx), with the houston police (city of houston) and with the houston fbi ignoring the author’s concern about his attempted murder committed by shell after the author has presented to shell his proprietary technology for gasoline manufacture from the air co2, not from petroleum (tyurin mv, et al. 2019) the attempted murder is of no interest for the corrupt by the major petroleum corporations in houston, tx houston fbi. the author has no intent to file the lawsuit against the houston fbi at any point, but he is inclined to make this case the public domain. houston fbi does not follow the established in the usa federal laws. availability of data and materials, all the data and materials are available if necessary from the author of this manuscript. the authors’ information. the author is the owner of his mentioned texas businesses microbial biocatalyst international, inc. and inorgcarbdiesel, inc. the work has been done at the corporate site with the usps address p. o. box 300230, houston, tx 77230. 6 references 1. shenderov ba, serkova gp, tyurin mv (1984) susceptibility of clinical non-fermenting gramnegative bacteria to antibacterial drugs // antibiotiki 29 (3):191–195. 2. tyurin mv (2021) expression in situ of the recombinant human erythropoetin and recombinant insulin. j diabetes metab. 12:900. doi: 10.35248/2252-5211.21.12.900 3. tyurin mv (2021) successful treatment of diabetes ii in adult patient and new prospects of recombinant vaccine and recombinant proteins engineering in situ. j diabetes metab. 12:871-875. 4. tyurin m.v. ph.d. thesis: ”antibiotic resistance and antagonistic activity of lactobacilli” 1990, the ussr research institute for antibiotics, moscow, the ussr. 5. http://syngasbiofuelsenergy.com. 6. parkhillj,wren b.w.,thomson n.r.,titball r.w.,holden m.t.,prentice m.b.,sebaihia m.,james k.d.,churcher c.,mungall k.l.,baker s.,basham d.,bentley s.d.,brooks k.,cerdeñotárraga a.m.,chillingworth t.,cronin a.,davies r.m.,davis p.,dougan g.,feltwell t.,hamlin n.,holroyd s.,jagels k.,karlyshev a.v.,leather s.,moule s.,oyston p.c.,quail m.,rutherford k.,simmonds m.,skelton j.,stevens k.,whitehead s.,barrel b.g. (2001).genome sequence of yersinia pestis, the causative agent of plague. nature. 2001 oct 4; 413 (6855): 523-7. doi: 10.1038/35097083. 7. tyurin m, kiriukhin m (2013). 2,3-butanediol production by engineered acetogen biocatalyst during continuous fermentation of syngas or co2/h2 cmi 02 (02), 262−267 (2022) manuscript central 266 manuscript central m.d., ph.d blend. appl 8. tyurin m, kiriukhin m. (2013). selective methanol or formate production during continuous co2fermentation by the acetogen biocatalysts engineered via integration of synthetic pathways using tn7-tool. world journal of microbiology and biotechnology. 29 (9)1611-1623. doi: 10.1007/s11274-013-1324-2. 9. tyurin m. (2013). gene replacement and elimination using λredand flp-based tool to re-direct carbon flux in acetogen biocatalyst during continuous co2/h2 blend fermentation. journal of industrial microbiology&biotechnology. 40 (7):749-758. doi: 10.1007/s10295-013-1279-1. 10. berzin v, kiriukhin m, tyurin m. (2012) selective production of acetone during continuous synthesis gas fermentation by engineered biocatalyst clostridium sp. macet113. letters of appl microbiol. 55(2):149-54. doi: 10.1111/j.1472765x.2012.03272.x. 11. tyurin m, kiriukhin m. (2013). expression of amplified synthetic ethanol pathway integrated using tn7-tool and powered at the expense of eliminated pta, ack, spo0a and spo0j during continuous syngas or co2 /h2 blend fermentation. j appl microbiol. 114(4):1033-45. doi: 10.1111/jam.12123. 12. tyurin m, kiryukhin m, berzin v. (2012) electrofusion of untreated cells of the newly isolated acetogen clostridium sp. mt351 with integrated in the chromosome erm(b) or cat leading to the combined presence of these antibiotic resistance genes 1in the chromosome of the electrofusion products. journal of biotech research. 4:1-12. 13. berzin v, kiriukhin m, tyurin m. (2013) cre-lox66/lox71-based elimination of phosphotransacetylase or acetaldehyde dehydrogenase shifted carbon flux in acetogen rendering selective overproduction of ethanol or acetate. appl biochem biotechnol. 195(3):181-8. http://www.ncbi.nlm.nih. gov/pubmed/22941272. 14. berzin v, kiriukhin m, tyurin m. (2013) selective n-butanol production by clostridium sp.mtbutoh1365 during continuous synthesis gas fermentation due to expression of synthetic thiolase, 3-hydroxy butyryl-coa dehydrogenase, crotonase, butyryl-coa dehydrogenase, butyraldehyde dehydrogenase and nad-dependent butanol dehydrogenase. appl biochem biotechnol. 169(3), 950-959. doi: 10.1007/s12010-012-0060-7. 15. bifidobacterium breve. normal gastrointestinal bacterium. 1855. begey’s manual of determinative bacteriology, ninth edition. 16. tyurin mv, padda rs. nitrogen gas reducing commercial acetogen biocatalyst suitable for direct and selective reduction of co2 inorganic carbon to organic carbon and atmospheric nitrogen to fuel isobutanol during continuous fermentation of co2 + h2 + n2 gas blend. irjaset. 2019. 3:1-10. 17. primer3_results.cgi release 0.4.0. 18. tyurin mv, donskih ee, shenderov ba, goncharova gi (1990) plasmid dna isolation method for bifidobacteria. antibiot khimioter 35 (7): 21–22. how to cite this article: m.d., ph.d d.r.m.v.t. vaccines against potential pathogens[vaccine against plague. ]. clinical medicine insights. 2022;262−267. https://doi.org/10.52845/cmi/20223-1-4 manuscript central cmi 02 (02), 262−267 (2022) 267 introduction materials and methods results discussion declarations references clinical medicine insights received 12 may 2021 | revised 20 june 2021 | accepted 30 july 2021 | published online 9 aug 2021 cmi journal 2 (3), 155−162 (2021) issn (o) 2694-4626 research article diagnostic yield of endoscopic ultrasonography–guided fine-needle aspiration (eus-fna) for solid pancreatic masses sara ghani∗ | mouna salihoun* | hadj omar el malki 1,2 | mohamed acharki * | nawal kabbaj * *efd-hepatogastroenterology unit, ibn sina hospital, mohammed v university of rabat-morocco. 1,2biostatical, clinical research and epidemiological laboratory (lbrce), medical school, university mohammed v. souissi, rabat, morocco abstract background: endoscopic ultrasound-fine-needle aspiration (eus)-fna is one of the most sensitive and accurate modalities, for detecting and staging pancreatic masses and for obtaining a histological diagnosis. our stud-ies aim to assess the diagnostic yield of eus-fna in solid pancreatic masses. methods: forty-five patients with solid pancreatic masses on im-agery were included out of 230 eus performed between september 2018 and january 2020. all the patients, underwent eus-fna using 19g or 22g needles. all the masses were divided into 2 groups based on mass size: group a (< 30 mm) and group b (> 30mm). sensitivity, nega-tive predictive value (npv), and diagnostic accuracy were respectively evaluated. the specificity and positive predictive value were 100% in both groups. statistical analysis was performed using spss, and the significance level was set at p <0.05. results: overall, sensitivity and diagnostic accuracy were significantly higher in group b (80,7% vs 46% (p=0,01), and 89,2% vs 58,8%(p=0,02)). only the sensitivity was significantly higher with 19 g (p=0,02) in group a. in group b, the sensitivity and diagnostic accuracy were higher with 22g (71% vs 50% (p=0,6), 93,3% vs 69,5% (p=0,5), despite more passes were performed with 22g (2,55 ± 0,59 vs 1,96 ± 0,56 p = 0.001). the multivariate analysis showed that the risk of getting a negative eus-fna is 6,46 times higher in group a (p=0,009). conclusion: the diagnostic yield of eus-fna is correlated at the pancreatic mass size and the risk to get a negative eus-fna is 6,46 times higher for masses <30mm. keywords: eus-fna, solid mass, needle size, puncture route, lesion size. copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/) cmi journal 2 (3), 155−162 meerp ltd 155 https://creativecommons.org/licenses/by-nc-nd/4.0/ 1 background: pancreatic cancer is the seventh leading cause of death from cancer in the world. the diagnosis is often difficult at an early stage and subsequently delayed (1). the arrival of endoscopic ultrasound-fine-needle aspiration (eus)-fna, allowed the diagnosis and staging of pancreatic mass lesions. it is one of the most sensitive and accurate modalities for detecting and evaluating pancreatic mass and for obtaining a histological diagnosis (2). however, many factors can affect the diagnostic yield of eus-fna. our studies aim to evaluate the factors affecting the diagnostic yield of eus-fna in solid pancreatic masses. 2 methods: study population: we retrospectively included all the patients with a solid pancreatic mass, who underwent eus-fna using the 19g or the 22g needle, between september 2018 and january 2020 at endoscopy and gastroenterology unit of ibn sina university hospital. in total, 230 eus with 112 fnas were performed by two endosonographers during this period. patients with cystic lesions were excluded from the present study (figure1). among all patients, four underwent surgery; 3 cases of neuroendocrine tumor (net) and 2 cases of solid pseudopapillary neoplasm (spn) and the final diagnosis was similar to the fna histology (figure 1). figure 1: 1: flow chart of the current study study design: the study was divided into two groups based on the mean size of the pancreatic mass, obtained by endoscopic ultrasonography measurements: group a (< 30 mm) and group b (> 30 mm). overall, fifteen patients had first negative eus-fna, subsequently, a second eus-fna was performed in 5 patients and only the final diagnosis was considered. the main indication of the eus-fna was to obtain histological subtype for unresectable pancreatic cancer in 29 cases (64,5%) and suspected pancreatic cancer in 16 cases (35,5%). eus-fna procedure: the radial echoendoscope was introduced in our unit in 2015, and the linear echoendoscope became available in august 2018. all eus procedures were performed under deep sedation with propofol. a linear echoendoscope (pentaxhitachi) was used by two endosonographers according to esge recommendations (3). once the pancreatic mass has been identified, the operators measure the size in section, assess the local extension, then choose the puncture route according to the mass location, the distance between the mass and the probe and their preferences. the mass was punctured via the transgastric or the transduodenal route using 19g or 22g (medi-globe ®). in the beginning, only 19gwas available in our endoscopy unit until march 2019, 22g became available. several needle passes were performed with fanning and the samples were directly placed in cytolyt® according to the standard esge protocol (3), then sent to an advanced pathologist for analysis. all specimens were classified as malignant, benign or negative (nondiagnostic). all patients were kept under observation after the procedure (figure 2). supplementary information the online version of this article (https://doi.org/xx.xxx/xxx.xx) contains supplementary material, which is available to authorized users. corresponding author: sara ghani efd-hepatogastroenterology unit, ibn sina hospital, mohammed v university of rabat-morocco. email: saraghanimed@gmail.com cmi journal 2 (3), 155−162 meerp ltd 156 mailto:saraghanimed@gmail.com diagnostic yield of endoscopic ultrasonography–guided fine-needle aspiration (eus-fna) for solid pancreatic masses figure 2: inser on of the needleinto the pancrea c mass in this study, the final diagnosis of malignancy and benignity was established based on clinical signs, biology, image features, and histopathology of the surgical specimen and the eus-fna. (1) absence of clinical, biological, imagery and eus-fna criteria of malignancy (with 6 months minimum of follow-up). (2) presence of criteria of malignancy and positive surgical specimens. (3) presence of clinical, biological, imaging and eus-fna criteria of malignancy. (4) presence of clinical signs, biology and imaging criteria of malignancy with negative eus-fna. outcomes measurements: the primary outcomewas themeasures of the overall diagnostic yield of eus-fna in the pancreatic solid masses, then in each group and with each needle. the sensitivity was defined by the percentage of malignancies diagnosed by eus-fna. the diagnostic accuracy was defined by the percentage of positive histology obtained by eus-fna. the absence of clinical, biological, imaging and eusfna criteria of malignancy was considered a true negative. the presence of clinical, biological and imaging criteria of malignancy with negative eusfna, was considered to be a false negative. there were no false positives. the histology of the surgical specimens was similar to the first histology obtained by eus-fna. the secondary outcomes were the measures of the difference between; the size of the mass and needle used; mass location; puncture site; the number of needle passes; fanning, and positive fna (table 1). table 1: diagnos c yield in each group data and statistical analysis: statistical analysis was done using spss® software (ibm, armonk, new york, usa). the means +/standard deviation (sd) and frequency, percentage were used respectively for quantitative variables with normal distribution and qualitative variables. the difference between the size of the mass, the number of needles passes in positive eus-fna was done using student’s t-test. significance was set at p <0.05. the univariate analysis was done with fisher’s exact test. sensitivity, specificity, positive and negative predictive value and diagnostic accuracy were calculated based on the final diagnosis and compared using fisher’s exact test. significance was set at p <0.05. the results of the multivariate analysis were studied using binary regression analysis, and only factors with p < 0,2 in the univariate analysis were introduced. the significance level was set for p < 0.05. data are presented with odds ratios (or) and their respective 95% confidence intervals (ci). 3 results: fifty eus-fna (21,7%) were performed on 45 patients over this period out of 230 eus. the mean age was 56,42 ± 14,1 years, and the mean size of the mass was 39,46 ± 16, 82mm. there were 17 masses (37,8%) in group a and 28 masses (62,2%) in group b. the 19g needle was used in 23 cases (51,1%) cmi journal 2 (3), 155−162 (2021) meerp ltd 157 the final diagnosis (4, 5): meerp ltd ghani et al. and the 22g in 22 cases (48,9%) with 2,24 ± 0,64 passes per lesion, without any major complication. the histology showed malignancy disease in 62,1% (table 2). table 2: demographic characteristics of the patient in each group (fisher’s exact test) * (2 spn+ pancreatic metastasis) primary outcomes: overall, sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were respectively :73,6%,100%, 100%, 41%, and 77,7%. sensitivity, negative predictive value (npv), and diagnostic accuracy in groups a and b were respectively: 46,15% vs 88% (p=0,03), 36,3% vs 50% (p=0,9), 58,5% vs 89% (p=0,02). there is a significant difference in the sensitivity and diagnostic accuracy of each group, they increased significantly as the mass size increased (p=0,03 et 0,02). the negative predictive value was not significant in the groups (p=0,9). however, the specificity and the positive predictive value (ppv) are 100% in both groups (table 3). table 3: diagnos c yield in each group fisher’s exact test the sensitivity and diagnostic accuracy with needles 19g and 22g in group a were respectively: 50% vs 33,3% (p=0,02) and 50% vs 71% (p=0,6). there is a statistically significant difference in sensitivity with needles 19g and 22g in group a. the sensitivity and diagnostic accuracy of needles 19g and 22g in groupbwere: 80%vs 93,3% (p=0,6) and 69,5% vs 93,3% (p=0,5), this difference was not statistically significant (table 4). meerp ltd cmi journal 2 (3), 155−162 (2021) 158 table 4: diagnos c yield of 19g and 22g needles in each group secondary outcomes: diagnostic yield of endoscopic ultrasonography–guided fine-needle aspiration (eus-fna) for solid pancreatic masses table 4: 7: mul variate analysis of factors could affect the percentage of nega ve eus-fna. 4 discussion: overall, sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were respectively :73,6%,100%, 100%, 41%, and 77,7%. crino et al. showed in their study that the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were respectively: 85.2%, 81.8%, 93.7%, and 80.4% (6). several studies have been interested in factors affecting the diagnostic yield of eus-fna (2–7), and the first outcome is mass size.we showed through this study that the diagnostic yield is statistically correlated to the mass size, in particular for masses > 30mm in size. sensitivity and diagnostic accuracy were respectively: 88% and 89%. by multivariate analysis, we showed that only size is considered as a potential factor to affect eus-fna. many studies have shown that the sensitivity and diagnostic accuracy increase significantly as the size of the pancreatic mass increases. sugiura et al. demonstrate that sensitivity and diagnostic accuracy are significantly higher for lesions >10mm in size, and increase as the lesion size increases. cmi journal 2 (3), 155−162 (2021) meerp ltd 159 we performed a univariate analysis of all variables that could affect the outcome of the eus-fna. a significant difference was found in mass sizes and the positive fna (p=0,02) calculated using stu-dent’s t-test. no significant difference between pos-itive fna and diameter of the needle used (p=0,5), mass location (p=0,2), puncture route (p=0,5), and number of passes (p=0,3) was found (table 5). table 5 : univariate analysis of all variables fisher’s exact test therefore, there was a significant difference in the number of passes with the 22g needle (p=0,001) (table 6). table 6: number of passes of each needle in multivariate analysis, independent variables included the mass size (groups a and b), the negative eus-fna, the location of the mass. we found that the risk of obtaining a negative eus-fna is 6,46 times higher in group a (mass < 30mm) (confidence interval (ci) :1,6-26,13, p=0,009). moreover, the mass location was not a significant factor in affecting the percentage of negative eus-fna (table 7). student’s t-test meerp ltd ghani et al. in their study, they divided the patients into five groups according to the lesion size (a<1cm; b: 12cm; c: 2-3cm; d: 3-4cm and e>4cm), and they found that the sensitivity and the diagnostic accuracy were respectively: 89.9% vs 95% vs 97.4%; 98.5% vs 98.7% (p < 0,01) and 91.7% vs 96.4% vs 97.7% 98.6% vs 98.7% (p = 0,03) (7). a multi-centric study including 164 patients with solid pancreatic masses, has shown that the sensitivity and diagnostic accuracy were 83% and 85% for lesions between 28,5mm and 41,3mm in size (8). the second outcomes are the size of the needle, number of passes and fanning. three sizes of eusfna needles are commercialized: 19g, 22g, and 25g (9). the choice of the needle depends; on the mass size, the puncture route and the preference of endosonographers (10). the needle 22g is the most commonly used (11). in our study, only the sensitivity was significantly higher with the needle19g for masses with a size < 30mm (p=0,02). there was no significant difference in diagnostic accuracy (p=0,6) between needles in group a. for masses > 30mm in size, sensitivity and diagnostic accuracy were higher with the needle 22g (71% vs 50% (p=0,6), 93,3% vs 69,5% (p=0,5). this difference is not significant. a prospective randomized trial conducted by itoi et al. showed that the sensitivity of the needle 19g was significantly higher than 22g for the diagnosis of malignancies (12). an algorithm has been proposed by bang et al regarding the choice of the needle (13). by univariate analysis, we showed that there was no significant difference between the diameter of needles 19g and 22g and fna positive: 93,3% vs 69,5% (p=0,5). a randomized trial conducted by ramesh and al. has shown the same result regarding the performance of 19g and 22g (14). there was no significant difference between the number of needle passes and fna positive (p=0,8) in our studies. esge recommends 5 passes for solid pancreatic masses (15). leblanc et al. have shown that sensitivity increases as the number of passes increase with the needle 22g (16). a randomized trial showed that there was no significant difference in diagnostic accuracy between the fanning and the standard technique (p=0,05). however, a few passes were required with fanning to establish the diagnosis of malignancy (17). 5 conclusion: we showed in the current study, that the risk to get a negative eus-fna is 6,46 times higher for masses <30mm and the sensitivity of 19g needle for malignancy was higher than 22g needle for these masses. list of abbreviations: eus-fna: endoscopic ultrasound-fine-needle aspiration 19g needle: 19 gauge needle 22g needle: 22 gauge needle net: neuroendocrine tumor spn: solid pseudopapillary neoplasm sd: standard deviation ci: confidence intervals or: odds ratios ppv: positive predictive value npv: negative predictive value declarations: ethics approval and consent to participate not applicable. consent for publication not applicable. availability of data and materials: the datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. acknowledgements: not applicable. the authors declare that they have no competing interests. funding: not applicable authors ‘contributions: all authors declare that they have all participated in the design, execution, and analysis of the paper, and that they have approved the final version. meerp ltd cmi journal 2 (3), 155−162 (2021) 160 diagnostic yield of endoscopic ultrasonography–guided fine-needle aspiration (eus-fna) for solid pancreatic masses references 1. prashanth r, tagore s, g v. epidemiology of pancreatic cancer: global trends, etiology and risk factors. world j oncol. 2019;10(1):10–27. 2. okasha h, el-kassas m, el-gemeie e. endoscopic ultrasound-guided fine needle aspiration versus percutaneous ultrasound-guided fine needle aspiration in diagnosis of focal pancreatic masses. endosc ultrasound. 2013;2(4):190– 190. 3. polkowski m, larghi a, weynand b. learning, techniques, and complications of endoscopic ultrasound (eus)-guided sampling in gastroenterology: european society of gastrointestinal endoscopy (esge) technical guideline. endoscopy. 2012;44:190–206. 4. ayres lr, kmiotek ek, lam e, telford jj. a comparison of endoscopic ultrasound-guided fine-needle aspiration and fine-needle biopsy in the diagnosis of solid pancreatic lesions. canadian journal of gastroenterology and hepatology. 2018;2018:1–6. 5. park sw, chung mj, 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280−286 (2022) issn (o) 2694-4626 research article sacroiliitis in patients with low backache with normal lumbosacral spine mri dr. bushra mohsen abdulla1* | dr. fatimah hameed khairullah2 1mbchb, diploma of radiology, alsader teaching hospital-najaf health directorate 2 mbchb, diploma of radiology, alhabobi teaching hospitalthiqar health directorate abstract the detection and characterization of sacroiliac lesions on mr imaging has been well established, but its presence during evaluation of low backache cases has not been fully analyzed. aim: determine the presence of sacroiliitis in cases with low back ache found to have a normal lumbosacral spine mri and analyze its prevalence and radiological patterns patients and methods: a diagnostic study recruit 72 patients, they referred for lumbosacral spine mri (1.5 tesla) unit (16 channel coil) in alsadermedical city between march and august of the last year. patients with abnormal lss mri were excluded .information was taken from all patients about past medical and surgical history. patients with normal lss mri were further evaluated for sij fast spin echo mri applying the following study protocol: fse coronal t1 wi & t2 wi stir if abnormal finding seen then intravenous contrast gadolinium-dtpa about 0.1 mmol/ kg of body mass was injected and rescanned 10 minutes after injection to rule out the existing sacroiliitis or other sij abnormalities. results: 72 patients with mean age of 33.2 ± 10.11 years ,male to female ratio was (1:2.483), a small but significant number of patients with sacroiliitis seen in patients with normal lss mri, there was no significant statistical differences between patients with normal finding and those with sacroiliitis. three-fifth of the patients show narrowing of the joint space and one fifth show widening. the study revealed that all the patients had articular erosion and one fifth of the patients showed bone marrow edema. conclusions: sacroiliac joint lesions accounts small but significant number of lower backache patients. the enforcement of the diagnostic value and utility of adding a single fat suppressed sequence of the lumbo-sacral region in the coronal plane; adds marginally to the scan time but increases the yield of identifying incidental or manifest sacroiliac involvement in all cases referred for mri for low backache. keywords: sacroiliitis, lumbosacral spine, magnetic resonance image. manuscript central used to avoid complications of hemodialysis manifested in uremic state including anorexia, nausea, vomiting leading to malnutrition, fluid and electrolyte imbalance leading to volume overload, hyperkalemia, metabolic acidosis, and hyperphosphatemia, as well as abnormalities related to hormonal or systemic dysfunction such as hypertension, anemia, hyperlipidemia, and bone disease, timely diagnosis of proteinenergy-wasting (pew) is important for early initiation of nutritional intervention and treatment. in addition, education plans should be prepared to mediate the nutrient intakes and identify the patient’s difficulties and provide practical help. keywords: renal dialysis, nutritional status, hemodialysis, malnutrition copyright : © 2022 the authors. published by publisher. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). cmi 03 (02), 280−286 280 https://doi.org/10.52845/cmi/2022-3-1-4 https://creativecommons.org/licenses/by-nc-nd/4.0/ 1 introduction t he diagnosis of infectious sacroiliitis is difficult, many times delayed because of its insidious clinical presentation with nonspecific and poorly localized signs, frequently simulating abdominal syndromes, lumbar discopathies or lumbosciatalgia. ct and mri allow an earlier diagnosis, but are not able to define the etiologic agent. generally radiographic alterations can be observed only two or three weeks after the first symptoms onset while on contrast-enhanced mri, alterations can be observed within up to three days, showing mri higher sensitivity (1-3). ct findings in the infectious process are the same of those observed in the sacroiliitis of spondyloarthropathies, except for the juxtarticular bone demineralization considered as the earliest finding besides signs suggestive of soft tissues involvement and unilaterally of the process(4). mri, besides determining alterations in the affected sacroiliac joint and in the contiguous bone, also clearly demonstrates the involvement of adjacent soft tissues or collections, frequently posteriorly to the iliopsoas muscle these findings being highly suggestive of infectious involvement and not seen in spondyloarthropathies(1,3,4-7). the intravenous gadolinium injection can more accurately define these soft tissues involvement(4,5,7). the main disadvantages of mri are: high cost, low availability, and long duration of examination (30 minutes) although the latter is well tolerated by the majority of patients included (1, 2 8, 9) 10-16-13-18) aim of study: the aim of this study was to determine the presence of sacroiliitis in cases with low backache found to have a normal lumbosacral spine mri and analyze its prevalence and radiological pattern. 2 | patients and methods a diagnostic correlative study done prospectively to include(72) patients (21male and 51 female) aged ( 17-55 years) at mri unit in al-sader-medical city, alnajaf governorate/ iraq for a period of six months (from march 2017 to august 2017). all selected patients were already referred to the mri unit for lumbosacral spine evaluation because of low backache. lss fast spin echo mri was done for the patients using mri machine philips acheiva 1.5 tesla. the applied matrix was: 512x224, slice width: 4 mm. protocol of lss mri is: t2wi sagittal, t1wi sagittal, t2wi axial and t1 wi sagittal qualitative and quantitative composition: active substance: dimeglumine gadopentetate 1ml aqueous injection solution contains 469 mg of gadopentetate dimeglumine (corresponding to 0.5 mmol of gadopentetate dimeglumine, corresponding to 78.63 mg of gadolinium). patients with normal lss mri were further evaluated &examines for sij mri by coronal t1 wi & t2 wi stir if abnormal finding seen then we further evaluate the patient with intravenous contrast gadolinium (magnevist® 0.5 mmol/ml) about 0.1 mmol/ kg to rule out the existing sij abnormalities that explaining patient symptoms. we evaluate the features of active inflammation; peri-articular bone marrow edema, synovitis and capsulitis/ enthesitis peri-articular edema, visible as a region of increased signal intensity of bone marrow in fast spin echot2weighted images, and the enhancement after contrast media administration was evaluated in t1 +contrast image inclusion criteria: patients who have low back ache with normal lss supplementary information the online version of this article (10.52845/cmi/2022-3-2-1) contains supplementary material, which is available to authorized users. cmi 03 (02), 280−286 manuscript central 281 manuscript central dr. bushra mohsen abdulla et al. mri, between the age of (17-55 year) were included. exclusion criteria: any patient with abnormal finding in lss mri examination was excluded from this study even if he/ she has abnormality in sij. data collection: age, gender, past medical and surgical history documented in questionnaire. ethical consideration: data and information of the participants were kept confidentially and not disclosed to unauthorized personal the study protocol was approved by the council of faculty of medicine/ kufa university and the department of radiology, official agreements were obtained, and patients agreements were obtained. statistical analysis data of the studied group were entered and analyzed using the statistical package for social sciences, spss, version 24. descriptive statistics presented as mean, standard deviation (for the age), frequencies and proportions (for categorical variables). chi square test was used to compare patients with and without sacroiliitis with regard to age group and gender. level of significance, p. value of less than or equal 0.05 was considered as significant. results presented in tables and figures with an explanatory paragraph for each. the studied group consisted of 72 patients, with a mean age of 33.2 ± 10.11 (range 17 – 55) years, females were 51/72, represented 70.8% of the studied group, (figure 1 a and b). according to the findings of the studied group, only 7 patients (9.7%) had sacroiliitis, while the remaining 65 patients had not, (figure 2). 3 | results figure 1. a and b: age and gender distribution of the studied group (n = 72) furthermore, the 7 patients with sacroiliitis were compared to those with no sacroiliitis regarding the age and gender, this comparison revealed no statistically significant differences between the two subgroups neither in age, nor gender, indicated that the incidence of sacroiliitis was insignificantly affected by the age or gender of the patient, in both comparison (p>0.05), (figure 3 a and b). the clinical characteristics of the 7 sacroiliitis patients are shown in tables (3, 4, 5& 6) in addition to (figure 3. 2). manuscript central cmi 03 (02), 280−286 (2022) 282 figure 2 distribution of sacroiliitis among the studied group figure 3a.distribution of sacroiliitis according to age of the studied group figure 3b: .distribution of sacroiliitis according to gender figure 4: joint space characteristics of the patients with sacroiliitis regarding the joint space characteristics, narrowing was reported in 5 patients (71.43%) and widening in 2 patients (28.57%), (figure 4). the lesion characteristics of the 7 patients with sacroiliitis revealed that all of them (100%) had articular erosions, in addition, 2 patients had marrow edema (28.57%), (figure 5) . figure 5: pattern of mri in sacroiliitis patients (n =7) (figure 5) summarizes the sacroiliitis patients mri pattern, including 5 narrowing, 2 widening joint space, 7 articular erosions and 2 marrow edema cmi 03 (02), 280−286 (2022) manuscript central 283 4 | discussion the true prevalence of sacroiliac joint lesions is unknown in most population groups, either with or without low backache. this study analyses the presence of sacroiliitis in mri of lumbar spine referred for low backache, signifying the importance of this less highlighted entity in correct assessment of low backache. low back ache is a common referral cause in routine mri practice. clearly, it is one of the most common symptoms evaluated and treated by practitioners. it has been observed in usa that annually a 15% to 20% of the population has an episode of lumbosacral pain with low back symptoms occurring in 50% of working age adults (1) low backache is associated manuscript central dr. bushra mohsen abdulla et al. with a wide range of clinical disorders. the commonest group is mechanical disorders, which occurs in more than 90% of all episodes of backache, 10% of the remaining patients with backache have symptoms related to systemic illness, like cancer, inflammatory back disease or infection (10 ). in our study we found 28.57% of the patients had marrow edema in the evaluation of the sacroiliac joint. mri of normal sacroiliac joint reveals an intermediate signal of the cartilage of the synovial compartment on t1 and t2 images limited by the signal void of bone cortex. on t1fse and fast stir images the cartilage has an intermediate to high signal. the marrow on t1, t2 and t1fs images has a homogeneous intermediate signal. fat suppressed images are extremely useful in imaging of cases with sacroiliitis. fat suppression causes rescaling of signal intensities, categorizes cartilage as the brightest structure(6,9) this additive effect along with the darkened appearance of fat in adjacent soft tissues and sacral, iliac and lumbar marrow, renders improved visualization of structures and increases the conspicuity of lesion, thereby improving their pickup rate. there are two fat suppressed sequences that are available: t1weighted with fat suppression (t1fs) and fast short tau inversion recovery (fast stir) sequences. these are superior to t1 and t2 images, in demonstrating the changes of sacroiliitis(11). the study was conducted by hanly et al (12) has proposed that subchondral bone marrow edema is the earliest manifestation of the acute sacroiliitis, since 57% of their patients with subchondral bone edema did not present any sign of articular cartilaginous alteration. this theory is histopathologically corroborated by another study, by means of open biopsy in patients with initial stage of disease, where the earliest finding was subchondral inflammation. the sequence with highest sensitivity and specificity in detecting per articular bone marrow edema is the stir sequence, since, differently from the conventional t2weighted spin-echo sequence, it saturates de fat, differentiating it from fluid (1, 11)). the limitation of this finding — subchondral bone marrow edema — is that it also occurs in early phases of the degenerative process resulting from vascularization of fibrous tissue. for differentiating them, it is important to observe the site of the edema, i.e., hyper signal on the synovial portion of the sacroiliac joint indicates inflammatory disease, and, on the ligamentous portion, indicates degenerative disease(13) the patient's age should be taken into consideration, since osteoarthritis is frequent in elder, asymptomatic patients. these alterations are characterized by marginal osteophytes, subchondral sclerosis, and eventually articular fusion(8,14) but unfortunately in our study we found that the incidence of sacroiliitis was insignificantly affected by the age or gender of the patient when compare to those with no sacroiliitis (p value more than 0.05) probably because of low sample size in this study. in normal population the sacroiliac joint space is influenced by age, gender, bone mass index and childbirth (15). below the 40 years old the joint space is 2.49 ±0.66mm and above that age there is a high incidence of joint space narrowing (less than 2mm) and non-uniform joint space (15)33). obese patients, multiparous women (with 3 or more childbirths) had a high prevalence of non-uniform joint space as well as shortening of joint space in multiparous women (15). we found in our study 71.43% of the patients have narrowing and 28.57% of the patients have widening, this in agreement with bigos et al(1) 74% of the patients show joint space narrowing. this is mean missing early detection of sacroiliitis, since narrowing of sacroiliac joint is consider as stage 3(1,8, 12,16) . in our study we found 100% of the studied patients have articular erosion. partial volume artifact between the synovial and ligamentous compartments can be misinterpreted as erosions. there is normally a region of high signal at the immediate subchondral marrow, on fast stir images, which can be mistaken for early sacroiliitis. a patchy distribution of fat within the bone marrow as the sole finding should not be considered as an indicator for sacroiliitis(17,18) manuscript central cmi 03 (02), 280−286 (2022) 284 low backache is one of the commonest referral in mri scan centers .sacroiliitis which is a demonstrable cause of low backache is often missed clinically or under estimate during routine mri scanning of the lumber region. sacroiliac joint lesions accounts for a small but significant number of low backache as evident from this study. this study highlights the diagnostic value and utility of adding a single fat suppressed sequence of the lumbo-sacral region in the coronal plane. this adds marginally to the scan time but increases the yield of identifying incidental or manifest sacroiliac involvement in all cases referred for mri for low backache. recommendations: 1-to include fat suppressed sequence of lss, coronal plane in every patients with lss mri 2-to emphasize and alert the clinician about the significance of sacroiliac joint as a cause for low backache. of sacroiliitis on plain radiography.a prospective, longitudinal study. j rheumatol 1999;26:1953–1958 7. haliloglu m, kleiman mb, siddiqui ar, cohen md. osteomyelitis and pyogenic infection of the sacroiliac joint.mri findings and review.pediatrradiol 1994;24:333–335 8.braun j, van der heijde d. imaging and scoring in ankylosing spondylitis. best pract res clinrheumatol 2002;16:573–604. 9.bollow m, biedermann t, kannenberg j, et al. use of dynamic magnetic resonance imaging to detect sacroiliitis in hla-b27 positive and negative children with juvenile arthritides. j rheumatol 1998;25:556–564 10.nachemson a: the lumbar spine: an orthopedic challenge. spine 1976;1:59-71 11. bellussi a, busirizzi e, schininá v, de santis a, bibbolino c. stir sequence in infectious sacroiliitis in three patients. clin imaging 2002; 26:212–215 12. hanly jg, mitchell mj, barnes dc, macmillan l. early recognition of sacroiliitis by magnetic resonance imaging and single photon emission computed tomography. j rheumatol 1994;21: 2088– 2095. 13. battafarano df, west sg, rak km, fortenbery ej, chantelois ae. comparison of bone scan, computed tomography, and magnetic resonance imaging in the diagnosis of active sacroiliitis. semin arthritis rheum 1993;23:161–176. 14. puhakka kb, jurik ag, egund n, et al. imaging of sacroiliitis in early seronegativespondylarthropathy. assessment of abnormalities by mr in comparison with radiography and ct. actaradiol 2003;44:218–229. [ links ] 15.demir m, mavi a, gümüsburun e, bayram m, gürsoy s, nishio h. anatomical variations with joint space measurements on ct. kobe j med sci 2007;53(5):209–217. 16.blum u, buitrago-tellez c, mundinger a, et al. magnetic resonance imaging [mri] for detection of active sacroiliitis: a prospective study comparing conventional radiography, scintigraphy, and contrast enhanced mri. j rheumatol 1996;23: 2107–2115. 17. van der linden s, valkenburg ha, cats a. evalua¬tion of diagnostic criteria for ankylosing 5 conclusions 6 references 1. braun j, sieper j, bollow m. imaging of sacroiliitis. clinrheumatol 2000;19:51–57. 2..oostveen jcm, van de laar mafj.magnetic resonance imaging in rheumatic disorders of the spine and sacroiliac joints.semin arthritis rheum 2000;30:52–69 3. resnick d. bone and joint imaging. 2nd ed. philadelphia: wb saunders,1996 4. bellussi a, busirizzi e, schininá v, de santis a, bibbolino c. stir sequence in infectious sacroiliitis in three patients. clin imaging 2002; 26:212–215 5.ahlström h, feltelius n, nyman r, hallgren r. magnetic resonance imaging of sacroiliac joint inflammation. arthritis rheum 1990;33:1763–1769. 6.oostveen j, prevo r, den boer j, van de laar m.early detection of sacroiliitis on magnetic resonance imaging and subsequent development manuscript centralcmi 03 (02), 280−286 (2022) 285 manuscript central dr. bushra mohsen abdulla et al. how to cite this article: dr. bushra mohsen abdulla et al. sacroiliitis in patients with low backache with normal lumbosacral spine mri clinical medicine insights. 2022;280−286. https://doi.or g/10.52845/cmi/2022-3-2-1 manuscript central cmi 03 (02), 280−286 (2022) 286 spondylitis: a proposal for modification of the new york criteria. arthritis rheum 1984;27(4):361– 368. 18-bigos s, bowyer o, braen g, et al. acute low problems in adults. clinical practice guideline no.14.ahcpr publication no. 95-0642. rockville(md): agency for health care policy and reasearch, public health service,us department of health and human services; 1994. introduction causes of nutritional disorder in hd inadequate food intake abnormal nutrient metabolism aim and objectives methodology result assessment of nutritional status of hd. patients prevalence of malnutrition using subjective global assessment body mass index in the study patients bmi and sga score laboratory investigation association between nutrient intake and sga discussion conclusions references clinical medicine insight received 10 june 2020 | revised 15 july 2020 | accepted 10 aug 2020 | published online 19 sep 2021 doi: https://doi.org/10.52845/cmi/2020v1i1a5 cmi journal 1 (1), 27−35 (2020) issn (o) 2694-4626 research article perception of nurses’ work in psychiatric clinic dr. kratika daniel 1∗ dr vivek daniel 2 1associate professor, faculty of pharmacy, mandsaur university, mandsaur, m.p. india 2associate professor, department of pharmacy, jees, nandurbar, maharashtra, india2associate abstract purpose: this study aims to determine the siege and related factors of nurses working in psychiatric clinics. method: this study was conducted as a related description design. the sample of the study consisted of 204 nurses working in psychiatric clinics. the data was collected using questionnaires generated by researchers from literature and workplace psychological abuse scales. descriptive statistics (frequency and percentage) and chi-square independence test are used to determine whether there is a significant relationship between variables. results: the conditions for more frequent siege behaviors are that nurses have graduate education, work at night, are dissatisfied with work methods and institutions, have been besieged before, and have an understanding of the number of legal persons and consulting services related to go. conclusion: the nursing service management department of the hospital should effectively organize the types of employment and develop strategies that can improve nurse satisfaction. it is believed that raising nurses’ awareness of siege will effectively reduce psychological violence in high-risk wards. keywords: siege, workplace violence, mental health, psychiatry, psychiatric nurse, mental health nurse copyright : © 2020 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). 1 introduction mobbing is a nonphysical form of workplace violence (wbi 2014), a concept which has different meanings such as deterring and pressure, psychological violence, bullying, rudeness, hostile attitude, psychological terrorism in workplace (leymann 1996) and it threatens employee safety and productivity in the workplace (johnston et al. 2009), reduces business performance cmi journal 1 (1), 27−35 meerp ltd 27 open access journal https://doi.org/10.52845/cmi/2020v1i1a5 https://orcid.org/0000-0001-8880-4238 https://orcid.org/0000-0001-5914-9748. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://medicineinsights.info/index.php/cmi/index perception of nurses' work in psychiatric clinic (yıldırım 2009), work and workplace satisfaction and involves the intention of withdrawal from work (wachs 2009, davenport et al. 2003), causes psychological and physical traumas on person, results in many negativities for the employee and the organization. mobbing is a situation that creates conflict through showing annoying behavior that targets a certain person for a long time and systematically (at least once a week and lasts for at least 6 months). at the same time, it is a direct or indirect psychological attack expressed through abusive conduct, threatening, humiliating, exclusion and intimidation (zapf 1999, davenport et al. 2003, wbi 2014). leymann, who explained the concept of mobbing for the first time, defines it as ‘psychological violence or psychological terrorism towards one person or more that leaves people helpless and vulnerable through systematic hostile and unethical communication in business life’ (leymann 1996, karsavuran 2014). once mobbing/psychological violence in workplace is categorized into subtitles; it is actualized through systematic behaviors to targeted person as threat/intimidation, blocking communication with others and isolation from social relations, humiliation/underestimation, direct physical/sexual violence towards occupational skills. mobbing has significant negative effects on work satisfaction, self-esteem and burnout experience as well as having psychological, physical and behavioral effects (bradbury and hutchinson 2015, nielsen and einarsen 2012, iglesias andvallejo 2012, giorgi et al. 2015). institutions where there is mobbing, not only the victim but also the witnesses are affected. these people are both sorry for the real victim and concerned about being victimized. organizations also pay a heavy cost because of mobbing (johnston et al. 2009, iglesias and vallejo 2012, khoshknab et al. 2015, yıldırım and yıldırım 2007, karsavuran 2014). mobbing, which is a state of psychological violence, not only affects supplementary information the online version of this article (10.52845/cmi/2020v1i1a5) contains supplementary material, which is available to authorized users. corresponding author: dr. kratika daniel dr. kratika daniel email: kratika.daniel@meu.edu.in employees and institutions in the health sector but also affects the quality of patient care and patient safety, leads to medical errors, creates interdisciplinary conflict and stress in healthcare professionals (hamilton 2007, johnston 2009). for this reason, mobbing in the workplace experienced by nurses who play a critical role in patient care has a particular importance such as decline in patient care quality. the main source of mobbing formation is expressed as personal traits (personal ambition, envy, jealousy, gender, marital status etc.) (adams 1992). heavy workload and difficult working conditions, unresolved conflicts, lack of sense of trust and justice, ineligible and oppressive executive trigger mobbing behaviors in situations (johnston et al. 2009; park et al. 2015). organization climate from organizational factors is another factor related to mobbing. when there are negative behaviors in the organizations, which means the organizational climate is negative, the employee feels oneself as a mobbing victim and this causes health problems and burnout experience for the employees (giorgi ve ark. 2015). the organizational culture which tolerates violence in the workplace is another important factor that creates mobbing. in the organizations in which the lines for the mobbing behavior are not drawn, the climate changes and these behaviors are unintentionally supported. nursing is a group of professions where the female sex dominates, and people who show mobbing behavior and the victims are female nurses at high levels. from this point of view, being a female dominant profession group is closely related to mobbing. nurse executives are usually the ones who show the real mobbing behavior in the profession. it can be said that personal traits such as personal insecurity, bad interpersonal communication skills, low self-esteem and being unqualified for the position play a role on abuse of the authority (johnston et al. 2009). as a result of an international study conducted in 2008, including the united states and 17 other countries, it is stated that according to the employees, employee safety is not prioritized in the working environment. approximately 93% of the responders are nurses and they stated that mobbing, which is one of the types of workplace violence, is increasingly being seen among nurses (johnston et al. 2009). cmi journal 1 (1), 27−35 (2020) meerp ltd 28 mailto:kratika.daniel@meu.edu.in meerp ltd dr. kratika daniel and dr vivek daniel studies on workplace violence show that healthcare professionals are 16 times more exposed to mobbing and nurses are 3 times riskier in this group (kingma 2001). another study shows that female nurses are the primary victims of mobbing activities (iglesias and vallejo 2012). in a study conducted in uk, it is reported that approximately 95% of the nurses’ face behaviors assessed within the scope of mobbing in the workplace (kingma 2001). according to other international studies; in the study conducted by fute et al. (2015), it is stated that 90% of the nurses are exposed to verbal assault/abuse. likewise, in other studies, it is seen that mobbing perception of the nurses is formed especially with the verbal behaviors of violence (efe and ayaz 2010, yıldırım 2009, ovayolu et al. 2014, pai and lee 2011, wbi 2014, naime 2012). in the study on workplace violence which was conducted on 1377 nurses, hader (2008) determined that the most frequent types of violence according to the nurses’ perspective are intimidation, sudden burst of anger, threatening and disruptive behaviors which are categorized under the title of mobbing. yıldırım (2009) determined that nurses face most frequently personal and occupational bullying. quine (1999) identified mostly reported mobbing behaviors as changing rules unfairly to raise difficulties, hiding necessary information, creating pressure which blocks production, ignoring, exclusion and isolating from society with hostile attitude. efe and ayaz (2010), who examine nurses’ state of exposure to mobbing and its causes, show that while about 10% of the nurses are exposed to mobbing according to the result of the applied mobbing scale, the results obtained according to nurses’ own declarations are 33%. öztürk et al. (2007) reported that 39% of the nurses were mobbing victims, yet 42% of the victim groups were found to be real mobbing victims. when the studies are examined, trying to determine and measure the mobbing victimization directly by ignoring the pre-existing negative attitudes of the individuals related to exposure to mobbing explains shady height of the results. these differences in results show us the vagueness as to what kind of behaviors nurses perceive as mobbing. each negative behavior faced in the work environment is not mobbing. in order to raise awareness for nurses about this subject, it is an important issue needed to be practiced with them to determine which behaviors and processes should be assessed as mobbing. when factors affectingmobbing in the workplace are taken into consideration, it is shown that working in psychiatry units is a factor (richter 2006, johnston et al. 2009, acar et al. 2014, sinat 2007). although there have been a lot of studies on mobbing, a study conducted with psychiatric nurses who are under more risk of stressful working environment that triggers mobbing has not been encountered. that studies focus generally on rates of mobbing on nurses but it is not clear which behaviors/situations are perceived as mobbing by the nurses and that each negative behavior is perceived as mobbing in the institutions, this study was planned. research questions determined within this scope are; -what is the mobbing perception of the nurses working in psychiatry clinics? -what are the affecting factors of the mobbing perception of the nurses working in psychiatry clinics? 2 methods type of research the research was conducted as descriptive and correlational research to determine the mobbing perceptions of nurses working in psychiatry clinics and the related factors affecting perceptions. population and sample of the research medical faculty hospitals, private mental health hospitals in istanbul which has the most power to represent turkey, ministerial psychiatric hospitals in istanbul and 350 nurses working in psychiatry clinics of training and research hospitals formed the population of the research. the sample of the study consisted of nurses working in psychiatry clinics (n=296) in 6 hospitals that allowed the research to be carried out. the sample size (survey return rate is 69%) was formed with 204 people (table 1). nurses who worked in the same psychiatry clinic at least for 4 months before the sample selection and accepted to participate in the study were included in the research. data collection tools 22 questions including participants’ individual, occupational traits and states related to mobbing were meerp ltd cmi journal 1 (1), 27−35 (2020) 29 perception of nurses' work in psychiatric clinic asked with ‘information form’ developed by the researcher (atasoy 2010, yavuz 2007). information form includes 3 sub-sections in total. in terms of individual traits; questions as to demographic data such as age, gender, marital status, having children, in terms of occupational traits; questions about educational status, years of experience and working times, satisfaction, department worked, duty, working times, number of patients being cared, type of employment, income status, union membership, in terms of mobbing states; questions about exposure to mobbing, institutional features about mobbing, consultancy and legal compliance are taken place. ‘workplace mobbing scale’, which is used in the study to determine nurses’ mobbing perception, is a 28 point scale including mobbing beheviors in workplace and it is prepared in rating (4 likert type) question form to determine the mobbing rate and behavior types (tınaz 2006). the scale consists of 4 factors and these are work-related behaviors, disreputable behaviors, excluding behaviors, and verbal, written and visual attacks. chi-square was used in the analysis of data, mean and frequency tests were utilized. also, explanatory factor analysis was carried out to classify the articles, which are interrelated and measure the same dimension, in the questionnaire. test results were evaluated according to 5% (p<.05) significance level. cronbach alpha reliability coefficient of the scale was determined as .93. cronbach alpha values were determined according to the factors as; .86 for the first dimension, .82 for the second dimension, .80 for the third dimension and .79 for the fourth dimension. in order study to be conducted, required ethics committee approval and verbal, written consent of the nurses were obtained. the cronbach alpha valua of scale .92 in this study that indicates ‘workplace mobbing scale’ is valid and reliable instrument in turkish population. 3 results findings belonging to the individual traits of 204 nurses who participated in the research are seen in table 2. 74% of the participating nurses are women, 40% are between the ages 31-40, 31% are between the ages 21-30, 58% are married and 54% have child. when findings related to the occupational features of the nurses are examined, 58% of them are satisfied with the institution they work with and 54% are satisfied with the type of employment. 34% are undergraduates and 35% are associate degree graduates. 86% are service nurses and 43% are working day/night shifts. when traits of the nurses in terms of mobbing are examined, it is seen that 53% of them were exposed to mobbing during their professional life, 80% of them had no information about the legal dimension of mobbing and its counseling and 59% of them did not receive in-service training related to mobbing. the responses of the nurses to the articles of ‘workplace mobbing scale’ are shown in table 3. as it is seen in table 3, while behaviors evaluated within ‘work-related behaviors’ sub-dimension of the workplace mobbing scale are the most frequently encountered mobbing behaviors, behaviors belonging to sub-dimension of ‘verbal, written and visual mistreatments’ and ‘excluding behaviors’ are least encountered mobbing behaviors. a significant difference was determined between satisfaction from the institution, education status, type of employment and satisfaction status, period of occupational experience, exposure to mobbing and knowing the processes of consultancy in case of mobbing from independent variables and subdimensions of workplace mobbing scale. it was determined that nurses who are partially satisfied with the institution and type of employment and who are not satisfied with their work and constantly work at night, nurses with high level of education and professional experience between 16-20 years encounter more mobbing behaviors. it was seen that nurses who stated that they had faced with mobbing are mostly exposed to work-related behaviors from sub-dimensions ofworkplacemobbing scale. it was found that people who know from which institution or whom they can receive consultancy or the legal dimension of the situation in case of mobbing are exposed to more excluding behaviors. cmi journal 1 (1), 27−35 (2020) meerp ltd 30 meerp ltd dr. kratika daniel and dr vivek daniel 4 discussion although there are many studies in the literature that measure the frequency of nurses’ exposure to mobbing, it is not clear with how much frequency a behavior is mobbing, and what the mobbing perceptions of the people are. the majority of negative situations in workplaces are attributed to mobbing, which is the starting point of this study. psychiatry clinics are units that are more stressed in terms of working conditions and that working conditions are heavier due to nurse inadequacy. the aim of this study, which is based on the hypothesis that psychiatric nurses are at more risk for the factors leading to the formation of mobbing, is to determine the behaviors and related factors ofmobbing perceptions of nurses in general, specifically of psychiatric nurses. in this context, most of the nurses who participated in the research are women, married and have children. when the age ranges are examined, the group with the highest frequency is 31-40 years old. 97% of the sample is consisted of nurses working in public institutions and nurses under the age of 40 represent 71% of the sample. it was determined in this study that nurses did not differ according to individual features of their mobbing perceptions. as the female gender is more common, most of them are married and have children, it can be considered that the study reflect the profile of public hospitals employees. in this study, there is not any difference between the individual features of nurses in terms of gender, marital status, having children, age and behaviors perceived as mobbing. similarly, köksal (2011) could not find a significant relationship between age and exposure to mobbing. in the study of yavuz (2007) themed as ‘factors affecting mobbing perceptions in employees’, it was seen that as the age increases, the mobbing perception increases. efe and ayaz (2010) determined that nurses under the age of 25 and akyil et al. (2012) determined that young nurses are exposed to more mobbing behaviors. in their studies, geçici and sağkal (2011) found that female nurses are more likely to encounter mobbing behaviors. tınaz (2006) and tanoğlu (2006) interpreted this situation as mobbing behaviors are encountered more frequently in the health sector where women work more intensively and women prefer to show passive aggressive behavior towards their same-gender. yavuz (2007) found that employees’ mobbing perceptions did not differ according to gender. while psychiatry clinics are an area where male nurses are employed more, female gender has a 74% rate in this study. in order to explain the relation between gender and behaviors perceived as mobbing, studies in which male nurse sample is more, similar to age independent variable, are needed. when findings related to occupational features of nurses are examined, as the level of education gets higher, the level of exposure to mobbing behaviors evaluated within the sub-dimension of work-related behaviors is at higher level. significant conclusion was drawn in terms of behaviors that are disreputable for nurses with postgraduate education level. in the study of yavuz (2007), it was found out that the employees’ mobbing perceptions increase with the increase of education level. in their studies, köksal (2011), bardakçı and günüşen (2016) encountered parallel findings with this study. this situation can be evaluated as indicating the competition within the institutions and it can be considered that competition comes off as a reaction against mobbing and employees’ promotion. contrary to mentioned studies, akyil et al. (2012) and efe and ayaz (2010) determined that younger and inexperienced nurses with lower education levels are exposed to more mobbing behaviors. they associated this situation to the fact that education in vocational schools is not sufficient for communication skills and mobbing/conflict management. nurses, who are dissatisfied with their work are more likely to encounter mobbing behaviors. in other words, as satisfaction decreased, nurses were found to be more likely to encounter four different dimensions of mobbing behaviors. when nurses’ type of employment are examined, those who are ‘always on night’ shift and are not satisfied with their work reported thay they are exposed to significantly more mobbing behaviors than all other employees. similarly, akyil et al. (2012) and lin and liu (2005) reported that the level of mobbing perceptions of nurses working at night were higher. in the study of dilman (2007) it was stated that the nurses’ level of satisfaction from the institution they work in and type of employment is high and that there is not any significant meerp ltd cmi journal 1 (1), 27−35 (2020) 31 perception of nurses' work in psychiatric clinic relation between type of employment and exposure to mobbing behavior. this situation was explained as administration of nursing services is effective and it cares about personnel satisfaction. according to our country’s standards, large number of nurses are involved in team work in hospitals during the day shift, fewer staff are employed in night shifts, and as a matter of fact only single personnel is employed in most units. chronic nurse inadequacy increases the level of stress of the employees and reduces the level of interpersonal interaction. this situation facilitates the emergence of conflicts. the relationship between inappropriate working conditions and the occurrence of mobbing behaviors was explained by tong et al. (2017). various factors such as the level and type of communication, being not able to carry workload, sleeplessness and fatigue, biological unbalance can cause nurses working ‘always on night shift’ encounter more disreputable behaviors and verbal, written and visual mistreatments. the results of the research show that there is a significant difference between the level of satisfaction from the institution and type of employment and mobbing behavior (tong et al. 2017). employees are more likely to face mobbing behaviors as their level of satisfaction decreases. more detailed studies to be done about this subject should be used to assess the working conditions of the nurses. nurses with 16-20 years of professional experience are more exposed to disreputable and excluding behaviors. fışkın (2011) found that the rate of mobbing encountered by the people who have 5-9 years of professional experience is 80%. according to the research result of bahçe (2007); mobbing behaviors are mostly encountered by employees between 11 and 15 years of professional experience. akyil et al. (2012) reported that nurses with less professional experience have higher rates of mobbing. when looking at the results of different studies, the relationship between mobbing behaviors and years of professional experience has different results. it is thought that more research in this field with homogeneous and large sample groups are needed to be done. in the research, nurses (n:109, 53%), who stated that they are exposed to mobbing throughout their career, encounter more work-related behaviors. most of the nurses who stated that they are exposed to mobbing behaviors reported that they did not encounter subdimension behaviors as disreputable, excluding, verbal, written and visual mistreatments. in the study of dilman (2007), it was seen that 70% of the nurses are exposed to mobbing behavior, in the study of fışkın (2011), the result was 65% and in the study of bardakçı and günüşen (2016), it was 29%. in terms of mobbing experience rate, research results differ from one study to another. studies show that nurses encounter high level of mobbing behaviors and although the subject is not new, it is still a serious problem in their profession. on the other hand, when literature knowledge is taken into consideration, systematical exposure to behaviors is needed in order for people to be regarded as mobbing victims. employees should be informed that exposure to any of the behaviors assessed under the mobbing behavior should not be considered asmobbing. it was found that people who know from which institution or whom they can receive consultancy or the legal dimension of the situation in case of mobbing are exposed to more excluding behaviors. in the study of arısoy (2011) , it was stated that the situation of 70% of the nurses not knowing what their legal rights and obligations are affects their exposure to mobbing. aksakal et al. (2015) noted that nurses with mobbing experience are less likely to adopt concrete actions such as receive counseling, resort to the jurisdiction, or ask help from professional associations. akyil et al. (2012) found that nurses’ awareness of mobbing is increasing, that they will be able to make oral and written complaints in response to future mobbing behaviors and will take an active role in following this process. on the other hand aksakal et al. (2015), bardakçı and günüşen (2016) indicate that nurses prefer to remain unresponsive in case of mobbing actions and they share their experiences with family and close friends only. an employeewho is aware of what his/her legal rights and obligations are, may be able to identify the mobbing behavior, have the ability to produce an appropriate solution to the situation, and differ from other employees by expressing the situation. this may cause the person to appear as standing out against senior management and administration, that is why his/her colleagues may be uncomfortable to be with him/her and avoid being called together. cmi journal 1 (1), 27−35 (2020) meerp ltd 32 meerp ltd dr. kratika daniel and dr vivek daniel nurses who reported that they had encountered mobbing behaviors at least once in their professional life stated that the behaviors mostly encountered by them are ‘every work done by me is observed in details, works below my professional skills or damage my self-esteem are required from me, irrational duties and aims which are impossible to complete are set, i am not recognized in work-related subjects or i am interrupted when i speak, my decisions related to work are questioned and people show negative gestures or glances towards me’. when mostly encountered mobbing behaviors by the nurses are evaluated within the typology of leymann, they belong to the groups of ‘showing yourself and blocking communication’ and ‘aggression towards person’s quality of life and professional status’. in the study of dilman (2007), behavior patterns with highest score are determined as ‘always being interrupted, behaving as if i did not exist in the environment, being ignored, indirectly control of me and the works done by me’. the most common behaviors in dilman (2007)’s study are within the work-related behaviors from sub-dimensions of workplace mobbing scale. üye (2009) stated that mobbing behaviors, which nurses are exposed to with the highest rate, are within ‘disreputable and excluding behaviors’ sub-dimension of workplace mobbing scale. fışkın (2011) determined that 65% of the nurses encountered similar sub-dimension behaviors with this study in the scope of mobbing behaviors. sa and fleming (2016) determined the most common mobbing behaviors for the nurses as ‘being charged with works that are impossible to finish, restricting the area of responsibility and request of works below professional skills’. as it is seen, nurses mostly encounter behaviors within the sub-dimension of work-related and disreputable behaviors. 5 conclusions independent variables can be predicted more clearly by wider sampled studies with nurses working in psychiatry hospitals at private sector and other cities. as the satisfaction from the institution and the type of employment decreases within the scope of the occupational features of the nurses, the percentage of the nurses encountering all the sub-dimension behaviors of themobbing increases. nursing services administrations in hospitals should effectively organize the type of employment and specify strategies that will increase nurses’ level of satisfaction from the institutions. nurses with postgraduate education are more likely to encounter disreputable behaviors. a significant relation was detected between all sub-dimensions of workplace mobbing scale and exposure to mobbing during career. it was found that people who know from which institution or whom they can receive consultancy or the legal dimension of the situation in case of mobbing are exposed to more excluding behaviors. nurses should be informed about the mobbing with in-service training programs related to mobbing planned at regular intervals in institutions, updated information about the legal dimension related to mobbing should be given to nurses, and information about the centers where counseling can be received should be given. according to the nurses’ responses to workplace mobbing scale, the mostly encountered behaviors within work-related and excluding behaviors are; ‘every work done by me is observed in details, works below my professional skills or damage my self-esteem are required from me, irrational duties and aims which are impossible to complete are set, i am not recognized in work-related subjects or i am interrupted when i speak, my decisions related to work are questioned and i am the one who is always seen as the responsible of every problem’. the results of the study on mobbing should be shared with the nursing services administration and nurses in order to expand awareness. references 1. acar, p, kıyak,m,&sine, b. 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(2015). psychological violence in the healthcare settings in iran: a cross-sectionalstudy. nursing andmidwifery studies, 4(1). how to cite this article: d.k.d., d.v.d. perception of nurses’ work in psychiatric clinic. clinical medicine insight. 2020;27−35. https://doi.org/ 10.52845/cmi/2020v1i1a5 meerp ltd cmi journal 1 (1), 27−35 (2020) 35 introduction methods results discussion conclusions clinical medicine insights received 25 dec 2020 | revised 22 jan 2021 | accepted 28 feb 2021 | published online 30 mar 2021 doi: https://doi.org/10.52845/cmi/2021-2-1-4 cmi journal 2 (1), 80−97 (2021) issn (o) 2694-4626 review article obesity and non-communicable diseases: part ii cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, arthritis shashi k. agarwal, md ∗ 12227 us highway 1, #309 north brunswick, nj 08902,usa abstract obesity is increasing all over the world. an excess body weight, as recognized by a body mass index of more than 25, is associated with several chronic diseases, increased disability, and early mortality. its main impact is on non-communicable diseases, such as cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, and arthritis. successful weight loss strategies through healthy lifestyle behaviors and bariatric surgery have been associated with a decrease in morbidity, an improved quality of life, an increase in disease-free years, and improved longevity. keywords: obesity, non-communicable diseases, cancer, diabetes mellitus, chronic kidney disease, dementia, arthritis copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). 1 introduction the prevalence of overweight and obesity is increasing globally and is expected to reach 1.35 billion and 573 million respectively by 20301. major health organizations recommend that a healthy lifestyle should include adherence to a normal body weight (a body mass index or bmi of 18.5–24.9 kg/m2), regular physical activity (150 min/week of moderate to vigorous physical activity), and a healthy diet (ideally 32 g/day of dietary fiber, 400 g/day of fruit and non-starchy vegetables, 0 g/week of processed meat, and <500 g/week of red meat), and avoidance of smoking and moderation in alcohol intake2. healthy lifestyles help not only prevent but also help decrease the undesirable impact of several diseases3−5. besides a reduction in morbidity, the overall health quality of life is improved in these patients and mortality is decreased6−8. li et al. using data from the nurses’ health study and the health professionals follow-up study (total of 123,219 participants), estimated that adherence to all five healthy lifestyles increases the lifespan at age 50 by 14 years in females and 12.2 years in males, when compared with those with zero low-risk factors9. a normal body weight is a major lifestyle factor in the prevention of noncommunicable diseases10. as mentioned in part i of this manuscript, a bmi becmi journal 2 (1), 80−97 meerp ltd 80 open access jpurnal https://doi.org/10.52845/cmi/2021-2-3-5 https://orcid.org/0000-0003-0007-5582 https://creativecommons.org/licenses/by-nc-nd/4.0/ https://medicineinsights.info/index.php/cmi meerp ltd shashi k. agarwal, md tween 25 and 29.9 kg/m2 is considered overweight, while a bmi of >30 kg/m2 is considered obese11. the global burden of disease project, in a metanalysis of 239 prospective studies in four continents, reported a j shaped relationship between bmi and all-cause mortality12. this research included >10 million people and recorded 385,879 deaths during amedian follow up of 13.7 years12. the lowest mortality was in individuals with a bmi of 20.0 to 25.0 kg/m212. allcause mortality increased both below and above this bmi range12. the most dramatic increase in morbidity and mortality was noted in individuals who became obese12. obesity is further divided into class 1 (30.0-34.9 kg/m2), class 2 (35.0-39.9 kg/m2), and class 3 (40 kg/m2 or greater)13. mortality increases as the class of obesity increases12. the global burden of disease project reported that mortality increased by 45% for grade i obesity, by 94% for grade 2 obesity, and 176% for grade-3 obesity12. the beneficial effect of weight loss has also been reported14. the swedish obese subjects study showed a 29% reduction in overall mortality (after 10.9 years of monitoring) in obese patients who underwent surgical intervention for obesity14. the problems associated with obesity in several chronic medical conditions are discussed in this twopart manuscript. part i discussed the role of obesity in cardiovascular diseases (cvd), chronic respiratory diseases, depression, and liver diseases. this part discusses its effect on cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, and arthritis. 2 discussion noncommunicable diseases (ncd) are common conditions affecting humans15. cancer has become supplementary information the online version of this article (10.52845/cmi/2021-2-1-4) contains supplementary material, which is available to authorized users. corresponding author: shashi k. agarwal, md shashi k. agarwal, md 2227 us highway 1, #309 north brunswick, nj 08902,usa email: usacardiologist@gmail.com the king of all maladies and is on its way to replacing cvds as the number one killer in the world16. it is estimated that 1 in 5 men and 1 in 6 women developed cancer in 2016, resulting in the deaths of 1 in 8 men and 1 in 10 women17. the most common global cancers are those involving the lung, colorectum, stomach, breast, prostate and liver17. type 2 diabetes mellitus (dm) is one of the most common metabolic disorders worldwide18. it results from a combination of reduced insulin secretion by pancreatic βcells and peripheral insulin resistance19. prediabetes is associated with an increased risk of developing dm20. this disease is associated with significant microvascular (retinopathy, nephropathy, and neuropathy) andmacrovascular (coronary artery disease, stroke, peripheral artery disease) pathology21. it reduces the life expectancy of the affected individual by approximately six years22. cardiovascular disease is extremely common in diabetics and cardiovascular complications are responsible for more than 50% of diabetes related deaths23. diabetes is now considered an independent risk factor for cvd24. prediabetes is also associated with a higher risk of atherosclerotic cardiovascular disease and all-cause mortality25. chronic kidney disease (ckd) is defined by the presence of kidney damage or an estimated glomerular filtration rate (egfr) less than 60 ml/min/1.73 mt2, persisting for 3 months or more, irrespective of the cause26. it has become a worldwide public health problem27. dm is the leading cause28. ckd is a progressive disease, and as it worsens, the affected individuals need peritoneal dialysis or hemodialysis or kidney transplantation29. it affects most systems of the body and often leads to atherosclerotic cardiac disease, poor cognitive dysfunction, and a poor quality of life30−32. dementia is a common worldwide disease33. alzheimer’s disease (ad) is themost common form of dementia and is responsible for about 70% of the cases34. ad is a progressive and irreversible neurodegenerative disease, associated with amyloid plaques and neurofibrillary tangles in the brain35. the world alzheimer report estimates that 50 million people worldwide have dementia, and this number is projected to increase to 82 million by 2030 and to 152 million by 205036. it leads to loss of independence, poor quality of life, and premature institutionalization37. meerp ltd cmi journal 2 (1), 80−97 (2021) 81 mailto:usacardiologist@gmail.com obesity and non-communicable diseases: part ii cardiovascular diseases, respiratory diseases, depression, liver diseases it is also a major cause of death38. treatment remains symptomatic, as a definitive cure is lacking39. arthritis is of many types40. osteoarthritis (oa) is the most common type and a major global cause of disability41. it is characterized by progressive cartilage degradation, synovitis, osteophyte formation, and subchondral bone sclerosis42. it usually affects the knees and the hip and is associated with considerable pain and disability43,44. rheumatoid arthritis (ra) is an autoimmune arthritis and is characterized by symmetrical polyarthritis oftenwith systemic manifestations45. gout is an autoinflammatory joint arthritis, induced by monosodium urate crystals that are deposited in joints (and soft tissues)46. hyperuricemia is usually the underlying abnormality47. gout and hyperuricemia are both rising globally48,49. 2.1 cancer obesity has been linked to an increased risk for several cancers, including those of the breast (postmenopausal), colon and rectum, corpus uteri (endometrium), esophagus (adenocarcinoma), gallbladder, kidney, liver, meningioma, multiple myeloma, ovary, pancreas, stomach (cardia), and thyroid50. a recent report from the world cancer research fund and the american institute for cancer research also indicated a potential link between body fatness and advanced prostate cancer and cancers of the mouth, pharynx, and larynx51. excess body weight and cancer is more than twice as high in women (368,500 cases) as in men (175,800 cases)52. males demonstrate an increased risk for neoplasms of the colon, rectum, and prostate, while women have an increased risk for cancers of the breast, endometrium, and gallbladder53. islami et al estimated that excess body weight was associated with 60.3% of uterine cancers, 33.9% of liver cancers, 11.3% of breast cancers in women, and 5.2% of colorectal cancers54. laubysecretan et al. estimated that an increase of every 5 kg/m2 rise in body mass index resulted in a 5% increase in the risk of colorectal cancer and a 50% increase in the risk of endometrial cancer55. central obesity is also positively associated with cancer56. obesity induces a more rapid cancer progression57,58 and is associated with reduced efficacy of certain drugs59. obese patients also have more cancer recurrences and tend to develop secondary primary cancers more often60. obesity cancer survivors report a reduced quality of life61,62. obesity is also associated with decreased survival, both in children63 and adults64. morbidly obese patients (bmi >40) exhibit a 52% higher mortality rate in men and a 62% higher mortality rate in women, when compared to those with normal weight65. obesity contributes to a pro-carcinogenic environment by producing a pro-inflammatory state66, initiating several sex and growth hormonal changes67, increasing blood levels of insulin and insulinlike growth factor-168, promoting oxidative stress69, cell proliferation and angiogenesis70, and inhibiting apoptosis/cell death71. mechanical effects of excess fat may also play a role in some cancers72. 2.2 diabetes mellitus studies indicate that more than 85% of people with dm are overweight or obese73. this number is on the increase, and it is estimated that by 2025, more than 300 million people worldwide will have dm associated with obesity74. scientific data reveals that an increase in bmi, central obesity and an increase in body weight prognosticate the development of dm75−77. a study from the uk found that the risk of developing future dm was four times higher in obese children and obese adolescents78. weight loss helps79. in the diabetes prevention program, a median weight loss of 5.5% over 2.8 years reduced the risk of converting from prediabetes to diabetes by 58%80. bariatric surgery not only results in a weight loss of 20% to 30% but also induces dm remission rates ranging from 23% to 60%81. in the look ahead (action for health in diabetics) trial, besides a lower aic and a reduced need for diabetic medications, patients also reduced their hospitalizations and health care costs, besides experiencing a reduction in sleep apnea, improved mobility, and a better quality of life82,83. weight reduction is associated with an improvement in cardiovascular morbidity and mortality in these patients84. in a more recent direct trial, weight loss was associated with sustained remissions of dm in more than a third of people at 24 months85. obesity causes chronic inflammation, biotoxicity and adipocyte induced loss cmi journal 2 (1), 80−97 (2021) meerp ltd 82 meerp ltd shashi k. agarwal, md of insulin sensitivity, and these factors contribute to the development of dm86. 2.3 kidney diseases obesity is a major cause of chronic kidney disease ckd87−94. a high bmi is often associated with the presence of proteinuria in individuals without kidney disease95−98. furthermore, in numerous large population-based studies, high bmi appears to be associated with the development of low egfr99,100. obesity is also associated with a more rapid progression of the disease. often leading to end stage renal disease (esrd)101−109. obese patients have a higher risk of complications during and after renal transplantation surgery110. as noted with cvds and dm, central obesity seems to be more important than bmi as a risk factor for ckd in several crosssectional studies111. a waist circumference (wc) >102 cm and a waist hip ratio (whr) of 0.9 in females, and a wc >88 cm and whr >0.8 in males, is associated with an increased risk of ckd, even if the bmi is normal112. higher abdominal girth has been associated with albuminuria113,114, decreased egfr115, and a higher incidence of esrd116, independent of bmi level. visceral obesity (bmiindependent) also predicts poorer renal outcomes, including mortality in patients with esrd117 and after kidney transplant118. weight loss helps kidney disease119−125. in obesity related glomerulopathy, a weight loss of 12% resulted in a decrease in proteinuria by >80%119. weight loss with bariatric surgery also results in improvement in kidney function120−125. an association between obesity and nephrolithiasis has also been described, particularly with uric acid and calcium oxalate calculi126−129. obesity is also associated with an increased risk of cancer of the kidney130,131. in a meta-analysis, guh et al estimated that this increased risk was 1.82 for men and 2.64 for women132. despite the deleterious effects of obesity on ckd and its progression, several studies have noted that obesity may result in lower mortality rates in patients with advanced ckd and esrd133−136. this obesity paradox in these individuals may reduce mortality by providing better protein and energy reserves, a higher muscle mass with enhanced antioxidant capacity, and lower circulating actin and higher plasma gelsolin levels137,138. obesity impacts the kidneys via production of adiponectin, leptin and resistin139−141. there are more inflammatory cytokines141, increased oxidative stress142, abnormal lipid metabolism143, activation of the renin-angiotensin-aldosterone system144, and increased production of insulin with insulin resistance145,146. there may be a direct pressure effect of the increased perirenal fat also.147 obesity is also closely associated with dms, htn, and atherosclerosis, which are also important risk factors for ckd148,149. 2.4 alzheimer's disease the relationship between increased bmi and dementia is well established150,151. in a review of 19 longitudinal studies including 589,649 people aged 35 to 65 years, followed up for up to 42 years, obesity was associated with late life dementia150. this was also reported in another metanalysis (1.3 million adults aged ≥18 years) where a higher body mass increased the dementia risk by a rr of 1.3151. a systematic review and a meta-analysis also reported a link between obesity and ad152,153. xu et al. reported that obese individuals at midlife developed dementia at a mean odds ratio of 3.88154. visceral obesity is also pathogenic for ad155,156. in a longitudinal study of 6,583 individuals, those with the largest abdominal diameter appeared to have a three-fold risk of developing dementia, when compared with those with the smallest diameter155. another study observed that a larger waist-hip ratio was associated with decreased hippocampal volume156, the latter often seen in patients with ad157. although some studies have noted that older people often have low body weight when they exhibit dementia, this low body weight is often deceptive as a causative factor158,159. it seems that dementia often takes 10 years to set in and during this time, bmi may decline in these individuals due to comorbidities and otherwise poor health160. although other lifestyle changes help, weight loss also plays an important preventive and therapeutic role in ad161. it has been projected by an australian study that in meerp ltd cmi journal 2 (1), 80−97 (2021) 83 obesity and non-communicable diseases: part ii cardiovascular diseases, respiratory diseases, depression, liver diseases 2050, dementia in old age can be reduced by 10% by decreasing midlife obesity by 20%162. a metaanalysis of seven rcts (468 participants) and 13 longitudinal studies (551 participants) of overweight and obese adults without dementia, (mean age 50 years), reported that weight loss of 2 kg or more in people with bmi greater than 25 was associated with a significant improvement in attention and memory163. obesity is also a well-known risk factor for dm164, dyslipidemia165, cardiovascular diseases166, and cerebrovascular diseases167 all known risk factors for ad. obesity induces adipokine dysregulation leading to central nervous system inflammation168−172. the resultant increase in microglia causes reduced synaptic plasticity and impaired neurogenesis173. microglia also interfere with insulin action and can result in aβ accumulation and reduce the tau protein degradation seen in ad173. 2.5 arthritis obesity is commonly seen in patients with knee and hip osteoarthritis174.obesity is traumatic to the knees175. the excessive joint loading in obese patients is thought to alter gait and movement strategies, resulting in joint malalignment and cartilage degeneration176. obese patients undergoing total knee arthroplasty experience increased revision rates, lower functional scores, and increased complications, including infection, when compared to non-obese patients177−179. obese individuals also suffer from increased osteo-arthritis of non-weight bearing joints180. the actions of pro-inflammatory adipokines and cytokines are implicated in this181. obesity is also significantly associated with ra182−184.a meta-analysis of 11 studies concluded that obese patients had a relative risk of 1.31 for ra185. females are at a higher risk when compared to males186,187. central obesity, even with normal bmi, appears to be worse in this relationship188. obesity also deleteriously impacts ra progression throughout the course of the disease189,190. in a meta-analysis, liu et al found that obese patients had decreased remission during therapy and overall experienced poorer outcomes191. interventions to prevent and reverse obesity help improve the outcomes and quality of life in ra patients191. obese patients with ra also exhibit higher comorbidity rates, negatively affecting ra prognosis192. the major damage is conveyed by adiposity related adipocytokines, which exert pro-inflammatory effects193,194. several other potential mechanisms, such as vitamin d deficiency, sex hormone differences, and insulin resistance, may also play a role195. gouty arthritis is also causally connectedwith obesity196. in an evaluation of 10 prospective studies, involving 27,944 cases with a median follow-up of 10.5 years, aune et al. found that the relative risks for gouty arthritis were 2.67, 3.62, and 4.64 for people with a bmi of 30, 35, and 40 kg/m2, respectively, compared with people with a bmi of 20 kg/m2196. 3 conclusion obesity has a causal relationship with most major ncds197. obese children usually end up being obese in their adult life198. the increasing prevalence of obesity in children and adolescents portends an increase an increase in ncds during adulthood in these individuals199. the evidence for the preventive and therapeutic effects of maintaining a normal bmi is persuasive200. most studies also reveal the benefits of weight loss on ncds, including via bariatric surgery79,120,162. it is therefore clear that obesity is an important lifestyle that needs to be targeted to decrease the ncd burden, both in children, adolescents, and adults. acknowledgment: none funding: none conflict of interest: none references 1. kelly t, yang w, chen cs, reynolds k, he j. global burden of obesity in 2005 and projections to 2030. int j obes (lond) 2008;32:1431– 1437. 2. https://www.wcrf.org/dietandcancer/cancer-pr evention-recommendations. accessed october 11, 2020. cmi journal 2 (1), 80−97 (2021) meerp ltd 84 meerp ltd shashi k. 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the global burden of disease study 2013. lancet. 2015;386:2287–2323. how to cite this article: agarwal s.k,, md. obesity and non-communicable diseases: part ii cancer, diabetes mellitus, kidney dis-eases, alzheimer’s disease, arthritis. clinical medicine insights. 2021;80 −97. https://doi.org/ 10.52845/cmi/2021-2-1-4 meerp ltd cmi journal 2 (1), 80−97 (2021) 97 introduction discussion cancer diabetes mellitus kidney diseases alzheimer's disease arthritis conclusion clinical medicine insights received 15 sep 2020 | revised 25 oct 2020 | accepted 20 nov 2020 | published online 15 dec 2020 doi: https://doi.org/10.52845/cmi/2020-1-1-7 cmi journal 1 (1), 50−58 (2020) issn (o) 2694-4626 review article smoking and non-communicable diseases. part ii cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, arthritis shashi k. agarwal, md ∗ 12227 us highway 1, #309 north brunswick, nj 08902,usa abstract tobacco smoking is responsible for significant global morbidity and mortality. it has adverse effects on non-smokers exposed to secondhand and third-hand smoke. e-cigarettes are also harmful to human health. smokeless tobacco also contains many toxic substances. nicotine is the common addicting substance in all tobacco concoctions. several well done studies confirm that no amount of tobacco exposure is safe. this second part of themanuscript discusses the deleterious effects of smoking on five non-communicable diseases, viz., cancer, diabetes mellitus, chronic kidney disease, alzheimer’s disease, and arthritis. keywords: smoking, non-communicable diseases, cancer, diabetes mellitus, chronic kidney disease, alzheimer’s disease, arthritis copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). 1 introduction i t is estimated that over a billion people smoke globally1. first-hand smoke is the smoke that enters the smoker’s mouth directly and is also known as mainstream smoke2. side-stream cigarette smoke emanates from the burning ends of a cigarette. environmental tobacco smoke or secondhand smoke is a combination of side-stream smoke (85%) and the exhaled main-stream smoke (15%)3. third-hand smoke is the gas and particulate residue from tobacco products, including smoked cigarettes, that cling to surfaces such as skin, hair, clothing, and furniture4. these pollutants adhere strongly to these surfaces, are difficult to removewith traditional cleaning methods, and may persist for minutes to months. supplementary information the online version of this article (10.52845/cmi/2020-1-1-7) contains supplementary material, which is available to authorized users. corresponding author: shashi k. agarwal, md shashi k. agarwal, md 2227 us highway 1, #309 north brunswick, nj 08902, usa email: usacardiologist@gmail.com cmi journal 1 (1), 50−58 meerp ltd 50 open access journal https://doi.org/10.52845/cmi/2021-2-3-13 https://orcid.org/0000-0003-0007-5582 https://creativecommons.org/licenses/by-nc-nd/4.0/ mailto:usacardiologist@gmail.com https://medicineinsights.info/index.php/cmi/index meerp ltd shashi k. agarwal, md smoked tobacco includes products like cigarettes, ecigarettes andwater pipes5. smokeless tobacco products include loosely chewed tobacco leaves, tobacco paste and tobacco-based concoctions such as snus, naswar, gutka and snuffs6. cigarette smoke has thousands of gaseous and particulate substances, with many being toxic and cancer provoking7. water pipe smoking is immensely popular in the middle east but has now become fashionable globally. water pipe (also known as hookah, narghila, argileh, hubble bubble, goza, and sheesha in different countries) smoking contains many of the same toxicants as cigarette smoking.8. water pipe smoking may result in the inhalation of 50–100 times the smoke volume during a single smoking session, when compared to that inhaled from a single cigarette9. electronic cigarettes (e-cigarettes) are battery-powered devices providing aerosol vapors for inhalation10. these vapors are usually produced by heating a liquid that has propylene glycol and/or vegetable glycerin, nicotine and flavoring. though they are significantly lower in carcinogens and toxins, they still cause harm11. smokeless tobacco provides nicotine like cigarettes, with a slower absorption and still has more than 20 carcinogens12. of all the known constituents, nicotine is the addictive substance in tobacco, smoked or taken in otherwise13. toxic compounds in tobacco-derived smoke are nitrosamines and polycyclic aromatic hydrocarbons14,15. other toxic materials found in both tobacco cigarette/waterpipe smoke and ecigarette vapor are volatile organic compounds and inorganic compounds such as metals and carbon monoxide. carbon monoxide is toxic to humans, even at low concentrations16. e-cigarette liquid usually contains, propylene glycol, and glycerine, in addition to nicotine. the inhaled e-cigarette vapor contains toxic compounds derived from these three ingredients17. smokeless tobacco also contain harmful substances like nitrosamines, polycyclic aromatic hydrocarbons, and aldehydes18. in general, no tobacco product is safe. the estimated economic cost associated with smoking is 1.8% of global gross domestic product. in 2012, the world’s total medical expenditure for smoking-attributable diseases reached 467 billion us dollars, accounting for 5.7% of the global health expenditure. meanwhile, the total economic cost of smoking (including medical expenditures and productivity losses) in 2012was 1852 billionus dollars, accounting for 1.8% of the global gross domestic product. almost 40% of the economic cost occurs in low-income or middle-income countries. 2 discussion noncommunicable diseases (ncds) are the leading cause of mortality, killing more than 36 million people each year, globally19. they are responsible for 63% of all annual deaths. developing countries bear the main brunt of this enormous mortality, with almost 80% of ncd deaths occurring in low and middle income countries20. modifiable behavioral health risk factors such as smoking tobacco, inadequate vegetable and fruit consumption, high alcohol consumption, physical inactivity and obesity increase the risk of ncd morbidity and mortality21. tobacco smoking is a major player in this deleterious association. ncd diseases discussed in this manuscript include cancer, diabetes, chronic kidney diseases, alzheimer’s disease, and arthritis. cancer is the second leading cause of death (after cardiovascular disease) in 2017, accounting for 17% of all global deaths31. cancer related mortality exceeds that caused by communicable diseases such as human immunodeficiency virus/acquired immunodeficiency syndrome, tuberculosis, and malaria., combined31.cancer prevalence is rising and commonly involves the bladder, breast, colon, rectum, lung, cervix and head and neck22. in 2018, globocan estimated that 18.1 million people had been diagnosed with cancer, with 9.6 million people dying from it, worldwide23. diabetes is increasing in prevalence in several developed and in most developing countries45,46. according to the international diabetes federation there are 451 million adults live with diabetes worldwide in 2017 and this number is projected to increase to 693 million by 204547. type 2 diabetes accounts for 90–95% of diabetes cases and is caused by insulin resistance and progressive loss of β cell function and mass. diabetes is associated with an increase in meerp ltd cmi journal 1 (1), 50−58 (2020) 51 smoking and non-communicable diseases. part ii cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, arthritis mortality from several co-morbid conditions, such as cvds, chronic kidney disease, cancer and liver diseases48. it also increases the risk of infections with adverse outcomes. diabetes is solely responsible for 1.5 million deaths worldwide. it also contributes to an additional 17.5 million deaths each year49. type 2 diabetes invariably leads to the development of several microvascular (retinopathy, nephropathy, and neuropathy) and macrovascular (coronary artery disease, stroke, peripheral artery disease) complications24. deaths from diabetes (dm) have increased by more than 60% since 2000 and now rank in the top 10 causes of death25. the worldwide prevalence of chronic kidney disease (ckd) is estimated to be 8–16%58. ckd is associated with a reduction in the glomerular filtration rate (egfr) <60 ml/min/1.73 m259. there are usually structural renal abnormalities also noted. untreated ckd usually progresses to end-stage renal disease (gfr<15 ml/min), requiring dialysis or kidney transplant. ckd increases the risk of developing cardiovascular diseases, mineral and bone disorders, and anemia. worldwide, a 31.7% increase of ckd mortality was observed over the last decade60. lifestyle factors, including smoking, alcohol, obesity, and physical inactivity have been implicated in the promotion of ckd. chronic kidney disease (ckd) affects over 10% of the population worldwide. it was ranked 16th among the leading causes of death in 2016 and is expected to become the 5th leading cause of death by 204026. diabetic kidney disease is the leading cause of ckd27. cognition is involved in attention, memory, language, orientation, performance, judgment and problem-solving skills. a decline occurs with age and is considered normal.mild cognitive impairment is a pre-dementia stage. alzheimer’s disease (ad), a progressive disease, accounts for 50–70% of dementia cases66. according to thewho, 44 million had ad globally in 2016. this number is on the increase and is projected to reach 82 million by 2030 and 152 million by 205067. alzheimer’s disease and other dementias afflict nearly 44 million people worldwide28. the annual healthcare expenditure for ad patients, was $277b in 2018 and expected to go up to $1100b annually by 2050. the two main kinds are osteoarthritis and rheumatoid arthritis. osteoarthritis (oa) is leading cause of pain and disability among adults all over the world. it affects almost 1 in 3 people over age 6575. osteo-arthritis exhibits cartilage loss while rheumatoid arthritis affects the synovial joints resulting in synovitis, joint erosion, and cartilage damage. arthritis is of over 100 types, the most common being rheumatoid arthritis, osteoarthritis, psoriatic arthritis and inflammatory arthritis29. these diseases result in considerable functional disability in the sufferers, especially with increasing age. all these diseases are not only non-communicable but usually chronic. cdc30 defines chronic diseases as “conditions that last 1 year or more and require ongoing medical attention or limit activities of daily living or both.” noncommunicable diseases are gradually replacing infectious diseases as the major health burden in the developing countries. deaths from noncommunicable diseases are also on the rise, globally. as discussed in the previous part of this 2 part manuscript, smoking is one lifestyle that plays an important adverse role in the genesis and progression of these diseases. cancer smoking is strongly associated with cancer, accounting for 19% of all cancer cases32. tobacco smoke is full of carcinogens33. active smoking has been associated with cancer of lamost every organ of the human body. it is estimated that smoking accounts for 81.7% of lung cancers, 73.8% of larynx cancers, 50% of esophageal cancers, 46.9% of bladder cancers and 28.8% of all cancer deaths32. other methods of smoking tobacco, such as water pipe smoking34. electronic nicotine delivery system (ends) smoking35, and heat-not-burn (hnb) smoking36 have also been implicated in increasing the cancer risk. second-hand smoke also increases the risk of cancer37. smokeless tobacco also poses a risk, causing cancers of the oral cavity, esophagus, and pancreas38. smoking after the diagnosis of cancer demonstrate a poor treatment response and enhanced treatment-related toxic effects39. they risk getting recurrrences40 and are more likely to cmi journal 1 (1), 50−58 (2020) meerp ltd 52 meerp ltd shashi k. agarwal, md develop a primary second cancer41, compared to non-smokers. they are also subject to an increased mortality42. this mortality risk is reduced by 30% to 40% with smoking cessation43. overall, smoking cessation after cancer diagnosis may have benefits that equal or exceed those achieved by cancer treatments44. smoking cessation is difficult with almost 80% of smokers relapsing within the first month of abstinence, and only about 5% achieve long-term abstinence. diabetes mellitus any kind of tobacco smoke exposure increase the risk of type 2 diabetes50. it is estimated that 11.7% of diabetes cases among men and 2.4% of diabetes cases among women are probably connected with active smoking51. this association appears to be dose-response related. in 2014, the surgen general reported that active smoking increases the risk of t2d by 30–40% in active smokers compared to non-smokers52. in a meta-analysis of 88 prospective studies of almost 6 million participants, pan and group found that passive smoking was associated with a 22% increased risk of incident type 2 diabetes in never smokers compared to never smokers not exposed to passive smoke51. alternate tobacco smoking methods and smokeless tobacco products also appear to impact diabetes development53. smoking during pregnancy increases the risk of gestational diabetes mellitus54 and may also increase the risk of future diabetes in the offspring55. infants exposed to secondhand cigarette smoke also experience an increased risk for t2d development. active smoking has been associated with reduced appetite and weight loss. on the other hand, smoking cessation is often associated with weight gain. several studies reported that diabetes risk was increased in individuals who had recently quit smoking, raising a concern about elevated diabetes risk with smoking cessation56. this phenomenon occurs more frequently during the first 3 years post-cessation and appears to be related to an increase in body weight upon withdrawal of nicotine56. smoking appears to acutely worsen glucose tolerance, alter peripheral insulin signally and impair beta cell function57. chronic kidney disease in an analysis of 15 prospective cohort studies involving 65,064 incident ckd cases, xia et al. found an increased risk of ckd in smokers vs nonsmoker61. smoking enhances its progression62. it is also associated with a higher incidence of death from end-stage renal disease (esrd) in both males and females63. smoking cessation reduces the risk of incident ckd64. smoking is an independent risk factor for the development of ckd. previous studies have demonstrated that nicotine causes tubule-interstitial injury and plays a central role in smoking-mediated renal dysfunction65. alzheimer’s disease smoking has been linked to increased cognitive decline several studies reported that smokers were 1.9–4.3 times more likely to develop ad than nonsmokers68. nicotine has short-term enhancing effects, and this may help explain the high rate of smoking in individuals with psychiatric disorders and the difficulty in quitting in this population69. however, in the long run smoking harms cognitive function and may lead to the development of neurodegenerative disorders including ad70. secondhand smoke is also harmful to cognition with an increase in cognitive impairment of 24% noted in older adults with such an exposure71. smoking during pregnancy can harm fetal brain development, while cigarette smoking at an earlier age is associated with future cognitive impairment72. smoking in ad patients is associated with oxidative stress, neuroinflammation, and impaired neuroprotection73. structural abnormalities such as a thinner anterior cingulum and prefrontal lobe have also been noted in these patients74. arthritis smoking is a risk factor in knee and hip oa, causing an increased proliferation of chondrocytes76. it increases pain and cartilage loss in these patients. however, ameta-analysis of 48 observational studies and data from the 5th knhanes study of individuals over the age of 50 suggest the smoking and osteoarthritis may not be significantly associated77. some studies have shown that cs intensity and duration are causally related to the risk of ra meerp ltd cmi journal 1 (1), 50−58 (2020) 53 smoking and non-communicable diseases. part ii cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, arthritis development78. this increased risk appears to persist even after cs cessation 3 conclusion tobacco use, especially cigarette smoking, is an important cause of global morbidity and mortality. tobacco consumption in any form harms nearly every organ of the human body. it is adversely involved in the genesis and progression of 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diseases. part ii cancer, diabetes mellitus, kidney dis-eases, alzheimer’s disease, arthritis. clinical medicine insights. 2020; 34−42. https://doi.org/10.5284 5/ cmi/2020-1-1-7 cmi journal 1 (1), 50−58 (2020) meerp ltd 58 introduction discussion conclusion cmi 03 (03), 322−329 manuscript central 322 clinical medicine insights doi: https://doi.org/10.52845/cmi/2022-3-3-2 cmi 03 (03), 322−329 (2022) issn (o) 2694-4626 research article open access journal what does comorbid status implication with the end status of corona virus disease (covid-19) patients? melati noormaulidya putri 1 , muhammad syarif 1 , iwan aflanie 2 , endah labati s 2 , fauzie rahman 3 , husnul fatimah 4 , zuhrufa wanna yolanda 4 , corresponding author: fauzie rahman fauzie21@ulm.ac.id 1 undergraduate student of public health study program , faculty of medicine, lambung mangkurat university 2 medical study program, faculty of medicine, university of lambu ng mangkurat 3 public health study program , faculty of medicine, university of lambung mangkurat 4 association of alumni faculty of medicine, university of lambung mangkurat. abstract background: the prevalence of confirmed cases of covid-19 is quite high and tends to continue to increase. based on data, south kalimantan province in early mid-2021 experienced a high spike in cases, resulting in a large number of deaths, especially in the city of banjarbaru. covid-19 active cases in south kalimantan in july 2021 were recorded at 5,279 cases (12.41%) out of a total of 42,527 positive cases. many research results on risk factors for covid-19 cases, the results vary widely. people with comorbidities are a very vulnerable group. objective: to analyze whether comorbid status has implications for the final status of covid-19 patients in inpatients at the idaman hospital, banjarbaru city. methods: quantitative research using an observational design through a case-control approach. the population is 300 respondents and the research sample is 60 respondents with a sample group of 30 people and a control group of 30 people. the data used is data from the case form report (cfr). the dependent variable in this study was the final status (died/recovered) in inpatients diagnosed as positive for covid-19 at the idaman hospital, banjarbaru city, while the independent variables were age, gender, hypertension, diabetes mellitus, pneumonia, heart failure, kidney failure. chronic chronic disease (ckd) and stroke (cva). data were analyzed univariately and bivariately with chi-square to obtain adjusted or. results: analysis using the chi-square test showed that chronic kidney failure (p=0, 026) has implications for the mortality status of patients with a risk of dying 10 times compared to patients without comorbidities, and heart disease (p=0.045) with a risk of dying 6 times compared to patients without heart disease. conclusion: chronic kidney disease (ckd) and heart disease are the highest risk factors that affect death in patients with covid-19. keywords: covid-19, comorbidity, mortality copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/lic enses/by-nc-nd/4.0/). https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ cmi 03 (03), 322−329 manuscript central 323 manuscript central noorrmaulidya et al. introduction determination covid-19 declared a pandemic by the world health organization (who) on march 11, 2020, based on cases of covid-19 which is spreading rapidly infecting populations in many countries. sars-cov-2 or novel coronavirus is the name for a virus that plays a role in disease covid-19 or coronavirus disease. more severe illnesses, such as middle east severe acute respiratory syndrome, can follow a series of mild symptoms such as the common cold. the cause is a large family of dominant coronaviruses infecting the respiratory tract in the human body. the first reported case in indonesia coincided on march 2, 2021 (directorate general of disease prevention and control, 2020). the mode of transmission of the virus is by spreading through splashes of saliva produced by an infected person when coughing, sneezing, or even when the person exhales. droplets can't stay in the air, so they quickly fall and stick to other surfaces. even transmission can occur when breathing air containing the virus. the prevalence of confirmed cases of covid-19 is quite high and tends to continue to increase. based on data, south kalimantan province in early mid2021 experienced a high spike in cases, resulting in a large number of deaths, especially in banjarbaru city. active covid-19 cases in south kalimantan province in july 2021 were recorded at 5,279 cases (12.41%) out of a total of 42,527 positive cases (covid-19 task force, 2021). research conducted by sijia tian et al., entitled characteristics of covid-19 infection in beijingwith demographic, epidemiological, clinical, and laboratory tests for covid-19, it was found that the average age of the patients was 47.5 years and 51.5% were women, 73.3% of patients were residents of beijing, 26.0% of whom had been to wuhan, 60.4% had close contact with confirmed cases, the most common symptoms at onset of illness were fever (82.1%), cough (45.8%), fatigue (26.3%), dyspnea (6.9%) and headache (6.5%) . the average incubation period is 6.7 days, the time interval for getting sick and seeing a doctor is 4.5 days (tian et al., 2020). comorbid disease is a comorbid disease or congenital disease that can worsen the infection situation covid-19 and can also reduce the immune system (mazuki et al., 2021). the indonesian ministry of health stated that one of the vulnerable groups was exposed to covid-19 are people who have comorbid diseases, this group is also at high risk of death (indonesian ministry of health, 2020). the role of the family is important in disease prevention covid-19 so that prevalence can decrease (pranata, et al, 2021). case prevalence covid-19 with comorbidities globally by 57.7% and cases covid-19 noncomorbidity of 42.3%. comorbid disease in covid-19, that is hypertension, diabetes mellitus, cardiovascular disease (cvd), chronic obstructive pulmonary syndrome (copd), chronic kidney disease (ckd), cancer and other comorbidities including liver disease, gi disorders, immunocompromised, neurogical disorders, psychiatric disorders, metabolic disorders, blood disorders, transplant, chronic pancreatitis, connective tissue disorder, smoking, obesity, hyperlipidemia. percentage of patients covid-19 with the highest comorbid hypertension at 27.4% and followed by dm 17.4%, cvd 8.9%, copd 7.5%, cancer 2.6%, ckd 3.5%, other diseases 15.5% (bajgain dk., 2020) the results of the studies described previously showed that comorbidity was a risk factor for severity and mortality in patients covid-19. therefore, to answer this question, this research was conducted with the aim of analyzed whether comorbid status had implications for the final status of covid-19 patients in inpatients at the idaman hospital, banjarbaru city. methods this type of research is a quantitative study using an analytic observational design using a case control approach. the population in this study were all inpatients covid-19 at the idaman hospital of banjarbaru city 2021. number of positive confirmed patients covid-19 at the idaman hospital from january-march 2021, namely, a total of 300 people. the sample size for cases, namely, patients who were confirmed positive and had been declared dead were 30 cases, while for controls were 30 confirmed cases. covid-19 and declared cured. the source of data in this study is the medical record report at the cmi 03 (03), 322−329 manuscript central 324 manuscript central noorrmaulidya et al. idaman hospital, banjarbaru city the data that has been collected was analyzed univariately using the frequency distribution table for each variable and bivariate analysis with the chi-square test to determine the implications between the two variables and calculating the odds ratio (or), fisher's alternative test was used if the chi-square test did not meet the requirements. results and discussion a. characteristics of respondents table 1.1 distribution of respondents based on characteristics characteristics frequency (f) percent (%) age productive 46 76.7 non productive 14 23.3 gender woman 37 61.7 man 23 38.3 status healed 30 50 die 30 50 hypertension yes 31 51.7 not 29 48.3 diabetes mellitus yes 27 45 not 33 55 pneumonia yes 10 16.7 not 50 83.3 heart yes 11 18.3 not 49 81.7 ckd yes 9 15 not 51 85 stroke yes 4 6.7 not 56 93.3 data source: year 2021 table 1. shows the age distribution based on the productive age category as many as 46 people (76.7%) compared to non-productive age respondents as many as 14 (23.3%). gender was dominated by 37 women (61.7%) and the final status of patients for those who died 30 people (50%) and recovered as many as 30 people (50% %). several comorbid diseases that have implications for the status of inpatients at the idaman banjarbaru hospital, namely hypertension disease are 31 people (51.7%), diabetes mellitus are 27 people (45%), patients who have heart disease are 11 people (18.3%), patients with kidney failure (ckd) as many as 9 people (15%) and stroke patients as many as 4 people (6.7%). cmi 03 (03), 322−329 manuscript central 325 manuscript central noorrmaulidya et al. table 2. bivariate analysis variable case control 0r (95% ci) p-value n % n(%) (%) age 0.467 (0.135-1.609) 0.360 productive 21 70% 25 83.3% non productive 9 30% 5 16.7% gender 0.490 (0.170-1.414) 0.288 woman 21 70 16 53.3 man 9 30 14 45.7 hypertension 0.386 (0.136-1.094) 0.121 yes 19 63.3 12 40 not 18 36.7 11 60 diabetes mellitus 0.874 (0.316-2.418) 1,000 yes 13 43.3 14 46.7 not 17 56.7 16 53.3 pneumonia 2,739 (0.635-11.823) 0.299 yes 7 23.3 3 10 not 23 76.7 27 90 heart 6,000 (1,172-30,725) 0.045 yes 9 30 2 6.7 not 21 70% 28 93.3 ckd 10,545 (1,227-90,662) 0.026 yes 8 26.7 1 3.3 not 22 73.3 29 96.7 stroke 3,222 (0.316-32.889) 0.612 yes 3 10 1 3.3 not 27 90 29 96.7 data source: year 2022 analysis between individual characteristic variables and the patient's final status covid-19 shown in table 2. people with heart disease had 6 times the risk of dying compared to those without heart disease and it was not statistically significant (p=0.045). meanwhile, people who have kidney failure have a 10.5 times risk of dying compared to patients who do not have kidney failure and it is statistically significant (p=0.026). discussion according to the centers for disease control and prevention (cdc) shows that 94% of cases of death covid-19 in the united states occurs in patients with comorbidities. patients who have comorbidities need attention because their conditions are more vulnerable so that when infected, covid-19 can have fatal consequences. the ministry of health lists 12 co-morbidities covid-19 the most in positive patients covid-19. five of them are hypertension, diabetes mellitus, heart disease, lung disease, and kidney disease. people who already have this disease must strictly implement health protocols to avoid transmission covid-19 (cdc, 2021). in table 2 it is known that, out of 46 people of productive age, 21 people died as a result of covid-19, while out of 14 people who were unproductive, 9 people died. the results of bivariate analysis obtained p = 0.360 (α> 0.05), which means that there is no statistically significant implication between age and the final status of comorbid patients affected. covid-19. this is in line with the research of elviani et al, (2021) which stated that the majority of respondents were in the age range of 26-35 years, amounting to 141 respondents. this shows that this age is productive age. at productive age, the possibility of contracting covid-19 will be larger, this is due to high mobility and activities outside b. bivariate analysis results cmi 03 (03), 322−329 manuscript central 326 manuscript central noorrmaulidya et al. the home. the frequency and social interaction of productive groups is also higher. the center for strategic and international studies (csis) also stated that infection transmission came from groups with relatively high mobility, namely, relatively young age groups. deployment covid-19 in italy has struck every age group. initially, most of the recorded cases occurred among the elderly, but as the corona virus spreads, younger people are infected in greater numbers (kalantari, 2020). this means that all ages are at risk for infection covid-19, and productive age is the age most at risk due to high mobility and social activities. although it is risky, this can be prevented by continuing to follow health protocols (wearing masks, washing hands, doing physical and social distancing and avoiding crowds). the number of women as respondents in this study were 37 people, 21 of whom died due to covid-19, while the 23 men who were the respondents, 9 of them died. the results of statistical tests showed p = 0.288 (α> 0.05), which means that gender has no implications for the final status of comorbid patients affected covid-19. men are more sensitive to sars-cov-2 so that male gender is a risk factor covid-19bbecause they are more out of the house for working conditions and more in the community, therefore they are more likely to be infected. differences in behavior between men and women, especially in terms of health education, as well as their lack of attention to the issue of social distancing, are issues that should not be ignored (rashedi et al, 2020). there were 31 hypertension patients, 19 of whom died due to hypertension covid-19, while out of 29 people who did not suffer from hypertension, 18 people died. the results of statistical analysis showed p = 0.121 (α> 0.05) which means that there is no implication between hypertension status and the final status of comorbid patients affected covid-19. this is not in line with the data found in the data on comorbid conditions found in patients covid-19in indonesia until july 29, 2021, hypertension is still the most common comorbid condition, at 50.4%. in a study conducted by gunawan et al, regarding the effect of hypertension on infected patients covid-19. the study stated that hypertension can worsen the condition of infected patients covid-19this virus will bind to angiotensin converting enzyme 2 (ace2), an enzyme attached to the outer surface of several organs in the body, after binding to the enzyme, the virus can enter the organ and cause the patient to become infected. covid-19 (gunawan et al, 2020). there were 27 diabetes mellitus patients, 13 of whom died from diabetes mellitus covid-19. the results of statistical analysis showed p = 1,000 (α> 0.05) which means that there is no implication between hypertension and the final status of affected comorbid patients. covid-19. diabetes is the most common metabolic disease in the world. it is a disease that weakens the immune system. the number of people with diabetes in the world is increasing, especially in developing countries. researchers have shown that diabetes increases the risk covid-19. diabetic patients are less responsive to treatment and have a higher risk of death. in diabetic patients, innate immunity is compromised due to increased blood glucose levels so that glycosylation of cytokines impairs cytokine-dependent function of type 1 helper t lymphocytes (th1). pulmonary microangiopathy, oxidative stress-induced tissue damage in hyperglycemia, and pulmonary inflammation predispose patients to covid-19, as is the case in patients susceptible to tuberculosis (rashedi et al, 2020). these diabetic patients have a 2 times greater risk of developing severe or critical illness requiring treatment in an intensive care unit (longato et al, 2020; wang et al, 2020). on hospitalization, patients with diabetes mellitus are three times at risk of dying from diabetes mellitus covid-19. diabetes mellitus is an independent risk factor for age and gender (setyarini, 2021). there were 10 pneumonia patients, 7 of whom died from covid-19. the results of the statistical test analysis showed the p-value = 0.299, from the p-value in the statistical test results, the decision ho was rejected (p>0.05), which means that there is no implication between pneumonia and the risk of death from covid-19 in banjar regency. this is not relevant to the senewe research (2020) which states that the most common risk factor for comorbidities is pneumonia at 18.2% (senewe, 2020). patients with heart disease were found as many as 11 people, 9 of whom died from covid-19. the results of statistical analysis obtained p = 0.045 (α cmi 03 (03), 322−329 manuscript central 327 manuscript central noorrmaulidya et al. <0.05) which means that there are significant implications between heart disease and the final status of comorbid patients affected covid-19. odds ratio (5% ci:1.172-30,725) shows that covid-19 patients have a 6 times higher risk of dying than covid-19 patients who do not have comorbidities. comorbid factors covid-19 the third and fourth ranks are hypertension and cardiovascular system disease, with a percentage of 3.10% and 2.86%, respectively. this is in line with the analysis of 5 journals showing that from 2 journals that reported the presence of comorbid cardiovascular disease and hypertension, namely the research of satria et al (2020) and sanyasi & pramudita (2020) have contributed a fairly high number, which if added up to more than 5, 96%. cardiovascular disease and hypertension are associated with smoking, hypertension, and diabetes mellitus, which are thought to be at risk of increasing the excretion of ace2 receptors or angiotensin converting enzyme 2 (susilo et al, 2020). indeed, there are no research results that confirm the exact link between hypertension and severity covid-19 (yang et al, 2020). however, in general the severity covid-19it will be easier to occur in people with hypertension which are generally associated with complications of other health problems and factors of old age so that it is difficult to separate the influence of each factor. the results of yang & yan's (2020) study showed that 358 patients were infected covid-19 and confirmed by nasal and/or throat swab. 66 patients (18%) died of covid-19. 60.6% were male (or 1.87, p 0.041), 22.7% were >64 years old (or 2.097, p 0.041), and 83.3% were comorbid risk factors. diabetes mellitus (30.3%) (or 4.348, p 0.000) and cardiovascular disease (10.6%) (or 4.319, p 0.016) were the highest risk factors for death in covid-19. the presence of acute inflammation and decreased organ function (heart, kidney, liver, and hematology) experienced by patients at the beginning of treatment can increase the risk of death due to infection. covid-19 (setyarini, 2021). there were 9 patients with chronic kidney failure, 8 of whom died as a result of covid-19. the results of the bivariate analysis showed p=0.026 (α<0.05), which means that there are statistically significant implications between heart disease and the final status of comorbid patients affected covid-19. odds ratio (5% ci:1.172-30,725) showed that covid-19 patients had a 10 times higher risk of dying than covid-19 patients who did not have cardiac comorbidities. this is in line with a meta-analysis involving 76,993 patients in 10 publications that listed chronic kidney disease as one of the seven most common comorbidities in patients covid-19 hospitalized (emami et al, 2020). subsequent analysis found that chronic kidney disease was the most common risk factor for covid-19 weight worldwide at any age and explains the increased risk covid-19 severe for about one in four high-risk individuals worldwide (council et al, 2021). chronic kidney disease is well known to be a risk factor for severe bacterial and viral infections. many theories have explained why comorbid chronic kidney disease increases the risk of developing serious infectious diseases and even death. chronic kidney disease patients have pro-inflammatory status and functional effects on innate and acquired immune cells resulting in increased susceptibility to infection (ishigami et al, 2017). in addition, there is an increased risk of pneumonia and upper respiratory tract infections in patients with chronic kidney disease who may also be co-infected with covid19. there were 4 stroke patients, and 3 of them died due to covid-19. the results of the bivariate analysis obtained p=0.612 (α> 0.05), which means that there is no statistically significant implication between stroke and the final status of comorbid patients affected by covid-19. stroke or cva (cerebro vascular accident) is also one of the comorbid factors for covid-19 in indonesia. the results of the study in the form of a review of 5 journals, showed that there were 2 journals that clearly provided information on stroke as a comorbid factor for covid-19, namely, the research of satria et al (2020) and sanyasi & pramudita (2020). another study stated that there were 4 cases of patients diagnosed with covid-19 who were also suffering from a stroke or had a history of stroke (satria et al, 2020). these results are relatively new, because existing reports do not clearly mention stroke or cva as a comorbid factor for covid-19 (karyono & wicaksana, 2020). 56 patients with chronic diseases also mostly have experienced organ damage. when exposed to the corona virus, the damage to these organs can become more severe, cmi 03 (03), 322−329 manuscript central 328 manuscript central noorrmaulidya et al. intensive action to reduce person-to-person transmission of covid-19 is needed to control this outbreak, especially in vulnerable populations, especially those with comorbid hypertension and diabetes. it is also relevant to the research conducted by raden muhammad ali satria with the title analysis of risk factors for death with comorbid covid-19 (setyarini, 2021) conclusion comorbid status has implications for the final status of the patient covid-19at the idaman hospital in banjarbaru city. confirmed patient covid-19 with comorbid cardiac status with p=0.045 (or=6,000) and chronic kidney failure with p=0.026 (or=10,545) had a higher risk of death than patients without these comorbidities. the most dominant comorbid factors were patients with a history of chronic kidney failure. suggestion it is hoped that these findings can be used as a basis for policy making and educational program planning strategies to improve patient monitoring and treatment covid-19 especially in patients who have comorbid diseases and other noncommunicable diseases. communities and individuals can maintain their lifestyle by always adhering to health protocols. references 1. cdc. 2020. covid-19 data tracker world health organization. naming the corona virus disease [internet] is accessed at: https://www.who.int/emerhencies/diseases. 2. council ee, ortiz a, cozzolino m, fliser d, fouque d, goumenos d, et al. 2021. chronic kidney disease is a key risk factor for severe covid-19: a call to action by the era-edta. nephrol dial transplant. 36(1) :87–94. 3. elviani r, chairil a, januar s. 2021. age description in the incidence of covid-19. jmu. 9(2); 204-209. 4. emami a, javanmardi f, pirbonyeh n, akbari a. 2020. prevalence of underlying diseases in hospitalized patients with covid-19: a systematic review and meta-analysis. arch acad emerg med. 8(1):1–14. 5. gunawan, a., prahasanti, k., & utama, mr 2020. effect of comorbid hypertension on severity of patients infected with covid-19. husada implementa journal. 1(2); 136. 6. ishigami j, grams m, chang a, carrero j, coresh j, matsushita k. 2017. ckd and risk for hospitalization with infection: the atherosclerosis risk in communities (aric) study. am j kidney dis. 69(6): 752–61. 7. kalantari h, tabrizi ahh, foroohi f. 2020. determination of covid-19 prevalence with regards to age range of patients referring to the hospitals located in western tehran, iran. gene reports [internet]. available from:https://doi.org/10.1016/j.genrep.2020.10 0910 8. the work of kw, i made s, beny s. 2021. the relationship between comorbid diseases and the clinical degree of covid-19. medical science digest. 12(2): 708-717. 9. rashedi, j., poor, bm, asgharzadeh, v., pourostadi, m., kafil, hs, vegari, a., tayebikhosroshahi, h. and asgharzadeh, m. 2020. 'risk factors for covid-19', infez med, 28(4); 469-474. 10. setyarini ew, mayta sd. 2021. analysis of risk factors for transmission of covid-19 pandemic health workers in jombang regency. journal of research innovation. 2(2); 744-750. 11. directorate general of disease prevention and control. guidelines for preparedness for coronavirus disease (covid-19). jakarta: ministry of health of the republic of indonesia; 2020. 12. tian, s., hu, n., lou, j., chen, k., kang, x., xiang, z., chen, h., wang, d., liu, n., liu, d., chen, g., zhang, y., li, d., li, j., lian, h., niu, s., zhang, l., & zhang, j. (2020). characteristics of covid-19 infection in beijing. journal of infection, 80(4), 401–406. https://doi.org/10.1016/j.jinf.2020.02.018 13. world health organization. (2020). about covid-19. https://www.who.int/emergencies/ diseases/novel-coronavirus-2019/question-and -answers-hub/qa-detail/coronavirus-diseasecovid-19 14. indonesian ministry of health. (2020). the latest number of covid-19 cases.https:// covi d19. kemkes.go.id/category/ situasi-infectionemerging/ infocorona virus/#.x7y7nmgzbiu cmi 03 (03), 322−329 manuscript central 329 manuscript central noorrmaulidya et al. how to cite putri, m. n., syarif, m. ., aflanie, i. ., s, e. l. ., rahman, f. ., fatimah, h. ., & yolanda, z. w. . (2022). what does comorbid status implication with the end status of corona virus disease (covid-19) patients?. clinical medicine insights, 3(3), 322–329. https://doi.org/10.52845/cmi/2022-3-3-2 clinical medicine insights received 25 jul 2021 | revised 22 aug 2021 | accepted 18 sept 2021 | published online 01 oct 2021 doi: https://doi.org/10.52845/cmi/2021-2-4-1 cmi journal 2 (4), 201−223 (2021) issn (o) 2694-4626 review article diet and non-communicable diseases: part i cardiovascular diseases, respiratory diseases, obesity, depression, liver diseases shashi k. agarwal, md ∗ 12227 us highway 1, #309 north brunswick, nj 08902, usa abstract diet is involved in the development and progression of several chronic diseases. these include diseases that are responsible for a major health burden globally, such as cancer, cardiovascular diseases, obesity, diabetes mellitus, and depression. the scientific world is replete with studies on the impact of dietary factors and common diets on these ailments. prudent dietary habits sever both preventive and therapeutic roles in several non-communicable diseases. healthy diets are primarily plant-based, and low in red and processed meats and sugar-sweetened beverages. this manuscript discusses our understanding of the modulation of diet in order to mitigate cardiovascular diseases, respiratory diseases, obesity, depression, and liver diseases. keywords: diet, non-communicable diseases, cardiovascular diseases, respiratory diseases, obesity, depression, liver diseases copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). 1 introduction i t is estimated that almost 10% of the global burden of disease is related to poor diet1. the influence of diet has been noted with several ailments, including cardiovascular diseases2,3, diabetes mellitus4,5, cancer6,7, lung diseases8,9, gastrointestinal diseases10−12, kidney diseases13,14, neurological diseases15,16, mental disorders17−19, and arthritis20,21, and many others22−25. a poor diet reduces the quality of life26. it is also one of the leading causes of accelerated aging27, disability28, and excess mortality29. the seven countries study, reevaluated in 2017, highlighted the substantial influence of diet on health30. dietary interventions have become a core aspect of primary and secondary prevention of the most common non-communicable diseases (ncds)31. besides caloric restriction to avoid overweight and obesity (a body mass index below 25 kg/m2)32, a healthy diet is well balanced and consists of high consumption of non-starchy vegetables, fruits, whole grains, and legumes, a limcmi journal 2 (4), 201−223 meerp ltd 201 open access journal https://doi.org/10.52845/cmi/2021-2-3-7 https://orcid.org/0000-0003-0007-5582 https://creativecommons.org/licenses/by-nc-nd/4.0/ https://medicineinsights.info/index.php/cmi/index meerp ltd shashi k. agarwal, md ited to moderate consumption of nuts, seafood lean meats, low-fat dairy products, and vegetable oil rich in mono and polyunsaturated fats, and limitation or elimination of trans-fats, saturated fats, fried foods, sodium, red meat, refined carbohydrates, and sugarsweetened beverages33−35. several diets have become popular for their beneficial health effects36−38. the most common ones are the mediterranean39, dietary approaches to stop hypertension (dash)40, and vegetarian41 diets. the mediterranean diet is commonly followed in the olive-growing areas of the mediterranean region. these residents have a high intake of vegetables, whole grains, legumes, fresh fruit, non-refined cereals, nuts, and extra virgin olive oil. they have a moderate consumption of fish, poultry, and dairy, and a low intake of red meats (usually reserved for special occasions only) and sweets. their intake of alcohol is moderate and usually limited to red wine consumed during their main meals36,39. metaanalysis of cohort studies on this diet revealed a 10% reduction in cardiovascular events and 8% reduction in mortality39. the dash diet is low in sodium (< 2300mg/day) and has been promoted by thenational institutes of health to treat hypertension. it also encourages consumption of fruits and vegetables of different colors, fat-free or low-fat dairy products, whole grains, and various protein sources (e.g., seafood, lean meats, eggs, legumes, nuts, seeds, and soya) while limiting added sugars (< 10% of calories per day), saturated fats (< 10% of calories per day), and alcohol (≤ 1 drink per day for women and ≤ 2 drinks per day for men). besides effects on blood pressure, it also helps in improving other risk factors for cvd and diabetes mellitus37,40. a vegetarian diet is a plant-based diet, rich in whole grains, cereals, legumes, fruits, leafy ground vegetables, nuts, seeds, supplementary information the online version of this article (10.52845/cmi/2021-2-4-1) contains supplementary material, which is available to authorized users. corresponding author: shashi k. agarwal, md shashi k. agarwal, md 2227 us highway 1, #309 north brunswick, nj 08902,usa email: usacardiologist@gmail.com and sea vegetables38,41. the term semi-vegetarians is sometimes used to describe individuals who consume meat up to or less than once a week. lactovegetarians eat dairy products, ovo-vegetarians eat eggs, lacto-ovo vegetarians eat both dairy products and eggs, while a pesco-vegetarian eats fish, in addition to the plants42. a vegan usually consumes no food from animal sources43. the nature of vegetarianism often varies between different cultures and regions44−46. most european and north american vegetarians eat dairy products and eggs and are therefore lacto-ovo-vegetarians44. asian indian vegetarians are mainly lacto-vegetarians45. dairy intake is much less in chinese vegetarians when compared to western vegetarians46. vegetarian diets are specifically linked to a lower risk of coronary artery disease and type 2 diabetes43,47, while vegan diets, in addition, also help in losing weight43. the impact of diet on common chronic medical conditions is discussed in this two-part manuscript. part i discusses the relationship between diet and cardiovascular diseases (cvd), chronic obstructive pulmonary disease (copd), obesity, depression, and liver diseases. part ii discusses its impact on cancer, diabetes mellitus (dm), kidney diseases, alzheimer’s disease, and arthritis. 2 discussion cdc defines chronic diseases as “conditions that last 1 year or more and require ongoing medical attention or limit activities of daily living or both”48 most chronic diseases are ncds, and their incidence and prevalence is growing all over the world49. diet is an important modifiable risk factor for chronic diseases development and progression50−52. cardiovascular diseases (cvds) are a heterogeneous group of diseases of the heart and the circulatory system53. cvds are associated with extremely high morbidity and continue to be the leading cause of premature mortality worldwide54. it is estimated that by the year 2030, 23.6 million people will die of cvds per year55. the underlying cause is usually atherosclerosis56. chronic respiratory diseases are common non-communicable diseases57 and include chronic obstructive pulmonary disease (copd), meerp ltd cmi journal 2 (4), 201−223 (2021) 202 mailto:usacardiologist@gmail.com diet and non-communicable diseases: part i cardiovascular diseases, respiratory diseases, obesity, depression, liver diseases asthma, interstitial lung diseases, pulmonary sarcoidosis, and pneumoconiosis such as silicosis and asbestosis58. it is estimated that 545 million people in the world suffered from chronic respiratory diseases in 201759. they remain a leading cause of death and disability worldwide60. they caused more than 3.8 million deaths in 2017, which accounted for 7% of all global deaths and 9% of all ncd deaths61. obesity is an increasing public health problem worldwide62. besides its epidemic influence in adults, it is increasingly affecting children and adolescents63. obesity leads to a wide array of illnesses such as type 2 diabetes mellitus (dm)64, hepatic steatosis65, gallbladder diseases66, osteoarthritis67, and several cancers (such as those of the endometrium, breast, ovary, prostate, liver, gallbladder, kidney, and colon)68, in addition to the diseases discussed in this manuscript. even modest weight loss—5%decrease in bodyweight—has been shown to lower the risk of chronic disease69,70. its etiology is multifactorial, but diet plays an important role71. obesity increases mortality72. depressive disorders are the leading cause of global disability73. it is usually associated with a low mood, sadness, lack of energy, and an inability to enjoy life74. it also affects physical health75. overall, depression leads to a considerable reduction in the quality of life, medical comorbidity, and mortality76,77. chronic liver diseases have become a major international public health concern78−80. it is estimated that nonalcoholic fatty liver disease (nafld) has a prevalence of around 25% of the general population81. diet also plays a major role in alcoholic liver disease (ald)82 . diet also is associated with liver cancer83. chronic liver diseases cause more than 2 million deaths per year57. these diseases and their relationship with diet are discussed below. 2.1 cardiovascular diseases poor eating habits are a major modifiable risk factor for cardiovascular diseases (cvd)84−86. a plethora of scientific studies indicates that red and processed meat87, fried foods88, sugar-sweetened beverages89, excess alcohol intake90 and obesity91 have detrimental effects on cvds, while fruits and vegetables92,93, whole grains94, fiber95, tree nuts96, chocolate97, and coffee98 are cardioprotective. the most effective dietary intervention is probably salt restriction99. this leads to blood pressure (bp) reduction, which is associated with a substantial reduction in morbidity and mortality from cvds100. according to major us cardiology associations, a reduction of salt intake to <1500 mg/d101 should bring the bp down by about -5/6 mm hg systolic and -2/3 mm hg diastolic102. obesity is closely related to hypertension (htn)103, and weight reduction in obese individuals, via calorie restriction, or other dietary changes, is also associated with bp reduction104. the aha estimates that every 1 kg (2.2 lbs) weight reduction is associated with about a 1mmhg reduction in systolic bp105. a change in the quality of diet also helps105,106. a diet rich in fruits, vegetables, whole grains, low-fat dairy products and with a reduction in saturated and total fat has also been estimated to reduce systolic bp by -11 mm hg and diastolic bp by – 3mm hg105. both the dash diet107 and themediterranean diet108, help reduce bp in patients with htn. controlling htn helps reduce several cvds, including stroke109, heart failure110, and cardiac arrhythmias111. the major beneficial impact of a drop in bp is, however, on coronary artery disease112,113. in a recent longitudinal study of 153,082 us veterans, the dash diet was inversely associated with the incidence of coronary artery disease (cad)114. another study, a metaanalysis of cohort studies determined that adherence to the dash diet resulted in a 21% reduced risk of cad115. the lyon diet heart study, which evaluated the impact of the mediterranean diet on cad, found a reduction in coronary mortality of 65% after 46 months116. benefits of a healthy diet have also been recorded with stroke117, heart failure118, peripheral arterial disease119, and vasculogenic erectile dysfunction120. a high-fat diet has also been linked to an increase in cardiac arrhythmias121, and scd122. a cardiovascular healthy diet also helps reduce hypercholesterolemia123, dm124, and chronic kidney disease125 – all major risk factors for cvds. 2.2 respiratory diseases the adverse association between obesity and copd is well known126,127. obesity risks increase with the cmi journal 2 (4), 201−223 (2021) meerp ltd 203 meerp ltd shashi k. agarwal, md consumption of an energy-dense, high fat, and lowfiber diet, resulting in excess caloric intake128. the quality of diet also appears to influence copd129,130. several diets appear to reduce the development of copd from 25% to 54%131−133. the most important beneficial component of these diets appears to be a higher intake of fruits and vegetables134. consumption of fish135, and a lower intake of processed meats136. a diet rich in a higher intake of meat and potatoes, and a lower intake of soy and cereal has been associated with lower forced expiratory volume in one second (fev1) and an increased prevalence of copd137. in patients with diagnosed copd, patients on a diet with high consumption of fruits and vegetables demonstrated an annual increase in their fev1 while those on a usual diet showed a decrease in fevi during 3 years of followup138. several recent studies have confirmed the beneficial effects of fruits and vegetables in retarding the development and progression of copd139−141. several micronutrients are present in high amounts in fruits and vegetables, are associated with better lung parameters and their presence may explain their beneficial effect in patients with copd142,143. these include vitamin c142, alpha-tocopherol140, and beta-carotene143. their benefits have been attributed to a reduction in inflammation and oxidative stress144. fish oils are anti-inflammatory and are protective against the development of copd145. micronutrients like calcium, phosphorus, iron, potassium, and selenium also appear to be beneficial in these patients146. vitamin d supplementation, especially in those with severe deficiency, also helps in reducing the number of copd exacerbations147. diet also influences copd-related mortality148. walda et al noted an inverse trend for 20-year copd mortality, and a 100 g increase in fruit intake at baseline resulted in a 24% lower copd mortality risk149. obesity, which is usually associated with an energydense, low fiber, and high-fat diet, is common in asthma patients150 with harmful effects151,152. excess body weight is associated with reduced lung volumes, poorer asthma control and outcomes, and poorer quality of life151,152. excess adipose tissue induces immunometabolism disarray, increased oxidative stress, and decreased bioavailability of nitric oxide, producing or aggravating airway disease153. reduction in weight helps, as has been demonstrated by bariatric surgery studies that have resulted in dramatic improvements in asthma control and lung function154. a weight-reducing diet is therefore beneficial in asthma patients155. asthma is an inflammatory disease156, and the latter can be beneficially modulated with a judicious diet157. in adults with severe asthma, higher fat and lower fiber intake have been associated with increased eosinophilic airway inflammation158. reduction of dietary saturated fat intake reduces this inflammation159. in contrast, fruits, vegetables, and their antioxidants help lower airway inflammation160,161. a study from mexico demonstrated that fruit and vegetable intake was inversely associated with il-8 protein in nasal lavage of asthmatic children, indicating reduced inflammation162. in asthmatic adults, intake of tomato juice, which is abundant in the antioxidant lycopene, reduced airway neutrophil influx and sputum neutrophil elastase activity after just seven days of supplementation157. on the other hand, a diet characterized by highly processed foods, with high intakes of refined grains, processed and red meats, desserts and sweets, fried foods, and high-fat dairy products, with low intake of fruits and vegetables has harmful effects on asthma in children163−165. several case–control studies indicate that a diet rich in vegetables and fruits, may exert some protective effect against lung cancer166,167. cruciferous vegetables, such as broccoli, are rich in isothiocyanates, and these have cancer-preventive activity166. a high intake of total or saturated fat does not appear to increase the risk of lung cancer, as a pooled analysis of eight cohort studies showed168. however, high levels of nitrosamines (formed during cooking) in fried or well-done red meat, appear to increase lung cancer risk169,170. 2.3 obesity excess caloric intake without corresponding energy burn results inweight gain171. an imbalance between energy intake and expenditure, results in an increase in the number (hyperplasia) and size (hypertrophy) of adipocytes172,173. in other words, individuals consuming more calories than the recommended daily allowance according to the mets expended, are meerp ltd cmi journal 2 (4), 201−223 (2021) 204 diet and non-communicable diseases: part i cardiovascular diseases, respiratory diseases, obesity, depression, liver diseases likely to become overweight or obese171. excess calories are easier to consume with food rich is fats and sugars, and low in fiber174. ultra-processed foods are typical examples they are highly processed foods high in total energy, free sugars, saturated fats, sodium, and additives, and low in fiber, protein, phytochemicals, and micronutrients – with additives primarily to increase their shelf life without increasing their cost175. the foods include chips, carbonated soft drinks, sweet or savory snacks, confectionary, mass-produced packaged bread, buns, pastries, cakes, biscuits and desserts, prepacked breakfast cereals, preprepared meals, including pies, pasta and pizza dishes, reconstituted meat and meat products, ‘instant’ soup, and noodle dishes175. ultraprocessed foods account for about 50–60 % of the energy content in the usual diet of the average us, canadian, or british consumer176−178. several epidemiological studies have examined differences in body weight based on dietary patterns. findings from ahs, epic and the swedish mammography cohort studies found that omnivores had the highest prevalence of overweight and obesity compared to individuals eating less meat, such as plant-based diets179. the epic-panacea study showed that an increase in 250 g/day of meat led to a 2 kg weight gain after 5 years180. in a study examining a cohort of 49,098 taiwanese adults, the percentage of participants with a bmi ≥ 27 kg/m2 was significantly lower among those following a vegetarian diet (10.9%) as compared to those following a non-vegetarian diet (15.4%)181. the adventist health study also demonstrated that bmi increases as the number of animal foods in the diet increased182. in this study, vegans had the lowest bmi, followed by vegetarians, pesco-vegetarians, semi-vegetarians, and omnivores182. the european prospective investigation into cancer and nutrition (epic-oxford) study found that vegans gain significantly less weight as they age compared to omnivores183. plant-based diets also help in weight loss184,185, huang et al in ameta-analytic study found significant weight loss with plant based diets184, while barnard et al reported in another meta-analysis that plant-based diets were associated with a mean weight loss of −3.4 kg to 4.6 kg185. several subsequent clinical trials, including the new diets study186, her health study187, and the va beach diet study188, have also confirmed the weight loss benefit associated with plant-based diets. a prudent diet – plant based or restricted in calories, should ideally include 60% carbohydrate intake, 25% protein intake, and 15% fat intake189. weight loss in these patients is enhanced by combining exercise190 regular moderate-intensity aerobic exercise for at least 150 min per week or more than 300 min per week. resistance exercises at moderate intensity two times per week with 10 to 15 resistance exercise repetitions should also be part of this exercise regimen. 2.4 depression diet is a well-known factor associated with depression191−194. as mentioned before, a calorierich diet may result in obesity128. obesity is harmful to depression195. the prevalence of depression in obese individuals is twice as high as in those of normal weight196,197. an improvement in the diet, especially with calorie restriction resulting in weight loss may help with an improvement in depression symptoms198,199. depression can also lead to obesity, indicating that there is a bidirectional causality200−202. the quality of diet also has a major impact on depression203. lassale et al. in a review and analysis of 20 longitudinal and 21 cross-sectional studies, concluded that an inverse association between healthy diet and depression204. a recent meta-analysis confirmed that ‘healthy’ dietary patterns (regardless of the type) may contribute to the prevention of depressive symptoms205 . and this appears to be related in a linear dose-response fashion198. diets low in fruit and vegetables206, fish207, or legumes208, are associated with an increase in depression. diets rich in sugar, sodium, saturated fat209,210, meat, and eggs211,212 are associated with more depression. a diet with lower intakes of low-calorie foods is similarly harmful213. an unhealthy diet is often poor in several micronutrients, including tryptophan, inositol, magnesium, fiber, folate, and omega-3 fatty acids which are important for proper mental wellbeing214. however, dietary supplements do not appear to be very effective in reducing depression215. improper diet and obesity result cmi journal 2 (4), 201−223 (2021) meerp ltd 205 meerp ltd shashi k. agarwal, md in hpa axis dysregulation216. they also increase inflammation, oxidative stress, and other endocrine dysfunctions217. 2.5 liver diseases nonalcoholic fatty liver disease (nafld) is a progressive disease of the liver that ranges from hepatic steatosis (liver fat >5% of liver weight) to more severe steatohepatitis, (nash, hepatocellular inflammation}, with progression to fibrosis and endstage cirrhosis218. weight loss via caloric restriction remains the most viable option in the treatment of nafld and fibrosis219. reducing body weight by 710%with hypocaloric diets is the most efficacious in the treatment of nafld/nash and fibrosis220,221, with greater weight loss (≥10%) being associated with the highest rates of nafld/nash resolution and fibrosis regression222. however, histological improvements are also observed with as little as 35% weight loss223,224. a healthy diet, besides a diet that prevents excess body weight, is also important. several diets, including the mediterranean paleolithic, ketogenic, high-protein, plant-based, lowcarbohydrate, and intermittent fasting approaches all have shown beneficial health outcomes in these patients225. dietary ingredients that are beneficial include soluble and insoluble fiber, monounsaturated or polyunsaturated fatty acids, several micronutrients, vitamins e, c, and d, and several polyphenols (e.g., resveratrol, curcumin, caffeine, quercetin) are also helpful in nafld226,227. on the other hand, fructose and saturated fatty acids contribute to the pathogenesis of nafld228. alcohol intake in excess induces hepatic damage resulting in alcohol liver disease, which includes liver steatosis, fibrosis, cirrhosis, and alcoholic hepatitis229. these can be prevented by alcohol abstinence and the damaged liver can be helped with nutritional support. patients with ald usually suffer from malnutrition230, and this exacerbates the severity of the liver disease231. these patients may either have an intake of an unhealthy diet with too few essential nutrients or the alcohol may prevent the body from digesting and utilizing essential nutrients232. many ald patients suffer from protein-calorie malnutrition233 which increases complications. the american college of gastroenterology and the american association for the study of liver diseases guidelines recommend 1.2 to 1.5 g/kg per day of protein intake and 35 to 40 kcal/kg per d of body weight for energy intake in patients with ald82 besides these macronutrients, ald patients need several micronutrients to protect liver toxicity and distant complications include zinc234, magnesium235, selenium236, vitamins d237, vitamin e238, folate239, niacin240, and thiamine241. a proper nutritional support in patients with ald helps reduce infectious complications and improves 1-year mortality in such patients242,243. there is a strong association between obesity and hepatocellular carcinoma244,245 .the results show that diet plays an important role in hcc occurrence246. several diets have been noted to lower the risk of hepatocellular carcinoma247,248. these diets are usually rich in foods such as vegetables249,250, poultry251, fish252, wholegrains253, nuts254, tea255, and caffeinated coffee256,257. micronutrients such as vitamin e, vitamin b9, β-carotene, manganese, and potassium may help in reducing the development of hcc258. some fats, including monounsaturated fats259, may also have beneficial effects. however, data indicates that processed red meat consumption260 high-fat dairy foods261, and ingestion of sugar-sweetened beverages262 may increase hcc risk. heavy alcohol intake is also harmful263,264. 3 conclusion a healthy diet should provide adequate macro and micronutrients, and avoid harmful saturated fat, processed meats, sugar-sweetened drinks, excess salt, and excess alcohol. the beneficial effects of a prudent diet on several ncds are strong. water is also an important component of diet265. it comprises from 75%bodyweight in infants to 55% in the elderly. besides providing adequate hydration, plain water intake is associated with a decrease in sugar-sweetened beverages, and a decrease in caloric intake. water intake should not be forgotten as a beneficial component of a healthy diet. acknowledgment: none funding: none meerp ltd cmi journal 2 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in cirrhotic patients. nutr. res. 2019;61:82–94. doi: 10.1016/j.nutres.2018.10.002. 263. baecker a, liu x, la vecchia c, zhang zf. worldwide incidence of hepatocellular carcinoma cases attributable to major risk factors. eur j cancer prev. 2018;27(3):205-212. doi:10.1097/cej.0000000000000428. 264. yang jd, hainaut p, gores gj, amadou a, plymoth a, roberts lr. a global view of hepatocellular carcinoma: trends, risk, prevention and management. nat rev gastroenterol hepatol. 2019 oct;16(10):589-604. doi: 10.1038/s41575-019-0186-y. epub 2019 aug 22. 265. european food safety authority (efsa) panel on dietetic products, nutrition, and allergies. scientific opinion on dietary reference values for water. efsa j 2010;8:1459. how to cite this article: agarwal s.k, md diet and non-communicable diseases: part i cardiovascular diseases, respiratory dis-eases, obesity, depression, liver diseases. clin-ical medicine insights. 2021;201−223. https://doi. org/10.52845/cmi/2021-2-4-1 cmi journal 2 (4), 201−223 (2021) meerp ltd 223 introduction discussion cardiovascular diseases respiratory diseases obesity depression liver diseases conclusion references clinical medicine insights received 15 feb 2022 | revised 10 mar 2022 | accepted 15 mar 2022 | published online 30 mar 2022 doi: https://doi.org/10.52845/cmi/2022-3-1-5 cmi 03 (01), 278−279 (2022) issn (o) 2694-4626 research article is spike protein-related myocarditis becoming a common disease? head of holistic center, 13 haupt st., abtwil 9030, switzerland www.drdoepp.org, abtwil, switzerland copyright : © 2022 the authors. published by medical editor andeducational research publishers ltd. this is an open access articleunder the cc by-nc-nd license(https://creativecommons.org/ licenses/by-nc-nd/4.0/). manuscript central used to avoid complications of hemodialysis manifested in uremic state including anorexia, nausea, vomiting leading to malnutrition, fluid and electrolyte imbalance leading to volume overload, hyperkalemia, metabolic acidosis, and hyperphosphatemia, as well as abnormalities related to hormonal or systemic dysfunction such as hypertension, anemia, hyperlipidemia, and bone disease, timely diagnosis of proteinenergy-wasting (pew) is important for early initiation of nutritional intervention and treatment. in addition, education plans should be prepared to mediate the nutrient intakes and identify the patient’s difficulties and provide practical help. keywords: renal dialysis, nutritional status, hemodialysis, malnutrition copyright : © 2022 the authors. published by publisher. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). cmi 03 (01), 278−279 278 1 introduction i our clinical routine, we increasingly find patients who have myocardial damage. predominantly, they have undergone covid-19 infection and are considered to have "recovered." this applies to both vaccinated and unvaccinated patients. at first glance, this seems illogical. of course, on the one hand, vaccinated persons have covid-19 viruses in their organism and, on the other hand, they produce spike proteins, because a production of neutralizing antibodies is, after all, the purpose of vaccination. in unvaccinated people this is not so clear, because one part of them has "recovered", another part has not undergone any infection. it appears that they have inhaled spike proteins, which were exhaled by vaccinated persons. a reference in this situation, it is of interest that hannemann et al (1) recently demonstrated that cardiovascular damage was detectable in a quarter of hospitalized covid patients. this was apparently detectable several weeks after hospitalization. after a median interval of 67 days after the covid diagnosis (pet, mri, crp, lymphocytic blood count with t1 and t2 values, late-gadolinium enhancement, cardiac ejection fraction, and echocardiography) pathologic results were found in 17% of the 47 patients. the authors cited autoimmune responses triggered by the infection and a direct viral effect on the myocardium as possible mechanisms. spike proteins what is most likely the cause? spike proteins are known to occupy and block ace2 receptors in almost all body cells (3). this causes, for example, an increased viscosity and multiple microemboli in blood cells. we prove this by dark-field microscopy of vital blood directly after blood collection. it is a method which is not usually applied in laboratories, but it allows excellent insight into the current appearance and behavior of all blood cells. vital blood in all patients with the presence of myocardial damage, we found erythrocytes in the vital blood (2) that were rigid and no longer exhibited flexibility, and which also showed the so-called "money roll phenomenon". in this case, the erythrocytes stick together and are hardly able to flow through capillaries. at the same time, the oxygen uptake capacity is reduced. the result is an undersupply of oxygen to the body's cells. doepp, manfred md* https://doi.org/10.52845/cmi/2022-3-1-4 https://creativecommons.org/licenses/by-nc-nd/4.0/ the organs with the highest ace2 receptor density are the myocardium and the brain. this is understandable, since both organs have to be active non-stop and require a high atp production. therefore, we also examined the patients with myocardial weakness with regard to their cognitive performance. they all reported that they had noticed reductions in concentration and memory for some time. since we, the holisticcenter, strive to provide effective therapy in every case, we have decided to use the following means and methods, the probability that spike proteins cause a) increased blood viscosity, b) myocarditis, and c) brain function reductions, is high. we have developed a treatment which is nature based, sideeffects-free and effective. we assume that by using these procedures a long-covid-syndrome may be prevented. further research is needed. references 1. hannemann k et al. jama cardiol 2022 ; doi : 10.1001/jamacardio.2021.5505 2. https://en.wikipedia.org/wiki/dark-field_mi cros copy 3. manfred doepp. spike proteins may be dangerous. am j biomed sci & res. 2021 14(3). ajbsr.ms.id.001990. doi:10.34297/ajbsr.202 1.14.001990. 4. https://en.wikipedia.org/wiki/ouabain 5. https://en.wikipedia.org/wiki/carnosine 6. https://en.wikipedia.org/wiki/ubiquinol 7. https://en.wikipedia.org/wiki/dimethylethanola mine 8. https://en.wikipedia.org/wiki/glutathione 9. https://en.wikipedia.org/wiki/palmitoylethanola mide 10. https://en.wikipedia.org/wiki/phosphatidylserin e 11. https://en.wikipedia.org/wiki/aspirin 12. https://en.wikipedia.org/wiki/ginkgo_biloba 13. https://www.naturalnews.com/2021-06-28-dan delion-leaf-extract-blocks-spike-proteins-bindingto-ace2-receptor.html 14. y. l. zhang et al. suramin is an active sitedirected, reversible, and tight-binding inhibitor of protein-tyrosine phosphatases. in: j. biol. chem. 273, 1998, p. 12281–12287. pmid 9575179 pdf. cmi 03 (01), 278−279 manuscript central 279 for the myocardium: for the brain: for blood thinning: for better oxygen supply: for a blockade of the spike proteins: clinical results: strophanthin/ouabain (4) 3 mg enteric-coated capsules (3x1), l-carnosine (5) 500 mg capsules (2x1) and ubiquinol (6) 100 mg softgels (2x1). dmae (dimethylaminoethanol bitartrate, (7) 100 mg capsules (2x1), l-glutathione (reduced) (8) 500 mg (2x1), pea (palmitoylethanolamide, (9) 300 mg (2x1) and phosphatidylserine/choline mix (10) 100 mg each (2x1). aspirin (11) 81 mg tablets (1x1), ginkgo biloba (12) 240 mg capsules (1x1). taraxacum/dandelion (13) whole plant smoothies and suramin (14) as pine needle extract. singlet oxygen inhalation via a device (airnergy) 3 x 30 minutes/day, more often if needed. the improvements in patients' well-being were significant. there was no worsening in any case. the parameters used to assess the myocardial performance like pulse rate, blood pressure, and heart-rate-variability (hrv) showed clear improvements. conclusions: how to cite this article: manfred, d. . (2022). is spike protein-related myocarditis becoming a common disease?. clinical medicine insights, 3(1), 1278–1279. https:// doi.org/10.52845/cmi/2022-3-1-5 introduction causes of nutritional disorder in hd inadequate food intake abnormal nutrient metabolism aim and objectives methodology result assessment of nutritional status of hd. patients prevalence of malnutrition using subjective global assessment body mass index in the study patients bmi and sga score laboratory investigation association between nutrient intake and sga discussion conclusions references clinical medicine insights clinical medicine insights doi: https://doi.org/10.52845/cmi/2022-3-1-1 meerp ltd cmi 3 (1), 244−249 (2022) received 15 nov 2021 | revised 30 nov 2021 | accepted 25 dec 2021 |online available 8 jan 2022 case report open access issn (o) 2694-4626 primary malignant large b-cell non-hodgkin’s lymphoma of the scalp and cranial vault: a case report and an overview fatma kolsi1 | mehdi borni2∗ | ines cherif3 | marouen taallah4 | slim charfi5 | mohamed zaher boudawara 6 abstract primary non-hodgkin’s malignant lymphoma of the bone is a rare entity, accounting for 4% of all non-hodgkin’s malignant lymphomas (nhl). cranial vault involvement is rarer, found only in 0.2% of cases (1)(2). only few cases have been reported previously in the literature (3)(4). here, the authors are reporting a new case of primary malignant large b-cell non-hodgkin’s lymphoma of the cranial vault because of its rare occurrence. key words: nonhodgkin’s malignant lymphoma, scalp, surgery 1 introduction primary non-hodgkin’s malignant lymphoma of the bone is a rare entity, accounting for 4% of all non-hodgkin’s malignant lymphomas (nhl). femur, tibia and pelvis are the most common sites. cranial vault involvement is rarer, found only in 0.2% of cases (1) (2). the absence of involvement of the cerebral parenchyma and systemic or skeletal manifestation is also rare. only few cases have been reported previously in the literature (3) (4). primary malignant lymphoma of the bone is defined as an isolated bone lesion with no signs of other sites involvement and no blood-borne spreadwithin sixmonths of diagnosis (5). here, the authors are reporting a new case of primary malignant large b-cell non-hodgkin’s lymphoma of the cranial vault because of its rare occurrence. case report a 30-year-old young lady with no medical or surgical history was admitted from our outpatient department of neurosurgery for progressively growing of a painless scalp lump at the level of the parietooccipital right bone. there were no signs of raised intra cranial pressure mostly without headache. the patient confirmed no prior head trauma, fever, or general condition impairment. upon neurological examination, she was awake, alert and well oriented with no neurological disorder. local examination of her scalp swelling revealed a hard and well-defined nontender immovable solitary subcutaneous painless lump, measuring 7cm in diameter. she had no lymphadenopathy or hepatosplenomegaly and the rest of her body check-up showed no abnormalities including her lymph node areas. the complete blood count showed hemoglobin level of 11.4 g/dl, white blood cell count of 8500/mm3 with a platelet count of 331000/mm3. both blood serum ionogram and hemostasis assessment and evaluation were normal. 12346 department of neurosurgery – uhc habib bourguiba –sfax (tunisia), 5 department of pathology – uhc habib bourguiba –sfax (tunisia), 12346. address correspondence to: mehdi, borni, department of neurosurgery – uhc habib bourguiba –sfax (tunisia) supplementary informationthe online version of this article (https://doi.org/10.52845/cmi/2022-3-1-1) contains supplementary material, which is available to authorized users. fatma kolsi et al., 2022; published by meerp ltd, inc. this open access article is distributed under the terms of the creative commons license (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. meerp ltd 244 https://doi.org/10.52845/cmi/2022-3-1-1 https://doi.org/10.52845/cmi/2022-3-1-1 meerp ltd kolsi et al. fig. 1: axial brain computed tomography (ct) scan in parenchymal window (a, b) and bone window (c) showing expansive osteoly c lesion (a, b; yellow arrows) (c: white arrows) in the right parieto-occipital bone measuring 3.6 * 1 cm in diameter without perilesional edema or a midline shi ; d: three-dimensional ct reconstruc on showing bone lysis (black arrow). note the subcutaneous lump clearly visible (a, b; red arrows). fig. 2: axial brain magne c resonance imaging showing a fairly ly c bone mass inisosignal on t1-weighted image (a; white arrow) and discreet hypersignal on t2 sequence (b; white arrow) with homogenous enhancement a er gadolinium chelates injec on (c; white arrows). fluid a enuated inversion recovery sequence showed discreet hypersignal (d) and gre t2 ∗ weighted image revealed low intensity signal in favor of bone signal (e; ; yellow arrows). diffusion weighted image showing a significant restricted signal (f). further investigation through magnetic resonance imaging (mri) (figure 2) confirmed the fairly lytic bone mass in isosignal on t1-weighted image and discreet hypersignal on t2 sequence with homogenous enhancement after gadolinium chelates injection. the lesion comes into contact with the superior sagittal venous sinus without infiltrating it. diffusion weighted image showed a significant restricted signal with low apparent diffusion coefficient (adc) value on adc mapping. as part of the extension assessment, the thoraco-abdominopelvic ct, breast and thyroid ultrasound, as well as bone scintigraphy were without abnormalities. all these finding suggested thus a primary bone scalp lymphoma. meerp ltd cmi 3 (1), 244−249 (2022) 245 fig. 3: preopera ve (le image) and intraopera ve (right image) photographs in the opera ng room showing the supine posi on with pa ent's head fixed in mayfield head clamp turned slightly to the le side biparietal skin incision (red arrow) was performed and an excision of her bone mass through. preopera vely the mass was subcutaneous, hard, grayish, and easily cleavable (black arrows). the dura mater was intact and the bone scalp was found to be moth eaten (white arrows). a brain computed tomography (ct) scan (figure 1) was thus performed showing an expansive osteolytic lesion in the right parieto-occipital bone measuring 3.6 * 1 cm in diameter without perilesional edema or a midline shift. primary malignant large b-cell non-hodgkin's lymphoma of the scalp and cranial vault: a case report and an overview fig. 4: immediate axial postopera ve ct scan in parenchymal window before (a) and a er enhancement (b) showing the absence of tumor residue. axial ct in bone window (c) and three-dimensional reconstruc on (d) correct placement of the cranioplasty (e). cmi 3 (1), 244−249 (2022) meerp ltd 246 the patient underwent, under general anesthesia and in supine position with his head fixed in a mayfield head clamp turned slightly to the left side (figure 3), an excision of her bone mass through a large biparietal skin incision. the mass was subcutaneous, hard, grayish, and easily cleavable. the dura mater was intact and the bone scalp was found to be moth eaten. by the end a cranioplasty was performed covering the tumor bed. the mass along with the involved bone were sent for histopathological examination. postoperative course was uneventful. immediate postoperative ct scan (figure 4) showed the absence of tumor residue as well as correct placement of the cranioplasty. fig. 5: photomicrographs of a surgical specimen showing tumor prolifera on of similar morphology; tumor cells were round, of large size, with round nucleus, lobulated vesicles and small nucleoli, more or less prominent; mitoses were very numerous; this prolifera on massively infiltrates the bone ssue; it was in places delimited by a small cell lymphoid sleeve (a; he x 100). immunohistochemistry (b) showing diffuse immunoreac vity for leukocyte cd20. histopathological examination (figure 5) was con-ducted showing tumor proliferation of similar mor-phology on all samples; it is a dense proliferation in diffuse, partly lobulated layers; the tumor cells were round, of large size, with round nucleus, lobu-lated vesicles and small nucleoli, more or less promi-nent; mitoses were very numerous; this proliferation massively infiltrates the bone tissue; it was in places delimited by a small cell lymphoid sleeve. there were small areas of necrosis. on immunohistochem-istry tumor cells were massively immunoreactive for leukocyte common antigen (lca), cd20, oct 2, and bcl-6 and they meerp ltd kolsi et al. fig. 5: photomicrographs of a surgical specimen showing tumor prolifera on of similar morphology; tumor cells were round, of large size, with round nucleus, lobulated vesicles and small nucleoli, more or less prominent; mitoses were very numerous; this prolifera on massively infiltrates the bone s-sue; it was in places delimited by a small cell lymphoid sleeve (a; he x 100). immunohistochemistry (b) showing diffuse immunoreac vity for leukocyte cd20. histopathological examination (figure 5) was con-ducted showing tumor proliferation of similar mor-phology on all samples; it is a dense proliferation in diffuse, partly lobulated layers; the tumor cells were round, of large size, with round nucleus, lobu-lated vesicles and small nucleoli, more or less promi-nent; mitoses were very numerous; this proliferation massively infiltrates the bone tissue; it was in places delimited by a small cell lymphoid sleeve. there were small areas of necrosis. on immunohistochem-istry tumor cells were massively immunoreactive for leukocyte common antigen (lca), cd20, oct 2, and bcl-6 and they were weakly positive for cd 10. the proliferation index ki 67 was estimated to be 90%. all these feature were in favor of diffuse large b-cell non-hodgkin lymphoma fig. 6: brain mri in axial plane at 01 month postopera vely showing no signs of tumor recurrence on t1 and t2 weighted images as well as a er enhancement. our patient underwent, at our out-patient clinic, a physical examination, complete hemogram, and brain mri (figure 6). all these investigations did not revealed no signs of tumor recurrence. 2 discussion: primary bone lymphoma is a rare malignant tumor, which accounts for only 4% of non-hodgkin lymphomas (1). this entity is defined by the isolated presence of lymphoma in the bone without other distant localization within six months of diagnosis (5). bone involvement primarily affects the femur, humerus, pelvis, spine, mandible, and scapula. primary localization to the cranial vault remains extremely rare (6). it has been reported in immunocompromised or trauma patients. however primary nhl with extraand/or intra-cranial extension without systemic or skeletal involvement in a nonimmunocompromised or nontraumatic context is extremely uncommon (4). to our knowledge, only 19 cases had been reported previously in the literature (1) . the inaugural clinical signs revealing the disease are painless lump in the scalp observed in 90% of patients, headache due to bone destruction or tumor infiltration of the meninges in 30% of cases, and meerp ltd cmi 3 (1), 244−249 (2022) 247 were weakly positive for cd 10. the proliferation index ki 67 was estimated to be 90%. the patient was discharged of our department at day 4 postoperatively and addressed to the oncology’s department for further management. she received 3 cycles of systemic chemotherapy. the cycles were repeated after 3 weeks. signs of focal neurological palsy secondary to tumor infiltration of the cerebral parenchyma in 10% of cases (1) (6). lymphoma also may infiltrate the spaces within the diploe and along the emissary veins reaching the soft tissues on either side of the bone. in our patient, the painless scalp lump was the revealing mode with no other neurological symptoms. the parieto-occipital bone destruction as well as the sparing of the dura were both obvious peroperatively. iconographic data is not sufficient to confirm the diagnosis. thus, on mri, these lesions are relatively nonspecific, appearing in hypointense on t1-weighted sequences and hypersignal on that of t2 (2). possible differential diagnoses are primary malignant large b-cell non-hodgkin's lymphoma of the scalp and cranial vault: a case report and an overview iconographic data is not sufficient to confirm the diagnosis. thus, on mri, these lesions are relatively nonspecific, appearing in hypointense on t1-weighted sequences and hypersignal on that of t2 (2). possible differential diagnoses are osteomyelitis, metastatic or primary skull tumors, and intraosseous meningioma. these lesions are accompanied by significant cortical bone destruction unlike lymphoma. histologically, most cranial vault lymphomas are non-hodgkin’s large b-cell lymphomas expressing cd20 but not cd5, cd10 and cd23 (6). in our patient, immunohistochemistry showed a tumor cells immunoreactivity for lca (cd 45), cd20, oct 2, and bcl-6 with less important immunoreaction for cd 10. due to the rarity of cases described in the literature, the optimal treatment of primary lymphoma of the cranial vault has not been well established and no definite conclusion can be drawn. some authors rec-ommend surgery followed by radiotherapy in case of localized disease, and chemotherapy in case of metastatic progression (7). it must be remembered that first of all, since primary lymphoma of the cen-tral nervous system (cns) is multifocal and infiltrating, the role of surgery, unlike other brain tumors, is purely diagnostic. the place of surgery in primary bone lymphomas located in the cranial vault remains limited to the diagnosis of histopathology (bone biopsy). this dogma was recently challenged by a second analysis of the largest randomized trial of pri-mary cns lymphomas, which included 526 patients and found a survival benefit from first surgery (8) . further tests are needed to confirm these results and to this day it remains confined to its diagnostic role. in view of the low incidence and the paucity of the reported cases, it is still difficult to establish a definitive prognosis for this disease. el asri et al. (6) no systemic involvement at the time of diagnosis and continued to be symptom-free after treatment with follow-ups ranging from five months to 72 months. although it remains a rare entity, primary nonhodgkin’s malignant lymphoma should be cited in the differential diagnoses of expanding scalp lesions. the treatment must necessarily involve a multidisci-plinary therapeutic approach, including several spe-cialties including neurosurgery, radiotherapy and oncology 3 conclusion primary lymphoma of the cranial vault remains an extremely rare tumor. its treatment is still not well standardized. the most optimal therapeutic option is based on the combination of surgery and / or radiotherapy and chemotherapy. therefore, a thorough search is needed to improve the management of this disease as well as its prognosis. references 1. kosugi s, kume m, sato j, sakuma i, moroi j, izumi k. diffuse large b-cell lymphoma with mass lesions of skull vault and ileocecum. j clin exp hematop. 2013;p. 53215–53224. 2. fadoukhair z, lalya i, amzerin m, elkhanoussi b, sbitti y, boutayeb s. successfulmanagement ofprimarynonhodgkinlymphoma ofthe cranial vault. pan afr med j. 2011;850. 3. holtås s, monajati a, ur. computed tomography of malignant lymphoma involving the skull. j comput assist tomogr. 1985;p. 9725–9732. 4. agbi cb, bannister cm, ti. primary cranial vault lymphoma mimicking a meningioma. neurochir. 1983;p. 26130–26132. 5. dürr hr, müller pe, hiller e, maier m, baur a. malignant lymphoma of bone. arch orthop trauma surg. 2002;p. 12210–12216. cmi 3 (1), 244−249 (2022) meerp ltd 248 reported that 13 were still alive among 16 patients followed over a period of 12 months. in a review published by aquilina et al. (9), and among 16 patients with vault lymphoma, 6 had meerp ltd kolsi et al. 6. asri ace, akhaddar a, baallal h, boulahroud o, mandour c, chahdi h. primary lymphoma of the cranial vault: case report and a systematic review of the literature. acta neurochir. 2012;p. 154257–65. 7. brousse c, baumelou e,mp. lymphomes osseux primitifs : étude prospective de 28 cas. revrhum. 2000;p. 67627–67635. 8. weller m, martus p, roth p, thiel e, kagpsg. surgery for primary cns lymphoma? challenging a paradigm. neuro oncol;. 9. aquilina k, o’brien df, pj. diffuse primary nonhodgkin’s lymphoma of the cranial vault. br j neurosurg. 2004;p. 18518–523. how to cite this article: kolsi f., borni m., cherif i., taallah m., charfi s., boudawara m.z. primary malignant large b-cell nonhodgkin’s lymphoma of the scalp and cranial vault: a case report and an overview. clinical medicine insights. 2022;244−249. https://doi.or g/10.52845/cmi/2022-3-1-1 meerp ltd cmi 3 (1), 244−249 (2022) 249 introduction discussion: conclusion cmi 04 (02), 378−386 cmi journal 378 clinical medicine insights doi:https://doi.org/10.52845/cmi/2023-4-2-1 cmi 04 (02), 378-386 (2023) issn (o) 2694-4626 research article efficacy and safety of neoadjuvant chemotherapy with dose de-escalation tri-weekly nanoparticle albumin-bound paclitaxel and fec for human epidermal growth factor receptor 2-positive breast cancer kazumi kawase 1,* , kazuhiko yoshida 1 , keigo hara 1 , suguru hidaka 1 , and hiroshi takeyama 2 1 department of surgery, the jikei university school of medicine katsushika medical center, tokyo, japan 2 department of surgery, the jikei university school of medicine, tokyo, japan *corresponding author: kazumi kawase introduction neoadjuvant chemotherapy (nac) is the standard treatment for early and locally advanced breast cancer because it enables less extensive surgery and provides information on treatment effects. currently, the standard treatment for breast cancer is nac consisting of an anthracycline and taxanebased regimens. the most frequently used drugs are the solvent-based paclitaxel (sb-ptx) and abstract introduction: neoadjuvant chemotherapy (nac) is widely used for human epidermal growth factor receptor 2-positive (her2 + ) breast cancer. the standard nac regimen for her2 + breast cancer is an anthracycline, followed by taxane in combination with anti-her2 drugs. however, the risk of toxicities such as cardiac dysfunction and peripheral neuropathy occasionally requires dose reduction. nanoparticle albumin-bound paclitaxel (nab-ptx) is a new taxane used in nac. the aim of this study was to examine the effects of tri-weekly low-dose nab-ptx with anti-her2 drugs followed by fluorouracil, epirubicin, and cyclophosphamide (fec) as nac in patients with her2 + breast cancer. methods: patients with operable primary her2 + breast cancer in clinical stages i–iii were enrolled in this study. the nac regimen included four courses of nab-ptx (220 mg/m 2 ) concurrently with trastuzumab (6 mg/kg) tri-weekly, followed by four courses of fec75 (5-fluorouracil: 500 mg/m 2 , epirubicin: 75 mg/m 2 , and cyclophosphamide: 500 mg/m 2 ). pathological responses, adverse events, and follow-up data at 36 months were evaluated. results: among the 20 patients enrolled, 15 completed the treatment protocol. the pathological complete response (pcr) rates were 60.0% overall and 85.7% in hormone receptor-negative/her2 + patients. at 36 months, one secondary malignancy was observed. the most frequent adverse event was peripheral sensory neuropathy (25/42, 59.5%), which persisted in four (16%) patients at 36-month follow-up. conclusions: nac with low-dose tri-weekly nab-ptx followed by fec demonstrated favorable pcr and disease-free survival. peripheral sensory neuropathy remains a concerning long-term adverse effect in some patients, even after reducing the nab-ptx dosage. keywords: albumin-bound paclitaxel, human epidermal growth factor receptor 2, neoadjuvant chemotherapy, breast cancer, peripheral neuropathy copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/lic enses/bync-nd/4.0/). https://doi.org/10.52845/cmi/2023-4-2-1 https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ cmi 04 (02), 378−386 cmi journal 379 cmi journal kazumi kawase et al. docetaxel 1 ; however, their adverse effects (e.g., peripheral neuropathy and allergic reactions) are associated with the vehicles such as polyethylated castor oil and ethanol which are used in the formulation of these drugs that limits their longterm efficacy. nanoparticle albumin-bound ptx (nab-ptx) is a solvent-free, 130 nm particle form of ptx bound to albumin, which was developed to avoid such adverse effects. although nab-ptx has been utilized as a nac in breast cancer, toxicities such as peripheral neuropathy are still observed, necessitating dose reduction to complete the treatment. 2 in addition, the long-term adverse events of nab-ptx have not been widely examined, and thus further research is required. in 2014, we conducted a single-institution phase ii clinical study (nab-ptx220 study) with reduced doses of tri-weekly q3w nab-ptx and fec (5fluorouracil: 500 mg/m 2 , epirubicin: 75 mg/m 2 , and cyclophosphamide: 500 mg/m 2 ) to assess the efficacy and safety of dose-reduced nab-ptx as an nac. herein, we report these results, along with the long-term outcomes, including the adverse effects. material and methods nab-ptx220 study design women aged ≥20 years with histologically confirmed breast cancer were included in this study. the inclusion criteria were as follows: eastern cooperative oncology group performance status of 0–1; clinical stage t1c-3, n0/m0 or t1-3, n1/m0; adequate bone marrow, liver, and kidney function; estrogen receptor (er), progesterone receptor (pgr) and human epidermal growth factor receptor-2 (her2) expression status confirmed using core needle biopsy specimens; curative surgery were performed following neoadjuvant treatment. primary lesion and lymph nodes were detected using ultrasonography, computed tomography, or magnetic resonance imaging. no history of therapy, including chemotherapy, radiotherapy, hormonal therapy, and immunotherapy and malignancy. the written informed consent were obtained from all the participants. the her2 was defined as positive according to an immunohistochemical her2 protein staining score of 3+ in >10% of tumor cells, or her2 gene was regarded as amplified when the her2/chromosome enumeration probe 17 (cep17) ratio was >2.0 in a dual-probe assay by fluorescence in situ hybridization. er and pgr were considered as positive when immunohistochemical staining showed at least 1% positivity. cancer was considered as hormone receptor (hr)-positive when either er or pgr was positive. the patients were administered four cycles of nabptx (220 mg/m 2 q3w), followed by four cycles of q3w fec without using prophylactic granulocyte colony-stimulating factor. for anti-her2 treatment, q3w trastuzumab at 6 mg/kg (8 mg/kg as the loading dose) was administered concurrently with nab-ptx for four cycles. in addition, 13 cycles of trastuzumab were administered following the surgery. toxicities were evaluated according to the national cancer institute common terminology criteria for adverse events (ctcae) version 4.0. the protocol treatment was discontinued upon observation of any adverse events such as grade 4 non-hematologic toxicity, progression of the primary tumor, or lymph node metastasis. adjuvant systemic or radiation therapy was administered as needed. this study was approved by the institutional review board of the jikei university school of medicine [25-305(7440)]. assessment the primary endpoint of the nab-ptx220 study was the pathological complete response (pcr) rate, which is defined as the absence of histological evidence of residual invasive tumor cells in the breast and axillary lymph nodes (ypt0/tisypn0). the secondary endpoint was toxicity. follow-up all patients were followed up for at least 36 months; those who completed the treatment protocol and underwent surgery (n = 15) were analyzed for long-term follow-up. relapse-free survival (rfs) was calculated as the time interval (in months) between the date of enrollment and the first observation of tumor recurrence (metastatic recurrence, local, or regional relapse), death, or last follow-up. disease-free survival (dfs) was calculated as the time interval (in months) between the date of enrollment and the first observation of tumor recurrence (metastatic cmi 04 (02), 378−386 cmi journal 380 cmi journal kazumi kawase et al. recurrence and local or regional relapse), any second malignancy, death, or last follow-up. overall survival (os) was calculated as the time interval between the date of enrollment and death or last follow-up. this part was approved separately as observational study by the institutional review board of the jikei university school of medicine [ 32-484(10577)]. statistical analysis the pcr rates of previous neoadjuvant trials with anthracycline/taxane were 31.3%–65.2%. 3, 4 we estimated the required sample size of 17 by setting an efficacy of 60%, threshold efficacy of 35%, power of 80%, and the alpha value of 0.1% (onesided) using the binomial test. all analyses were performed using spss statistical software version 24.0 (spss, inc., chicago, il, usa), and the significance level for a two-sided test was set at 0.05. rfs and os were assessed using kaplan– meier estimates, and sub-groups were analyzed using the log-rank test. results patient characteristics twenty patients were enrolled in this study. the patient and tumor characteristics are presented in table 1. table 1. patient and tumor characteristics characteristic n (%) number of patients 20 (100.0) median age (range), years 61.5 (36–77) ps 0 1 13 (65.0) 7 (35.0) ct 1 2 3 2 (10.0) 15 (75.0) 3 (15.0) cn 0 1 2 8 (40.0) 9 (45.0) 3 (15.0) stage i ii iii 1 (5.0) 15 (75.0) 4 (20.0) histology invasive ductal carcinoma 20 (100.0) er negative (<1%) positive (≥1%) 8 (40.0) 12 (60.0) pgr negative (<1%) positive (≥1%) 12 (60.0) 8 (40.0) subtype hr + hr – 9 (45.0) 11 (55.0) ps, performance status; ct, clinical t stage; cn, clinical n stage; er, estrogen receptor; pgr, progesterone receptor; hr, hormone receptor cmi 04 (02), 378−386 cmi journal 381 cmi journal kazumi kawase et al. the median age was 61.5 (36–77) years. most patients had stage ii or iii disease, 60.0% of patients had clinically positive nodes at the initiation of chemotherapy, and 45% were hr + . regarding histology, all patients presented with invasive ductal carcinoma. outcomes during the study, four patients discontinued the treatment protocol (patient decision, n = 3; liver dysfunction, n = 1). in total, 16 patients completed the protocol treatment, one of whom violated the protocol (use of prophylactic granulocyte colonystimulating factor). therefore, we assessed all patients who underwent surgery (n = 20) as the intention-to-treat group and those who completed the protocol (n = 15) as the completed protocol treatment group (fig. 1). figure 1. study flow chart. er, estrogen receptor; pgr, progesterone receptor; her2, human epidermal growth factor receptor 2; hbv, hepatitis b virus infection; ptx, paclitaxel; nab-ptx, nanoparticle albumin-bound paclitaxel; fec, fluorouracil, epirubicin, and cyclophosphamide; gcsf, granulocyte colony-stimulating factor. operative procedures and pathological responses among patients who underwent surgery following completion of the treatment protocol are presented in table 2. cmi 04 (02), 378−386 cmi journal 382 cmi journal kazumi kawase et al. table 2. surgical procedure and pathological response cpt, completed protocol treatment; itt, intention-to-treat; bp, partial mastectomy; bt, total mastectomy; sn, sentinel lymph node biopsy; ax, axillary lymph node dissection in total, 60.0% of the patients achieved pcr, with 37.5% of hr + patients and 85.7% of hr – patients achieving pcr (table 3). table 3. tumor subtype and pathological response pcr,pathological complete response; hr, hormone receptor at 36 months following study enrollment, there was only one secondary malignancy in a patient who developed acute myeloid leukemia at 30 months after enrollment. the patient was treated with chemotherapy and hematopoietic stem cell transplantation and was disease-free with pcr at 60 months of follow-up. there were two locoregional recurrences at a median follow-up of 61.5 months, one secondary malignancy, no systemic recurrence, and no death from any disease. therefore, at the 61.6-month follow-up point, rfs, dfs, and os were 90%, 85%, and 100%, respectively. achieving the pcr or hr status did not affect the rfs of dfs. toxicity overall, 95.0% (19/20) of patients experienced at least one adverse effect. the toxicity profiles are listed in table 4. cpt n (%) itt n (%) total number of patients 15 (100.0) 20 (100.0) procedure (breast) bp bt 9 (65.0) 6 (35.0) 13 (65.0) 7 (35.0) procedure (lymph node) sn ax 9 (60.0) 6 (40.0) 12 (60.0) 8 (40.0) pathological response ypt0ypn0 yptisypn0 other 5 (33.3) 4 (26.7) 6 (40.0) 6 (30.0) 5 (25.0) 9 (45.0) pathological response among n1 patients ypn+ ypn0 2 (22.2) 7 (77.8) 3 (25.0) 9 (75.0) subtype ypt+ or n+ yptisn0 ypt0n0 % pcr p hr + hr – 5 1 1 3 2 3 37.5 85.7 0.06 cmi 04 (02), 378−386 cmi journal 383 cmi journal kazumi kawase et al. table 4. toxicity adverse event all grades, n (%) grade 3,n (%) arthralgia/myalgia 13 (65.0) peripheral neuropathy 11 (55.0) 1 (5.0) constipation 6 (30.0) fatigue 5 (25.0) nausea/vomiting 4 (20.0) mucositis 4 (20.0) skin rash 3 (15.0) neutropenic fever 2 (10.0) 2 (10.0) anorexia 2 (10.0) dose reduction 4 (20.0) treatment postponement 5 (25.0) treatment discontinuation 4 (20.0) the most frequent adverse event was peripheral sensory neuropathy (psn) (11/20, 55.0%), including grade-3 neuropathy in one patient (5.0%). among patients who experienced psn, 18.2% (2/11) complained of numbness and/or paresthesia in the foot following a median time of 61.5 (37–86) months of follow-up. two patients had grade 3 neutropenic fever during the fec treatment. discussion the aim of this study was to examine the effects of q3w low-dose nab-ptx (220 mg/m 2 ) followed by fec75 (5-fluorouracil: 500 mg/m 2 , epirubicin: 75 mg/m 2 , and cyclophosphamide: 500 mg/m 2 ) as a neoadjuvant treatment for her2 + breast cancer. the results revealed an overall pcr rate of 60.0% and excellent 3-year rfs and dfs. various studies have demonstrated the efficacy of nab-ptx in metastatic or advanced breast cancer. 5–8 in the metastatic setting, q3w nab-ptx (260 mg/m 2 ) showed a superior response than sbptx 175 mg/m 2 . 7 in addition, a randomized phase ii study in which patients with previously untreated metastatic breast cancer were administered nab-ptx 300 mg/m 2 q3w, 100 mg/m 2 weekly, 150 mg/m 2 weekly, or docetaxel 100 mg/m 2 q3w, weekly nab-ptx at 150 mg/m 2 demonstrated superior efficacy and safety over docetaxel. 10 subsequently, the nab-ptx dose, and schedule in neoadjuvant settings have been evaluated in several studies. in studies on nabptx combined with anthracycline therapy, the pcr rate for breast cancer including all subtypes (hr + /her2 + , hr – /her2 + , hr + her2 – , hr + her2 – ) has been 20%–40%. 11–15 in most studies, the dose of nab-ptx used has been 260 mg/m 2 q3w or 125 mg/m 2 weekly. the pcr rates varied according to the hr and her2 status, with a high pcr rate (60%–75%) observed in her2 + patients, particularly in hr – /her2 + patients. 11,12,16 initially, we used nab-ptx 260mg/m 2 q3w, however, as many patients were required nab-ptx dose reduction to 220mg, which is recommended usage as one step dose reduction in reference to the product document, we intended to proceed this study. we found a pcr rate of 85.7% in hr – /her2 + patients, which is comparable to that in previous studies, although we used a low dose of q3w nab-ptx (220 mg/m 2 ) and fec75. the geparsepto trial was performed to compare the effectiveness of weekly nab-ptx 150 mg/m 2 (reduced to 125 mg/m 2 following study amendment) with weekly sb-ptx 80 mg/m 2 followed by ec demonstrated that patients treated with nab-ptx had a significantly better dfs than patients treated with sb-ptx. 17 in this trial, a significantly higher pcr rate was associated with a significantly improved invasive dfs, and the estimated 36-month dfs was 91.8% in the hr – /her2 + subgroup. we observed comparable results with 36-month rfs, dfs, and os of 90%, 85%, and 100%, respectively. there was no survival difference depending on the hr status or pcr status, possibly because of our small number of patients. other studies utilized more aggressive therapeutic regimens for more aggressive tumors. the cmi 04 (02), 378−386 cmi journal 384 cmi journal kazumi kawase et al. addition of pertuzumab to trastuzumab in combination chemotherapy significantly improved the survival of patients with high-risk her2 + breast cancer. 18 the study which compared dosedense chemotherapy (either ac or fec) with standard chemotherapy in conjunction with paclitaxel and trastuzumab showed little benefit in patients with her2 + breast cancer. 19 however, dose de-escalation therapy has also been suggested as a means of reducing adverse events. hence, dose de-escalation therapies were explored to reduce the adverse effects of chemotherapy. cardiac toxicity is the most serious adverse event following anthracycline and antiher2 treatment. the risk of anthracyclineinduced cardiotoxicity is dose-dependent and increases with the cumulative dose. to avoid cardiac toxicity, several studies have utilized fec75, 3, 20 which was also applied in our study. in addition, anthracycline-free regimens have been tested for the treatment of selected low-risk tumors. in the neoadjuvant setting, a japanese trial that included patients with low-risk hr – /her2 + tumors reported a pcr rate of 66.7% using an anthracycline-free regimen of nab-ptx 260 mg/m 2 with q3w trastuzumab for four cycles. 21 most studies have reported acceptable toxicity profiles in terms of adverse events associated with nab-ptx. 7,15 however, according to the drug use survey for nab-ptx conducted in japan based on the criteria for approval during 2010–2011, numerous adverse events were observed. in this survey, 934 patients were evaluated to determine the safety profiles of a q3w nab-ptx dose of 260 mg/m 2 , with adverse events observed in 92.8% of patients, the most common of which were myelosuppression and psn. 22 both these adverse events occurred frequently following the second course of treatment and were the primary reason for discontinuation. in terms of treatment schedule, grade-3 or higher adverse events were more frequently observed with weekly administration 15 and higher drug doses. 5,11,14 in the geparsepto trial, long-term follow-up of treatment-related psn led to a significant decrease in the median time to resolve psn following nabptx 125 mg/m 2 as compared to nab-ptx 150 mg/m 2 . nab-ptx combination therapy with other agents such as bevacizumab or atezolizumab resulted in a higher rate of discontinuation or reduction. 23,24 in our study, despite the low-dose administration of nab-ptx, 55.0% of patients reported psn, and 18.5% continued to be symptomatic at 36 months following chemotherapy. most studies have reported psn as reversible, whereas in our study, even low-dose ptx caused prolonged psn. although this analysis was conducted as a phase ii study, the results reflected real-world data. de-escalation treatment has also been assessed to reduce adverse events resulting from nab-ptx. in the metastatic setting, a randomized phase ii trial in japan was performed to compare three different doses of q3w nab-ptx (260 vs. 220 vs. 180 mg/m 2 ) in patients with her2 – metastatic breast cancer; the results showed that the optimal treatment dose was 180 mg/m 2 . 25 however, to date, no study of de-escalation nab-ptx has been conducted in the neoadjuvant setting. in our study, the pcr rates were 37.5% (hr + /her2 + ) and 85.7% (hr – /her2 + ) with concurrent administration of nab-ptx 220 mg/m 2 and trastuzumab, respectively, which is comparable or even better than those reported in other studies using the standard dose of anthracycline and nabptx. because of the expected improved outcomes, low-dose nab-ptx can be considered an effective chemotherapeutic agent. our study had some limitations. first, this was a single-institution study with a limited number of patients. hence, there was likely some bias. on the basis of our results, more number of patients need to be assessed. second, psn was diagnosed based on subjective assessment by patients and physicians. the extent of toxicity was assessed using the ctcae criteria; however, the toxicity estimation may have changed according to each assessor. in conclusion, nac with low-dose q3w nab-ptx followed by fec demonstrated favorable pcr rates and dfs, particularly in patients with hr – /her2 + breast cancer. psn remains a concerning long-term adverse effect in some patients, even after reducing the nab-ptx administration dose. acknowledgments: we gratefully acknowledge all patients for their participation and contributions. cmi 04 (02), 378−386 cmi journal 385 cmi journal kazumi kawase et al. references 1. abu samaan tm, samec m, liskova a, kubatka p, büsselberg d. paclitaxel’s mechanistic and clinical effects on breast cancer. biomolecules 2019; 9: 789. 2. yamada k, yamamoto n, yamada y, mukohara t, minami h, tamura t. phase i and pharmacokinetic study of abi-007, albumin-bound paclitaxel, administered every 3 weeks in japanese patients with solid tumors. jpn j clin oncol 2010; 40: 404–11. 3. buzdar au, ibrahim nk, francis d et al. significantly higher 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al. nab-paclitaxel improves disease-free survival in early breast cancer: gbg 69-geparsepto. j clin oncol 2019; 37: 2226–34. 18. von minckwitz g, procter m, de azambuja e et al. adjuvant pertuzumab and trastuzumab in early her2-positive breast cancer. n engl j med 2017; 377: 122–31. 19. lambertinim, poggio f, bruzzone m, et al. dose-dense adjuvant chemotherapy in her2positive earlybreast cancer patients before and after the introduction of trastuzumab: exploratory analysis of the gim2 trial. int. j. cancer 202;147,160–169. 20. holmes fa, hellerstedt ba, pippen j et al. five-year results of a phase ii trial of preoperative 5-fluorouracil, epirubicin, cyclophosphamide followed by docetaxel with cmi 04 (02), 378−386 cmi journal 386 cmi journal kazumi kawase et al. capecitabine (wtx)(with trastuzumab in her2-positive patients) for patients with stage ii or iii breast cancer. cancer med 2018; 7: 2288–98. 21. tanaka s, matsunami n, morishima h et al. de‑escalated neoadjuvant therapy with nanoparticle albumin‑bound paclitaxel and trastuzumab for low‑risk pure her2 breast cancer. cancer chemother pharmacol 2019; 83: 1099–104. 22. nakamura s, iwata h, funano y, ito k, ito y. results of a drug use investigation of nanoparticle albumin-bound paclitaxel for breast cancer. gan to kagaku ryoho 2015; 42: 447–55 (in japanese). 23. rugo hs, barry wt, moreno-aspitia a et al. randomized phase iii trial of paclitaxel once per week compared with nanoparticle albumin-bound nab-paclitaxel once per week or ixabepilone with bevacizumab as first-line chemotherapy for locally recurrent or metastatic breast cancer: calgb 40502/ncctg n063h (alliance). j clin oncol 2015; 33: 2361–9. 24. schmid p, adams s, rugo hs et al. atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. n engl j med 2018; 379: 2108–21. 25. tsurutani j, hara f, kitada m et al. randomized phase ii study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer. breast 2021; 55: 63–8. cmi 04 (03), 393−395 cmi journal 393 clinical medicine insights doi:https://doi.org/10.52845/cmi/2023-4-3-1 cmi 04 (03), 393-395 (2023) issn (o) 2694-4626 short communication spontaneous hematoma of the renal pelvis: diagnostic and therapeutic difficulties nizar cherni 1 , abdallah chaachou 1 , wael ferjaoui 2 * , samir ghozzi 1 , mohamed dridi 1 , 1 department of urology, military hospital of tunis 2 department of general surgery, military hospital of tunis *corresponding author: wael ferjaoui introduction spontaneous haematomas of the kidney are rare. they pose two problems: the first is their aetiology, in which tumour pathology is dominant, and the second is their management. through a series of 7 cases of spontaneous hematoma of the kidney, we discuss the role of imaging in the etiological diagnosis and the management of this condition. material and methods: seven cases of spontaneous kidney haematoma were managed between december 2020 and january 2023. these were 5 women and 2 men, with a mean age of 61 years. discussion: the first case of hsr was described in 1856 by wunderlich, since when hundreds of cases have been reported in the literature. the clinical symptomatology varies according to the duration and extent of the bleeding. the typical clinical picture is represented by the lenk triad: back pain, signs of bleeding and a retroperitoneal mass [3, 4, 7]. ultrasound shows a peri-renal fluid collection, sometimes septated, without being able to make an accurate diagnosis of peri-renal haemorrhage. indeed, the peri-renal haematoma may be interpreted as a tumour or a renal abscess. the etiology of the haematoma is even more difficult to detect on ultrasound [2, 3, 5]. ct is the gold standard for diagnosis and our observations confirm these data [2-5, 7]. on images without injection, the haematoma has the same density as the renal parenchyma and merges with the shadow of the latter, which is more or less enlarged and deformed, surrounded by perirenal fat. after injection of contrast medium, the density of the renal parenchyma is enhanced and the haematoma, which does not change, appears well delimited [2, 3, 5]. the ct scan can also be used to study the renal parenchyma in contact with the haematoma in search of a possible tumour lesion or vascular malformation. however, the tumour may go unnoticed when its volume is small and aneurysms are only visible when they are large [2, 3, 5, 7]. because of its richness in contrast and its multiplanar approach, mri is more effective than ct in confirming the haemorrhagic nature of the collection and in visualising small tumours [3]. the role of arteriography in retroperitoneal haematomas is still debated in the literature [2, 7]. when the bleeding is active, arteriography can be used for embolisation. copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/lic enses/bync-nd/4.0/). https://orcid.org/0000-0002-4279-9370 https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ cmi 04 (03), 393−395 cmi journal 394 cmi journal wael ferjaoui et al. there are many different causes of spontaneous haematomas of the renal pelvis. kidney tumours are responsible in 61.2% of cases. these tumours are most often benign (31.5% of cases), dominated by angiomyolipomas. malignant tumours represent 29.7% of cases and are dominated by clear cell cancers. the other aetiologies are represented by the following vascular diseases causes in 17% of cases, dominated by periarteritis nodosa, infectious causes in 2.4% of cases, spontaneous rupture of a cyst, nephrosclerosis, pre-eclampsia. sometimes no cause is found (6.7% of cases) [5, 6]. the treatment is conditioned by the patient's clinical condition and the results of imaging and in particular the ct scan. in the case of a patient in shock, surgical exploration or arteriography with arterial embolisation is urgently required. in other cases, treatment should be considered at a distance from the haemorrhagic episode, at best the second week after the haematoma occurred, as spontaneous haemostasis has taken place and the clots are not yet organised. when the haematoma is secondary to a kidney tumour, extended nephrectomy is required. if the haematoma is secondary to a benign cause, simple monitoring of haematoma resorption can be considered. however, in the absence of an obvious cause, the choice between radical surgery or conservative treatment is not well defined [2, 3, 5, 7, 8]. some authors believe that simple surveillance may be sufficient. in this case, a repeat imaging study (ct +/mri) should be carried out at a distance. after 6 to 8 weeks, the haematoma has reabsorbed so that a tissue lesion can be found. appropriate surgical treatment will then be considered. evacuation of a large haematoma avoids the transition to abscessation and compressive phenomena leading to the progressive destruction of the kidney. other authors prefer nephrectomy because of the risk of underlying cancer [2, 4, 7]. figure 1: mri: upper polar renal mass with peri-tumoral haemorrhage figure 2: mri: perirenal haematoma with mass effect on the rest of the renal parenchyma. cmi 04 (03), 393−395 cmi journal 395 cmi journal wael ferjaoui et al. figure 3. uroscanner: right perirenal haematoma, and mid-renal tissue mass. conclusion: spontaneous hematoma of the renal pelvis poses problems in etiological diagnosis and management. the ct scan is the best examination to confirm the diagnosis but it can sometimes be misleading. arteriography should be performed whenever the ct scan is not conclusive, in cases of vascular pathology and in cases of angiomyolipoma with active bleeding. the treatment of choice remains nephrectomy if the tumour is malignant in appearance or if there is any doubt about the nature of the lesion. for benign lesions and in the absence of causes found after surgery, treatment is conservative. the fear of an undetected tumour requires close and prolonged surveillance. references: 1. wunderlich c. r. a. handbuch der pathologie und thérapie. 2nd ed. stuttgart: ebnert seubert, 1856. 2. mantel, l. sibert, d. thoumas, c. pfister, j. g. guerin, p. grise. hématomes spontanés de la loge rénale: stratégie diagnostique et thérapeutique. progrès en urologie. 1996, 6, 409-414. 3. h. boumdin, a.ameur, m. lazrek, d. atioui, a. beddouch, a. idrissi oudghiri. hématomes spontanés sous capsulaires du rein. a propos de 6 cas. annales d’urologie 36 (2002) 357360. 4. lallemand, o. dumont. hématome péri rénal spontané causé par un adénome rénal. progrès en urologie 2002, 12, 474-476. 5. f. dubosq, o. traxer, v. estrade, m. tligui, f. haab, p. thibault, b. gattegno. hématomes spontanés du rein: conduite à tenir diagnostique et thérapeutique. a propos de 7 cas. progrès en urologie 2004, 14, 295-301. 6. j. q. zhang, j.r. fielding, k. h. zou: etiology of spontaneous perirenal hemorrhage: a méta-analysis. j. urol., 2002; 167: 15931596. 7. benchekroun, m. alami, m. ghadouane, e. kasmaoui, m. marzouk, m. faik. hématome spontané sous capsulaire du rein d’origine non tumorale (à propos de cinq cas). progrès en urologie 2001, 11, 523-527. 8. s. m. mandouni, i. en nia, j. j. patard, b.lobel, f. guillé. l’embolisation artérielle dans les angiomyolipomes rénaux hémorragiques. progrès en urologie 2001, 11, 235-238. clinical medicine insights received 15 sep 2021 | revised 20 oct 2020 | accepted 25 nov 2020| published online 15 dec 2020 doi: https://doi.org/10.52845/cmi/2020-1-1-06 cmi journal 1 (1), 34−49 (2020) issn (o) 2694-4626 review article smoking and non-communicable diseases: part i cardiovascular diseases, respiratory diseases, obesity, depression, liver diseases shashi k. agarwal, md ∗ 12227 us highway 1, #309 north brunswick, nj 08902, usa abstract smoking tobacco is popular all over the world. it is however full of toxic chemicals, with many of them being carcinogenic. these chemicals affect every organ in the human body, leading to a wide array of disorders. this results in considerable suffering. frequent disability, and premature mortality. it is estimated that smokers lose several years of healthy life. smoking hookah or e-cigarettes is also harmful. smoking remains the number one preventable cause of several noncommunicable diseases. keywords: smoking, non-communicable diseases, cardiovascular diseases, respiratory diseases, obesity, depression, liver diseases copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). 1 introduction tobacco smoking is a major modifiable risk factor for a wide array of diseases1. besides nicotine, tobacco smoke also contains several thousand chemical compounds, either gaseous or particulate, and many of these are toxic2. in addition to the major non-communicable diseases discussed in this two-partmanuscript, tobacco smoke has been associated with complications of pregnancy and sudden infant death syndrome3. infants exposed to cigarette smoke either prenatal or after birth also increase their risk of orofacial clefts, periodontal disease, and dental caries4. smoking increases the risk of dental implant failure5. it also enhances aging, causing premature wrinkles6. it is estimated that 16 million adults are currently living with smokingrelated diseases in the united states7. smoking cessation reduces the risk of major chronic diseases8. cessation also helps reduce the severity of supplementary information the online version of this article (10.52845/cmi/2020-1-1-06) contains supplementary material, which is available to authorized users. corresponding author: shashi k. agarwal, md shashi k. agarwal, md 2227 us highway 1, #309 north brunswick, nj 08902, usa email: usacardiologist@gmail.com cmi journal 1 (1), 34−49 (2020) meerp ltd 34 open access journal https://doi.org/10.52845/cmi/2021-2-3-12 https://orcid.org/0000-0003-0007-5582 https://creativecommons.org/licenses/by-nc-nd/4.0/ mailto:usacardiologist@gmail.com https://medicineinsights.info/index.php/cmi/index meerp ltd shashi k. agarwal, md the disease9, improves the quality of life10, increases disease-free life11, and augments life expectancy12. smoking is the leading preventable cause of death worldwide13. 2 discussion cdc defines chronic diseases as “conditions that last 1 year or more and require ongoing medical attention or limit activities of daily living or both”14. most chronic diseases are noncommunicable. the five major diseases discussed in this part are cardiovascular diseases (cvd), respiratory diseases, obesity, depression, and liver diseases. cvds include coronary heart disease, high blood pressure (bp), stroke, heart failure, cardiac arrhythmias (including sudden cardiac death), peripheral arterial disease, deep vein thrombosis, and vasculogenic erectile dysfunction. they are a leading cause of morbidity and mortality, globally15. smoking remains the main modifiable lifestyle factor responsible for most of these diseases16. even low-tar cigarettes and smokeless tobacco have been shown to increase the risk of cardiovascular events in comparison to nonsmokers17. the main respiratory diseases are chronic obstructive pulmonary disease (copd), asthma, respiratory infections, and cancer. copd is a progressive and debilitating disease that causes a decline in lung function leading to cor-pulmonale, respiratory failure, and premature death18. it is responsible for over 3 million deaths annually19. the world health organization (who) predicts that copd will be the third leading cause of death, worldwide, in 203020. obesity is a pandemic and is associated with increased morbidity and mortality21. bodyweight classification is generally based on the calculation of body mass index (bmi)22. normal bmi is 18.5– 24.9 kg/m2, overweight is a bmi 25 to 29.9 kg/m2, and obesity is a bmi >30 kg/m223. central obesity (visceral or abdominal obesity) often confers worse health effects, even with a normal bmi24. this type of obesity can be determined by waist circumference, waist hip-ratio, or waist-height ratio25,26. depression is characterized by sadness, loss of interest and pleasure, feelings of guilt, feeling of worthlessness, low appetite, fatigue, and poor concentration27. it is estimated that it affects 350 million people worldwide28. depression increases the risk of physical ailments, especially cardiovascular diseases29. the global burden of disease study 2016 reported that depression is a major cause of disability30. it also increases suicide and all-cause mortality31. liver diseases are on the rise worldwide and are responsible for a considerable amount of morbidity and mortality32. they include non-alcoholic fatty liver (nafld), alcoholic liver disease, cirrhosis, and liver cancer33. hepatocellular carcinoma is highly lethal, with less than 10% living beyond 5 years34. cardiovascular diseases cigarette smoking is a major cause of cvds35. most cvds are due to atherosclerosis36. smoking accelerates this process by several mechanisms, including activation of inflammatory factors, dysregulation of the lipid metabolism, an increase in oxidative stress, and causing endothelial dysfunction37−39. smoking acutely elevates blood pressure40 through the stimulation of the sympathetic nervous system41. it also increases the risk of renovascular42, malignant43, and masked hypertension44. the causal impact of smoking on chronic hypertension is however unclear45. passive smoking has been associated with an increased risk of hypertension among adults46. several epidemiologic studies have indicated that there is an increase in the incidence of myocardial infarction and fatal coronary artery disease with smoking47,48. smoking raises the risk of coronary plaque rupture47, and this generates thrombosis at the site48. smoking is also associated with an increase in coronary spasms49,50. passive smoking also increases the risk of coronary artery disease51. in a metaanalysis of 29 prospective cohort studies, aune et al. found that smoking increased the relative risk of heart failure by 44%52. lu et al. confirmed this increased propensity in a recent mendelian randomization analysis study53. cigarette smoking is causally connected with 12.4% of acute strokes54. pre-stroke smoking also appears to worsen its prognosis when compared to never smokers55. smoking is also directly associated with a more than a twofold increased risk of atrial fibrillation56. smoking cessation lowers this risk56. sudden cardiac death meerp ltd cmi journal 1 (1), 34−49 (2020) 35 smoking and non-communicable diseases: part i cardiovascular diseases, respiratory diseases, obesity, depression, liver diseases is usually due to ventricular arrhythmias57, and this is also increased in smokers58. smoking has been linked with an increase in the risk of peripheral artery disease59,60 and abdominal aortic aneurysms61,62. smoking cessation is associated with a reduced rate of aneurysmal growth63. smoking can induce erectile dysfunction64 through multiple pathways, with disturbed nitric oxide signal transduction pathway being the main one65−68. smokers are also at an increased risk of venous thromboembolism69. this risk is partially increased by physical inactivity70 and the occurrence of smoking-related diseases in these patients71. smoking cessation reduces cardiovascular events72. it reduces these risks and mortality even if cessation happens after the development of a cvd73. smoking promotes atherosclerosis via vasomotor dysfunction, increased inflammation, and modification of lipids74. it also enhances thrombosis, via prothrombotic alterations in platelet function, antithrombotic/prothrombotic activity, and fibrinolytic factors75. respiratory diseases cigarette smoking is a major cause of copd76,77. copd is one of the most common and dangerous noncommunicable health disorders78. the lifetime risk for smokers getting copd is estimated to be over 20%79, with one recent study estimating the risk to be as high as 50%80. passive smokers are also at an increased risk of developing copd81. copd smokers, both current and past, exhibit an increased risk for lung cancer, cvds, and diabetes mellitus82−84. smoking cessation, especially at an early age, greatly helps reduce the symptoms and the rate of pulmonary function decline in these patients85,86. their quality of life also improves87, and mortality is reduced88. besides copd, asthma is also a major disease affecting the respiratory tract89. smoking increases the risk of developing asthma by 33% to 81%, when compared to nonsmokers90. continued smoking also increases the incidence of exacerbations and poor control in these patients91. it can also lead to a more severe pulmonary disease like copd92. second-hand smoke exposure, especially in children, also exacerbates asthma-related hospitalizations93,94. smoking has also been associated with chronic bronchitis and several interstitial lung diseases85,96. it is estimated that almost 90% of lung cancers are related to smoking97. secondhand smoke exposure also increases the risk of lung cancer in non-smokers98. smokers are alsomore susceptible to bacterial and viral pulmonary infections99−101. these include viral influenza and tuberculosis99,100. smoking also increases the risk of acute respiratory distress syndrome in covid infections101. tobacco smoke affects the lungs in several ways – it induces oxidative stress and apoptosis102−104, increases secretions from mucous glands105,106, and alters the histologic alveolar histology107,108. epigenetic factors may also be involved109. obesity the relationship between smoking and obesity is complex and published reports provide conflicting results110−112. while some studies have shown no significant association between smoking status and bmi110, others have suggested that smoking may be associated with lower bmi111 and smoking cessation with an increased bmi112. most individuals believe that smoking helps weight loss113−115, and fear of weight gain is often a cause of relapse among former smokers116. both smokers and nonsmokers believe that smoking is an efficient way to control body weight117. most scientific studies confirm that lower adiposity is common among active smokers118,119. nicotine acutely increases energy expenditure120 and may also help reduce appetite121,122. further, scientific studies find that former smokers have a higher level of obesity123, mainly due to an increase in bmi following smoking cessation124−126, thereby validating the smokers’ bias. however, current smokers tend to have a higher visceral (abdominal) obesity than non-smokers127−129. cat scans reveal higher levels of visceral adiposity to subcutaneous adipose tissue ratio in smokers130. second-hand smoke exposure also increases obesity, with adolescents having an increased 1.19 odds of obesity than those with no exposure to secondhand smoke131. in a study includingmore than 10million participants from 239 prospective studies, all-cause mortality was minimal for persons with bmi between 20 and 25; however, each 5-unit increase in bmi above 25 was associated with a 49%, 38%, and 19% higher risk of mortality, respectively132. therefore, there is a concern that cmi journal 1 (1), 34−49 (2020) meerp ltd 36 meerp ltd shashi k. agarwal, md weight gain after smoking cessation could increase the risk of chronic diseases and potentially attenuate the benefits of quitting smoking133. however, given the serious deterioration of health from smoking, the net effect is still better health outcomes after smoking cessation134. depression individuals with mental health conditions smoke more heavily135 and experience up to 18 years of reduced life expectancy when compared with the general population136. this major decrease in longevity is primarily due to premature mortality from smoking-related diseases137. depression is strongly linked with smoking – and this relationship is bidirectional138. in the national longitudinal study of adolescent health from the united states, goodman and capitman found that smoking in adolescents resulted in a higher risk of developing depressive symptoms139. in an australian casecontrol study, the age-adjusted odds ratio (or) for smoking more than 20 cigarettes per day and developing depression, was 2.18140. in a multinational study (who’s study on global ageing and adult health), the or for smoking associated with incident depression was 2.06141. in another study, current smokers who smokedmore than 20 cigarettes per day had the highest risk of developing depression142. a more recent systematic review of 148 studies, also found a positive association between smoking and depression143. another recent large study involving 10,036 individuals (gutenberg health study), found that current smoking was predictive of new-onset depression, with an or of 1.35144. secondhand smoke also increases the risk of depression, in children145, adolescents146, and adults147−149. this relationship is dose dependent150. depressed people also smoke more151−154. it is estimated that in the united kingdom, up to 31% of individuals with depression smoke151 while only 14% of the general population does152. depressed patients are more likely to increase their smoking over time153, and those who continue to smoke experience worse depressive symptoms compared to their abstinent counterparts154. liver diseases smoking is associated with worse outcomes in patients with nafld155,156. they are more apt to develop liver fibrosis155 and primary biliary cirrhosis156. patients with hepatitis b (hbv) who smoke increase their risk for hepatocellular cancer (hcc)157. smoking is also harmful to individuals with hepatitis c (hcv), increasing the risk of steatosis, fibrosis, and hcc158,159.tobacco smoking has been shown to delay wound healing post-liver transplant160 and to significantly increase vascular complications in these patients161. hcc is also more common in smokers162. lee et al. calculated that the relative risk ratio was 1.51 for this increased incidence, after conducting a metaanalysis of 38 cohort studies and 58 case-control studies, and after adjusting for hbv infection, hcv infection, and alcohol consumption163. smoking also increases hcc related mortality164. besides the multitude of carcinogens found in cigarette smoke, one chemical, 4-aminobiphenyl, has been specifically shown to increase the risk of hcc165. tobacco smoking has also been implicated in the reduction of p53, a tumor-suppressing gene and a common pathway of oncogenesis for many neoplasms166. alcohol is extremely harmful to the liver167. almost 90% of alcoholics smoke and most of them smoke at least one pack of cigarettes per day168. chronic smokers are also more likely to consume alcohol in excess169. smoking is also harmful in patients needing liver transplantation – a poor lung function often precludes liver transplantation170. following transplantation, smoking increases the risk of de novo malignancy171, vascular complications172, and non-graft-associated mortality173. 3 conclusion tobacco is highly addictive and extremely harmful. it increases the risk of developing and worsening the progression of several non-communicable diseases, including cardiovascular, respiratory, and liver diseases. it is also detrimentally associated with obesity and depression. there is no safe level of tobacco exposure including second-hand and third-hand exposure. smoking cessation can be achieved and is associated with alleviation of symptoms, decrease in meerp ltd cmi journal 1 (1), 34−49 (2020)) 37 smoking and non-communicable diseases: part i cardiovascular diseases, respiratory 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ltd cmi journal 1 (1), 34−49 (2020) 49 introduction discussion conclusion cmi 03 (03), 330−337 manuscript central 330 clinical medicine insights doi: https://doi.org/10.52845/cmi/2022-3-3-3 cmi 03 (03), 330−337 (2022) issn (o) 2694-4626 research article open access journal comparison of the efficacy and safety of succrosomial iron and elementar iron supplementation to treat iron deficiency and iron deficiency anemia in preschool children (3-6 years): protocol of a randomized clinical trial. katarzyna kozikowska 1,2 , wojciech bartmiński 3 , adam j. sybilski 1,2 corresponding author: katarzyna kozikowska 1 2nd department of paediatrics, centre of postgraduate medical education, warsaw, poland 2 department of paediatrics and neonatology, central clinical hospital of the ministry of the interior, warsaw, poland 3 family medicine clinic¸ central clinical hospital of the ministry of the interior, warsaw, poland abstract children are particularly vulnerable to iron deficiency and its consequences. the estimated prevalence of anemia in the world population is about 40%. according to who, 47% of preschool children and 25% of school-age children suffer from iron deficiency anemia. results of ongoing studies indicate that iron deficiency and anemia in children may impair their further development, both neurological and motor. the treatment of choice for iron deficiency and iron deficiency anemia is prolonged administration of oral iron preparations. iron ions not absorbed from the intestine determine frequent adverse effects, which become a reason to abandon therapy with the prolongation of supplementation. our study was designed to compare the efficacy of succrosomal and elemental iron supplementation in the treatment of iron deficiency and iron deficiency anemia in children aged 3-6 years by evaluating iron metabolism parameters. we also planned to assess the side effects of the studied supplements, the efficacy of the therapy with a single daily dose and the analysis of the occurrence and subsidence with the supplementation of clinical symptoms of iron deficiency or iron deficiency anemia in children aged 3-6 years. this is the single-center randomized comparative study. a total of 100 patients were planned to be enrolled in the study. iron supplementation will be administered for 12 weeks. the primary aim of the study is to demonstrate that the effect of the application of succrosomal iron preparation is not worse than in the case of the application of elemental iron. the secondary objectives are to evaluate the adverse effects of the compared preparations, the efficacy of iron supplementation administered in a single daily dose and assess the occurrence and treatment-related resolution of iron deficiency symptoms and iron deficiency anemia in the study population. key words: anemia, iron, iron deficit, children, supplementation copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/lic enses/by-nc-nd/4.0/). https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ cmi 03 (03), 330−337 manuscript central 331 manuscript central katarzyna kozikowska et al. introduction children are particularly vulnerable to iron deficiency and its consequences. a clinically latent iron deficit initially develops in deficiency conditions, followed by microcytosis with normal hemoglobin concentration, and the final stage is anemia [1]. the estimated prevalence of anemia in the world population is about 40% [2]. almost 80% of all cases are iron deficiency anemia [3]. it is estimated that 1.224 billion people worldwide suffer from it [4]. according to who, 47% of preschool children and 25% of school-age children suffer from iron deficiency anemia [5]. iron requirement during this period is high and difficult to cover with diet. results of ongoing studies indicate that iron deficiency and anemia in children may impair their further development, both neurological and motor [6,7,8]. the treatment of choice for iron deficiency and iron deficiency anemia is prolonged administration of oral iron preparations. the bioavailability of commonly used products is limited [9,10]. iron ions not absorbed from the intestine determine frequent adverse effects, which become a reason to abandon therapy with the prolongation of supplementation. studies conducted on tissue models indicate that intestinal absorption of succrosomal iron is nearly 3.5 times higher than previously used preparations [11]. in studies conducted to date, the efficacy of succrosomal iron is comparable, with a favorable safety profile. available studies indicate that using a lower dose of the preparation allows achieving a similar therapeutic effect with fewer reported side effects. so far, no studies have been published comparing the efficacy of succrosomal iron supplementation with elemental iron in children. study design hypotheses posed the study was designed to compare the efficacy of succrosomal and elemental iron supplementation in the treatment of iron deficiency and iron deficiency anemia in children aged 3-6 years by evaluating iron metabolism parameters. the primary objective is to demonstrate that the effect of succrosomal iron in the study population is no worse than the standard recommended elemental iron. we also planned to assess the side effects of the studied supplements, the efficacy of the therapy with a single daily dose and the analysis of the occurrence and subsidence with the supplementation of clinical symptoms of iron deficiency or iron deficiency anemia in children aged 3-6 years. material and methods study site and randomization procedure the single-center randomized comparative study will be conducted at the 2nd department of pediatrics of the medical center for postgraduate education of the central clinical hospital of the ministry of internal affairs and administration in warsaw. patients will undergo block randomization. the study compares two groups of patients: those supplementing with succrosomal iron (group 1, study group) and those receiving elemental iron (group 2, control group). it is planned to analyze the response to treatment in subgroups: patients diagnosed with isolated iron deficiency and iron deficiency anemia. study group sample size anticipating future statistical analysis and patients lost to follow-up, a total of 100 patients were planned to be enrolled in the study. inclusion criteria  age 3 to 6 years  iron deficiency assessed by hematological parameters according to who standards  iron deficiency anemia detected by hematological markers according to who standards exclusion criteria  severe anemia (hemoglobin -2 sd from the age-standard)  iron deficiency due to probable blood loss  anemia due to other causes, including genetic disorders (e.g., thalassemia, hemolytic anemia, etc.)  intravenous iron administration or blood transfusion within the past three months  current acute infection (time criterion) cmi 03 (03), 330−337 manuscript central 332 manuscript central katarzyna kozikowska et al.  history of intestinal malabsorption  coexisting chronic diseases except for asthma and allergies  intolerance to orally administered preparations regardless of the cause  prematurity with birth age <35 hbd  low birth weight <2500 g  child from a multifetal pregnancy  obesity (bmi > 90 pc according to who percentile grid)  iron supplementation (time criterion) randomization and blinding the study participants will be randomly assigned to one of two groups a succrosomal iron supplement group or an elemental iron supplement group. a diagnosis of iron deficiency or iron deficiency anemia in a child cannot be left untreated, so the placebo control group is waived. it is assumed that an even distribution of patients diagnosed with iron deficiency and iron deficiency anemia is achieved using block randomization within the groups. because of the need to calculate the individual dose of treatment, blinding will be done only for patients. intervention iron supplementation will be administered for 12 weeks. weight-adjusted iron will be administered daily in a single daily dose. study design study participants will undergo a systematic evaluation. the initial assessment will include a physical examination and laboratory tests: peripheral blood count, reticulocyte count, serum ferritin and iron levels, tibc, transferrin, transferrin saturation, crp. follow-up evaluation after 4, 8, and 12 weeks was scheduled. each assessment included a physical examination and laboratory tests: peripheral blood count, reticulocyte count, serum ferritin and iron concentration, tibc, transferrin, transferrin saturation, crp. duration of study the planned duration of iron supplementation in all patients is 12 weeks. the study is designed to end three months after the inclusion of the last participant. shortening the time of observation of individual patients could occur in the lack of improvement or worsening of hematological status during the observation or occurrence of adverse events, preventing further participation in the study. endpoints of the study the primary aim of the study is to demonstrate, based on the assessment of the change in hematological parameters, that the effect of the application of succrosomal iron preparation in the population of preschool children with diagnosed iron deficiency or iron deficiency anemia is not worse than in the case of the application of elemental iron. the secondary objectives are to evaluate the adverse effects of the compared preparations, the efficacy of iron supplementation administered in a single daily dose and assess the occurrence and treatment-related resolution of iron deficiency symptoms and iron deficiency anemia in the study population. upon completion of the study, the collected data will be summarized and statistically analyzed. reporting of adverse reactions according to the current who definition, an adverse reaction is defined as any untoward symptom or condition associated with using an investigational product in a patient. adverse effects occurring in connection with supplementation of the compared iron preparations, their frequency and severity, will be analyzed based on questionnaire data. severe and healthor life-threatening side effects of therapy to participants will be reported according to local requirements and practice. dropout a subject who develops circumstances that make it impossible to continue in the study will be dropped from the study. this applies particularly to the serious adverse events development, the lack of therapy effectiveness, or unsatisfactory patient compliance. withdrawal and discontinuation you have the right to refuse to participate in the study or to withdraw from it at any time. patients who do not complete the study, regardless of the reason, will not be included in the statistical cmi 03 (03), 330−337 manuscript central 333 manuscript central katarzyna kozikowska et al. analysis. withdrawal due to adverse reactions to therapy is a separate category. all adverse reactions observed during the conduct of the study will be included in the final analysis, regardless of whether or not they affected the conduct of supplementation according to the study protocol. discussion iron deficiency is the most common single nutritional deficiency worldwide. the most common form of anemia is iron deficiency anemia, affecting 20% of the population [12]. it results from systemic iron deficiency and is its final stage [13]. certain populations are particularly vulnerable to iron deficiency and the anemia caused by it, including children. the prevalence of isolated iron deficiency in children is estimated to be 27-48%, depending on the country [14-17]. iron deficiency anemia affects approximately 5% of children [16-24], but is estimated to be much more common [15,25,26]. we chose to study a population of children aged 3-6 years with a diagnosis of iron deficiency or iron deficiency anemia because of the high prevalence of the condition in this group. in addition, the registration indication for succrosomal iron includes patients older than three years of age. to date, there have been no studies comparing the efficacy of supplementation of different oral iron preparations. therefore, we intend to compare the efficacy of succrosomal iron supplementation with the current standard, elemental iron, in the study we designed. the use of block randomization will allow us to obtain an even distribution of patients with iron deficiency and iron deficiency anemia in the study groups. because of the need to calculate the individual dose of preparation, blinding will only be done on patients. in our study, the diagnoses of iron deficiency and iron deficiency anemia will be established based on who criteria. the diagnosis of isolated iron deficiency is made based on the measurement of plasma ferritin concentration. the values taken as the norm vary from author to author. some investigators consider a concentration of <10 ug/l as the lower limit of the norm [14,15]. however, most analyses take a concentration of <12 ug/l as the lower limit of normal [16,22]. because of this, in our work we will qualify iron deficiency as a decrease in plasma ferritin concentration below 12 ug/l. ferritin belongs to the group of positive acute phase proteins its concentration should be analyzed in conjunction with inflammatory markers. in our study, as in other authors, the presence of inflammation will be excluded by measuring the concentration of c-reactive protein (crp). iron deficiency anemia is diagnosed when the hemoglobin level is two standard deviations below what is considered normal. in children, normal hemoglobin concentrations vary according to gender and age. in the population of preschool children, normal values are identical for both sexes. according to who, in the population of preschool children, anemia is diagnosed with a hemoglobin concentration <11 g/dl. the sole determination of hemoglobin concentration is not sensitive and specific enough to diagnose iron deficiency anemia. mcv, mch, mchc, tibc and ferritin concentration should also be determined. on the other hand, according to the american academy of pediatrics guidelines, a complete iron assessment in a given patient should include the measurement of hemoglobin, ferritin, hemoglobin in reticulocytes (chr) and soluble receptor for transferrin type 1. chr is considered the most decisive and most sensitive marker of systemic iron deficiency [8,27]. the parameter reflects the pool of iron available to young rbc forms in the bone marrow. it is independent of inflammation and validated in children, but it is unavailable in most laboratories in polish conditions. chr will not be evaluated in our work, but it seems that a surrogate parameter for chr may be mch, which will be determined in all patients [28]. the soluble receptor for transferrin type 1 concentration reflects iron deficiency at the cellular level. the parameter has only been determined in adults, we do not have a range of standards, and we will not evaluate it. considering the above, in the planned study we will diagnose iron deficiency anemia based on the finding of decreased hemoglobin <11 g/l and ferritin <12 ug/l (with negative crp) with additional assessment of mcv, mch, mchc and tibc. cmi 03 (03), 330−337 manuscript central 334 manuscript central katarzyna kozikowska et al. after completion of supplementation of the compared iron preparations, based on the analysis of the change in hematological exponents in the study groups, we expect at least an equal increase in hematological exponents. oral iron supplementation is recognized as effective and safe management. the current regimens are based on administering an individually calculated daily dose in two or three parts. in isolated iron deficiency the recommended dose of elemental iron is 1-2 mg/kg b.w., in anemia 4-6 mg/kg b.w. intestinal absorption of iron from most oral preparations is 10-15%. limited absorption forces the administration of higher doses to achieve the intended therapeutic effect. unabsorbed iron ions are probably responsible for side effects of the therapy [29,30,31]. currently, lower daily doses are proposed to be administered at one time [32]. this treatment is supposed to be equally effective, with a lower risk of side effects and better patient compliance. in most patients, the recommended duration of therapy sufficient to saturate body iron reserves is three months. in iron deficiency, systemic reserves are used up first, followed by tissue reserves, so that the pool available for hematopoiesis remains unchanged for as long as possible. with supplementation, normalization of hematological parameters occurs rapidly an increase in reticulocytosis can be observed after 710 days and complete normalization of hemoglobin concentration after several weeks of therapy. the reserve pool, measured by plasma ferritin concentration, is rebuilt on average after three months, therefore the total time of supplementation in our study will be 12 weeks with three assessments of iron metabolism exponents before the end of supplementation. some patients discontinue supplementation prematurely due to side effects. the efficacy of such therapy is temporarily limited. on the other hand, once the reserve iron pool is replenished, iron administration does not benefit the patient and may be harmful. iron supplementation in patients without established deficiency may be potentially toxic [33, 34]. in our study, the total duration of supplementation will be 12 weeks. a follow-up evaluation of patients after 4, 8 and 12 weeks of treatment is planned. a 1 g/dl increase in hemoglobin after two weeks of supplementation is considered an adequate response to treatment. cyclic evaluation of patients in the project aims to trace the dynamics of changes in hematological parameters in the study groups and evaluate the adverse effects of supplementation. we will compare the efficacy of succrosomal iron with elemental iron in patients aged 3-6 years with diagnosed iron deficiency and iron deficiency anemia because of the high prevalence of the condition in this group and the limited efficacy of therapy with commonly used preparations. the too short duration of supplementation is responsible for the failure of standard therapy in most cases [35]. side effects of chronically taken iron supplements for some patients are the reason for premature discontinuation of therapy. the results of studies conducted so far with the use of succrosomal iron indicate that it is at least as effective as the previously used preparations, and the side effects are less frequent and less severe [36]. intestinal absorption of most iron preparations is 10-15%. achieving the intended therapeutic effect requires administering the higher dose of the preparation to the patient, the greater the deficit found initially. iron ions not absorbed from the gastrointestinal tract are responsible for side effects. it has been shown that in contrast to previously used products, succrosomal iron is absorbed along the entire length of the intestine [36, 37]. transport of iron ions occurs not only via the conventional pathway using a protein transporter in the membrane of the enterocyte but also via the transcellular and intercellular route [38]. when used in the succrosomal formulation, encapsulation of iron in microcapsules limits the release of iron ions in the intestinal lumen and promotes the formulation of an additional reserve pool available for increased demand within the enterocytes. in patients with refractory anemia resulting from chronic kidney disease, the use of succrosomal iron was comparably effective as repeated intravenous iron injections [39]. in patients with anemia secondary to malabsorption after bariatric surgery, succrosomal iron administration was as effective as intravenous iron preparations [40]. available data do not indicate the occurrence of serious or life-threatening adverse effects after the use of oral iron preparations, but their intake is not free of side effects. gastrointestinal symptoms such as abdominal pain, vomiting, or constipation cmi 03 (03), 330−337 manuscript central 335 manuscript central katarzyna kozikowska et al. are the most common, and tooth discoloration or rash may also occur [41]. iron supplementation with succrosomal iron is associated with fewer side effects, and they are less severe than previous therapies [42]. serious, life-threatening side effects have also not been observed. the need for iron supplementation in patients diagnosed with iron deficiency remains undisputed. our study is aimed not only to evaluate and compare the efficacy and safety of 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[clinical utility of reticulocyte hemoglobin content for the diagnosis of iron deficiency anemia in children]. zhongguo dang dai er ke za zhi. 2011 mar;13(3):212-5. chinese. pmid: 21426639. 28. albaroudi in, khodder m, al saadi t, turk t, youssef la. prevalence, diagnosis, and management of iron deficiency and iron deficiency anemia among syrian children in a major outpatient center in damascus, syria. avicenna j med. 2018 jul-sep;8(3):92-103. doi: 10.4103/ajm.ajm_169_17. pmid: 30090748; pmcid: pmc6057158. 29. natoli m., felsani a., ferruzza s., sambuy y., canali rscarino m.l. mechanisms of defence from fe(ii) toxicity in human intestinal caco2 cells. toxicol. in vitro. 2009;23:1510–1515. doi: 10.1016/j.tiv.2009.06.016. 30. ferruzza s., scarino m.l., gambling l., natella f., sambuy y. biphasic effect of iron on human intestinal caco-2 cells: early effect on tight junction permeability with delayed onset of oxidative cytotoxic damage. cell. mol. biol. 2003;49:89–99. 31. rimon e., kagansky n., kagansky m., mechnick l., mashiah t., namir m., levy s. are we giving too much iron? low-dose iron therapy is effective in octogenarians. am. j. med. 2005;118:11 42–1147. doi: 10.1016/j.amjmed.2005.01. 065. 32. gargallo-puyuelo cj, alfambra e, garcíaerce ja, gomollon f. iron treatment may be difficult in inflammatory diseases: inflammatory bowel disease as a paradigm. nutrients. 2018 dec 11;10(12): 1959. doi: 10.3390/nu10121959. pmid: 30544934; pmcid: pmc6316243. 33. cusick se, georgieff mk, rao r. approaches for reducing the risk of early-life iron deficiency-induced brain dysfunction in children. nutrients. 2018 feb 17;10(2):227. doi: 10.3390/nu10 0202 27. pmid: 29462970; pmcid: pmc5852 803. 34. hasan mi, hossain sj, braat s, et al. benefits and risks of iron interventions in children (brisc): protocol for a three-arm parallelgroup randomised controlled field trial in bangladesh. bmj open 2017; 7:e018325. doi:10.1136/bmjopen-2017-01 8325. 35. powers jm, daniel cl, mccavit tl, buchanan gr. deficiencies in the management of iron deficiency anemia during childhood. pediatr blood cancer. 2016 apr;63(4):743-5. doi: 10.1002/pbc.2 5861. epub 2016 jan 5. pmid: 26728130; pmcid: pmc4755821. 36. asperti m, gryzik m, brilli e, castagna a, corbella m, gottardo r, girelli d, tarantino g, arosio p, poli m. sucrosomial ® iron supplementation in mice: effects on blood parameters, hepcidin, and inflammation. nutrients. 2018 sep 21;10(10):1349. doi: 10.3390/ nu10101349. pmid: 30241424; pmcid: pmc6213119. 37. gómez-ramírez s, brilli e, tarantino g, muñoz m. sucrosomial ® iron: a new generation iron for improving oral cmi 03 (03), 330−337 manuscript central 337 manuscript central katarzyna kozikowska et al. supplementation. pharmaceuticals (basel). 2018 oct 4;11(4):97. doi:10.3390/ph1104 0097. pmid: 30287781; pmcid:pmc6 316120. 38. giordano g, napolitano m, di battista v, lucchesi a. oral high-dose sucrosomial iron vs intravenous iron in sideropenic anemia patients intolerant/refractory to iron sulfate: a multicentric randomized study. ann hematol. 2020 dec 2. doi: 10.1007/s00277-020-043613. epub ahead of print. pmid: 33263170. 39. darbà j, ascanio m. budget impact analysis of oral fisiogen ferro forte ® versus intravenous iron for the management of iron deficiency in chronic kidney disease in spain. clin drug investig. 2018 sep;38(9):801-811. doi: 10.1007/s40261-0180666-9. pmid: 29934762. 40. ciudin a, simó-servat o, balibrea jm, vilallonga r, hernandez c, simó r, mesa j. response to oral sucrosomial iron supplementation in patients undergoing bariatric surgery. the bari-fer study. endocrinol diabetes nutr (engl ed). 2018 jan;65(1):17-20. english, spanish. doi: 10.1016/j.endinu.2017.10.007. epub 2017 dec 7. pmid: 29233512. 41. cancelo-hidalgo mj, castelo-branco c, palacios s, haya-palazuelos j, ciria-recasens m, manasanch j, pérez-edo l (2013) tolerability of different oral iron supplements: a systematic review. curr med res opin 29:291–303. 42. mafodda a, giuffrida d, prestifilippo a, azzarello d, giannicola r, mare m, maisano r. oral sucrosomial iron versus intravenous iron in anemic cancer patients without iron deficiency receiving darbepoetin alfa: a pilot study. support care cancer. 2017 sep;25(9):2779-2786. doi: 10.1007/s00520017-3690-z. epub 2017 apr 9. pmid: 28391437; pmcid: pmc5527057. how to cite : kozikowska, k., bartmiński, w., & sybilski, a. (2022). comparison of the efficacy and safety of succrosomial iron and elementar iron supplementation to treat iron deficiency and iron deficiency anemia in preschool children (3-6 years): protocol of a randomized clinical trial. clinical medicine insights, 3(3), 330–337. https://doi.org/10.52 845/ cmi/2022-3-3-3 cmi 04 (02), 387−392 cmi journal 387 clinical medicine insights doi:https://doi.org/10.52845/cmi/2023-4-2-2 cmi 04 (02), 387-392 (2023) issn (o) 2694-4626 research article the biophysical modelling of the system theory janos vincze, gabriella vincze-tiszay health human international environment foundation, budapest, hungary *corresponding author: janos vincze introduction biophysics is a border science which deals with physical processes taking place in the living organisms and systems as well as with tools and methods used of their study. biophysics strikes for the revelation and recognition of physical phenomena, processes, laws etc. implied in biological problems. the biophysicist pursues studies with the methods of physics without leaving the soil of biology. for this very reason, a synthesis of the mentioned disciplines’ way of thinking, imaginations, concepts and working methods can be met in the biophysics. one may safely say today that living material is composed of exactly the same constituents and the interactions between the constituent particles are of the same nature as we see them in the lifeless world. life is not the consequence of non specific atomic characteristics but a concomitant of – by overall natural laws – highly organized, atoms otherwise occurring in the nature. 1 in the course of biological investigations, the tendency can be observed that for the better understanding of phenomena one makes use of the results of sciences governed by more and more general laws. biology starts with the observation, classification of living creatures but the study of life phenomena needs already explanation, generalization. advance has been meant by applying chemistry as biochemistry. although biochemistry can register immense results its scope remains limited. it has been found e.g. that proteins as enzymes perform various tasks in the living cells, it was also stated that dna carries the information responsible for the inheritance but a abstract modelling in this case should just complicate the situation. in this sense there are explicitly good models but it’s well known that there are also wrong things which, by modification, may work well. in this case model has given even more than it was originally for seen. in this respect, it’s without doubt that the biological modelling is a useful way of collaboration between the biologist and physicist. the system is a fundamental concept which is not defined. the biophysical approximation of the life processes leads always to the application of some kind of physical model. this definition has three essential factors. in the first place, it should need an object to be realized by the system. secondly, it is necessary for the components a well-defined settlement to be arranged. at last the information about the distribution of energy and matter according to the programme. the hierarchy of the systems will be built up according to a spiral line expanding in breadth and depth towards the infinity. one important mode to construct general systems is if we recognize the common phenomena occurring in the different specialized sciences and construct the systems applicable for such phenomena. let’s sketch out the hierarchy of the systems according to boulding. key words: biophysical modelling, system, hierarchy of the systems copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/lic enses/bync-nd/4.0/). https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ cmi 04 (02), 387−392 cmi journal 388 cmi journal janos vincze et al. deeper comprehension has been achieved by the help of physics. by studying the x-ray diffraction image of the dna-molecules, the double helix structure has been discovered and found explanatory for the hereditary mechanism. the xray diffraction study has brought about the recognition that protein molecules fulfill their tasks on the basis of their well-defined configuration. one hasn’t found so far another physical modality which could have implied any more unequivocal, decisive brakethrough. 2 modelling a biological model is called that partial set to be studied which has been selected from the set of our available knowledge, assumptions as well as from the results of the already completed biological experiments and investigations. hence the starting point of every modelling is some sort of an observable phenomenon. modelling in simplest formulation can be conceived as a sharp polarized inquiry of the respective phenomenon. there exist systems where the simplest model is the system itself. modelling in this case should just complicate the situation. in this sense there are explicitly good models but it’s well known that there are also wrong things which, by modification, may work well. model is evidently a model and not the reality but the abstracted copy of it from which we try to conclude to the reality and in the case of any mismatch we have to change the model. 3 the biologist has to abstract parts of the biological process substantial from the point of view of the model and has to select those essential points the physicist willingly accepts and in which he will be ready to collaborate. hereupon as a rule, the physicist used to suggest an already existing model of the wide arsenal of the physics applied for the description of natural phenomena. if there is a physical model disposable for the biological phenomenon then it will bring up a lot of possibilities offered by the physics to the biology which, of course, must be subjected to biologicallogical judgement. from many of them turns out that it’s worth dealing with and being subjected to biological experimentation. if our supposition has been justified by the biological experiment then we have got new knowledge in the long run. in this case model has given even more than it was originally for seen. in this respect, it’s without doubt that the biological modelling is a useful way of collaboration between the biologist and physicist. 4 we should steadily see also the strict limitations of the modelling. part of these limits is intensive and is best perceptible with the comparison that if we have a closer, focused look at an object it will necessarily get blurred or even disappear all beyond the scope of our observation. the other part of the limitations is extensive, the majority of the today’s models cannot take into consideration more but some distincted features. the mesh of the extensive and intensive limits, the complexity, underlines even more the necessity of modelling but it assures the conditions of the controllable advancement in a complicated spiritual (intellectual, mental) medium. forming a biophysical model is not the task of the biologist or physicist alone, a good model can successfully constructed only by common, collective-work. this is typically the task of the biophysicist and a problem which falls within the competence of this discipline. model is always an approximation, the user of the model has to take into consideration that he can approach only the absolute truth just through the endless series of relative truths. for this reason, he performs certain neglects in advance, he disregards certain things. the model is nothing but an abstracted phenomenon, a momentarily stopped biological system. 5 as soon as it has got a model it ceased to be alive but this should not exclude a model be built and the results of the biophysics be applied. the biophysical approximation of the life processes leads always to the application of some kind of physical model. this model usually carries just some features of the process but complies the requirement of the accuracy. accuracy is nothing else but to search for axiom for a complicated life process and it‘s usually a great deal of work. exactly from these difficulties germinates biophysics. the development of the biophysical science can be appraised on that we succeed in the investigation of ever complicated processes. accordingly, in the research one must declare the axiom of the deductive theories achieved by the study of the processes. you should clearly start with very simple examples. again, the more cmi 04 (02), 387−392 cmi journal 389 cmi journal janos vincze et al. complicated life processes we tackle, the higher we raise the scientific level of the biophysics. the system the expression „system” has been used for a wide range of phenomena. thus we speak of numerical systems, planetary systems, communication systems, regulatory systems, biological systems, teaching systems, political systems etc. part of these are conceptual constructions, the other part comprises physical entities. 6 the system itself is a fundamental conception of which we don’t give any definition, instead it will be circumscribed. temporarily, the following wide and broad circumscription could have been done for the system: any conceptual or physical entity made up of parts depending on each other. according to bertalanffy: systems are collectives of such interacting elements for which certain system laws can be applied. this characterization would not work as a kind of circulus vitiosus if an independent definition of the system laws were available but there was not. the system is a fundamental concept which is not defined. the behaviour of the system is consisted of the complexity of processes mutually connected with each other and characterized by function ties. generally spoken a function link between processes there exists only if each of them is needed to accomplish the desired output and if these all depend on each other. the nature of this mutual dependence can be exactly defined. both the output and the processes taking part in the function link can be defined by a set of certain characteristics regarded as variables. from the point of view of the output, processes will be regarded mutually consistent if the alteration of any variable describing one of the processes will influence the modification rate of any outputvariable and it also depends on every other substantial process variables. if, therefore, all variables are expressed by continuous quantities then any process-variable’s derivative of an output variable will be the function of all other process variables. 7 as to the systems, the heisenberg’s indefiniteness relation is of great significance because if the information expected by the researcher from the system is of the same order of magnitude as the system itself then the information cannot be applied for the system and cannot be even achieved without changing the system. this principle has been verified first in the physics but its significance is ever growing as we proceed through the biology towards the social sciences. the order in the stochastic systems is of nondeterministic nature but events occur – subsequently from the essential kind of the system itself – with a probability less than one and may perform chaotic behaviour. the former method of demonstrating suppose also fails simply because the hypothesis pertains not on the certainty but on the probability of the event. as a result, the successfulness of those methods dealing with the special systems and with the empirical investigations in the physics may be regarded as a fortunate accident owing really to the fact that the systems studied were large enough (not as those of heisenberg where the information is of the same order of magnitude than the system and the observation is part of the system) having a very insignificant probability character. 8 for practical reasons, let’s circumscribe the concept of the system more exactly as such an arrangement of the constituents which serves to reach the concrete purpose according to a certain programme. this definition has three essential factors. in the first place, it should need an object to be realized by the system. secondly, it is necessary for the components a well-defined settlement to be arranged. at last the information about the distribution of energy and matter according to the programme. thus any physical entity can be considered as a system if the output (outcome) of its behaviour will be conceived as the result of the interaction between the parts. many entities, therefore, can be treated both as elements and as systems depending on the decision of the investigator. the biological system can be described at least to some extent as a self-regulatory system. its four essential characteristics are as follows: 1. its elements have the disposal of life as an attribute. cmi 04 (02), 387−392 cmi journal 390 cmi journal janos vincze et al. 2. there is structural link between its components. thus for example, the nutrition is connected with the circulation and respiration and with the excretion as well. 3. the subgroups of different function are aware of each other’s behaviour through communication. this is mainly realized by the nervous and the endocrine system. 4. the living system has certain liberty of selection in respect to the ways of action and also to the goals (the result expected). in the interest of its self-preservation, it can select between foods, choose living space in the environment and a mate for the racepreservation. shortly speaking the four essential feature of the living systems is the sum of the content components, the structural construction, the communication and the ambiguous but interval parameters realizing the functions. it must be stressed by all means that the system is always just an approximate modelling but it enables us the better recognition of our environment and ourselves as well. the hierarchy of the systems the approximations of the investigations between the branches of science by interdisciplinary attitude clearly show the increasing interest for joining the knowledge into systems of wide spectra. if we don’t want the research between the branches of science to lead into limitlessness then we have to elaborate systems for the integration of the independent branches within which they can still maintain their distinctive character. 9 the hierarchy of the systems will be built up according to a spiral line expanding in breadth and depth towards the infinity. although the idea of the system and the necessity of building-up systems is not new-fangled (updated), systems were not enough stressed in the sciences for a long time. though as a result of the significant discoveries at the beginning of our century, a break-through has been achieved both in the field of physics and of mathematics, yet these were the last decades when the interdisciplinary attitude came across also in the biology. 10 but in addition there was a considerable contribution by the rapid development of other sciences like mathematics, physics, chemistry, technical sciences because their discoveries, methodologies and tools gave way for the biologists to probe deeply enough into the recognition of the living material. 11 at the same time, the results of the sciences penetrated stimulating and inspiring the biology in the form of analogy and terminology. one important mode to construct general systems is if we recognize the common phenomena occurring in the different specialized sciences and construct the systems applicable for such phenomena. the second construction mode would be to arrange the systems in a hierarchic system. 12 this in the same time would result in fixing the abstraction levels corresponding to the different degrees. this cannot be realized unequivocally. the second construction mode, the hierarchy of the levels will be investigated in details. generally speaking the different levels cannot be delimited unambiguously and it is the investigator to separate them artificially due to methodological reasons. systems are not divided into sub-, super and co-ordinated relations, respectively, in a well determined manner but they appear intermixed in the structural hierarchy. let’s sketch out the hierarchy of the systems according to boulding 13 as follows: 1.) the first level is that of the static structure. it could be called the level of the shells (skeletons). it is really the geography and anatomy of the universe: the localization scheme of the electrons around the nucleus, the scheme of the atoms in a molecular formula, the settlement of the atoms in a crystal, the anatomy of the gene, the cell, the plant, the animal, the map of the earth, the solar system, the stellar world. the organized theoretical knowledge starts with the exact description of these shells on almost every territory because no functional or dynamic theory can exist without this accurate description of the static conditions. 2.) on the second level you can see the simple dynamic system with its predetermined, necessary movements. it could have been called the level of the clockworks. from the human point of view, of course, it is the solar system as the great clock of the universe and the imposingly accurate predictions of the astronomers to bear witness to cmi 04 (02), 387−392 cmi journal 391 cmi journal janos vincze et al. the excellent quality of the clockwork applied. mechanical powers can be usually interpreted on this level, like the lever and the pulley but also more complicated machines like the steam-engine and the dynamo (generator). to the same level belongs the physics, chemistry and even the major part of the theoretical constructions of the economy, too. 3.) the next level is the steering mechanism or cybernetic system which could be otherwise called the thermostat level. this differs from the simple stationary equilibrium system in that its substantial part is the transmission and processing of the information. the equilibrium, therefore, will not be simply determined by the equations of the system but the system itself seeks to maintain – within limits – a certain equilibrium. the greatly important homeostatic model in the physiology is only one example for the cybernetic mechanism but the whole world investigated by the biologist and sociologist is full of such mechanisms. 4.) the fourth level is the „open system” or the self-sustaining structure. on this level the living begins to separate from that which is not living: this could be called the level of the cell. if we fall in with systems being able to reproduce and sustain themselves during matterand energyperfusion then we have to deal with something of the kind which we hardly can deny the name „life”. 5.) the fifth is the level of the genetic society the typical form of it rules over the flora and the empirical world of the botany. the major characteristics of this system are first the cell population formed by division of labour between the cells with its differentiated and mutually interrelated parts (roots, leaves, seeds etc.), secondly a sharp separation between genotype and phenotype which is related to the one-aimed or programmed growth. 6.) going upwards from the flora to the fauna gradually we reach the „animal” level which is characterized by motility, specific behaviour and by self-identification. here special informationreceivers are developing (like eye, ear, etc.) and as a result, the information-uptake grows enormously. in addition, the nervous system increasingly develops, after all the brain as the organ which organizes the information into structural knowledge or „image”. going upwards on the scale of the animal life, the behaviour becomes not only a reaction to any concrete stimulus in an ever raising degree but an answer to an „image” or structured knowledge or attitude formed from the environment as a whole. this image will lastly be determined, of course, by the information taken up by the organism, however, the relation between information-uptake and imaging (the construction of a picture) is extremely complicated. the process is not simply the accumulation of the accepted information – although it is often the case – but it will be structured in a manner which essentially differs from the information itself. once the imagestructure has been definitely formed the new information will hardly change on the picture: it quasi passes the loose structure without „colliding” with whatever. the image sometimes „catches” the information incorporating it, sometimes the information comes into collision with any core, „nucleus” of the image so that its whole will be transformed in a way that a seemingly inconsiderable stimulus will provoke a highly significant reaction, that is to say, the behaviour will change considerably and radically. thus the determination of the future behaviour of such systems will be aggravated, namely by the picture intercalated between the stimulus and the answer. 7.) follows the „human” level, that is the individual human being comprehended as a system. man is probably the only organism which knows that he will die, which takes into account – by forming his behaviour – his full lifespan and even more of it. man exists not only in a given time and space but in history, too, and his behaviour will be deeply influenced how he sees the course of time he lives in. 8.) the social level. the fundamental level of such systems is not even the individual – the human being as such – but the „role” that is those circumstances of the personality which are in relation with the organism or situation in question. what should be investigated on this level? the content and meaning of the informations, the nature and dimensions of the systems/scales of values, the transcription of images into history, the embarrassing and delicate symbolize of the fine arts, music, poetry. cmi 04 (02), 387−392 cmi journal 392 cmi journal janos vincze et al. 9.) in order to complete the hierarchy of the systems still we have to include the level of the psychical systems, too. there are also other aspects to classify our environmental world. below, you will find some other hierarchies of the systems. such kind of representation of this hierarchy has, among others, the advantage that it offers some idea about the shortcomings of our present – theoretical as well as practical – knowledge. matter is known to exist of two fundamental kind: that of discrete nature, of corpuscular structure and those physical domains/fields displaying steady feature and transmitting interactions between material parts. 14 the particles of corpuscular character and the physical domains can not be sharply separated from each other, there is no impassable barrier between the two outward forms of the matter, they can transform in each other. 15 under certain circumstances, these outward forms of the matter posses similar features, corpuscular generate spaces of different type, display continuous wave character, on the other hand, domains may have manifestations characteristic of particles. the material systems are in steady movement, motion is inseparable from the matter. references: 1. vincze, j.: biophysics 7. ndp p., bp., 1998. 2. vincze, j.: biophysics 15. ndp p., bp., 2000. 3. vincze, j.: biophysics 36. ndp p., bp., 2009. 4. ackerman, e.: biophysical science. prentice hall, bglewood, n. y., 1962. 5. vincze, j., vincze-tiszay, g. (2020) the biophysical modeling of the different regulations in the human organism. intern. j. inovat. studies med. sciences, 4(1):1–4. 6. vincze, j., vincze-tiszay, g. (2020). the biophysical modeling of the „sevendimensional” man. int. j. recent sci. res., 5(6):123–130. 7. grémy, p., pagés, j. c.: eléments de biophysique. ed. planunarion, paris, 1969. 8. 8 oncley, j. l., schmitt, p. o., williams, r. c, rosenberg, m. d., bol, r. h.; biopysical science. a study program. new york, wiley, 1959. 9. vincze, j.: biophysics 45. ndp p., bp., 2015. 10. pullman, b., weisebluth, m.: molecular biopysics. acad. press, n. y. 1965. 11. vincze, j., vincze-tiszay, g. (2020). some aspects of sciences from the biophysical point of view. int. j. software & hardware engin. 8(9):103–108. 12. vincze, j., vincze-tiszay, g. (2020). the human organism is a biophysicalbiopsychological system. technium, 2(7): 29–35. 13. vincze j., vincze-tiszay, g. (2020). the biophysical adjustment in the human organism. j. med. res. case report,2(3) 1–7. 14. vincze j., vincze-tiszay, g. (2023). the biophysical modelling of the equilibrium receptors. british journal of healthcare and medical research, 10(3): 66–70. 15. vincze j., vincze-tiszay, g. (2023). the human mind. philosophy study, 13(2): 60–67. clinical medicine insights received 15 feb 2022 | revised 18 feb 2022 | accepted 23 feb 2022 | published online 26 feb 2022 doi: https://doi.org/10.52845/cmi/2022-3-1-4 cmi 03 (01), 268−277 (2022) issn (o) 2694-4626 research article study of the nutritional status of end-stage renal disease patients on maintenance hemodialysis in hawary kidney center and nephrology unit at benghazi medical center safia s. elramli 1assistant professor, nutrition department, faculty of public health, university of benghazi) afaf omer sati, ebtesam mostafa , norhan elhassi( public health students abstract background: malnutrition, which is a powerful predictor of morbidity and mortality, is common in patients undergoing hemodialysis. there-fore, adequate nutrition is very important for such patients. nutritional management in hemodialysis patients is a very important factor for prognosis , a better overall outcome and quality of life. objectives: the current study mainly aimed to determine the nutritional status and prevalence of malnutrition and to investigate the relationship between nutritional markers, anthropometric parameters such as body mass index (bmi), and routine laboratory parameters with sga in patients undergoing hemodialysis. patients and methods: a cross-sectional study was carried out on hd patients in hawari nephro center and nephro unit of beng-hazi medical center from december 2019 to january 2020. a total of 155 hd patients were recruited for this study and assessed for nutritional status include both male and females aged 18 years and over with regular hemodialysis. outcome measures: measurements included questionnaire that elicited information on social demographic characteristics, patient’s medical history , and duration of hemodialysis. anthropometry, biochemical parameters were measured. sevenpoint subjective global assessment (7-point sga) was used to assess the nutritional state of hd patients. biochemical tests were obtained during the study period from medical files of the studied patients. data were analyzed using descriptive statistics. the chi-square test was applied to examine the study data. results: data shows that 58% of hdp were well-nourished while the remaining 39%, 3%had mild-to-severe malnutrition. regarding the prevalence of malnutrition in both gender, males group was mor preva-lent of malnourished than female group. sga score results indicated some significant correlations with patient’s post dialysis bmi and albumin ,however, there was a negative correlation between demographic characteristics as gender, income, education level, comorbid disease , clinical variable such as duration and frequency of hd and some biochemical tests as electrolytes, phosphorous ,hemoglobin, cholesterolwith sga scores. in addition, results show that insignificant correlation between nutrients intake, meals pattern of hd patients with sga. conclusions: observations of nutritional status are necessary to maintain the health status of dialysis patients. every strategy should be used to avoid complications of hemodialysis manifested in uremic state including anorexia, nausea, vomiting leading to malnutrition, fluid and electrolyte imbalance leading to volume overload, hyperkalemia, metabolic acidosis, and hyperphosphatemia, as well as abnormalities related to hormonal or systemic dysfunction such as hypertension, anemia, hyperlipidemia, and bone disease, timely diagnosis of proteinenergy-wasting (pew) is important for early initiation of nutritional intervention and treatment. in addition, education plans should be prepared to mediate the nutrient intakes and identify the patient's difficulties and provide practical help. keywords: renal dialysis, nutritional status, hemodialysis, malnutrition manuscript central used to avoid complications of hemodialysis manifested in uremic state including anorexia, nausea, vomiting leading to malnutrition, fluid and electrolyte imbalance leading to volume overload, hyperkalemia, metabolic acidosis, and hyperphosphatemia, as well as abnormalities related to hormonal or systemic dysfunction such as hypertension, anemia, hyperlipidemia, and bone disease, timely diagnosis of proteinenergy-wasting (pew) is important for early initiation of nutritional intervention and treatment. in addition, education plans should be prepared to mediate the nutrient intakes and identify the patient’s difficulties and provide practical help. keywords: renal dialysis, nutritional status, hemodialysis, malnutrition copyright : © 2022 the authors. published by publisher. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). cmi 03 (01), 268−277 268 https://doi.org/10.52845/cmi/2022-3-1-4 https://creativecommons.org/licenses/by-nc-nd/4.0/ 1 introduction one expanding global public health challenge is chronic kidney disease (ckd) , which is manifested by an irreversible deterioration of kidney function that may eventually lead to end-stage renal disease (esrd) and require renal replacement therapy such as renal transplantation or hemodialysis (hd) [1]. the main aim of hd is to rebalance the intracellular and extracellular fluid volume that is a characteristic function of normal kidneys. this is performed by transporting solutes (i.e. urea) from the blood to the dialysate and by transporting solutes (i.e. bicarbonate) from the dialysate to the blood [1]. kidney dysfunction is associated with defects in acid excretion, systemic inflammation, end-organ hormone resistance and uremic toxin accumulation. these abnormalities can further worsen kidney function, creating a vicious circle, adversely affect patients’ outcome[2]. 2 causes of nutritional disorder in hd 2.1 inadequate food intake in dialysis patients, the decrease in food intake is a major cause of pew and mortality [3]. multiple factors have been implicated .major causes of feeding restriction are comorbidities mainly cardiovascular disease and history of volume overload , hospitalizations, depression, low social status, dietary restrictions , multiple medical treatments, and accumulation of uremic toxic molecule[3] 2.2 abnormal nutrient metabolism energymetabolism:most studies on resting energy expenditure (ree) measurements in hd and pd patients reported ree values similar to that of controls [4]. in two studies, ree was found to be increased [3], and in one study in malnourished hd patients, ree was found to be decreased [4]. regarding the determinants of ree, it was shown that severe hyperparathyroidism , elevated serum crp and serum il-6 were associated with increased ree. amino acid and protein metabolism: in hd patients, plasma concentrations of amino acids( aas) are characterized by a relative decrease in plasma serine and essential aas except methionine, and an increase in citrulline and aspartate . tyrosine and histidine are considered as essential aas in renal failure [5]. these disturbances of plasma aas during chronic kidney disease ( ckd) have been attributed to the abnormal handling of aas not only in the kidneys but also in the hepatosplanchnic area[5]. protein-energy malnutrition is a common problem among patients on hemodialysis (hd). malnutrition can occur in up to 40% of the patients with renal failure and is associated with increased mortality and morbidity. therefore, management of the nutritional aspects of patients with chronic kidney disease (ckd) presents a number of challenges [6]. in hemodialysis patients (hdp), it is important to perform an early diagnosis of malnutrition (mn) and inflammation, which are represented by proteinenergy wasting (pew) as they are significant predictors of mortality , using the best clinically available tools to create specific nutritional strategies that can predict outcomes, evaluate therapeutic responses, and avoid severe nutritional deterioration [7]. this adds to the importance and significance of the presence of nutrition specialists in hd center for early detection of malnutrition and strategies to be implemented to prevent further deterioration [8]. the pathogenesis of malnutrition in dialysis patients the causes of both malnutrition and inflammation are numerous in chronic renal injury ( cri )patients with elevated serum levels of c-reactive protein( crp) and pro-inflammatory cytokines. patients may not ingest sufficient amounts of food because of loss of appetite. anorexia can be caused by factors such as the retention of uraemic toxins and chronic metabolic acidosis, which, moreover, is an important supplementary information the online version of this article (10.52845/cmi/2022-3-1-4) contains supplementary material, which is available to authorized users. cmi 03 (01), 268−277 manuscript central 268 manuscript central safia s. elramli catabolic factor [9]. in this regard, inadequacy of dialysis treatment may be an important cause of malnutrition. renal replacement therapy per se causes a loss of nutrients. during a hemodialysis (hd) session, a considerable quantity of amino acids may be lost (4–9 g in the fasting state and 8–12 g postprandially). in contrast, protein losses are negligible, unless multiple re-use of dialysis filters is practiced. hd can cause a loss of vitamins, particularly watersoluble vitamins. endocrine and metabolic disturbances of uremia, in particular insulin resistance, can reduce protein anabolism and favor catabolism. the role of psychological factors (depression) and socioeconomic factors (loneliness, invalidity, poverty) should never be neglected, considering that at present the majority of the dialysis population is composed of elderly patients [9]. acute concurrent illnesses can also contribute to malnutrition. finally, inadequate dietary prescription, due to the traditional physician’s preference of prescribing nutritional restriction rather than providing nutritional counselling, can further worsen malnutrition [9].the pathogenesis of chronic systemic inflammation in dialysis patients, which is associated with hyper catabolism and bodywasting, is complex and not yet fully understood. other non-dialysis related causes of elevated crp include co-morbid conditions, e.g. chronic heart failure with edema and the atherosclerotic process [10]. moreover, various chronic infections, such as chlamydia pneumoniae and dental or gingival infections may also contribute [10]. furthermore, it has been suggested that factors related to the dialysis procedure itself may contribute to maintaining chronic systemic inflammation. in order to prevent and treat malnutrition in dialysis patients, it is important to assess appropriately the nutritional status and to identify patients at risk [10]. methods to assess nutritional status in dialysis patients there is a single best nutritional marker in patients with cri, but that several nutritional markers should be evaluated together. the assessment of nutritional status should be based on a combination of clinical parameters with biophysical and biochemical parameters[11]. malnourished dialysis patients often have protein energy malnutrition with a reduction of both fat mass (fm) and lean body mass (lbm). therefore, clinical assessment of subcutaneous fm and muscle mass and a history of weight loss are important parts of routine nutritional assessment. percentage of standard weight and body mass index (bmi) are also important and easy to measure, although bmi is more useful for assessment of obesity than of malnutrition.most dialysis patients with malnutrition also have co-morbid diseases, in particular cardiovascular disease and inflammation, and the assessment of co-morbid conditions is an important part of the nutritional assessment of dialysis patients [11]. laboratory parameters used in clinical routine, such as proteins, serum levels of c-reactive protein (crp) and lipid profile may be influenced in hd patients by the inflammatory condition [11]. furthermore, it should be noted that other parameters, such as serum cholesterol concentration, experience a reverse epidemiology in patients onhd. however, both serum prealbumin levels in early stages of malnutrition and those of albumin (much later) are good nutritional markers [12]. during recent years, subjective global assessment of nutritional status (sga) has been used increasingly to assess nutritional status in many studies of dialysis patients (mainly crosssectional studies) and in patients with cri at start of dialysis therapy [13]. sga correlates well with other nutritional markers in patients with cri .furthermore, it has a high predictive value for mortality in these patient groups . however, one potential problem with sga is its subjective nature, which may reduce its reproducibility, thus small differences in sga score must be interpreted with great caution [13]. 3 aim and objectives the aim of this study was to study the prevalence of malnutrition among hemodialysis patients. objectives 1.to determine the prevalence of nutritional disorders (malnutrition, anemia, hypernatremia, hyperkalemia, and hyperphosphatemia) 2.to show the association between nutritional status and regular hemodialysis in both gender manuscript central cmi 03 (01), 268−277 (2022) 269 3.to identify the effects of demographic characteristics, chronic disease of hd patients on nutritional status 34to find out wither the frequency and duration of dialysis session per week are effect on nutritional status of hd patients 5.to determine whether nutritional status decline over time in patients receiving dialysis 4 methodology design: it was cross-sectional study random sample conducted at nephrology unit of benghazimedical centre and hawari nephrology center – libya, to determine the nutritional status of end-stage renal disease patients on maintenance hemodialysis aged from 18 to 83 years old. the access to this study was obtained following ethical approval after consultation with and permission of local medical research ethics committee, senior management, and site managers at benghazi medical centre and howari nephrology center. total sample was 155 patients includes both male and females aged 18 years and over with regular hemodialysis . criteria for inclusion the study the target of study consisted of patients with esrf with maintenance hemodialysis both male and female with libyan nationality. all enrolled patients should have completed a minimum of three months duration on hd exclusion criteria: patients had acute renal failure on hemodialysis , any patient with chronic renal failure or end stage renal failure did not start of hemodialysis , as well as patients on temporary hemodialysis due to other cause than renal failure. patients who were hospitalized for more than two weeks for a non-vascular access complication or had signs of active infection were excluded from the study patients from other nationality other than libyan nationality or patients younger than 18 years old were excluded. procedure and materials:the study will be carried out over 2 months period from december 2019 to january 2020 and included 155 patients with a mean age of 47.8 ; there were 92(59.4%) males and 63(40.6%) females . the researcher will seek approval to conduct the study and to discuss access with site mangers. researchers should be set to meet with participants to discuss the study, obtaining an informed consent, measurements, and data collections. researchers were set to meet with participants, the study was explained, and an informed consent obtained. a complete social and medical history , including details of the patient’s diet using 24 hours recall method and food frequency questionnaire , physical examination, and recording of the dry body weight was performed to calculate bmi . biochemical tests were obtained during the study period from medical files of the studied patients. the baseline laboratory tests included serum hemoglobin ,serum albumin, [total cholesterol, serum creatinine, crp, serum potassium ,sodium, calcium and phosphorus, and serum urea nitrogen. assessment of nutritional status as no single measure predicts overall nutritional status in patients with hd, amultidimensional approach has been proposed to include measurement of body composition, dietary intake, biochemical measures and muscle strength . however, this is clearly not practical for all patients in routine clinical practice and therefore the use of nutritional screening tools, such as subjective global assessment (sga) which incorporates important measures such as body mass index should be applied to the general hd patients to identify patients at risk of malnutrition. selected patients should then undergo more detailed assessment, including dietary intake, anthropometric evaluation and measurement of laboratory investigation. serum albumin level and body mass index (bmi) were the most predictive parameters of malnutrition [14]. however, the nutritional status of patients was assessed by extensive anthropometric measurements .whereas the biochemical markers of nutrition such as serum albumin, s. creatinine, crp ,s. cholesterol was unavailable for most patients as well as the detection of malnutrition can be problematic in hd cmi 03 (01), 268−277 (2022) manuscript central 270 manuscript central safia s. elramli patients as the body weight is influenced by fluid status and biochemical markers such as albumin, crp and haemoglobin are affected by the disease process. in clinical practice, therefore review of the patients albumin level, and body weight include recent changes and their dietary intake is approve helpful [14]. 5 result the aim of this study was to assessment the nutritional status and prevalence of malnutrition among hemodialysis patients in howari nephrology center and nephrology unit of bmc hospital in benghazi. 1.description of study participamnts the background characteristics of the participants are summarized in table (4.1.and 4.2) a total of 155 hd patients in this study were recruited for the study, the age ranges was between (18-83 years), the mean age was 47.48 , included 92 males and 63 females table (4.1)distribution of age 2. demographic characteristicand clinical information of the studied patients all participants enrolment in this study were on regular dialysis. approximately 23.9% did not earn an income (either unemployed or a housewife), and most patients (29% )had a monthly income of 5001000dinner ,while only 7% had income ,1500 dinner as shows in table(4.3) regarding the patient’s educational level, approximately 54.2% ,whereas 45.2% were illiterates as demonstrated in table(4.3) clinical information of the studied patients is presented in table(4,3) . most (56.8%) of studied hd patients reported that they have been do surgeries ,however, about 43,2% they do not. table (4,3) demonstrated that the highest percent of participants were have family history for chronic disease which was 60% ,while only 40% did not found history of chronic disease. and approximately 72% of the studied patients reported did not having family history of renal disease , only 27.3 confirmed with family history of renal disease. comorbid conditions in the study patients were mainly hypertension (htn)94 (60.6%) followed by diabetes mellitus (dm) 23(14.8%). a bout 23 (14.8% ) of the patients had both dm and htn. overall, 13(8.4%)of hd patients did not have any comorbid condition. table(4,3) demographic characteristic and clinical information of participants manuscript central cmi 03 (01), 268−277 (2022) 271 table(4.2) distribution of gender subjective global assessment (sga) score that was originally developed to assess post-operative nutritional state and is one of the methods suggested to assess nutritional status in hd patients. the sga was suggested by the national kidney foundation and has undergone several modifications . the sga comprises of five criteria, and includes medical history, physical examination, subcutaneous fat, muscle wasting and fluid retention. a score a indicated well nourished , score b mildly to moderately malnourished ,score c severely malnourished . the nutritional status of the patients indicated that (58%) were well-nourished while the remaining (39%, 3%) had mild-to-severe malnutrition [figure 4,1] below. (figure 4.1) prevalence of malnutrition among hd patients 6.2 body mass index in the study pa ents regarding the patient’s post dialysis bmi 43.3% were had normal bmi , 28.4% were overweight ,while 16.1%,7.1%,1.9% were grad1,2,and 3 obese respectively . however, 4.5% appeared to be under weight . the figure (4.2)shows all previously mentioned. cmi 03 (01), 268−277 (2022) manuscript central 272 6 assessment of nutritional status of hd. patients 6.1 prevalence of malnutri on using subjec ve global assessment manuscript central safia s. elramli figure (4.2)postdialysis bmi of study patients 6.3 bmi and sga score based on the results (table4.4 ) there was showed the post dialysis bmi had a highly significant association with sga scores { p-value 0.29}. table (4,4) correlation between post-dialysis bmi and sga 3.4. frequency of dialysis : based on the results (table 4,14)there was no association between frequency of dialysis and sga (p value-0.578). 6.4 laboratory inves ga on result revealed that hemoglobin level regarding both sex , the mean level of hbg among male group was 9.9ml/dl as well as the minimum level was 5.4ml/dl while the maximum level was 16.8ml/dl. about female group the mean hbg level was 9.5 while the maximum and minimum hbg level was 13.3 ml/dl and 9.5 respectively. table (4,6) hemoglobin level among gender table(4,7) laboratory result among both sex regarding biochemical indexes of nutritional status the table below(4,7) shows that the maximum and minimum level of serum cholesterol among male group was 198 ml/dl and 160ml/dl, whereas the maximum and minimum level among female group was 254ml/dl and 170 respectively we noted that all patients in our sample had hypercholesterolemia compared with normal level ,whereas urine albumin was high at maximum level in both groups. high loss of albumin in urine is marker of malnutrition. table(4,7) serum cholesterol-albumin in both sex manuscript central cmi 03 (01), 268−277 (2022) 273 correlation between sga score and biochemical tests correlational analysis was carried out between sga scores and laboratory results correlation (table4,8) no significant correlation was found between sga score and potassium level (p = 0.889), sodium level (p = 0.400), hemoglobin (p = 0.706),cholesterol level(p=0.764) and phosphate level (p = 0.562). however, significant positive correlation was found between sga core and albumin level (p = 0.031). table(4,8) correlation between sga and biochemical test 6.5 associa on between nutrient intake and sga table 4.9 below shows the association between nutrients intake among hd patients and sga parameters, based on result was showed a negative correlation , the correlation between sga scores and protein (p =0.652),calorie (p=0.998),cho(p=0.575),and fat(p=0.932). table (4,9) ): association between sga scores and daily nutrient intake 7 discussion in this study, we aimed to estimate the nutritional status of a sample of hd patients and potential significant predictors of nutritional status among the studied patients. nutritional status is an important predictor of outcome in esrd patients on maintenance hd. assessment of the nutritional status needs a systematic nutritional evaluation based on anthropometric, laboratory, and clinical parameters from which a malnutrition score can be calculated. with regard to association between bmi and sga score our result illustrated that 43.3% hd patients post dialysis bmi were had normal and most of them were well-nourished, while patients with underweight were severely malnourished. in addition, the result demonstrated that there was showed post dialysis bmi had a highly significant association with sga scores with p-value 0.29. similarly, study done by ekramzade et al. reported that hdpwithmn had a lower bmi than well-nourished patients [15]. cmi 03 (01), 268−277 (2022) manuscript central 274 manuscript central safia s. elramli another study was done by . mohammed (2014) convinced that post dialysis bmi had high significant association with sga [16] on the other hand, our results disagreed with the study of ghali and malik,[17 ] there was no significant effect of post dialysis bmi and sga . about frequency of dialysis , in present study most of participants in our sample were dialysis for 3 times a week was well nourished while the rest of them were mildly malnourished and five patients had sever malnourished among those patients also the result showed that frequency of hemodialysis non-significant correlation with sga. however, study was done by bohé and rennie (2006) [18]provided a significant analysis and discussion on the subject and reported that patients receiving dialysis three times a week lost 2 kg of lean body mass in a year [18]. some other studies also found severity of malnourished increased with increased dialysis frequency [19]. as demonstrated in our result, the correlation between sga scores and laboratory results were no significant was found with potassium level (p = 0.889), sodium level (p = 0.400), hemoglobin (p = 0.706),cholesterol level(p=0.764) and phosphate level (p = 0.562). however, significant positive correlation was found between sga core and albumin level. in contrast other study by stosovic etal (2011) have previously found that sga score was significantly correlated with hb level but not with albumin level or any other biochemical indicator[20]. the evident poor intake of high quality protein also reported in present study. in this study we also found that the association between nutrients intake among hd patients and sga parameters was a negative correlation. the correlation between sga scores and protein (p =0.652),calorie. (p=0.998),cho(p=0.575),and fat(p=0.932). poor protein and energy intake, comorbidities and inflammation were the predictors of mn in descending order of importance [21]. morais et al. performed a prospective study to investigate the association between nutritional status and food intake in hdp and the authors reported that nutrients intakes had a significant correlation with subjective global assessment, which was different to our findings reported here [22]. study was done by therrien etal (2015) [23] were analyzed nutrient intake of the subjects and found out that calorie and protein intakes were insufficient compared to the dietary intakes recommended for dialysis patients. 8 conclusions we conclude that the majority of our dialysis patients were well nourished, and followed by mildly malnourished. poor dietary knowledge and practices were encountered among these patients with poor biochemical parameters among the majority of them. this study showed the majority of patients reported a lower than recommended energy and protein intake the sga score results indicated that mn was moderately prevalent among patients undergoing hd. these results show some significant correlations between the nutritional status and patient characteristics (i.e. post dialysis bmi and biochemical tests as albumin ) , however , our result shows that hdp had un-significant relation between demographic characteristics , clinical variable and some biochemical tests such as gender, income, education level, comorbid disease , and frequency of hd , electrolytes, phosphorous ,hemoglobin, cholesterol with sga scores. we also found that a negative correlation between nutrients intake among hd patients with sga parameters. therefore, these findings should increase the awareness of healthcare providers for interventions to enhance the nutritional status for hdp, especially those who are elderly, have multiple comorbid diseases, , have a long dialysis vintage or live alone. consequently, efficient screening in hdp for risk factors of mn and simultaneously performing a nutritional evaluation and assessment whenever possible should facilitate early dietary intervention to avoid further deterioration and nutritional depletion. further interventional studies should be conducted in different nephrology center in benghazi and with a larger sample size to repeat these results so that they are proven with greater certainty. 9 references 1.mushi l, marschall p, flessa s. the cost of dialysis in low and middle-income countries: a systemmanuscript central cmi 03 (01), 268−277 (2022) 275 atic review.bmc healthserv res.2015;15(1):506. doi: 10.1186/s12913-015-1166-8. 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14.don br, kaysen g. serum albumin: relationship to inflammation and nutrition. semin dial. 2004; 17(6) : 432 -7 [doi][pubmed] 15.ekramzadeh m, sohrabi z, salehi m, ayatollahi m, hassanzadeh j, geramizadeh b, sagheb mm. adiponectin as a novel indicator of malnutrition and inflammation in hemodialysis patients. iran j kidney dis. 2013;7(4):304–308 16. mohammed fa, farhood hf, atheemwtwtma. prediction of malnutrition using modified subjective global assessment-dialysis malnutrition score in patients on chronic hemodialysis. j community med health educ. 2014;4(3):291. 17. . ghali ej, malik as. effect of blood flow rate on dialysis adequacy in al-kadhimiya teaching hospital. iraqi j med sci. 2012;10:260–264 18. . bohe j, rennie mj. muscle protein metabolism during hemodialysis. j ren nutr. 2006;16(1):3–16. doi: 10.1053/j.jrn.2005.07.005 19. lowrie eg, li z, ofsthun n, lazarus jm. measurement of dialyzer clearance, dialysis time, and body size: death risk relationships among patients. kidney int. 2004;66:2077–84. 20. stosovic md, naumovic rt, stanojevic mlj, et al. could the level of serum albumin be a method for assessing malnutrition in hemodialysis patients? nutr clin pract 2011;26:607-13. 21. jahromi sr, hosseini s, razeghi e, meysamie a, sadrzadeh h. malnutrition predicting factors in hemodialysis patients. saudi j kidney dis transpl. 2010;21(5):846–851 22. morais aa, silva ma, faintuch j, vidigal ej, costa ra, lyrio dc, trindade cr, pitanga kk. correlation of nutritional status and food intake in hemodialysis patients. clinics (sao paulo) 2005;60(3):185–192. 23. therrien m, byham-gray l, beto j. a review of dietary intake studies in maintenance dialysis patients. j ren nutr. 2015;25:329–338 cmi 03 (01), 268−277 (2022) manuscript central 276 manuscript central safia s. elramli how to cite this article: s.s.e. study of the nutritional status of end-stage renal disease patients on maintenance hemodialysis in hawary kidney center and nephrology unit at benghazi medical center . clinical medicine insights. 2022;268−277. https://doi.or g/10.52845/cmi/2022-3-1-4 manuscript central cmi 03 (01), 268−277 (2022) 277 introduction causes of nutritional disorder in hd inadequate food intake abnormal nutrient metabolism aim and objectives methodology result assessment of nutritional status of hd. patients prevalence of malnutrition using subjective global assessment body mass index in the study patients bmi and sga score laboratory investigation association between nutrient intake and sga discussion conclusions references clinical medicine insights received 27 mar 2021 | revised 25 apr 2021 | accepted 20 may 2021 | published online 30 jun 2021 doi: https://doi.org/10.52845/cmi/2021-2-2-4 cmi journal 2 (2), 110−124 (2021) issn (o) 2694-4626 review article exercise and non-communicable diseases: part i cardiovascular diseases, respiratory diseases, obesity, depression, liver diseases shashi k. agarwal, md ∗ 12227 us highway 1, #309 north brunswick, nj 08902,usa abstract physical activity has established itself as a major risk factor for many chronic diseases. individuals who lead a sedentary life have higher morbidity and mortality. exercise, a subcategory of physical activity, is usually planned and structured involving large muscle groups. it is a major recommendation from all professional health associations to prevent and beneficially modulate the course of several chronic diseases. there are also emotional benefits and exercising individuals experience a better quality of life. this manuscript discusses the beneficial effects of exercise on five major non-communicable diseases, namely cardiovascular diseases, respiratory diseases, obesity, depression, and liver diseases. keywords: exercise, non-communicable diseases, cardiovascular diseases, copd, obesity, depression, liver diseases copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). 1 introduction physical activity (pa) is defined as any bodily movement produced by the contraction of skeletal muscles resulting in a substantial increase in resting energy expenditure1. exercise is defined as ’any sport or activity that works large groups of muscles, is continually maintained and performed rhythmically2. physical activity includes all movement that increases energy use, whereas exercise is planned, structured physical activity3. exercises may be aerobic or resistance, butmay also involve stretching, balance, and gait workouts and non-traditional activities such as tai chi and yoga4−6. activities such as walking, cycling, jogging, and swimming are primarily aerobic exercises. they increasemitochondrial density, insulin sensitivity, oxidative enzymes, blood vessel compliance and reactivity, lung function, immune function, and cardiac output5. resistance exercises include workouts with free weights, weight machines, bodyweight, or elastic resistance bands6. they result in improvements inmuscle mass, body composition, strength, physical function, bone mineral density, insulin sensitivity, blood pressure, cmi journal 2 (2), 110−124 meerp ltd 110 open access journal https://doi.org/10.52845/cmi/2021-2-3-11 https://orcid.org/0000-0003-0007-5582 https://creativecommons.org/licenses/by-nc-nd/4.0/ https://medicineinsights.info/index.php/cmi/index exercise and non-communicable diseases: part i cardiovascular diseases, respiratory diseases, obesity, depression, liver diseases lipid profiles, and cardiovascular health7. stretching increases the range of motion around joints and enhances flexibility8. balance training can reduce falls risk by improving balance and gait9. activities like tai chi and yoga combine flexibility, balance, and resistance exercises10. besides the physical benefits, all exercises benefit mental and emotional health11. the world health organization recommends that adult men and women should accumulate at least 150 min of moderate-intensity physical exercise per week and young people aged 5–17 years should accumulate at least 60 min of physical exercise of moderate to vigorous intensity daily12. the benefits of exercise for common chronicmedical conditions are discussed in this two-part manuscript. part i discusses the role of exercise in cardiovascular diseases (cvd), chronic obstructive pulmonary disease (copd), obesity, depression, and liver diseases. part ii discusses its role in cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, and arthritis. 2 discussion the centers for disease control and prevention (cdc) defines chronic diseases as “conditions that last 1 year or more and require ongoing medical attention or limit activities of daily living or both”13. chronic diseases are usually non-communicable diseases (ncds) and inflict a heavy global health burden14. they include cvd (including hypertension, coronary artery disease, stroke, and heart failure), cancers, chronic respiratory diseases (chronic obstructive pulmonary disease, sleep apnea, and asthma), diabetes, alzheimer’s disease, chronic kidney disease, arthritis, depression, obesity, and liver diseases (nonalcoholic and alcoholic hepatitis, visupplementary information the online version of this article (10.52845/cmi/2021-2-2-4) contains supplementary material, which is available to authorized users. corresponding author: shashi k. agarwal, md shashi k. agarwal, md 2227 us highway 1, #309 north brunswick, nj 08902,usa email: usacardiologist@gmail.com ral hepatitis, cirrhosis of the liver)15. cardiovascular diseases are the leading ncds worldwide and are the leading cause of loss of disability-adjusted life years and deaths globally16. chronic respiratory diseases (such as asthma, chronic obstructive pulmonary disease (copd), and lung cancer) contribute significantly to the rising burden of ncds globally17. overweight/obesity is a pandemic – its worldwide prevalence has doubled since 1980, and it is now affecting nearly a third of the world’s population18. affected individuals face an increased risk of a multitude of comorbidities, including cardiovascular disease, diabetes, and many cancers19. depression is a common disease and is on the increase20. depression cases worldwide registered an increase of 49.86% incident cases increased from 172 million in 1990 to 25,8 million in 201720. depression affects both mental and physical health and is often a potentially lethal disease21. the burden of liver diseases, such as nonalcoholic fatty liver disease (nafld), alcoholic liver disease, and hepatocellular carcinoma, continues to rise worldwide22. several personal factors play an important role in the genesis and progression of chronic ncds – both modifiable and non-modifiable23. non-modifiable risk factors include heredity, age, race, and gender24. lifestyle behaviors are modifiable risk factors and include diet, obesity, smoking, and alcohol consumption24. another modifiable risk factor is sedentary behavior and exercise24. the beneficial effects of increased physical activity, including structured activity such as exercise, on ncds, are enormous25,26. its effect on cardiovascular diseases, respiratory diseases, obesity, depression, and liver diseases is discussed in this manuscript. 2.1 cardiovascular diseases a reduction in sedentary time and an increase in exercise time beneficially modulate cvds27−29. exercise lowers cvd risk in a dose-dependent manner; moderate physical activity is associated with a 26% reduction in cvd risk, whereas high-intensity activities impart a 42% risk reduction30−32. physical activity and pro-active physical exercise can even slow down or reverse cvd progression33−37. regular pa also reduces the risk of cvd mortality, both cmi journal 2 (2), 110−124 (2021) meerp ltd 111 mailto:usacardiologist@gmail.com meerp ltd shashi k. agarwal, md in healthy individuals38 and in cardiac patients39,40. moderate to high-intensity exercise has been shown to increase life expectancy by 1.3 to 3.7 years and active individuals remain free of cvd 1–3 years longer than their sedentary peers41. aerobic exercise lowers blood pressure (bp) by 57 mmhg42 while dynamic resistance training lowers bp by 2–3 mmhg43 in adults with hypertension (in both unmedicated and medicated patients). interestingly, the magnitude of these bp reductions rivals the magnitude of those obtained with firstline antihypertensive medications44. exercising as little as one day per week is as effective as pharmacotherapy for reducing all-cause mortality among hypertensive patients45. in coronary artery disease patients, exercise reduces angina, myocardial infarction, and sudden cardiac death46. following a myocardial infarction, exercise reduces re-infarction, cardiac mortality, and all-cause mortality47. physical inactivity48 and low levels of fitness49 are also risk factors for stroke. following a stroke, moderate to high-intensity aerobic exercise (of 20–40 min and 3–5 days per week) helps improve physical fitness, maximal walking speed, and walking endurance50. exercise is preventive for heart failure (hf)51,52. khan et al. demonstrated that men in the top quartile of longterm fitness levels had a 53% lower risk of developing hf52. in those with established heart failure53, exercise improves their quality of life54, reduces hospitalizations55, and lowers mortality56. physical activity has been noted to reduce the risk of atrial fibrillation57. several studies have shown that exercise not only helps prevent peripheral artery disease (pad)58 but also helps improve walking distance59 and the quality of life in these patients60,61. physical activity often reduces the risk of erectile dysfunction (ed)62. it also helps improve function in men with established ed63. exercise also helps reduce several cvd risk factors, such as smoking64, obesity65, diabetes mellitus66, hyperlipidemia67, alcohol abuse68, chronic kidney disease69, depression70, loneliness71, psychosomatic stress71, sleep disturbances72, and illicit drug use73. many mechanisms play a role in the beneficial effects of exercise74. regular exercise can help to reduce weight, reduce blood pressure, and improve lipid disorders, including raising hdl, decreasing ldl, and lowering triglycerides75. it also decreases insulin resistance, reduces blood coagulation and systemic inflammation76. vigorous physical activity reduces heart rate, increases myocardial oxygen supply, improves myocardial contraction and stroke volume, establishes electrical stability, and increases physiological cardiac hypertrophy77−79. however, older adults with chronic medical conditions must be careful about exercising vigorously, and stress testing may be required in people with known cvd80. further, in certain conditions, such as decompensated congestive heart failure or severe aortic stenosis, exercise may be restricted or contraindicated81. 2.2 respiratory diseases exercise, both aerobic and resistance, decreases respiratory symptoms and leads to significant improvements in functional capacity in patients with respiratory diseases82. the benefits of exercise training in patients with copd have been documented in several systematic review meta-analyses and in two cochrane reviews83,84. exercise training is an essential strategy in managing copd, and results in an improvement in 6-minute walk test (6mwt) distance84. several studies using an incremental cycle ergometer test to measure maximal exercise capacity also showed a significant improvement in those patients allocated to pulmonary rehabilitation84. besides a reduction in exerciseinduced hyperinflation, there is an increase in muscle function, delaying the onset of peripheral muscle fatigue and resulting in less dyspnea and an increase in exercise tolerance84. people with copd often have comorbidities that markedly affect their functional capacity85. these include chronic heart disease, metabolic syndrome, musculoskeletal or neurological comorbidities, and many types of cancer86. many of these chronic co-morbidities also improve with regular exercise in patients with respiratory diseases87. the role of exercise in the management of asthma is not well listed in professional organization guidelines. studies suggest that exercise improves asthmarelated symptoms and cardiopulmonary fitness88,89. meerp ltd cmi journal 2 (2), 110−124 (2021) 112 exercise and non-communicable diseases: part i cardiovascular diseases, respiratory diseases, obesity, depression, liver diseases exercise training may lower the ventilatory requirementd of mild and moderate exercise thereby reducing the likelihood of provoking exercise-induced asthma90. in addition, a 12-week aerobic training program demonstrated reductions in bronchial hyperresponsiveness and serum pro-inflammatory cytokines91. there was a decrease in asthma exacerbations in adults with moderate to severe persistent asthma91. the quality of life (qol) also improved in these patients91. exercise training has an established role in cystic fibrosis (cf) management92. a cochrane review (total number of 15 studies with 487 participants) examined the effects of exercise on cf93. physical exercise in these patients improves exercise capacity, pulmonary function, and qol93. there is an increase in sputum clearance through a combination of hyperventilation, mechanical vibration, coughing, and changes in sputum rheology, thereby improving the much-needed bronchial hygiene in patients with cf94. patients with interstitial lung disease also exhibit pulmonary benefits95−97. they experience less breathlessness95. their walking distance (during the 6mwt) improves96. similar benefits have been documented by several other studies97. these patients also report an improved qol with exercise rehabilitation and training97. in patients with pulmonary arterial hypertension, exercise training improves right ventricular function98. benefits have also been reported in patients with asbestosis and pulmonary fibrosis99. 2.3 obesity sedentary behavior is also associated with obesity100. regular exercise help prevent obesity, maintain weight or even lose weight101. a study of >4500 adults from the u.s. national health and nutrition examination survey showed that greater (moderate to vigorous intensity) physical activity was associated with a lower body mass index or bmi102. there is a significant body of evidence supporting the effect of physical activity in both short-term and long-term weight loss in adults103−105. current recommendations from the american college of sports medicine state that pa between 150 and 250minutes per week helps prevent weight gain, pa between 150 and 250 minutes per week provides modest weight loss, while pa >250 minutes per week helps lose clinically significant weight loss101. however, recent work by flack et al suggests that exercise closer to 300 minutes per week is needed for weight loss as there is an approximately 1000-kcal pe week compensatory response that accompanies exercise106. jakicic et al reported that moderate to vigorous pa accumulated in bouts that were >10 min in duration was effective for weight loss at 18 months107. these bouts also helped maintain >10% weight loss from 6 to 18 months. bouts of exercise of <10 min in duration were not effective. a study found that combining 5% to 7% (intentional) weight loss with regular physical activities, such as lifestyle activities or resistance training, resulted in improved mobility and lower extremity physical performance in overweight or obese older adults108. resistance exercises are also effective, but data indicates they produce only minimal reductions in body weight. these exercises, however, help increase the loss of fat mass and help increase fat-free mass. the result is a reduction in the risk of several ncds101. 2.4 depression depressed people have lower levels of pa109 and higher levels of sedentary behavior110. a recent analysis of data from the brazilian national health survey, (59,399 individuals), found that a lack of pa for leisure was associated with depression in young males, middle aged, and older adults111. several other studies have confirmed the protective effects of physical activity on depression112,113. hamer et al noted that risk reduction for depression was noted at a minimal level of at least 20 min/week of any physical activity, with a greater risk reduction with activity at a higher volume and/or intensity114. in a systematic narrative review of 30 prospective cohort studies, mammen and faulkner reported that 25 of the 30 studies found that pa resulted in reduced incident depression115. in a study of 49 studies (266,939 participants), schuch and stubbs found that pa lowered the risk of depression by between 17% to 41%, across all ages and in all continents of the world116. cmi journal 2 (2), 110−124 (2021) meerp ltd 113 meerp ltd shashi k. agarwal, md exercise has recently also shown promise as an effective non-pharmaceutical treatment for depression117−120. exercise of lower duration or lower intensity also imparts a reduction in depressive symptoms118,119. a cochrane review and metaanalysis of 35 randomized controlled trials (1356 individuals) found that exercise was moderately effective at reducing depressive symptoms in depressed adults117. dunn et al. found that in patients with mild to moderate severity of major depressive disorder or mdd, a reduction in symptoms was noted in 47% of patients with exercise (17.5 kcal/kg/week) for 12 weeks120 . in their study, they found that rates of response and remission with exercise were comparable to the rates reported in trials of cognitive-behavioral therapy and antidepressant medication. schuch et al in a meta-analysis of 25 studies (757 individuals randomized to exercise and 730 to control conditions) found a significant antidepressant effect with exercise121. patients with depression also have a higher risk of type ii diabetes122 and cardiovascular disease123 and exercise helps reduce the risk of both. exercise therapy also improves general physical health, body image, patients coping strategies with stress, and the quality of life in depressed individuals124. it also helps them become more independent in activities of daily living124. evidence suggests that both exercise and antidepressant medication may alleviate depression through several processes, such as increased expression of neurotrophic factors125,126 and reduced systemic inflammation127. these influence neuronal growth and plasticity, leading to an increase in neurons, synaptic connections between neurons, and cerebral vasculature128−130. there is evidence that exercise induces increases in hippocampal, prefrontal cortex, and anterior cingulate cortex volume131. 2.5 liver diseases physical inactivity and its related reduced cardiorespiratory fitness have been associated with increased nonalcoholic steatohepatitis (nash) severity132. among obese people, sedentary individuals have an increased risk of having a fatty liver in comparison with weight-matched physically active individuals133. these data provide support for the hypothesis that increasing physical activity through exercise, defined as a planned, structured, and repetitive physical activity with a specific intensity, frequency, and duration, has beneficial effects on nonalcoholic fatty liver disease (nafld)134−136. the american gastroenterological association, the american association for the study of liver diseases, and theamericancollege ofgastroenterology all recommend physical exercise as a treatment for nafld137. whitsett et al. conducted a systematic review of 18 studies and concluded that exercise significantly reduced hepatic fat content138. wong et al demonstrated in a randomized trial of 145 nash patients, aerobic and resistance exercise along with dietary restriction resulted in a 64% remission rate compared to a 20% remission rate in the nonintervention control group139. several randomized trials provide evidence that aerobic exercise and resistance exercises are both effective in reducing liver fat140,141. this occurs even if there is no loss in body weight. exercise in patients with nash may also reduce progression to hepatocellular cancer142. exercise has a direct effect on the liver. aerobic and resistance training improve insulin resistance, liver fatty acid metabolism, and mitochondrial function143. exercise also affects inflammation144. the result is a reduction in liver fat in these patients. hepatitis c (hcv) patients are at an increased risk of cvd and have a lower qol145. studies have shown that hcv patients have lower physical activity than the general population146. exercise in these patients not only reduces the cvd risk but also improves their qol147. an improvement in the cognition function of these patients with exercise has also been noted148. in cirrhotic patients, exercise can improve endurance and functional outcomes without any adverse effects149. in this systematic narrative review, moderate-intensity aerobic exercise or resistance training, 4 days/week, 20 minutes, for at least 8 weeks, helps cirrhotic patients to improve their cardiorespiratory system149. pretransplant exercise helps to improve the physical and mental status of the patient while on the waitlist. an exercise and nutritional program appear to benefit their cardiopulmonary and musculoskeletal meerp ltd cmi journal 2 (2), 110−124 (2021) 114 exercise and non-communicable diseases: part i cardiovascular diseases, respiratory diseases, obesity, depression, liver diseases functions150. the patients notice an improved functional status and a sense of well-being. following transplantation, exercise trainingwas associatedwith a shorter length of hospital stay and a reduced 90-day readmission rate151. 3 conclusion physicians often overlook exercise 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improving functional status and sarcopenia while on the transplant waiting list. liver transpl. 2018 jan;24(1):122-139. doi: 10.1002/lt.24958. 151. al-judaibi b, alqalami i, sey m, qumosani k, howes n, sinclair l, chandok n, eddin ah, hernandez-alejandro r, marotta p, teriaky a. exercise training for liver transplant candidates. transplant proc. 2019 dec;51(10):33303337. doi: 10.1016/j.transproceed.2019.08.045. how to cite this article: agarwal s.k, md, exercise and non-communicable diseases: part i cardiovascular diseases, respiratory dis-eases, obesity, depression, liver diseases. clin-ical medicine insights. 2021; 110−124 . https://doi. org/10.52845/cmi/2021-2-2-4 meerp ltd cmi journal 2 (2), 110−124 (2021) 124 introduction discussion cardiovascular diseases respiratory diseases obesity depression liver diseases conclusion cmi 03 (02), 297−303 manuscript central 297 clinical medicine insights doi: https://doi.org/10.52845/cmi/2022-3-2-2 cmi 03 (02), 297−303 (2022) issn (o) 2694-4626 research article maldi-tof analysis of mitochondrial peptides adam good 1 , alicia wells 1 , ben katz 2 , michael alexander 1,3 , dmytro klokol 3,4 , mike k.s. chan4 , michelle b.f. wong4 , desiree c.t. cox 3 , jonathan r.t. lakey 1,4 corresponding author: jonathan rt lakey phd, msm, professor emeritus university of california irvine 1 university of california, irvinedepartment of surgery, 2 university of california, irvinedepartment of chemistry, 3 biopep, 4621 technology drive, golden, co, 80403, usa 4 european wellness group, klosterstrasse 205id, 67480, edenkoben, germany 5 university of california, irvinedepartment of biomedical engineering introduction peptides are linear polymers formed by a series of amino acid residues that are linked together through peptide bonds [1]. in comparison to proteins, which typically contain between 50 and 2000 amino acid residues and have a mean molecular weight between 5.5 and 22 kda, peptides have fewer than 50 residues and a reduced weight. a unique set of proteins and peptides are produced in each cell line and these play a part in the regulation of biological homeostasis [2]. peptides have been demonstrated to play an important role in modulating transcription, transmission of biological information, and in restoring the genetic alterations that occur with age [3, 4]. these peptides are signaling molecules that act as regulatory factors through their interaction with dna and histone proteins. moreover, the physiological process of aging is highly influenced by the peptidergic regulation of homeostasis. as part of the aging process, the frequency and strength of signals to the mitochondria declines, causing signals to be sent back to the nucleus that cause the arrest of cell proliferation and initiation of apoptosis (haas, 2019; akbari, kirkwood, and bohr, 2019) [5-6]. abstract short peptides are known to play an important role in modulating transcription, in transmitting biological information and in restoring the genetic alterations that occur with aging. this paper aims to describe a method of identifying the population of peptides within a peptide cocktail formulation. a sample of lung-derived mito organelle (mo) peptides (lbs) of specific pathogen free (spf) mammalian rabbits sourced from charles river labs were analyzed by mass spectrometry and chromatograms were generated for further examination. the experimentally derived peaks were compared between two batches of lbs mo peptides using maldi-tof mass spectroscopy. the following report outlines the experimental methods and the results from performing maldi-tof mass spectrometry on various peptides from the company european wellness (ew). keywords: peptides, mito organelles (mo) peptides, mass spectrometry, maldi-tof copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/lic enses/by-ncnd/4.0/). https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ cmi 03 (02), 297−303 manuscript central 298 peptide therapy aims to renew the strength of signals received by cells to either induce peptide production or renew normal signaling processes, thereby rejuvenating and revitalizing tissues as well as the organism as a whole [3, 4, 7-9]. although the content of peptides is similar between cells, the function and morphology of each cell defines the contents of its biologically active substances and unique ultrastructures. moreover, certain biologically active substances are predominantly synthesized or accumulated in specific tissues. since the signaling activity and function of peptides is largely based on the cell type, peptide therapy utilizes organ-specific extracts to target diseased or aging tissue. due to the short lengths of peptides (<45 residues) and their low molecular weights, their biosynthesis and extraction processes permit mass production and distribution for use in therapeutic treatments [3]. through years of research and extensive global practice, mf-plus has manufactured two products, nano organo peptides (nops) and mito organelles (mo) peptides, which are intended for use in both animals and humans as a revitalization therapy [10]. mito organo (mo) peptides are biologically extracted mixtures of cellular peptides that have predominantly mitochondria-specific functions [11]. although cells of different organ systems have similar functions, variations in cellular functions between organs creates the differential expression of peptides, which can be utilized for various therapeutic purposes. mo peptides are organ-specific extracts that are aimed at revitalizing and rejuvenating mitochondrial activity, thereby regenerating cells and organisms as a whole [12,13]. despite the numerous studies highlighting the therapeutic effectiveness of mo peptides, little is known of the exact makeup of these formulations. matrix-assisted laser desorption/ionization time of flight (maldi-tof) mass spectrometry has been able to identify and quantify analytes in complex solutions and allows for highly sensitive, fast and high-throughput analysis [14,15]. in addition, it is thought to be able to identify the population of peptides derived from peptide cocktail formulations. the mass spectrometer produces a readout of peaks plotted in relative abundance against mass-to-charge ratios. by searching the experimentally-derived peaks against a database of known proteins, it may be possible to identify the peptides. the following report outlines the experimental methods and the results of performing maldi-tof mass spectrometry on various ew peptides. 2. materials and methods two batches of lbs mo201901 ew peptides were suspended in saline solution upon collection. formulations with the characterization lbs were extracted from lung samples in specific pathogen free (spf) mammalian rabbits sourced from charles river labs. all samples were kept on ice throughout the duration of the experiment and were handled using good laboratory practices. sample preparation the thermofisher scientific bca protein assay protocol was utilized to determine the protein concentrations of the unknown peptide solution. triplicate sample readings were obtained for the peptide solution using the tecan infinite f200 microplate reader at a wavelength of 570 nm. sample preparation of lbs mo samples peptides from the lbs mo samples were withdrawn at a volume of 30 µg/ml and pipetted into auto column tubes in an agarose gel. sample mixtures were separated by molecular weight with sds-page and coomassie™ blue staining to visualize the proteins. an individual protein band was cut out from the gel and placed into a lowbinding, siliconized microcentrifuge tube. proteins were then de-stained in the tube with 100μl of a 1:1 methanol and water solution and vortexed. the gel piece was further washed by removing the de-stained solution in the tube and adding 400μl of water. tubes were shaken for 15 minutes at room temperature, and the de-staining was continued until the gel became colorless with a minimum of 3 repeats. after destaining, 400μl of 100% acetonitrile was added to dehydrate the gel for 10 minutes and dried by vacuum centrifugation after removal of the supernatant. disulfide bonds were removed with the addition of 100μl of 10mm dithiothreitol (dtt) to the gel and then the gel was incubated for 45 minutes at 55°c. the solution was removed and 100μl of 55mm iodoacetamide was added to the gel and then incubated for an additional 30 minutes at cmi 03 (02), 297−303 manuscript central 299 room temperature under low light conditions, allowing trypsin to access cleavage sites. the solution was then added to 400μl of the gel and a wash solution (50% per volume acetonitrile, 25mm ammonium bicarbonate) was added. the gel was then incubated at room temperature and vortexed three times for 15 minutes. the gel was subsequently dehydrated with 400μl of 100% acetonitrile for 10 minutes and dried in a vacuum centrifuge after removal of the supernatant. enzyme digestion a ph 8 protease trypsin solution diluted 1:1000 with 25mm ammonium bicarbonate was prepared and diluted to a final concentration of 10 20 μg/ml. trypsin was added to the gel and it was incubated on ice for 1 hour. the solution was removed and replaced with 25mm ammonium bicarbonate to cover the gel. the gel was then incubated at 37°c overnight. peptide extraction the supernatant containing the peptides was transferred to a new microcentrifuge tube. a gel extraction solution of 50% per volume acetonitrile, 1% trifluoroacetic acid (tfa) and 49% water was added, which was followed by incubation at room temperature and a vortex cycle of 20 minutes. this solution was combined with the supernatant from the peptides in the new microcentrifuge tube. analysis 10μl of a 1:1 solution of 0.1% tfa and 100% acetonitrile was added to 10μl of each sample. 1μl of dmp was added onto the maldi plate. 1μl of sample solution was then applied with 1:1 0.1% tfa and 100% acetonitrile onto the same spot as the dmp and the spot was allowed to dry. the samples were run on maldi in triplicate and the peaks were compared against a database to identify the key peptides and amino acids found in the samples. data analysis data was analyzed using the chromatogram tool in masslynx software. replicates for each batch were analyzed together and chromatograms for each were generated. the masses of the three most prominent peaks were deconvoluted and the key peptides and amino acid components were determined against open-source databases. 3. results the concentration of peptides in each batch was initially determined via the thermofischer™ scientific bca protein assay (figure 1). the average protein concentration of 252.0 μg/ml ( 12.83μg/ml) and 260.6μg/ml ( 32.23μg/ml) was determined for batch 1 and batch 2 respectively. there were no statistically significant differences between batches (p = ns). figure 1. average protein concentration (ug/ml) of batch 1 and 2 lbs mo201901 peptides. standard error bars are included. no statistically significant differences were found between batches (p=ns). manuscript central jonathan rt lakey et al. cmi 03 (02), 297−303 manuscript central 300 the samples were then separated by molecular weight with sds-page and digested with the protease trypsin. once prepared, the samples were run on maldi-tof in triplicate and chromatograms were generated (figure 2). the deconvoluted masses of batch 1 (figure 3) and batch 2 (figure 4) of lbs mo show similarity in major protein components. the deconvoluted masses in batch 1 represent five major components with sizes of 14,969 da, 15,300 da, 8,449 da, 8,294 da and 4,618 da respectively. batch 2 results showed six major protein masses of 14,969 da, 15,301 da, 8,294 da, 8,449 da, 5,436 da, and 6,214 da respectively. figure 2. chromatograms obtained from batch 1 (a) and batch 2 (b) of lbs mo201901. red arrows pointing upwards on the x-axis of each chromatogram identify peaks that correspond to differing peptide components in the solution. the green, blue, and red chromatograms associated with both batch 1 and batch 2 illustrate different runs of the sample. figure 3. deconvoluted mass spectrometry data obtained from lbs mo batch 1. five peptide fragments are ordered from left to right in decreasing order of abundance within the sample. the relative sizes of peptides from left to right are 14,969 da, 15,300 da, 8,449 da, 8,294 da and 4,618 da respectively. cmi 03 (02), 297−303 manuscript central 301 figure 4. deconvoluted mass spectrometry data obtained from lbs mo batch 2. six peaks representing six major peptide fragments are ordered from left to right in decreasing order of abundance within the sample. the relative sizes of peptides from left to right are 14,969 da, 15,301 da, 8,294 da, 8,449 da, 5,436 da, and 6,214 da respectively. 4. discussion short peptides are known to play a critical role in modulating the transmission and transcription of biological information and have been shown to decline throughout the natural process of aging [2]. peptide therapy aims to either reinstate normal signaling patterns by renewing the strength of the signals received by cells or induce the cells to begin to produce peptides of their own [16]. since different tissue types produce different peptides, peptide therapy utilizes organ-specific extracts to target aging or diseased tissue with the goal of revitalizing normal peptidergic signaling in these regions and improving overall health and wellbeing [17]. through years of testing and development, european wellness (ew) and mf-plus have manufactured mito organelles (mo) peptides that are intended for use in peptide therapy in both animals and humans [18]. despite numerous studies demonstrating the potential of mos in therapeutic applications such as cosmetics [19] and regenerative organ repair [11], little research has been done to investigate and identify the key peptides in these solutions. mass spectrometry (ms) is a chemical analysis technique that enables the direct identification of molecules based on their mass-to-charge ratios and fragmentation patterns [20]. by comparing experimental ms data with that of well-established open-source databases, the identity of the molecules, peptides, or proteins can be found within a solution. due to the low-cost and rapid application of ms in identifying the components of unknown solutions, our study employed ms as our primary method of identification. maldi-tof utilizes a protein fingerprinting method in which the sample is digested by a proteolytic enzyme such as trypsin and used to generate an ms spectrum that can be searched against existing databases [21, 22]. matched hits are ranked according to a scoring method in which the candidate protein that contains more proteolytic peptides has a higher score and generally represents the most probable protein/peptide. the desirability of maldi-tof also includes the speed at which each run is performed– often less than one minute to obtain– and the speed at which analysis can be performed against a database. conclusion: the results of our study using maldi-tof to analyze the mo lbs sample indicated that there were five major peptide products of interest in batch 1 and six major peptide products in batch 2 (figure 3 and 4). following deconvolution, five manuscript central jonathan rt lakey et al. cmi 03 (02), 297−303 manuscript central 302 peptides were identified in batch 1 (figure 3) with masses of 14,969 da, 15,300 da, 8,449 da, 8,294 da and 4,618 da. batch 2 identified four of the same peptides– 14,969 da, 15,301 da, 8,294 da, 8,449 da in size– and two additional peptides of 5,436 da, and 6,214 da in size (figure 4). slight differences in peptide products between batches is likely due to the heterogeneous nature of cellularly-derived solutions and differences that occurred during the extraction process. further research must be conducted to confirm the identity of the peptides and discover their significance in peptide therapy. supplementary materials: the following supporting information can be downloaded at: www.mdpi.com/xxx/s1, figure s1: title; table s1: title; video s1: title. author contributions: conceptualization, j.l., m.w., m.c., d.k., d.c.; methodology, b.k., m.a.; validation, b.k.; formal analysis, b.k.; investigation, a.w., a.g., b.k.; data curation, a.w., a.g., b.k.; writing—original draft preparation, a.w., a.g.; writing—review and editing, a.w., a.g., j.l.; visualization, j.l., m.w., m.c., d.k.; supervision, j.l., m.w., m.c., d.k., d.c., b.k., a.m.; project administration, j.l., m.w., m.c., d.k., d.c., b.k.; funding acquisition, j.l., m.w., m.c., d.k., d.c.. all authors have read and agreed to the published version of the manuscript. funding: this research was funded by a grant to the university of california, irvine from european wellness biomedical group. institutional review board statement: not applicable data availability statement: the data presented in this study are available in the study outlined. acknowledgments: the authors wish to acknowledge the support of the department of surgery and the core mass spectrometry laboratory of the university of california, irvine for their support. conflicts of interest: the funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. references 1. berg, j. m.; tymoczko, j. l.; stryer, l., primary structure: amino acids are linked by peptide bonds to form polypeptide chains. in biochemistry. 2002; 5. 2. caputi, s.; trubiani, o.; sinjari, b.; trofimova, s.; diomede, f.; linkova, n.; diatlova, a.; khavinson, v., int j immunopathol pharmacol. 2019;33:2058738 419828613. 3. khavinson, v. k., lin'kova, n. 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quantitative mass spectrometry: an overview. philosophical transactions. series a, mathematical, physical, and engineering sciences, 2016; 374(2079): 20150 382. manuscript central jonathan rt lakey et al. clinical medicine insights received 27 mar 2021 | revised 25 apr 2021 | accepted 28 may 2021 | published online 30 jun 2021 doi: https://doi.org/10.52845/cmi/2021-2-2-5 cmi journal 2 (2), 124−143 (2021) issn (o) 2694-4626 review article exercise and non-communicable diseases: part ii cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, arthritis shashi k. agarwal, md ∗ 12227 us highway 1, #309 north brunswick, nj 08902,usa abstract non-communicable diseases (ncds) are the leading global cause of death and disproportionately afflict those living in low-income and lower-middle-income countries. healthy lifestyle behaviors, including eating a high-quality diet, non-smoking, engaging in moderate to vigorous physical activity, and drinking alcohol in moderation, have been associated with a lower risk of ncds, a decline in worsening, and a reduction in associated mortality. the first part of this twopart series discussed exercise and its effects on cardiovascular and respiratory diseases, obesity, depression, and liver ailments. this second part discusses the deleterious effects of smoking on five noncommunicable diseases, viz., cancer, diabetes mellitus, chronic kidney disease, alzheimer’s disease, and arthritis. this manuscript highlights the benefits of exercise, in reducing the incidence, progression, and premature mortality of ncds. keywords: exercise, non-communicable diseases, cancer, diabetes mellitus, chronic kidney disease, alzheimer’s disease, arthritis copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). 1 introduction exercise (or lack of it) is fast becoming a major lifestyle factor in the prevention and treatment of major non-communicable diseases1. it is also used to treat back pain2 sports injuries3, osteoporosis4, inflammatory bowel disease5, neurodegenerative diseases (such as parkinson’s disease)6, huntington’s disease7, multiple sclerosis8, anxiety disorders9, and many other ailments10−11. exercise helps increase confidence, improve socialization, brings happiness, and helps improve sleep12,13. the overall quality of life is also improved14. a recent us study suggested that moderate to vigorous physical activity could significantly reduce general premature mortality and increase life expectancy15. cmi journal 2 (2), 124−143 meerp ltd 125 open access journal https://doi.org/10.52845/cmi/2021-2-3-11 https://orcid.org/0000-0003-0007-5582 https://creativecommons.org/licenses/by-nc-nd/4.0/ https://medicineinsights.info/index.php/cmi/index meerp ltd shashi k. agarwal, md the world health organization recommends that adult men and women should accumulate at least 150 min of moderate-intensity physical exercise per week, while young people aged 5–17 years should accumulate at least 60 min of physical exercise of moderate to vigorous intensity daily16. 2 discussion chronic ncds are common conditions affecting humans17. they are gradually replacing infectious diseases as the leading health burden across the world18. the centers for disease control and prevention (cdc) of usa defines chronic diseases as “conditions that last 1 year or more and require ongoing medical attention or limit activities of daily living or both”19. they estimate that six in ten adults in the usa have a chronic disease, while four in ten have two or more chronic diseases19. in a recent study, ng et al reported that most individuals develop at least one chronic disease during their lifetime20. rosella et al found that in the ontario population, two-thirds of individuals had four or more chronic conditions at the time of their death21. more and more deaths globally, are now attributable to chronic ncds22. according to the world health organization (who), chronic ncds accounted for 71% of the 57 million global deaths in 201623. chronic non-communicable diseases include cardiovascular diseases (cvds) (such as hypertension, coronary artery disease, stroke, and heart failure), cancer, chronic respiratory diseases (such as chronic obstructive pulmonary disease, sleep apnea, and asthma), diabetes mellitus, alzheimer’s disease, chronic kidney disease (ckd), arthritis, depression, obesity, and liver diseases (such as nonalcoholic supplementary information the online version of this article (10.52845/cmi/2021-2-2-5) contains supplementary material, which is available to authorized users. corresponding author: shashi k. agarwal, md shashi k. agarwal, md 2227 us highway 1, #309 north brunswick, nj 08902,usa email: usacardiologist@gmail.com and alcoholic hepatitis, viral hepatitis, cirrhosis of liver)24. there is overwhelming evidence that exercise also confers significant benefits in the prevention and management of these diseases25,26. as discussed in part i of this two-part manuscript, it has significant benefits for cardiovascular diseases, respiratory diseases, obesity, depression, and liver diseases. this manuscript will discuss its benefits for cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, and arthritis. cancer was diagnosed in 18 million individuals in 201827. cancers of the lung (2.09 million cases), breast (2.09million cases), and prostate (1.28million cases) were themost common in this group27. cancer was responsible for 9.6 million deaths globally in 201828. today, cancer-related mortality exceeds that caused by communicable diseases such as human immunodeficiency virus/acquired immunodeficiency syndrome, tuberculosis, and malaria, combined29. diabetes mellitus (dm) is also a common chronic disease30. it is mainly categorized into 2 major subtypes, type i dm (t1d) and type ii dm (t2d)31. t1d is an autoimmune disorder, with several genetic, epigenetic, and environmental factors playing a role in its genesis32. t2d is characterized by insulin resistance and accounts for 90-95% of all diabetes cases31. it often leads to the development of several microvascular (retinopathy, nephropathy, and neuropathy) andmacrovascular (coronary artery disease, stroke, peripheral artery disease) complications33. deaths from dm continue to increase all over the world34. ckd has an estimated prevalence of 10.6%13.4%35, and its prevalence is growing rapidly36. ckd progresses to end-stage kidney disease requiring a kidney transplant, and these numbers are also on the increase37. it is estimated that the number of people requiring renal replacement will double to 5.4 million by 203038. this population has a mortality rate that is over 100-fold compared to that seen in the normal population39. dm continues to be the leading cause of ckd40. dementia affects around 50 million people worldwide and this number is projected to increase to 152 million by 205041. alzheimer’s disease (ad) is the most common dementia and is caused by amyloid-beta peptide accumulation in the medial temporal lobe and neocortical structures42. treatment for ad is symptomatic as there is no meerp ltd cmi journal 2 (2), 124−143 (2021) 126 mailto:usacardiologist@gmail.com exercise and non-communicable diseases: part ii cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, arthritis cure available at this time43. arthritis is of over 100 types, the most common being rheumatoid arthritis, osteoarthritis, psoriatic arthritis, and inflammatory arthritis44. osteoarthritis (oa) is the most prevalent chronic joint disease and is associated with cartilage loss45,46. it usually affects the knees, although it can affect any joint45,46. it is a major cause of disability in older adults47. rheumatoid arthritis (ra) is a chronic, systemic, immune-inflammatory disease, especially affecting the synovial joints resulting in synovitis, joint erosion, and cartilage damage48. its etiology includes several genetic, environmental, and endogenous factors49. lifestyle changes can beneficially modify chronic ncds50. the detrimental but modifiable lifestyle factors include tobacco smoking, inadequate vegetable and fruit consumption, excessive alcohol consumption, physical inactivity, and obesity51. part i reviewed the benefits of exercise for cardiovascular diseases, respiratory diseases, obesity, depression, and liver diseases. this manuscript will discuss its benefits for cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, and arthritis. 2.1 cancer in 1986, winningham et al suggested that physical activity may play a major role in oncology52. the cancer modulating effect of exercise has been confirmed by several subsequent studies53−55. behrens and the group found that low physical activity accounted for 6% of all cancers in germany53. they reported that physical inactivity resulted in an increase in endometrial cancer by 15%, renal cancer by 17%, liver cancer by 24%, and lung cancer by 19%53. according to islami and the group, physical inactivity accounted for 2.9% of all cancer cases in the us54. they estimated that physical inactivity accounted for 26.7% of uterine cancers, 16.3% of colorectal cancers, and 3.9% of female breast cancers54. a recent umbrella review, including 19 reviews, 26metaanalyses, and 541 original studies, evaluating physical activity and cancer risk, concluded that regular physical activity is beneficial in preventing 7 major cancers (colon, breast, endometrium, lung, esophagus, pancreas, and meningioma)55. the greatest beneficial impact appears to be on breast and colon cancer56. in a meta-analysis of 38 cohort studies in 2016 by pizot et al, breast cancer risk was reduced by 12-21% in the most physically active women than in those who were least physically active57. in another more recent study, exercising 7 hours a week reduced colon cancer risk by 40%58. several studies have also reported significant reductions in physical activity in cancers of the stomach59, kidney60, bladder60, and endometrium61. minimal amounts of exercise may have protective effects62, although there appears to be a dose-dependent relationship63−65. following a cancer diagnosis, exercise is associated with better clinical outcomes66−69. animal studies have demonstrated a decrease in cancer tumor growth with exercise67. exercise therapy before the initiation of chemotherapy is associated with improvements in tolerance to cancer treatment68. benefits are also noted with exercise pre-surgery69. pretreatment exercise results in mitigation of the significant functional decline often noted in cancer patients68,69. exercise during treatment also demonstrates clinical benefits70−83. these patients notice an improved tolerance to chemotherapy and surgery69.70. their hospital stay is decreased69. they have fewer side effects and less fatigue71,72. their aerobic endurance, strength, flexibility, and body composition improves73. they become more physically fit and have increased energy levels and vitality74. there is an improvement in sleep quality75 and a reduction in depression76 and anxiety77, often experienced by these patients. exercising cancer patients also improve their self-esteem71. their qol improves78. exercise helps decrease metastasis and cancer recurrence79,80. benefits of exercise have also been seen in individuals after metastasis has occurred81. survival is increased82,83. regular exercise continues to be recommended by various world health organizations for cancer patients84−88. physical activity induces several cancer-preventive changes in the human body, including reducing adipose tissue, improving insulin resistance, reducing inflammation, enhancing immune function, modulating sex hormones and growth factors, and enhancing resistance to oxidative stress and dna damage89. in patients with established malignant cmi journal 2 (2), 124−143 (2021) meerp ltd 127 meerp ltd shashi k. agarwal, md tumors, physical activity/exercise paradigms regulate intra-tumoral vascular maturity and perfusion, hypoxia, and metabolism and augment the antitumor immune response90. more than 40% of patients diagnosed with cancer have comorbid ncds, such as diabetes, obesity, chronic obstructive pulmonary disease, and heart failure91. cancer itself may increase the risk of developing some of these diseases92,93. breast cancer survivors experience an increased risk of cardiovascular disease92 and cardiovascular mortality93. patients with nonmetastatic breast cancer demonstrate a 23% adjusted reduced risk of cardiovascular events, with exercise94. exercise benefits for cancer, therefore, also extend to coexisting ncds. 2.2 diabetes mellitus several studies have stressed the value of regular physical activity as part of lifestyle changes to help prevent or delay type 2 diabetes95,96. church et al found that a weight loss of only 5%-7% achieved with physical activity at least 150–175 min/week and dietary energy restriction demonstrate reductions of 40%–70% in the risk of developing type 2 diabetes in people with impaired glucose tolerance97. a systemic review of randomized controlled trials found that lifestyle changes, including exercise, had a preventive effect on the development of t2d in people with impaired glucose tolerance. while the control group had a diabetes incidence of 9.3% to 67.7%, in this study, the lifestyle intervention group demonstrated a reduced incidence of 3% to 46%98. a recent systematic review of 53 studies done by balk et al found that, compared with usual care, diet and physical activity promotion programs improved several cardiometabolic risk factors and reduced the incidence of type 2 diabetes99. exercise, especially moderate to vigorous, confers several benefits on patients with both type i and type ii diabetes100. aerobic exercise in type i diabetes helps by decreasing insulin resistance and improving lipid levels and endothelial function101. in t2d, aerobic exercise reduces blood glucose, a1c, triglycerides, blood pressure, and insulin resistance102. both t1d and t2d patients lose weight and become more cardio-metabolically fit with aerobic exercise. as a result, the cardiovascular risk diminishes103−105. the latter is important as diabetics have a higher risk of developing cvds106. cvds are responsible for most deaths in these patients107. many diabetic patients are obese, and exercise also helps them get more physically fit and function better108. resistance exercises are also helpful in t2d109,110. these patients generate more muscle mass, more bone mineral density, and become stronger109. there is also improvement in the cardiometabolic profile109. resistance exercises in t1d, if done before aerobic exercises, minimize the risk of exercise-induced hypoglycemia110. flexibility and balance exercises help diabetics improve their joint mobility, which often deteriorates with the combination of hyperglycemia and aging111. stretching exercises increase the range of motion of joints and improve flexibility in these patients112. diabetics may have gait and balance problems, especially if peripheral neuropathy is present113. balance training in these patients can therefore help reduce the risk of falls114. both yoga and tai chi may help improve glycemic control and many qol parameters115,116. aerobic activity also helps reduce mortality in both types i and type 2 diabetes117. exercise stress testing before starting an exercise program is recommended for previously sedentary diabetics or those with cardiovascular autonomic neuropathy118. 2.3 chronic kidney disease the role of sedentary behavior and exercise on gfr and albuminuria, or both, has been extensively studied119−123. sedentary behavior increases the risk of developing ckd, while physical exercise reduces this risk124−126. in a prospective analysis of the cardiovascular health study, greater baseline physical activity was associated with a lower risk of gfr decline >3 ml/min/1.73 m2 per year over 7 years of follow-up127. in the second national health and nutritional examination survey, highly active people, when compared with inactive people, demonstrated a reduced risk for developing kidney failure or dying of ckd over a mean of 13 years128. a recent study has also confirmed the preventive benefits of exercise in ckd129 . meerp ltd cmi journal 2 (2), 124−143 (2021) 128 exercise and non-communicable diseases: part ii cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, arthritis once ckd has developed, physical activity in the affected individual slows down130. this deterioration in physical performance is evidenced by a decreased walking capacity, muscle strength, balance, and fine motor skills131−134. with the initiation of dialysis, physical functioning does not improve135 and continues to deteriorate136 usually becoming a major disability137. the national kidney foundation recommends that patients with ckd on dialysis be “counseled and regularly encouraged by nephrology and dialysis staff to increase their level of physical activity”138. this is because several studies have demonstrated that physical activity benefits patients with ckd139. exercise in these patients is associated with not only a slower decline in egfr, but often an improvement140,141. in a meta-analysis of 13 rcts totaling 421 patients with ckd, zhang et al concluded that exercise therapy was associated with a +2.6 ml/min increase in egfr142. greenwood et al in a retrospective longitudinal cohort study estimated that each extra hour of sedentary behavior was associated with a worsening of kidney function, while each extra hour of total physical activity was associated with a better kidney function143. exercise training in dialysis patients prevents muscle atrophy and improves functional capacity and quality of life144,145. benefits of exercise have also been noted in renal transplant patients146. besides the benefits for the kidneys, exercise in ckd patients improves aerobic and functional capacity147,148. it improves peak/maximum oxygen consumption, strength, fine motor skills, and balance149,150. there is a reduction in cardiovascular outcomes151. several benefits have also been noted with exercise following renal transplantation152. overall, exercise in ckd patients imparts a better prognosis, a better quality of life, and better survival153−155. exercise (aerobic, resistance, and flexibility) has been recommended for ckd patients by major kidney organizations156−158. exercise is usually feasible, and well-tolerated in ckd patients, including those on dialysis and those following renal transplantation159−161. physical activity may be associated with gfr and albuminuria via mechanisms such as modulation of inflammation, endothelial function, the reninangiotensin system, and renal sympathetic nerve activity162−164. the beneficial change in gfr and albuminuria may also be mediated by modification of risk factors such as t2dm blood pressure, adiposity, and dyslipidemia, by increased physical activity165−168. 2.4 alzheimer's disease exercise and brain health are intricately associated169. several cross-sectional, longitudinal observational studies and narrative reviews have discussed the benefits of exercise on cognitive function170−172. meta-analytic reviews have concluded that older adults are protected against cognitive decline if they engage in exercise173−175. northey and his group noted after analyzing 36 studies that physical exercise, in people over the age of 50, improved cognitive function, irrespective of their baseline cognitive status173. falck et al conducted a systematic review and meta-analysis of 48 studies involving adults aged 60 or older and noted that exercise was associated with an improvement in cognitive function174. chen et al recently performed a meta-analysis of 33 rct studies and concluded that exercise interventions improve executive function175. executive functions mainly originate in the prefrontal cortex and include attentional control, working memory, inhibition, and problem-solving. they are all important aspects of cognition. hamer and chida in a systematic review involving 163,000 non-psychotic participants found that the risk of dementia and ad was lowered by 28% and 45% with physical activity176. lautenschlager et al found that in older adults with mild cognitive impairment, 142minutes of extra exercise per week improved cognition177. twomore recent meta-analyses have also confirmed the slowing effects of aerobic exercise on cognitive decline, in patients with mci or even ad178,179. zheng et al evaluated 11 studies involving 1497 participants and found that in patients with mci, aerobic exercise improved global cognitive ability and memory178. panza and colleagues in a meta-analysis of nineteen studies, which included 1,145 subjects, reported that exercise training may delay the decline in cognitive function that occurs in individuals who are at risk of or have develcmi journal 2 (2), 124−143 (2021) meerp ltd 129 meerp ltd shashi k. agarwal, md oped ad179. in patients with ad, exercise results in an improvement in cognitive function180, decreased neuropsychiatric symptoms, and a slower decline in activities of daily living181. and, consequently, reduced caregiver burden182. patients with ad experience fewer side effects183 and better adherence to medications184, with exercise. the mechanisms behind the exercise-related improvement in brain health have been well studied185,186. exercise preserves neurogenesis187,188 and helps beneficial neuroplasticity189. exercise also helps improve diabetes, hypertension, obesity, stress, depression, and inflammation, which are also risk factors for dementia190. in conclusion, physical activity is inversely associated with the risk of developing and the progression of dementia. 2.5 arthritis the beneficial role of exercise in osteoarthritis is also persuasive191−195. improved pain and functional outcomes after exercise therapy in oa are well demonstrated by numerous meta-analytic studies191,192. goh et al showed that exercise not only significantly reduced pain and improved function in patients with oa, but improved performance and qol in these patients as compared with usual care at 8 weeks193. both traditional exercises such as aerobic, resistance, and flexibility, and non-traditional exercises such as tai chi, yoga, and aquatics are effective in the management of knee and hip osteoarthritis194. in their systematic review of 44 clinical trials involving patients with knee osteoarthritis, there was an improvement in physical function and the quality of life, and these effects lasted up to six months after cessation of land-based therapeutic exercises195. severe hip osteoarthritis is one of the main causes of disabling pain, functional impairment, and reduced quality of life in elderly patients196. in a review of 10 rcts, researchers concluded that land-based therapeutic exercises can reduce pain and improve physical function among people with symptomatic hip oa197. landand aquatic-based physical activities help patients with both knee and hip oa to reduce pain and increase mobility, muscle strength, joint flexibility, and aerobic endurance198. initially, aquatic exercises may be deployed. the buoyancy of the water decreases joint loading, which can help decrease pain, and warm water may also have a therapeutic effect199. once patients become more mobile, they can transition to land-based exercises. exercise should be the main intervention for oa patients193,200. weesandt and his group in a review concluded that osteoarthritis can be successfully managed and treated through exercise, with minimal risk of negative consequences201. rheumatoid arthritis also responds well to physical exercise202−208. these patients notice an improvement in joint health and mobility. they increase their aerobic work capacity and become more physically active. they notice an improvement in endurance, strength, and dynamic balance. rheumatoid fatigue and cachexia are reduced. there is also an improvement in psychological well-being. increased physical activity and exercise also help reduce the impact of systemic manifestations of ra209, such as increased inflammation, disturbed vascular function, and increased cardiovascular risk in these patients210−212. despite these benefits, ra patients have lower physical activity levels than healthy individuals213−215, with 71 % of ra patients not participating in regular physical activity216. exercise is relatively safe as compared with pharmacological treatments in the management of arthritis217. the american college of rheumatology/arthritis foundation guidelines for the management of arthritis of the hip and knee emphasize the importance of regularly performed physical exercise as an important therapeutic intervention218. 3 conclusion exercise plays a major preventive and therapeutic role in most non-communicable diseases. it imparts positive physical and psychological health outcomes. it is safe and feasible for most ncd patients. it can help maintain or increase physical independence over time and decrease caregiver burden. most professional associations of ncds emphasize the incorporation of exercise for the prevention and management of these diseases. acknowledgment: none meerp ltd cmi journal 2 (2), 124−143 (2021) 130 exercise and non-communicable diseases: part ii cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, arthritis funding: none conflict of interest: none references 1. suzuki k. chronic inflammation as an immunological abnormality and effectiveness of exercise. biomolecules. 2019 jun 7;9(6):223. doi: 10.3390/biom9060223. 2. galán-martín ma, montero-cuadrado f, lluch-girbes e, coca-lópez mc, mayoiscar a, cuesta-vargas a. pain neuroscience education and 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03 (03), 318−321 (2022) issn (o) 2694-4626 case report open access journal treatment of cancers with a novel combination of re-purposed pharmaceuticals and some nutriceuticals. reginald marsh 1 , tinte itinteang 2 corresponding author: reginald marsh 1 ma, phd, fss. retired, honorary associate professor auckland university, school of medical and health sciences. 480c devonport road tauranga, new zealand. 2 mb bs, phd. minister, ministry of health, kiribati introduction in 2014 a 63 year old woman diagnosed with cll leukaemia (lymphocyte count 6.6) approached our centre. aware of the limited and non-curative treatment already available for cll she felt there was nothing to lose by trying, through her family doctor, any other reasonable approach we might suggest. we were then at the gillies-mcindoe research institute (gmri) which had successfully treated infants with infantile haemangiomas using low dose beta-blockers to inhibit the renin-angiotensin system (ras) [1,2]. the basic idea was that the renin-angiotensin system might also be central in the growth of tumours which might be responsive to similar treatment. as the patient was already taking a beta-blocker, propranolol was easily substituted and titered up to a total of 80mg once daily. while propranolol had a significant effect on the leukocyte count something extra was needed and aliskiren a renin blocker was added. after the propranolol and aliskiren administration there was a decline in the lymphocyte count but gradually it returned to around its previous value. our laboratory studies showed that when the ‘classical’ ras pathway is inhibited, bypass loops such as cathepsins b d & g, and cox2 take over its role. a wave-like response pattern in the lymphocyte counts appeared, that is common in cll, averaging around eight [3]. to deal with the cathepsins we added curcumin (with piperine to increase its solubility and uptake) titered up to a dose of 300mg od. as a cathepsin b blocker[4,5] and aspirin enteric coated 100mg bd.. curcumin and aspirin are both cox2 inhibitors, aspirin also inhibits cox1. our data below ( table 1) of the earlier interventions over the first half of the study showed that there was a correlation of r = 0.773 abstract a 63 year old woman with cll leukaemia offered to try a novel treatment being developed at our centre. beginning with propranolol and aliskiren several additional compounds were tried over time, aspirin, curcumin and bromelain were retained. over the succeeding eight years her lymphocyte count has risen slowly and was presently stable around 35,000. a few weeks ago when bromelain was increased to 500mg pd the lymphocytes dropped to 32.1. the patient still continues to lead a normal life with no side effects, the only complaint being tiredness. this treatment we infer to inhibit cancer growth at least. key words : cancer treatment, repurposed pharmaceuticals plus nutriceuticals. copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/lic enses/by-ncnd/4.0/). https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ cmi 03 (03), 318−321 manuscript central 319 manuscript central reginald marsh et al. (p = 0.009) (60% of the total variance) between our interventions (increasing dosages) and declines in the lymphocyte numbers. the mean of post-intervention values is significantly lower than the pre-intervention mean (t = 2.94, p = 0.016).(used spss v.22) and the second-to-last entry arose from a brief withdrawal of aliskiren leading to a lymphocyte increase from 9.6 to 10.8 declining to 8.5 when the aliskiren was restarted. table1: patient’s lymphocyte count (per 1,000) by treatments added or removed over time. date treatments (mg per day) lymphocytes date treatments (mg per day) lymphocytes 2014 2016 06/27 propranolol 30 6.1 01/02 6.8 07/02 propranolol 60 6.8 02/03 8.1 08/27 6.4 03/06 doxycycline 7.7 09/10 7.4 03/12 doxycycline wd* 10.8 09/17 6.9 03/22 9.6 10/17 7.9 04/18 8.4 11/18 enalapril 60 propranolol 30 8.4 05/16 9.2 12/01 7.4 06/23 8.6 12/26 enalapril wd* 8.9 07/19 9.5 2015 07/25 metformin 500 01/14 aspirin 300 08/08 metformin,1000 01/29 7.6 08/19 9.4 03/10 8.0 09/15 9.6 03/21 propranolol 60 10/13 aliskiren wd* 04/09 7.8 10/31 metformin wd* 11.6 05/17 7.4 11/05 aliskiren 130 06/09 8.1 11/22 8.5 06/19 propranolol 90 12/31 10.7 07/06 6.6 2017 08/07 8.2 01/31 9.9 09/07 propranolol 120 7.6 03/14 10.7 09/21 propranolol 80 aliskiren 150 8.0 04/13 11.9 10/20 7.8 06/20 14.2 12/01 8.0 07/27 15.0 12/19 curcumin 600 08/31 curcumin 1500 13.0 10/10 celebrex 8.6 11/17 celebrex wd * aspirin 400 17.2 *wd=withdrawn 2018 01/05 15.1 unexpected outcomes sometimes followed the introduction of new possible treatment regimes which were purportedly related to cancer decline. the inclusion of doxycycline produced a rise in lymphocytes from 7.7 to 10.8 in a month (2016/03/12) returning to 8.4 two months after its withdrawal. aliskiren was withdrawn at 8.6 to allow metformin 500mg pd to be introduced cmi 03 (03), 318−321 manuscript central 320 manuscript central reginald marsh et al. (2016/16/06). this caused a rise to 9.6 in a month, 2 months later the dose was increased to 1000 producing in a month an increase to11.6 which upon withdrawal of all metformin and reintroduction of aliskiren returned to 8.5 (2016/11/22). after about three years of treatment celebrex was substituted for aspirin as a cox2 inhibitor. (the belief then was that cox1 was not involved in cancer.) the result was that lymphocytes rose from a count of 8.6 to 13.9 in about three weeks so the celebrex was withdrawn and replaced with aspirin. at about that time (2017/10/10) lymphocyte count became 8,600 and her matutes score was 4. her doubling time of 51 months compared well with a common doubling time of 12 months for typical lymphocyte counts for this cancer. her karyotype shows 13q14.3 x 2 (homozygous) deletion. extrapolating the likely trajectory for the progress of her condition shows a much more optimistic position than those with 13q deletions who have already been treated conventionally or are awaiting it [6]. since then there has been a gradual rise in her lymphocyte count to a level of 35,000 after eight years of treatment. this increase in level may be related to unforeseen misadventures from a triple vaccination (boostrix dtpa), taking melatonin (a propranolol inhibitor) for sleep regulation and a probable bite from a white tailed spider requiring steroid treatment. after each of these disruptions there was difficulty in reducing lymphocyte counts, suggesting some cancer resistance to apoptosis, thus the lymphocyte count may have been inflated by senescent cells. this was responded to using co-enzyme q10 [7] (ubiqinone then the more soluble ubiquinol). recently, (18/2/2022) we substituted quercetin (with bromelain for solubility) for co-enzyme q10 assuming, given quercetin’s reputation as an apoptosis promoter, that it might reduce the white blood cells (wbc) as well as the lymphocyte count. over nine weeks wbc remained around 42.2 but lymphocytes declined from 35.9 to 35.0. after leaving the gmri we have continued treatment for another four years. with doses gradually augmented, her levels for the last five months have been around lymphocytes 35.0, wbc 42.3, ggt 37. about the level traditionally used to start regular monitoring, and half the usual level to trigger chemotherapy intervention. however , three weeks ago we withdrew quercetin because of patient’s headaches and increased the bromelain from 156mg pd to 500mg pd. her latest levels are lymphocytes 32.1, wbc 39.1 and ggt 28.0. presumably the purported apoptosis effect of bromelain is reducing both the senescent cells and the cancer activity [8]. discussion the level of ggt (28) suggests little cancer activity at present [9] (at diagnosis it was 215). the present treatment is: aliskiren 150mg od., propranolol 40mg tid, curcumin (with piperine) 500mg tid, aspirin (enteric) 100mg tid, bromelain 500mg od.. now aged 71 the patient lives alone, enjoys a normal life, the main complaint being tiredness, but she does her garden, does some voluntary work, and takes extended solo camping trips driving for up to two months throughout the country. while this regime may or may not cure cll, at least, it seems to inhibit the progress of the cancer with practically no side effects. from our laboratory studies we were aware that the above approach to treatment may also apply to other forms of cancer. the results by tan et.al.[10]. helps to support this and the two studies complement each other, namely that the similar treatments used probably inhibit the progress of cancers. while other people have tried using some of these medications by themselves we are unaware of other attempts to use these pharmaceuticals and nutriceuticals together to treat cancer. acknowledgements: the study was begun when both authors were working at the gillies-mcindoe cancer research centre (gmri) in wellington, nz. rm from the faculty of medicine, auckland university and ti was the chief scientific officer at the gmri. thanks to patient christine and her original gp dr pat scarlett for their forbearance and cooperation; also to dr swee tan (director of the gmri) for his participation in the earlier stages of this venture. cmi 03 (03), 318−321 manuscript central 321 manuscript central reginald marsh et al. sources of support: the research did not receive a specific grant from funding agencies in the public, commercial or not for profit sector . references 1. itinteang t. brasch h. tan s. day d. expression of components of the reninangiotensin system in proliferating infantile hemangioma may account for the propranolol induced accelerated involution. j.plast,reconstr.surg. (2011) doi:10:1016/jb jps.2010.08.039. 2. tan c. itinteang t. leadbitter p. marsh r. tan s. low-dose propranolol regimen for infantile haemangioma. j.ped. & child health.(2015) apr,51(4) 419-24. doi:10.1111 //jpc.12720. 3. munro m. wickremesikera a. davis p. itinteang t. et.al. renin-angiotensin system and cancer: a review. integrative cancer science and therapies. (2017) v.4 (2)3-6. doi: 10.15761/icst. 1000) v.4 (2)3-6. 4. prasad s. tyaji a. aggarwal b. recent developments in delivery, bioavailability, absorption and metabolism of curcumin: the golden pigment from golden spice.cancer res.treat.. (2014) jan; 6 (1): 2-18. doi: 10.4 143 /crt.2014.46.1.2. 5. jin g. yang y. liu l. zhao j. et.al. combination curcumin and (-)epipigalloc atechin-3-gallate exhibits colorectal carcinoma microenvironment-included angiogenesis by jak/sat3/il-8 pathway. oncogenisis. 6,8e 384 (2017). doi: 10.1038/oncsis.2017.84. 6. h. stileenbauer s. benner a. leupolt e, et. al. genomic aberrations and survival in chronic lymphocytic leukemia. new england j. medicine.(2000) 343:1910-1916. doi: 10.105 6/nejm 200012283432602. 7. cancer treatment. coenzyme q10 (pdq) health prof. version. (2020) 4 june. national cancer centre. 8. novas l. et.al. stability, purification and application of bromelain: a review. biotechnol.prog. jan-fe 2016; 32 (1). 5-13. doi: 10.102/btpr.190.rpub2015 nov 17. 9. strasak a. rapp k. brant l. hilbe w. et.al. association of y-glutamyltransferase and risk of cancer incidence in men: a prospective study. cancer research.(2008) may. strasak a. et.al. doi: 10. 1158/00085472.can-07-6686. 10. tan s. et. al. treatment of glioblastoma with re-purposed renin-angiotensin system modulators: results of a phase i clinical trial. j. clinical neuroscience (2021) 95:48-54. doi: 10.1016/j.jocn. 2021.11.023. how to cite: marsh, r., & itinteang, t. . (2022). treatment of cancers with a novel combination of re-purposed pharmaceutic als and nutriceuticals. clinical medicine insights, 3(3), 318–321. https://doi.org/10.52 845/cmi/2022-3-3-1 cmi 03 (04), 338−342 manuscript central 338 clinical medicine insights doi: https://doi.org/10.52845/cmi/2022-3-4-1 cmi 03 (04), 338−342 (2022) issn (o) 2694-4626 case report open access journal a giant zenker’s diverticulum revealed by dysphagia a rare case report houda tahiri 1 , nawal kabbaj 2 , mouna salihoun 3, mohamed acharki 4 corresponding author: houda tahiri 1 intern in gastroenterology, department of gastroenterology ‘efd-hge’ – mohamed v university, rabat, morocco. 2 phd of gastroenterology, department of gastroenterology ‘efdhge’ – mohamed v university, rabat, morocco. 3 phd of gastroenterology, department of gastroenterology ‘efdhge’ – mohamed v university, rabat, morocco. 4 md in gastroenterology, department of gastroenterology ‘efdhge’ – mohamed v university, rabat, morocco. introduction zenker’s diverticulum (zd) is a rare condition [1] first described by abraham ludlow in 1769 [2]. however, it was friedrich von zenker, a german pathologist, who recognized that zd results from increased intra-pharyngeal pressure [3]. it is located proximal to the upper eosophageal sphincter ( ues ) usually on the posterior hypopharyngeal wall [3]. it rarely occurs before the age of 40 years [4]. the first and most common symptom is a progressive dysphagia, but can have many severe consequences [5]. the mainstay of the treatment of zd has been surgery for a long time, however endotherapy using flexible endoscopes has evolved over the last years [6]. we report this case, with a review of the literature, to recall the clinical, endoscopic and radiological charesteristics of zd with the different therapeutic modalities. case report a 58 years old man, with a history of chronic smoking, presented a progressive dysphagia for over 10 years that initially started for solid food and later fluids, regurgitation of undigested food, and chronic cough. he had no odynophagia but noticed some weight loss. the patient had no abstract zenker’s diverticulum, which is an alimentary tract pouch localized in the area of the upper esophageal sphincter, constitutes a rare condition. it’s even rarer when its size exceed 7cm. most patients are elderly and the aetiology remains unknown. the diagnosis is easily established based on radiogram with barit and esophago-gastroduodenoscopy. treatment has been for a long time surgical. recently, endoscopic treatment has becoming increasily popular and is the treatment of choice of many hospital centers for its good results and low morbidity. we highlight, in this paper, the importance of considering the diagnosis of zenker’s diverticulum in clinical practice, not only due to the severe consequences, but also due to the existence of effective therapeutic methods when diagnosed. key words : zenker’s diverticulum, dysphagia, surgery, endoscopic treatment conflict of interest : there is no conflict of interest. copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/lic enses/by-nc-nd/4.0/). https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ cmi 03 (04), 338−342 manuscript central 339 manuscript central houda tahiri et al. similar condition in his family members. during clinical examination, the general condition of the patient was preserved. he was slighty pale but the cardiovascular and abdominal examination were normal. lymph node areas were normal too. an upper gastrointestinal endoscopy was performed, revealing a large oesophageal diverticula at 15cm of the oral cavity with a normal mucosa ( figure 1 ). figure 1 : endoscopic photos of the patient revealing : left : (a) zenker’s diverticulum entrance (b) esophagus entrance. right : the fundus of the zenker’s diverticulum. the oesophageal lumen was deviated, making very difficult the progress of the endoscope through it. a barium swallow was requested, revealing a large oesophageal diverticula at the height of the fifth cervical vertebra, measuring 7x6x7cm ( figure 2 ) and a small amount of barium passing through the rest of the distal oesophagus. figure 2 : barium swallow revealing the giant zenker’s diverticulum of the patient. cmi 03 (04), 338−342 manuscript central 340 manuscript central houda tahiri et al. given the enormous volume and the duration of the diverticulum, and after a discussion with the surgical team, the patient was scheduled for a diverticulectomy. discussion zenker’s diverticulum is a rare cause of dysphagia, but it is the most common diverticulum in the upper gastrointestinal tract [5]. the incidence rate in the american population is believed to be between 0.01% and 0.11% [6]. however the true incidence is difficult to establish since the number of asymptomatic patient is unkown. zd usually occurs between the seventh and eighth decades of life, and rarely before the age of 40 years [6]. it’s more common in male than female [10]. our patient was a 58 years old man. the most common structure where zd is located is killian’s triangle caracterised by the highest susceptibility to create diverticula for its low resistance. then, the increase of pressure during swallowing, pushes esophageal tissue layers outside the esophagus to the mediastinum retropharyngeal space, forming a pouch with gates limited by muscles [7]. a genetic predisposition has not been proven until now [5]. zd may occur in different positions (illustration 1) with most of the time the entrance at the top and the fundus at the bottom, which was the case of our patient. this position is associated with a highest risk of retention of ingesta [8]. illustration 1 : different positions of zenker’s diverticulum in relation to the esophageal lumen according to morton-bartney’s classification (table 1), diverticula are divided into three categories : small diverticula that measures less than 2cm, medium diverticula that measures between 2cm and 4cm and large diverticula measuring more than 4cm [10]. table 1: morton-bartney’s classification [10] size of diverticulum type of diverticulum <2cm small diverticulum 2-4cm medium diverticulum >4cm large diverticulum zd are more frequently less than 4cm in length [9]. the size of our patient’s diverticulum was very large measuring 7cm, which is very rare. the symptoms are specific and the most common one is an increasing dysphagia (80-90 % ) due to esophagus constriction by a filled diverticulum [6,11] which was the case of our patient. regurgitations of undigested food are also one of the most usual symptoms ( 60% ) and can lead to chronic cough, repeated episodes of aspiration and some aspiration pneumonia (30-40% ) [6,11]. our patient described regurgitations and chronic cough too. however, symptoms can become more severe with the weight loss and malnutrition (20% ) [6,11]. a higher incidence of carcinoma has been noticed (0,4-1,5%) then the diagnostic should be suspected when a sudden increase in the severity of dysphagia and/or a development of alarm symptoms such hematemesis, hemoptysis or local pain occurs [6]. physical examination findings are few and usually seen in severe cases. it includes findings of malnutrition, voices changes, neck mass and crepitus [10,12]. our patient has a subnormal physical examination. cmi 03 (04), 338−342 manuscript central 341 manuscript central houda tahiri et al. the diagnosis is based on a radiogram with barite that reveals a diverticulum filled with contrast on the side of the esophagus [13] esopgastroduodenoscopy (egd) may be useful in zd. however, manometry is not useful in the routine diagnostic approach due to catheter dislocation during examination impeding the proper analysis [5]. our patient had undergone both of egd and barium swallow to make a diagnosis. treatment of zd depends on diverticulum size and clinical manifestation. asymptomatic patients or diverticulum with a size smaller than 1cm do not need a specific treatment [5]. thus, treatment of zd is indicated for all symptomatic patients, expected patients with high morbidity [6]. there are several therapeutic approaches concerning zd. the surgical one, has been for long time the treatment of choice for an established pharyngeal pouch [10]. the open approach consists of a diverticulectomy with or without a cricopharyngeal myotomy, or a diverticulopexy . unfortunately, pharyngeal pouch surgery has long been associated with a risk of significant complications such as fistula, infection, vocal cord paralysis and aspiration [15]. the flexible endoscopic approach, known for its low morbidity, is accomplished by a gastroenterologist. it is advantageous for high-risk elderly patient who can benefit from a brief procedure without general anesthesia and the need for hyperextension of the neck. it consists of severing the septum between the diverticulum and esophagus that contain the cricopharyngeus. the division of the septum allows food and liquid to flow out of the diverticulum into the esophagus rather to lodge within the diverticulum [16]. three principal techniques are employed : needle-knife incision, argon plasma coagulation or monopolar coagulation using forceps. several case series have demonstrated the efficiency and safety of cricopharyngeal myotomy using a flexible endoscopic approach [16,17].however, larger diverticula (>3cm) may requires several procedures because of 1,5-2cm incision performed in multiple sessions. some rare complications can follow flexible endoscopic therapy, it includes throat pain, aspiration, perforation and bleeding [6].the endoscopic approach allows a clinical resolution in 84% to 96% of cases in one month depending on differents studies [18, 19, 20] . the surgical approach, in comparison with the endoscopic treatment, is associated with higher morbidity and a longer period of hospitalization ( 5-6 days vs 1-2 days ). the oral feeding is implemented after 5-6 days in comparison with 2 days after an endoscopic procedure [5]. thus, the endoscopic approach is interesting for its low morbidity and low cost [5]. however, it should be noted that despite of attractiveness of the endoscopic treatment of zenker diverticulum, we must adapt the type of treatment to the case of the patient and the characteritics of the diveticulum. thus, surgery treatment remains an option which was the case with our patient. conclusion zd is an anatomic abnormality with a wide range of symptoms. its presence should always be considered in clinical practice especially in case of dysphagia. effective therapeutic methods, as the endoscopic myotomy, are interesting for its safety and efficiency. however, the surgical treatment remains an option, especially for the giant zenker’s diverticulum. references 1. watemberg s, landau o, avrahami r. zenker’s diverticulum: reappraisal. am j gastroenterol 1996; 91: 1494–8. 2. ludlow a. a case of obstructed deglutition from a preternatural dilatation of and bag formed in the pharynx. medical observations and enquiries by a society of physicians in london, 2nd edn 1769; 3: 85–101. 3. zenker f a, von ziemssen h. krankheiten des oesophagus. in: von ziemssen h, (ed.). handbuch der speciellen pathologie and therapie, vol. 7 (suppl). leipzig: fcw vogel, 1877; 1–87. 4. maran a g d, wilson j a, al muhanna a h. pharyngeal diverticula. clin otolaryngol 1986; 11: 219–2. 5. piotr n, ireneusz w k . zenker’s diverticulum : aetiopathogenesis, symptoms and diagnosis. comparison of opérative methods 2013. cmi 03 (04), 338−342 manuscript central 342 manuscript central houda tahiri et al. 6. ferreira c , simmons d.t, baron t.h. zenker’s diverticula : physiopathology, clinical presentation, and flexible endoscopic management dis eosophagus 2008 ; 21 : 1-8. 7. lerut t, coosemans w, decaluwe h, et al. zenker’s diverticulum. multimedia manual of cardiothoracic surgery 2009 ; 224 : 2881. 8. silverstein fe, tytgat gnj. atlas of gastrointestinal endoscopy. medycyna praktyczna, krakow 1998 ; 302. 9. grabowski k, milnerowicz s, tabola r. large zenker’s diverticulum as a cause of high obstruction of the esophagus. gastroenterol pol 2005 ; 12 : 545-7. 10. siddiq m a, sood s, strachan d. pharyngeal pouch (zenker’s diverticulum). postgrad med j 2001 ; 77 :506-511. 11. christiaens p, roock de w, olmen v, and al. treatment of zenker’s diverticulum through a flexible endoscope with a transparent obliqueend hood attached to the tip and a monopolar forceps. endoscopy 2007 ; 39 : 137-40. 12. christopher p . m.d. zenker’s diverticulum. may 6, 2004. 13. stemerman dh, mercarder v, kramer g, and al. an unusual presentation of zenker’s diverticulum. clin imaging 1996 ; 20 : 112-4. 14. smith sr, genden em, urkenml. endoscopic stapling technique for the treatment of zenker diverticulum vs standard open-neck technique. arch otolaryngol head neck surgery 2002 ; 128 : 141-4. 15. achkar e. zenker’s diverticulum. digestive disease 1998 ; 16 : 144-151. 16. ishioka s. endoscopic incision of zenker’s diverticula. endoscopy 1995, 1995 ; 27 : 4337. 17. mudler c j j. zapping zenker’s diverticulum : gastroscopic treatment. can j gastroenterol 1999 ; 13 : 405-7. 18. huberty v, el bacha s, blero d, le moine o, hassid s, devière j. endoscopic treatment for zenker's diverticulum: long-term results (with video). gastrointest endosc. 2013; 77:701-7. 19. herrero egea a, pérez delgado l, tejerogarcés galve g, guallar larpa m, orte aldea c, ortiz garcía a. treatment of zenker’s diverticulum: comparison of different techniques. acta otorrinolaringol esp2013; 64:1-5. 20. vogelsang a, preiss c, neuhaus h, schumacher b. endotherapy of zenker's diverticulum using the needle-knife technique: long-term followup. endoscopy 2007;39:1316. how to cite tahiri, h., salihoun, m., acharki, m., & kabbaj, n. (2022). a giant zenker’s diverticulum revealed by dysphagia. clinical medicine insights, 3(4), 338–342. https://doi.org/10.52845/cmi/20223-4-1 clinical medicine insights received 25 dec 2020 | revised 20 jan 2021 | accepted 24 feb 2021 | published online 30 mar 2021 doi: https://doi.org/10.52845/cmi/2021-2-1-3 cmi journal 2 (1), 64−79 (2021) issn (o) 2694-4626 review article obesity and non-communicable diseases: part i cardiovascular diseases, respiratory diseases, depression, liver diseases shashi k. agarwal, md ∗ 12227 us highway 1, #309 north brunswick, nj 08902,usa abstract obesity has become a pandemic. obesity is associated with a wide array of physical and emotional health ailments. it is associated with a reduced quality of life. comorbid disorders often result in premature mortality. although bmi is the widely used standard for defining overweight and obesity, abdominal or visceral obesity has a more significant association with several noncommunicable diseases.weight loss is beneficial in halting the deleterious effects of excess body weight. part i of thismanuscript, discusses the harmful effects of obesity on cardiovascular diseases, respiratory diseases, depression, and liver diseases. keywords: obesity, non-communicable diseases, cardiovascular diseases, respiratory diseases, obesity, depression, liver diseases copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). 1 introduction obesity is growing exponentially all over the world1. obesity is recognized and classified according to a person’s body mass index (bmi)2. bmi is a person’s weight [kilograms] divided by the square of his or her height [meters])2. according to theworld health organization (who), a bmi between 20 and 25 kg/m2 is normal, a bmi between 25 and 30 kg/m2 is considered overweight, while a bmi of >30 kg/m2 represents obesity3. these numbers are different for the asian population (asian people have a high risk of type 2 diabetes and cvd at a lower bmi) 3. obesity is further divided into 3 classes (class 1, bmi > 30 and < 35; class 2, bmi > 35 and < 40; class 3, bmi > 40)4. in the usa in 2017-2018, 42.2% of all adults were obese5. europe has the second highest proportion of overweight or obese people, with obesity rates of over 30% in most countries6. several lowand middle-income countries, like china, india, and brazil, have also seen a major rise in the prevalence of obesity7−9. it has also been increasing at an alarming rate in african countries10. theglobal burden of disease group reported in 2017 that “since 1980, the prevalence of obesity has doubled in more cmi journal 2 (1), 64−79 meerp ltd 64 open access journal https://doi.org/10.52845/cmi/2021-2-3-5 https://orcid.org/0000-0003-0007-5582 https://creativecommons.org/licenses/by-nc-nd/4.0/ https://medicineinsights.info/index.php/cmi meerp ltd shashi k. agarwal, md than 70 countries and has continuously increased in most other countries”11. excessive weight gain is not limited to adults, it also affects children and adolescents12. this puts them at a higher risk to developmajor noncommunicable diseases like diabetes and cardiovascular diseases at a younger age13. it is estimated that obesity will affect 1.12 billion people by 203014. bmi is unable to specify the type of collection of fat – subcutaneous adiposity or visceral adiposity15. the latter represents central obesity or abdominal obesity15. abdominal fat is metabolically active16, unlike subcutaneous fat – it induces inflammation17, insulin resistance18, and a procoagulant state19, resulting in a high risk of several chronic diseases. subcutaneous fat, on the other hand, protects the body from lipotoxicity15,20. several anthropometric measurements are now routinely done to objectively diagnose central obesity21,22. these include the waist circumference (wc), waist hip ratio (whr), and the weight height ratio (whtr)21,22. wc is measured to the nearest 0.1 cm at the umbilical level while standing23. it should ideally be <102 cm inmales and <88 cm in females23. thewhr is normal if it is 0.85 or less in women and 0.9 or less in men24. thewhtr is calculated by dividing thewc by height (< 0.5 (no central obesity) and > 0.5 (central obesity)25. besides the nine chronic diseases discussed in this two-part manuscript, obesity is also implicated in several other disorders, including gastroesophageal reflux disease26, pancreatitis27, osteoporosis28, infertility29,30, and can increase complications related to pregnancy31. it may lead to psychosocial distress and obese people may have low self-esteem and feelings of rejection32. they often have heightened anxiety, body image dissatisfaction, and may face weight bias and sigma33,34. stigma supplementary information the online version of this article (10.52845/cmi/2021-2-3-5) contains supplementary material, which is available to authorized users. corresponding author: shashi k. agarwal, md shashi k. agarwal, md 2227 us highway 1, #309 north brunswick, nj 08902,usa email: usacardiologist@gmail.com may also be exhibited by health care providers35. obesity may also lead to disqualification from the us military36. it reduces the health quality of life37. it is associated with an increase in disability and mortality38,39. most of the deaths attributable to obesity occur due to cardiovascular diseases40. according to the gbd 2015 obesity collaborators, obesity accounted for about four million deaths worldwide41. it is amajor cause of preventable death, second only after smoking42. obesity care is also expensive43. in the us alone, obesity related health care is over $150 billion yearly44. the obesity paradox is a phenomenon where obesity is associated with increased survival, especially in hospitalized patients45. it has been observed in chronic diseases such as heart failure46, coronary artery disease47, and end-stage kidney disease48. it has also been observed in acute conditions such as pneumonia49, sepsis50, acute respiratory distress syndrome (ards)51, and other critical illness52. several hypotheses have been advanced to explain this phenomenon53−57. the health effects of obesity on common chronic medical conditions are discussed in this two-part manuscript. part i discusses the relationship between obesity and cardiovascular diseases (cvd), chronic obstructive pulmonary disease (copd), depression, and liver diseases. part ii discusses its impact on cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, and arthritis. 2 discussion the centers for disease control and prevention (cdc) defines chronic diseases as “conditions that last 1 year or more and require ongoing medical attention or limit activities of daily living or both”58. most chronic diseases are noncommunicable diseases (ncds) and are gradually replacing infectious diseases as the major health burden in developing countries59. out of the 17 million premature deaths (under the age of 70) due to noncommunicable diseases in 2015, 82% were in lowand middle-income countries59. the ncds discussed in this part include cardiovascular diseases (such as hypertension (htn), coromeerp ltd cmi journal 2 (1), 64−79 (2021) 65 mailto:usacardiologist@gmail.com obesity and non-communicable diseases: part i cardiovascular diseases, respiratory diseases, depression, liver diseases nary artery disease, stroke, and heart failure (hf)), chronic respiratory diseases (such as chronic obstructive pulmonary disease (copd), lung cancer, tuberculosis, lung infections, asthma, and interstitial lung diseases) depression, and liver diseases (such as nonalcoholic and alcoholic hepatitis, viral hepatitis, cirrhosis of liver). cardiovascular diseases (cvd) are the leading cause of morbidity worldwide60. they are also the leading cause of global mortality and were responsible for 17.9 million deaths in 2016 (representing 31% of all global deaths)61. of all the global deaths in 2015, 82% were in lowand middle-income countries61. cvds were responsible for 37% of these deaths61. men and women were nearly equally affected59. the most common underlying pathology is atherosclerosis (especially in myocardial infarction, ischemic stroke and peripheral arterial disease)60. the most frequent chronic respiratory diseases encountered include chronic obstructive pulmonary disease (copd), lung cancer, tuberculosis, lung infections, asthma, and interstitial lung diseases (ild). chronic respiratory diseases are responsible for about 7.5 million deaths per year, and account for approximately 14% of annual deaths worldwide63,64. copd is the most common cause, and is usually due to tobacco smoking65. these patients experience airflow limitation, and copd can be diagnosed by the fev1 /fvc ratio of less than 0.7066. asthma is a chronic inflammatory disorder of the airways67. globally, one in two hundred and fifty deaths are due to ashtma68. the physical quality of life is impaired by bronchial symptoms69, while social life is also impaired by rhinitis co-morbidity70. obstructive sleep apnea syndrome results from upper airway obstruction71. periods of reduced or absent airflow through the nose or mouth cause loud snoring and the hypoxemia is usually terminated by arousal72. sleep is especially disturbed in these patients73. major depressive disorder (mdd) is the primary cause of disability worldwide74. it can be diagnosed by the presence of at least five of the following symptoms occurring independently of physical illness, normal bereavement, alcohol or drugs: abnormal depressed mood; abnormal loss of interest and pleasure; appetite or weight disturbance; sleep disturbance; disturbance in activity (agitation or slowing); abnormal fatigue or loss of energy; abnormal self-reproach or inappropriate guilt; poor concentration or indecisiveness; and morbid thoughts of death or suicide75. the five diagnostic symptoms, which should include abnormal depressed mood or loss of interest and pleasure, are present nearly every day for at least two weeks after the diagnosis75. theworldhealth organization predicts that depression will generate the greatest global burden by 203076. liver diseases affect more than 10% of the world population77. the leading liver disease globally (40% of all liver diseases) is nonalcoholic fatty liver disease (nafld). other common liver diseases are hepatitis b virus (hbv) (30%), hepatitis c virus (hcv) (15%) and excessive consumption (11%)77. these patients may progress to cirrhosis of the liver or develop liver cancer78. 2.1 cardiovascular diseases obesity has a strong detrimental relationship with cvds79,80. an increased cvd risk of 6% for each 1.1 kg/m2 increase in bmi was noted by emberson et al. among 6452 british men81. weight loss, on the other hand, reduces cvds82. in the look ahead trial, with amedian follow-up of 10.2 years, weight loss decreased cvd outcomes82. a 10% body weight reduction in the first year of the study resulted in a 21% lower risk of the primary cvd outcome and a 24% reduced risk of the secondary outcome compared with individuals who were weight stable or gained weight82. obesity has been associated with an increased risk of htn83, coronary artery disease84,stroke85,86, hf87,cardiac arrhythmias88, and sudden cardiac death (scd)89. it is estimated that obesity may result in a 3.5-fold increase in the likelihood of being hypertensive, and obesity may be responsible for about 70% of htn in adults90,91. an increase in weight by 5% appears to increase the incidence of hypertension by 20–30%92. on the other hand, weight loss is effective in lowering blood pressure (bp)93. studies indicated that a 10 kg weight loss would result in a 6 mmhg in bp94. obese patients are twice as likely to have coronary artery disease and their lesions are more complex95,96. they do not heal well after coronary artery bypass grafting97 and have a higher mortality98. obesity is cmi journal 2 (1), 64−79 (2021) meerp ltd 66 meerp ltd shashi k. agarwal, md an independent risk factor for heart failure (hf)99. in the framingham heart study of 5881 patients,an increase in bmi of 1 kg/m2 increased the risk of heart failure by 5% in men and 7% in women100. they also do not do well after a left ventricular assist device implantation101 or heart transplant surgery102. bariatric surgery induced weight loss in hf patients resulting in a significant reduction in their new york heart association classification103. ischemic stroke risks are also increased in obese patients104. in the physicians’ health study, men with bmi >30 kg/m2 had a >2fold increase in risk for stroke105. in a prospective study of >39,000 healthy women, those with bmi >35 kg/m2 had a 3-fold increase in the risk of ischemic stroke compared with women with bmi <20 kg/m2106. it is estimated that for each 1-u increase in bmi, there is an increase of 4% in the risk of ischemic stroke107,108. obese patients also have a higher risk of atrial fibrillation, with the risk being 1.52 times compared to that of the normal weight population109. obesity increases the risk of scd110. there is also a detrimental association noted between obesity and several other cvds, including aortic stenosis111, peripheral artery disease112, erectile dysfunction113, and venous thromboembolism114. obesity is also associated with diabetes mellitus, dyslipidemia, and sleep apnea syndrome – disorders that further increase the risk of cardiovascular disorders115. obesity results in several pathophysiological mechanisms that damage the cardiovascular system. the adipose tissue releases proinflammatory adipokines, elevates free radicals, causes endothelial dysfunction, and activates macrophages, t cells, and b cells within fat deposits leading to atherosclerosis116. 2.2 respiratory diseases increased bmi results in reduced lung function, with reductions in forced expiratory volume in 1 s (fev1) and forced vital capacity (fvc)117,118. obesity is detrimentally associated with obstructive sleep apnea (osa)119 and bronchial asthma120. obesity promotes osa by causing enlargement of soft tissue structures within and surrounding the airway121. an excess of fat deposition has also been observed under the mandible and in the tongue, soft palate, and uvula122. further, obesity may reduce lung volumes by a combination of increased abdominal fat mass123 and disturbed neuroanatomic interactions124. several longitudinal epidemiological studies have shown that obesity is a major risk factor for asthma in children125,126. obesity and weight gain during pregnancy in the mother are both associated with an increased risk of asthma in the offspring127. several prospective studies in adults have also found a relationship between obesity and incident asthma128,129. obesity in adults with asthma has been associated with reduced response to asthma medications, resulting in worse disease control, higher risk of hospitalization and lower quality of life, when compared to lean asthma patients130,131. weight loss intervention by caloric restriction132 or bariatric surgery leads to an improvement in asthma outcomes133. abdominal or central obesity, even with a normal bmi, appears to be linked with an increased risk of lung cancer134. yu et al estimated this increased risk to be 40% greater in these patients 135. carreras-torres et al, using mendelian randomization, recently reported that genetically predicted bmi,whr, and insulin resistance increased the risk of lung cancer, especially for squamous cell and small cell lung cancer136. an obesity paradox has been noted in copd patients, especially those with severe disease137. patients with a higher bmi survive longer when compared to those with low or normal bmi138. it has been suggested that the severity of copd may be overestimated in obese patients, as when co2 levels and muscle mass and exercise capacity are looked at, there appears to be no obesity paradox139. 2.3 depression several studies have found that obesity and mental health problems are linked140−142. simon et al concluded that there was an approximately 25% increase in mood disorders and anxiety in obese patients143. obesity and depression also frequently co-exist144,145 and the presence of one not only increases the risk of the other, but also causes significant adverse health outcomes when they co-occur146,147. the prevameerp ltd cmi journal 2 (1), 64−79 (2021) 67 obesity and non-communicable diseases: part i cardiovascular diseases, respiratory diseases, depression, liver diseases lence of depression in obese individuals is estimated to be twice as high as in those of normal weight148. negative body image, and low selfesteemare common in obese patients149. they also face stigma in social and professional lives150,151. these factors contribute to the development and maintenance of depression152,153. other pathophysiological processesmay also play a role in this connection154,155. depression also increases weight gain and obesity156−160. depressed individuals may be less physically active and indulge in excessive ‘comfort’ eating156−158. certain antidepressant medications can also contribute to weight gain159,160. the relationship between obesity and depression is therefore bidirectional161. the biological pathways include genetic influence162, hpa axis disturbances163,164, immuno-inflammatory dysregulation166, and insulin abnormalities167. 2.4 liver diseases nafld is prevalent in obese individuals168. obese individuals have a prevalence of 30% to 37% of nafld169. in those who have undergone bariatric surgery, the prevalence rises to 84% to 96%170. li et al. estimated that obesity produced a 3.5-fold increased risk of developing nafld171 and is more closely related to waist circumference172. pang et al. in a meta-analysis, concluded that for each 1 unit increase in waist circumference, the odds ratio of nafld increased by 1.07, and for each 1 unit increase in bmi, the odds ratio increased by 1.25173. obesity also worsens the prognosis in patients with hepatitis174. obese patients with alcoholic hepatitis, are twice as likely to die in the short term, compared to those who are nonobese174. obesity is also common in chronic hcv infected individuals175. this increases their risk of developing serious liver related complications and dying early176. antiviral treatment in these patients may sometimes result in weight gain177. 3 conclusions the increasing epidemic of obesity has resulted in a greater development, aggressive progression, and poor outcomes for many common chronic diseases and ailments. the evidence for the preventive and therapeutic effects of a bmi of 25 or more on ncds is strong. weight loss, including that with bariatric surgery, helps most obesity related conditions. acknowledgment: none funding: none conflict of interest: none references 1. kolahi aa, 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hepatitis c infection with direct-acting antivirals. j gen internmed. 2020 jul;35(7):20252034. doi: 10.1007/s11606-020-05782-6. how to cite this article: agarwal s.k,, md, obesity and non-communicable diseases: part i cardiovascular diseases, respiratory diseases, depression, liver diseases. clinical medicine insights. 2021;64−79. https://doi.org/ 10.52845/cmi/2021-2-1-3 meerp ltd cmi journal 2 (1), 64−79 (2021) 79 introduction discussion cardiovascular diseases respiratory diseases depression liver diseases conclusions clinical medicine insights received 28 june 2021 | revised 24 july 2021 | accepted 19 aug 2021 | published online 31 aug 2021 doi: https://doi.org/10.52845/cmi/2021-2-3-6 cmi journal 2 (3), 185−200 (2021) issn (o) 2694-4626 review article alcohol and noncommunicable diseases: part ii cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, arthritis shashi k. agarwal, md ∗ 12227 us highway 1, #309 north brunswick, nj 08902 usa abstract excessive alcohol consumption is common. it leads to the development of several ncds and is associated with considerable disability and high mortality. its intake has been linked with an increase in many cancers, including the common breast and prostate cancer. light-to-moderate drinking is associated with a lower incidence of type 2 diabetes, but excessive alcohol consumption leads to increased morbidity and mortality in these patients. compared with no consumption, moderate consumption of alcohol-associated with a reduced risk of ckd. however, the association with heavy alcohol intake and ckd is not clear, although it also appears to be overall inverse in nature. excessive alcohol intake also targets the brain and promotes ad – although mild to moderate intake may be safe. alcohol consumption is negatively associated with the prevalence of knee oa. there appears to be an inverse association between alcohol consumption and ra incidence. alcohol consumption, usually when taken in more than a moderate amount. may also trigger gout. in general, alcohol intake in low to moderate amounts appears to be safe for ncds described in this communication, except for cancer, where no amount is a safe amount. keywords: alcohol, non-communicable diseases, cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, arthritis copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). 1 introduction a lcohol consumption is common in our society1. it is estimated that in 2016, 32.5% of the world’s population had at least one alcoholic drink in the past 12months2. globally, men tend to drink more than women3. a standard drink contains 12–15 g of pure ethanol and this is found in 12 ounces of regular beer, 5 ounces of wine, and 1.5 ounces of distilled spirits4. in most european cmi journal 2 (3), 185−200 meerp ltd 185 open access journal https://doi.org/10.52845/cmi/2021-2-3-10 https://orcid.org/0000-0003-0007-5582 https://creativecommons.org/licenses/by-nc-nd/4.0/ https://medicineinsights.info/index.php/cmi/index alcohol and noncommunicable diseases: part ii cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, arthritis countries, alcoholic drinks are often referred to as by units, with one unit being equivalent to 8-10 grams of alcohol, with typical drinks containing 1–3 units of alcohol5. moderate alcohol intake is considered as two standard drinks a day for men and one standard drink a day for women6,7. heavy drinking is defined as a long-term, high-dose intake, of >60 g/day in men and >40 g/day in women8. binge drinking is considered as 4 or more drinks for women and 5 or more drinks for men over a 2-hour period9,10. compulsive excessive alcohol intake leads to alcohol use disorder11. it is estimated that 20% of patients seen by primary care physicians consume alcohol in amounts that are harmful to their health12. alcohol was responsible for 8.9% in males and 2.3% in females for disability-adjusted life years in 2016, globally13. griswold et al also calculated that in 2016, alcohol consumption was responsible for 6.8% of male deaths and 2.2% of female deaths all over the world13. of these deaths in 2016, 21.3% were due to digestive diseases, 19% due to cardiovascular diseases and diabetes, 12.9% due to infectious diseases, and 12.6% due to cancers14. the health-related financial burden attributable to alcohol misuse is also extremely high, and in 2010, it cost the united states $249 billion15. the relationship between alcohol consumption and cardiovascular diseases (cvds), respiratory diseases, depression, and liver diseases was discussed in part i of this manuscript. 2 discussion noncommunicable diseases (ncd) are common conditions affecting humans16. this part of the manuscript discusses the relationship between alsupplementary information the online version of this article (10.52845/cmi/2021-2-3-6) contains supplementary material, which is available to authorized users. corresponding author: shashi k. agarwal, md shashi k. agarwal, md 2227 us highway 1, #309 north brunswick, nj 08902, usa email: usacardiologist@gmail.com cohol and cancer, diabetes mellitus (dm), chronic kidney disease (ckd), alzheimer’s disease (ad), and arthritis. cancer is expected to replace cvds as the number one killer in the world17. the most common global cancers are those involving the lung, colorectum, stomach, and liver18. however, many common cancers can be ‘cured’ if caught early19. breast cancer, the most common nonskin cancer among women, if detected while still in localized form has a 5-year survival rate of 98%, compared with a survival rate of 72% by stage iii and just 22% by stage iv20,21. many other cancers demonstrate a similar prognosis depending on the time of their diagnosis22. basal cell carcinoma and squamous cell carcinoma of the skin are the most common human cancers and are 100% treatable if found early. diagnosing cervical cancer in a pre-cancerous stage can assure a near 100% survival rate. however, if discovered in sate iii, the rate drops to just 32% and if diagnosed in stage iv, it is a dismal 16%. prostate cancer is 98% survivable for 5 or more years if it is diagnosed when it is limited to the prostate gland. while if diagnosed at stage iv, the survival rate is only about 28%. colon cancer can be 90% survivable if detected early; the survival drops to 39% if it is detected when it has spread22. dm is one of the most common metabolic disorders worldwide23. and its prevalence is rapidly rising in lowand middleincome countries24. according to the world health organization, the number of people with diabetes rose from 108 million in 1980 to 422 million in 201424. in the united states, 9.3% of americans had diabetes (29.1 million persons) in 2014, with a lifetime risk calculated at almost 40%25. it is caused by a combination of defective insulin secretion by pancreatic β-cells and the inability of insulin-sensitive tissues to respond to insulin26. diabetes mellitus is associated with significant microvascular (retinopathy, nephropathy, and neuropathy) and macrovascular (coronary artery disease, stroke, peripheral artery disease complications27,28. dm reduces the life expectancy of the affected individual by approximately six years29. ckd refers to kidney damage or an estimated glomerular filtration rate (egfr) less than 60ml/min/1.73 mt2, persisting for 3 months or more, irrespective of the cause30. it is a worldwide public health31. in 2017, ckd affected almost 700 million cmi journal 2 (3), 185−200 (2021) meerp ltd 186 mailto:usacardiologist@gmail.com meerp ltd shashi k. agarwal, md people in the world32. those affected with ckd exceed those with diabetes, osteoarthritis, copd, asthma, or depressive disorders33. hypertension and diabetes mellitus are the main causes34. ckd is a progressive disease, ultimately resulting in the need for peritoneal dialysis or hemodialysis, or kidney transplantation35. the major cause of morbidity and mortality in ckd is due to cardiovascular events36. ckd also leads to frequent hospitalization37and poor quality of life38. ckd results in more deaths than tuberculosis or hiv and is presently ranked as the 12th leading cause of death out of 133 conditions in the world33. dementia is a common worldwide disease39, with adbeing responsible for 50% to 70% of these cases40,41. it is characterized by pathologies: β-amyloid plaque deposition and neurofibrillary tangles of hyperphosphorylated tau42. this disorder continues to increase in lowand middle-income countries43. its etiology is unclear but appears to be related to a complex interplay between genetic and environmental factors44. ad produces cognitive impairment and functional decline, often leading to institutionalization45,46. there is no cure for ad, and treatment remains symptomatic47. the qol of these patients is markedly reduced and ad remains a major cause of death48. arthritis is of many types, and osteoarthritis is the most common49. it is a major health concern, affecting about 240 million people globally50. it reduces the quality of life and results in considerable disability and mortality51. it usually affects the knees and the hip, resulting in chronic pain, stiffness, joint instability, and joint deformities52. it is associated with considerable disability53. pathologically, it is characterized by progressive cartilage degradation, synovitis, osteophyte formation, and subchondral bone sclerosis54. osteoarthritis (oa) cases are predicted to rise in the coming decades due to the aging population, increasing obesity, and high rates of traumatic knee injuries55. rheumatoid arthritis (ra) is autoimmune arthritis and is characterized by symmetrical polyarthritis oftenwith systemic manifestations56,57. ra is often associated with persistent pain, deformity, and disability58. it also accelerates cardiovascular disease in these patients59. gout is an autoinflammatory joint arthritis60, caused by the deposition ofmonosodium uratemicrocrystals in joints and tissues61. hyperuricemia is central to its development62. in an acute flare-up, monoarthritis develops rapidly and affects the big toe in 50% of cases (other joints commonly affected include the ankle, midtarsal, knee, wrist, finger, and elbow)63. the affected joint is red, tender, hot, and tumid with extreme pain64. diagnosis may be confirmed by finding monosodium urate crystals in synovial fluid or tophus aspirates65. 2.1 cancer alcohol is a known carcinogen66,67. its consumption increases the risk of several cancers68,69, especially those affecting the mouth, throat, larynx, esophagus, liver, colorectal tissues, and breast70. bagnardi et al. reviewed 222 articles in 2013, (comprising of about 92 000 light drinkers and 60 000 non-drinkers with cancer and concluded that light drinking increases the risk of oropharyngeal cancer by 17%; esophageal squamous cell carcinoma by 30% and breast cancer by 5%71. in a recent analysis, published in 2018, islami et al. found that alcohol intake was the thirdlargest contributor to all cancer cases among women and the fourth largest contributor among men72. in women, besides causing 28.4% of esophageal cancers, 27.4% of the oral cavity and pharyngeal cancers and many breast cancers were associated with alcohol72. alcohol was associated with 46.3% of all oral cavity and pharyngeal cancers in men72. they estimated that alcohol intake was responsible for 5.6% of cancer cases and 4.0% of all cancer-related deaths72. alcohol intake has also been linked with an increase in other cancers, such as gastric cancer73, colo-rectal cancer74, prostate cancer75, and some skin cancers76. it also increases the risk of a second aerodigestive-tract cancer77. there may be a doseresponse relationship between alcohol and cancer78. however, most people are unaware of the increased risk of cancer even after the first drink79. the american cancer society recommends not drinking alcohol to lower cancer risk80. despite these recommendations, most people, including cancer survivors continue to drink81. alcohol is an irritant to the upper aerodigestive tract82. acetaldehyde is the first and primarymetabolite of alcohol and is strongly implicated in cancer development83. its intake is associated with abmeerp ltd cmi journal 2 (3), 185−200 (2021) 187 alcohol and noncommunicable diseases: part ii cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, arthritis normal production of reactive oxygen and nitrogen species, aberrant dna methylation, altered folate metabolism, disturbed immune surveillance and inflammatory response and increased estrogen levels in breast cancer cases84−86. 2.2 diabetes mellitus alcohol intake is generally considered beneficial for type 2 diabetes prevention, provided it is consumed in moderate amount87. in a large study involving 22,778 twins and 580 incident cases of type 2 diabetes during 20 years of follow-up, carlsson et al documented this phenomenon88. some previous studies have estimated that moderate alcohol consumptionmay reduce the incidence of type 2 diabetes by 30%-40%89−91. in a recent meta-analysis of 20 observational studies, undertaken by baliunas et al. in 2009, a peak reduction in risk for type 2 diabetes mellitus (t2dm) was noted at 24 g/day among women and 22 g/day among men, relative to never drinkers, with risk increasing in a dose-dependent manner above these levels92. however, in a major meta-analysis of 38 studies representing 1,902,605 participants and 125,926 cases of type 2 diabetes, knott et al found a risk reduction only inwomen (<71 g/day) when compared to current non-drinkers and never drinkers93. irrespective of the level of alcohol consumption, no risk reduction was noted in men93. several biological mechanisms have been proposed to explain the apparent reduction in risk of t2dm among moderate drinkers94. these include the antiinflammatory hypothesis, which posits that alcohol may beneficially alter the expression of inflammatory proteins94 and a possible stimulatory effect of alcohol upon the synthesis of hdl95. after an analysis of results reported by 14 intervention studies, alcohol consumption was associated with reduced fasting insulin concentrations and improved insulin sensitivity among women96. reduced duration of drinking, or initiating alcohol intake at a later age, also appears to decrease the risk of t2dm97. heavy alcohol intake has been associated with a higher risk for dm in many studies98,99. in a study of 2366 koreans monitored over 10 years, consumption of more than 2 units of alcohol per day was associated with an increase in the risk of t2dm100. a reduction in the maximum intake of alcoholic beverages not only decreases the risk of development of t2dm but also improves survival among established diabetic subjects especially if this reduction is done in early adulthood101,102. several mechanisms may cause this harm, including alcohol-related increase in metabolic syndrome103,104. the increase in alcohol-related hypertension tends to aggravate cardiovascular complications103. long-term alcohol intake also results in pancreatic islet dysfunction and apoptosis104. overall, the relationship between alcohol consumption and risk of t2dm appears to be jor u-shaped association105. 2.3 kidney diseases comparedwith no consumption,moderate consumption of alcohol may be associated with a reduced risk of ckd106. moderate alcohol use was associated with a lower risk of ckd or end-stage kidney disease (eskd) in several previous reports107−110. in ametaanalysis of prospective cohorts. not only moderate but also high amounts of alcohol use have been associatedwith a lower risk of incident ckdor eskd111. however, heavy alcohol consumption or chronic alcohol consumption is positively associated with ckd112−116. a mendelian randomization study also found a causal link between heavy alcohol intake and an increased risk of end-stage kidney disease117. in another mendelian randomization study, park et al also confirmed the deleterious role of alcohol on the risk of eskd118. mechanisms of alcohol-induced kidney damage include oxidative stress injury, increase in blood pressure, and activation of the renin-angiotensinaldosterone pathway119−121. further alcohol and other substances in alcohol may also influence kidney function by effects on other body systems122,123. bottom line – alcohol is a double-edged sword in ckd. it may be safe to drink to a low or moderate degree with ckd but heavy or binge drinking is harmful124. cmi journal 2 (3), 185−200 (2021) meerp ltd 188 meerp ltd shashi k. agarwal, md 2.4 alzheimer's disease several studies have documented the protective effects of low to moderate amounts of alcohol on dementia125−127. epidemiological studies have also reported a similar effect in ad128. in a recent large meta-analysis of 91 articles on ad, anstey et al confirmed this association129. animal and cell culture studies also show that low or moderate concentrations of ethanol exhibit a protective effect on ad in vitro and in vivo130-133. heavy drinking is however harmful to the brain134−138. in a 5year follow-up study of 13,342 men and women, piumati et al reported that reaction time declined more with alcohol intake of 12 units per week when compared to those who drank less134. in a large study (of 31 million people over 5 years), researchers found that alcohol use disorders were associated with increased dementia risk135. heavy alcohol intake induces harmful brain changes, cognitive impairment, and dementia136,137. similar deleterious findings have been noted in ad patients with higher alcohol intake138. changes consistent with increased cognitive deficits have also been noted in ad mice models 1-month post alcohol drinking139. in the 23year uk whitehall study (9087 participants), abstinence or heavy drinking were both associated with a higher risk of dementia140. overall, the association between alcohol intake and dementia appears to be u-shaped with low or moderate amounts of alcohol being protective against aβ toxicity in hippocampal neurons and high intake increasing neuronal cell death and neurodegeneration141. however, alcohol drinking is not recommended for ad protection142. 2.5 arthritis there is no concrete evidence of an association, beneficial or otherwise, between moderate alcohol consumption and oa143,144. this has been noted in the finnish cohort studywith an observation period of 22 years143 and the nurses’ health study144. moderate amounts of alcohol intake are associated with antiinflammatory effects145. zhang et al found no evidence of alcohol consumption with hscrp or knee oa146. some studies have found that chronic and excessive intake of alcohol raises inflammation147,148. kc et al noted pathological oa-like changes in animals with chronic alcohol intake149. a similar radiological knee oa effect, rather than a symptomatic effect, was seen in korea in patients with alcohol consumption150. the clinical implications of the relationship between alcohol intake and oa. therefore. remain unclear. the 2009 the swedish eira study (epidemiological investigation of rheumatoid arthritis) and the danish cacora study (casecontrol study on rheumatoid arthritis) found that limited amounts of alcohol decrease the risk of ra incidence151. lu et al concluded that moderate alcohol intake was associated with a better functional status in ra patients152. another study found that low levels of alcohol consumption (about three drinks per week) over at least ten years lowered the risk of ra incidence by half compared with non-drinkers153. however, increased frequency of alcohol consumption may be harmful in ra154. in the västerbotten intervention program cohort of 386 individuals, no association was seen between alcohol intake and the risk of ra155. baker et al reported that ra patients tend to reduce alcohol intake with higher disease activity, disability, comorbidity, and poor quality of life156. overall, there appears to be no clear benefit of alcohol consumption in ra. alcohol may precipitate gout at lower urate levels157. beer intake appears to be more associated with gout than spirits, and spirits more than wine158,159. chronic alcohol intake also is also harmful to gout patients160,161. high alcohol intake may impair the production of oxypurinol and stimulate urate production in the body160,161. 3 conclusion low to moderate alcohol intake appears to be safe, and even protective in dm, ckd, and ad. there may be no “safe” level of alcohol use when it comes to cancer. no definite association can be gleaned from published studies between alcohol and oa and ra. gout suffers may consider abstaining from alcohol. high levels of alcohol intake are in general, harmful for ncds. the 2015 u.s. dietary guidelines for 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[editorial]. lancet 2004;363:1251–2. 159. choi hk, atkinson k, karlson ew, willett w, curhan g. alcohol intake and risk of incident gout in men: a prospective study. lancet 2004;363:1277–81. 160. ralston sh, capell ha, sturrock rd. alcohol and response to treatment of gout. bmj 1988;296:1641–2. 161. faller j, fox ih. ethanol-induced hyperuricemia: evidence for increased urate production by activation of adenine nucleotide turnover. n engl j med 1982;307:1598–602. meerp ltd cmi journal 2 (3), 185−200 (2021) 199 alcohol and noncommunicable diseases: part ii cancer, diabetes mellitus, kidney diseases, alzheimer’s disease, arthritis how to cite this article: agarwal s.k,, md. alcohol and noncommunicable diseases: part ii cancer, diabetes mellitus, kidney dis-eases, alzheimer’s disease, arthritis. clinical medicine insights. 2021;185−200. https://doi.org/10.5284 5/cmi/2021-2-3-6 cmi journal 2 (3), 185−200 (2021) meerp ltd 200 introduction discussion cancer diabetes mellitus kidney diseases alzheimer's disease arthritis conclusion clinical medicine insights received 16 apr 2022 | revised 18 may2022 | accepted 30 may 2022 | published online 14 june 2022 doi: https://doi.org/10.52845/cmi/2022-3-2-4 cmi 03 (02), 304−311 (2022) issn (o) 2694-4626 research article prevalence and determinants of retinopathy among patients with diabetes mellitus: thiqar 2022 wajida saa'd bunyan1* | ali abed saadoon2 | muslim nahi saeed3 | zahraa jumaa flayh4 | hussain ameer abd alrazzaq4 1.assist profersor, mbchb, msc. ophthalmogist, department of surgery 2. professor, community physician, mbchb,ph.d 3. assist professor, family physician, mbchb, ph.d 4.medical student all affiliated to college of medicine, university of thi-qar background: retinopathy among patients with type 2 diabetes appears to be a public health problem in iraq; it is serious eye disease lead to sever visual impairment and blindness if not detected early. objective: to estimate the prevalence of retinopathy among patients with type 2 diabetes mellitus who attended national center of diabetes of thi_qar and to determine the risk factors of diabetic retinopathy. methods: this cross-sectional study was conducted at national center of diabetes of thi_qar between april and may 2022. 162 type 2 iraqi diabetic patients both sexes were included in this study. diabetic retinopathy was diagnosed by an ophthalmologist depending on the international clinical diabetic retinopathy severity scale approved by aao and i co. socio-demographic, clinical and laboratory data were obtained from patients themselves, these variables include sociodemographic, (sex and age), the participants residence, clinical data include, smoking, hypertension or if the patient is currently using prescribed antihypertensive drugs, if have retinopathy and nephropathy, height and weight are measured. result: from 492 patients with diabetes mellitus, 272 patients (55.2%) had retinopathy (48 males, 42 females). the mean±sd of the age was 53.85 years. more than two third of patients were above 48 years old. 54.4% were hypertensive,26.6% cigarette smokers and 2.22% electronic hooka conclusion: this study showed high prevalence of diabetic retinopathy among type 2 diabetic patients, with poor control of blood glucose, high triglyceride, longer diabetes duration, hypertension, insulin treatment and age and gender as factor to develop retinopathy. keywords: ritinopathy, dm, thiqar ,2022 manuscript central used to avoid complications of hemodialysis manifested in uremic state including anorexia, nausea, vomiting leading to malnutrition, fluid and electrolyte imbalance leading to volume overload, hyperkalemia, metabolic acidosis, and hyperphosphatemia, as well as abnormalities related to hormonal or systemic dysfunction such as hypertension, anemia, hyperlipidemia, and bone disease, timely diagnosis of proteinenergy-wasting (pew) is important for early initiation of nutritional intervention and treatment. in addition, education plans should be prepared to mediate the nutrient intakes and identify the patient’s difficulties and provide practical help. keywords: renal dialysis, nutritional status, hemodialysis, malnutrition copyright : © 2022 the authors. published by publisher. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). cmi 03 (02), 304−311 304 abstract https://doi.org/10.52845/cmi/2022-3-1-4 https://creativecommons.org/licenses/by-nc-nd/4.0/ 1 introduction d iabetic retinopathy (dr) is a microvascular disorder caused by the long-term effects of diabetes, which results in vision-threatening retinal degeneration and eventually blindness. (1) many studies have found that hypertension, obesity, male sex, high triglyceride levels, hbalc greater than 7%, smoking, nephropathy and long-term diabetes are all risk factors for dr (2_8). diabetic retinopathy affects people who have diabetes mellitus, whether they are diagnosed or not. the risk of developing diabetic retinopathy is directly related to the patient's age and diabetes duration, as well as poor glycemic control and blood pressure fluctuations (9). diabetic retinopathy is the main cause of blindness in working age adults around the world, about 93 million people with diabetic retinopathy. the middle east is home to six of the top ten countries with the highest diabetes prevalence (bahrain, kuwait, lebanon, oman, saudi arabia, and united arab emirates). the prevalence of diabetic retinopathy is about 19% in the uae to 64% in jordan, 37%in iraq, 29.6 in iran, 55% in yemen (10). diabetic retinopathy is diagnosed by an ophthalmologist or optometrist by using comprehensive dilated eye exam, this should be occur shortly after diagnosis with dm in patient with type 2 dm, early detection and treatment can help to prevent complications and slow the disease's course (11). primary, secondary, and tertiary preventative efforts for the dr epidemic can all be generally characterized. primary, secondary, and tertiary preventative efforts for the dr epidemic can all be generally characterized. the goal of primary prevention is to prevent or delay the start of the disease (in this case, mild dr in those with diabetes). it necessitates a greater understanding of the risk of dr and blindness in diabetic patients, system-level lifestyle changes such as increased physical activity or dietary changes, pharmaceutical therapies for glycemic and blood pressure control, and systematic screening for the beginning of dr. secondary prevention requires the implementation of programs to slow the progression of dr, with a focus on systemic risk factor control, regular dr screening to track the progression of mild dr to vision-threatening stages, and the development and implementation of evidence-based management guidelines. ophthalmologists have focused on tertiary prevention of dr blindness based on timely laser photocoagulation treatment and ocular surgery, but increasingly on the widespread use of antivegf for vtdr, including dme and pdr, especially in high-income nations. aim the aim of this study is to estimate the prevalence of retinopathy among patients with type 2 diabetes mellitus among 224 people in thi_qar. justification retinopathy among patients with type 2 diabetes appears to be a public health problem in iraq; it is serious eye disease lead to sever visual impairment and blindness if not detected early. supplementary information the online version of this article (10.52845/cmi/2022-3-2-4) contains supplementary material, which is available to authorized users. cmi 03 (02), 304−311 manuscript central 305 2 | methodology study design: descriptive, cross -sectional study study patterns: face to face interview place & time of study: the study took place in thi qar governate , study began at 20th of january 2022 and ended at 28th of april 2022 study population: diabetic patient in thi-qar. exclusion outside thi-qar this cross sectional study was conducted on 492 diabetic patients attending to diabetes center in thi_qar between april and may 2022. these patients were initially diagnosed as diabetics by physician and diagnosis of retinopathy was done by an ophthalmologist. sample as a convenience sample, collected through face to face interview for 5 days per week. manuscript central wajida saa'd bunyan et al. ethical consideration: ethical consent had been attained from the scientific committee of community medicine department / college of medicine / thiqar university and also from the associate scientific dean of the same college, and take from counselling of ophthalmology by al-habbobi hospital, with agreement of patient to be one of my samples in research. variables of interest: age, gender, socioeconomic status, marital status, occupation, type of dm, duration, type of treatment, signs of retinopathy, diabetic retinopathy (dr) is a specific microvascular ocular complication associated with diabetes.1 the global prevalence of chronic microvascular complications like dr is increasing due to the increasing prevalence of diabetes worldwide as well as the increased survival of people with diabetes. laboratory data were obtained from patients files in diabetic and endocrinology center, these variables include socio-demographic, (sex and age), the participants residence, clinical data include, smoking, hypertension or if the patient is currently using prescribed antihypertensive drugs, if have retinopathy and nephropathy, height and weight are measured. all patient underwent blood investigation hba1c (good glycemic control if hba1c is less than 7%) and triglycerides (tg) investigation. the prevalence of dr was calculated using the number of patients with dr as the numerator and the total number of t2dm as the denominator. statistical analysis: ualitative data had been analyzed by using spss (statistical package for social science), were percentage and chi square had been calculated, p value <0.05 is significant. epidemiological analysis: 3 | results manuscript central cmi 03 (02), 304−311 (2022) 306 in total, 492 diabetic patient consulting the ophthalmological unite randomly selected different types diabetic patients were included (272) of them were with diabetic retinopathy. their ages ranged from 15 to 82 years, with a mean sd of 53.82 (12.51) years and a median of 53 years. 55.2% (n = 272) of them were diagnosed with dr. as seen in table, the mean age of male and female diabetic retionpathy patients were 56.02 years and 58.92 years. the mean age of patients with dr was significantly higher (p < 0.001) in comparison to patients without dr (57.37 vs. 53.82 years) prevalence of diabetic retinopathy among diabetic patients from the type 2 diabetic patients recruited in the study the prevalence of dr was (55.5%). the prevalence of dr was higher among patients' males and patients with hypertension and nephropathy. from the total participants, 54.4% had hypertension as a co-morbidity, 53.3% had nephropathy, and 71.1% had family history of dm. however, in this study factors such as, gender, occupational status, alcohol drinking status, types of diabetes, and having awareness about diabetic retinopathy did not show statistically significant association with dr either on a bivariable or a multivariable logistic regression analysis. figure three retinopathy according to types of dm cmi 03 (02), 304−311 (2022) manuscript central 307 table show distribution of age, gender, occupational status, control, association with other disease, smoking and drinking alcohol among diabetic retinopathy patient. manuscript central wajida saa'd bunyan et al. figure five: diabetic retinopathy according to smoking status our study, which is similar to sparrow study concluded that the severity of dr was related to male sex (3). this finding also echoed a malaysian study in a teaching hospital whereby the risk of developing dr was higher among the older population due to the vascular changes in the retinal circulation (13). with advancing age, dr can result in blindness in the elderly if left untreated. aside from that, our research found that the length of time from t2dm diagnosis was linked to dr. the likelihood of developing dr increases as the length of t2dm diagnosis increases. this was in line with previous research, however in the other investigations (14,13,15) the or was larger. furthermore, diabetes treatment is crucial in the development of dr. the hba1c level can be well controlled if diabetes is well managed. poor diabetes care, on the other hand, can result in suboptimal hba1c levels, which can increase the risk of developing dr. this study found a robust link between hba1c and the development of dr, similar to earlier research (14, 15). a drop in hba1c of 1.0 percent was linked to a 37.0 percent reduction in microvascular problems (16). hba1c levels, on the other hand, are ambiguous and may be a non-significant finding in dr (13). furthermore, the primary factor of dr was lifetime exposure to high blood glucose levels. this study found that early intervention in blood sugar control is critical for reducing the incidence of diabetes mellitus. to put it another way, glycemic management is protective against dr (17). strict nutrition control, a healthy lifestyle, physical activity, and low stress levels can all help. aside from lifestyle changes and pharmacological therapy, more extensive non-pharmacological care options for dr include pancreas transplant and islet cell transplantation (18). in comparison to medication therapy, islet cell transplantation has demonstrated encouraging effects in delaying the progression of dr. patients who got the transplant, on the other hand, had superior baseline hba1c control than the non-transplanted group in the above-mentioned study (19). as a result, more research is needed to get a better understanding of the effect of islet cell transplantation on dr (18). manuscript central cmi 03 (02), 304−311 (2022) 308 4 | discussion this study was a single-center registry-based study in diabetic retinopathy among diabetes patients who attended the diabetic clinic in thi_qar. the prevalence of diabetic retinopathy in type 2 diabetic patients was 55.5%. considerable increase in the burden of diabetic complications including dr. comparison among studies is difficult because the prevalence of retinopathy has varied widely depending on the methodology and populations. the prevalence of diabetic retinopathy in this study is higher than prevalence of retinopathy among type 2 diabetes of other articles, the higher prevalence reported in this study could be due to the difference in the selection of study sample. the prevalence of dr in this study is comparable to the rj, et. al. study in 2003 in australia (2). other study in africa also have shown lower prevalence of dr from this study (4). other study shows a lower prevalence of dr among type 2 diabetic patients (5). sparrow et. al. (2003) in england found a higher overall rate of retinopathy (3). the patient's age was linked to the development of dr (p=0.002). according to certain studies, there is a link between dr and age. aging, high blood glucose, and high blood pressure promote microvascular loss of blood vessels, which worsens with time, hence diabetic retinopathy is primarily caused by aging and the length of diabetes (6,12). gender may also identify as a risk factor in in terms of medical care, the broad availability of continuous insulin pump therapy has been linked to a lower dr rate and better outcomes than conventional insulin therapy (19). to keep diabetes under control, the medical staff and patients must collaborate closely. long-term, the advantages of intensive blood sugar control with lower glucose variability can arrest the progression of dr and other dm consequences such diabetes nephropathy, peripheral vascular disease, and coronary heart disease (20). moreover, this study highlighted the association between dr and diabetic nephropathy. this was aligned with the asian korean study that reported a 19.3% prevalence rate of dr among patients with nephropathy (21). the pathophysiology of both dr and diabetic nephropathy is similar. in advanced retinopathy when structural changes are detected in the cell membrane of the eye, similar changes will also be seen in the kidney cells (22, 23). hypertension was found to have a strong link with the severity of retinopathy in this investigation. studies in the asian population revealed that diabetes patients with hypertension have twice the chance of developing retinopathy (24, 25). in western countries, similar findings have been recorded (26,14). hypertensive individuals have impaired retinal autoregulation, leaving them unable to defend themselves from fluctuations in blood pressure caused by hyperglycemia in diabetic patients, which compromises retinal perfusion regulation (27). finally, this study did not explore the association between geographical factors and dr. therefore, future research should explore the impact of geographical factors towards the development of dr in sabah. based on the study results, necessary modifications in the management plan of dr can significantly improve the quality of life of diabetic patients. also another important notes were the patient's age was linked to the development of dr. according to certain studies, there is a link between dr and age. aging, high blood glucose, and high blood pressure promote microvascular loss of blood vessels, which worsens with time, hence diabetic retinopathy is primarily caused by aging and the length of diabetes (28,29). gender was not identified as a risk factor in our investigation, which concurs with anchorman et alfindings.’s in isfahan (30). sparrow's study, on the other hand, found that the severity of dr was linked to male sex (31). most studies on diabetic changes in the eye show that high blood pressure is significantly associated with diabetic retinopathy, and consider hypertension to be an established risk factor for dr because it causes blood vessel destruction, especially when it is associated with high blood glucose (32,33). hypertension showed a significant association with dr, but these findings contradict those of the segato et al. study, which found that hypertension was not related to dr (34) manuscript centralcmi 03 (02), 304−311 (2022) 309 5 | conclusion dr was found to affect one-third of patients who attended the diabetic clinic of thi_qar. the prevalence of dr increased with longer duration of diabetes, high hba1c level, presence of significant albuminuria, and impaired protective sensation and may have association with gender, age and other disorder like nephropathy and hypertension. diabetic patients should be encouraged to stringently control their diabetes and comorbidities. appropriate management of associated risk factors can alleviate dr and other cardiovascular complications. recommendation recommend going further in this study to record many populations and for longer duration and to include other risk factors apart from the duration of the disease to induce dr. we can reduce the prevalence of diabetic retinopathy by developing an integrated health and social care pathway, further education and better communication between all the relevant parties hence it is extremely crucial to spread knowledge regarding diabetic retinopathy through television, newspaper, posters in all hospitals and other health centers as it will motivate and encourage the diabetic patients to undergo a timely eye examination and thus engage individuals so an manuscript central wajida saa'd bunyan et al. manuscript central cmi 03 (02), 304−311 (2022) 310 initial details and comprehensive eye examination should be performed and project to encourage the physicians to send the patients for retinal checkups to diagnose them earlier and also, educate the patients about the screening schedules of dr. subsequent examinations for type i and type ii diabetic patients should be repeated annually in the absence of retinal changes, otherwise shorter intervals are recommended (35,36). references 1. eisma jh,dulle je,fort pe, current knowledge on diabetic retinopathy from human donor tissues. world journal of diabetes. 2015 mar 15 2. tapp rj, shaw je, harper ca, de courten mp, balkau b, mccarty dj, taylor hr, welborn 3. ta &zimmet pz: the prevalence of and factors associated with diabetic retinopathy in the australian population. diabetes care, 2003; 26:1731-37. 4. sparrow jm, mcleod bk, smith td, birch mk &rosenthal ar: the prevalence of diabetic retinopathy and maculopathy and their risk factors in thetype 2diabetic patients of an english town. eye, 2003, 7 (pt1): 158-63. 5. sidibe eh: diabetic retinopathy in dakar and review of african literature: epidemiologic elements. diabetes metab, 2000, 26:322-24. 6. norymberg ck, neumann e & dekel h: complication-free duration and the risk of development of retinopathy in elderly diabetic patients. arch intern med, 2008, 158:641-44. 7. wright ad& dodson pm: me and accord eye studies. eye (lond), 2011; 25:843-49. 8. janghorbani m, amini m, ghanbari h &safaieeh: incidence of and risk factors for diabetic retinopathy in isfahan, iran. ophthalmic epidemiol, 2003, 10:81-95. 9. robyn j, jonathan e, alex h, et. al. the prevalence of and factors associated with diabetic retinopathy in the australian population. diabetes care, 2003; 26(6):1731-37. 10. wang y,lin z,zhai g,ding x,wen l,li d,zou b,feng k,liang y,xie c, prevalence of and risk factors for diabetic retinopathy and diabetic macular edema in patients with early and late onset diabetes mellitus. ophthalmic research. 2020 apr 30; 11. lee r, wong tien y sabanayagam c. eye vis (lond). 2015; 2:17. 12. american diabetes association professional practice committee. diabetes care. 2022; 45(supplement_1): s185-s194. doi: 10.2337/ dc22-s012. 13. abu el asrar am, al-rubeaan ka, al-amro sa, kangave d & moharram oa: risk factors for diabetic retinopathy among saudi diabetics. int ophthalmol, 2009;22:155-61. 14. abougalambou ssi, abougalambou as. risk factors associated with diabetic retinopathy among type 2 diabetes patients at teaching hospital in malaysia. diabetes metab syndr clin res rev. 2015;9(2):98–103. 15. yau jwy, rogers sl, kawasaki r, lamoureux el, kowalski jw, bek t, et al. global prevalence and major risk factors of diabetic retinopathy. diabetes care. 2012;35(3):556–64. 16. raman r, ganesan s, pal ss, kulothungan v, sharma t. report no 2. bmj open diabetes res care. 2014;2(1): e000005. 17. stratton im, adler ai, neil haw, matthews dr, manley se, cull ca, et al. prospective observational study . bmj open. 2000; 321:405– 12. 18. ferris fl, nathan dm. preventing diabetic retinopathy progression. ophthalmology. 2016;123(9):1840–2. 19. fiorina p, shapiro amj, ricordi c, secchi a. the clinical impact of islet transplantation. am j transplant. 2008;8(10):1990–7. 20. robertson rp. islet transplantation a decade later and strategies for filling a half-full glass. diabetes. 2010; 59:1285–91. 21. zabeen b, craig me, virk sa, pryke a, chan akf, cho yh, et al. insulin pump therapy is associated with lower rates of retinopathy and peripheral nerve abnormality. plos one. 2016;11(4):1–10. how to cite this article: bunyan, w. s. ., saadoon, a. a. ., saeed, m. n. ., flayh, z. j. ., & alrazzaq, h. a. abd . (2022). prevalence and determinants of retinopathy among patients with diabetes mellitus: thiqar 2022. clinical medicine insights, 3(2), 304–311. https:// doi.org/10.52845/cmi/2022-3-2-4 22. lee wj, sobrin l, lee mj, kang mh, seong m, cho h. the relationship between diabetic retinopathy and diabetic nephropathy in a population-based study in korea (knhanes v-2, 3). investig ophthalmol vis sci.2014;55(10):6547 –53. 23. lim mcc, shu yl, cheng bcl, wong dwk, sze go, chong la, et al. diabetic retinopathy in diabetics referred to a tertiary centre from a nationwide screening programme. ann acad med singapore. 2008;37(9):753–9. 24. klein r, knudtson md, lee ke, gangnon r, klein bek. the wisconsin epidemiologic study of diabetic retinopathy xxii. ophthalmology. 2008;115(11):1859–68. 25. raman r, rani pk, reddi rachepalle s, gnanamoorthy p, uthra s, kumaramanickavel g, et al. 2009;116(2):311–8. 26. wong ty, cheung n, tay wt, wang jj, aung t, saw sm, et al. 2008;115(11):1869–75. 27. eva m. kohner m, stephen j. aldington d, irene m. stratton ms, susan e. manley p, rury r. holman m, david r. matthews m, et al. united kingdom prospective diabetes study. arch ophthalmol. 1998;116:297–303. 28. wright ad& dodson pm: me and accord eye studies. eye (lond), 2011; 25:843-49. 29. abu el asrar am, al-rubeaan ka, al-amro sa, kangave d & moharram oa: risk factors for diabetic retinopathy among saudi diabetics ophthalmology, 2009;22:155-61. 30. janghorbani m, maini m, ghanbari h &safaiee h: incidence of and risk factors for diabetic retinopathy in isfahan, iran. ophthalmic epidemiol, 2003, 10:81-95. 31. sparrow jm, mcleod bk, smith td, birch mk &rosenthal ar: the prevalence of diabetic retinopathy and maculopathy and their risk factors in thetype 2diabetic patients of an english town. eye, 2003, 7 (pt1): 158-63 32. international council of ophthalmology (ico) international clinical guideline: diabetic retinopathy (initial and follow up evaluation). available as at: http//www.icoph.org/:/guide/ guidedi.htmlat,2006;15:105 33. van leiden ha, dekker jm, moll ac, nijpels g, heine r, bouter l, et. al.: blood pressure, lipid and obesity are associated with retinopathy: the hoom study. diabetes care,2002; 25(8):1320-25. 34. segato t, midena e, grigoletto f et. al.:the epidemiology and prevalence of diabetic retinopathy in the veneto region of north east italy. veneto group for diabetic retinopathy. diabet med, 2008; 8:511-16. 35. curtis tm, gardiner ta, stitt aw. microvascular lesions of diabetic retinopathy: clues towards understanding pathogenesis? eye. 2009;23(7):1496–508. american diabetes association. standards of medical care in diabetes—2016. diabetes care. 2016;39(suppl 1):s1-s106. manuscript centralcmi 03 (02), 304−311 (2022) 311 introduction causes of nutritional disorder in hd inadequate food intake abnormal nutrient metabolism aim and objectives methodology result assessment of nutritional status of hd. patients prevalence of malnutrition using subjective global assessment body mass index in the study patients bmi and sga score laboratory investigation association between nutrient intake and sga discussion conclusions references blank page issn (o) 2694-4626 doi: https://doi.org/10.52845/cmi/2022-3-2-5 cmi 03 (02), 312−317 (2022) original article charecteristics of pressure sore of spinal cord injury patients attentded at crp. md. mahbub hossain 1 , most.rabia khatun 2 , umme habiba 3 corresponding author: md. mahbub hossain abstract: purpose: the purpose of the study is to identify the characteristics of pressure sore of spinal cord injury patients attended at crp. objectives: to evaluate the characteristics of pressure sore among spinal cord injury patient attended at crp. methodology: method of the study was a cross sectional type of descriptive study which was conducted through face to face interviews, by using questionnaire with informed consent of the participants. data were numerically coded and used in excel and spss 20 version software program. result: most of the participants had pressure sore 43% (n=13) participants were buttocks, 17 %( n=5) participants had pressure sore in coccyx region, 26% (n=8) participants had pressure sore in sacral region and 13 %( n=4) participants had pressure sore in leg. among 30 participants, according to the degree of pressure sore, 13% (n=4) participants had one degree of pressure sore, 30% (n=9) participants had two degree of pressure sore, 40% (n=12) participants had three degree of pressure sore and 17% (n=5) participants had four degree of pressure sore. conclusion: pressure sore is a serious complicated among sci patients for which a lot of patients are dying every year. we must prevent pressure sore in order to improve rehab serious of sci at institutional setting. hospitals admit neurological impaired patients including sci must administered appropriate measure to prevent ulcer. key words: pressure sore, spinal cord injury, causes of pressure sore, convulsion, urinary incontinence, lifting. 1.1 background: pressure ulcers are one of the most common secondary complications of spinal cord injury (sci) ( kroll et al., 2007). increasing prevalence rates amongst individuals with sci are attributed to repeatedly spending prolonged periods of time in the seated position coupled with limited mobility and sensation ( chen et al., 2005). 1 lecturer of pmk nursing college, department of nursing, palli mongal karmosuchi,zirabo, ashulia, savar, dhaka, bangladesh 1 . 2 principal of pmk nursing college, department of nursing, palli mongal karmosuchi,zirabo, ashulia, savar, dhaka, bangladesh 2 . 3 nursing officer (s.s.n) of national institute of traumatology and orthopaedic rehabilitation (nitor), department of nursing, sher-e-bangla nagar, dhaka-1207, and bangladesh3. supplementary information the online version of this article contains supplementary material, which is available to authorized users. jan-erik lane 2022; published by current science, inc. this open access article is distributed under the terms of the creative commons license (http://creativecommons.org/licenses/by/4.0),which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited cmi 03 (02), 312−317 manuscript central 312 clinical medicine insights https://doi.org/10.52845/cmi/2022-3-2-5 http://creativecommons.org/licenses/by/4.0),which within rehabilitation, individuals with sci are taught and encouraged to perform regular repositioning movements in order to redistribute the build-up of pressure around the ischial tuberosity and sacral regions. these repositioning movements include vertical push-ups, lateral and forward leans. although recommended as often as every 15–30 minutes (national pressure ulcer advisory panel, 2007). research has shown that concordance with regular repositioning is poor (yang et al.,2009). wheelchair users are reported to spend as much as 18 hours per day in their wheelchair, with many (54.7%) repositioning less often than once an hour (yang et al., 2009). pressure ulcer management has become a nationwide healthcare priority. the scope of the problem is significant on multiple levels. estimates indicate that 1–3 million people in the united states (us) develop pressure ulcers each year (salcido.,2012). tissue injury is related to both extrinsic and intrinsic factors. extrinsic factors include pressure, shear, friction, immobility, moisture. intrinsic factors relate to the condition of the patient, such as sepsis, local infection, decreased autonomic control, altered level of consciousness, increased age, vascular occlusive disease, anemia, malnutrition, sensory loss, spasticity, and contractures (bauer and philips. 2008). it is known that relieving skin pressure over a bony prominence for 5 minutes every 2 hours will allow adequate perfusion and prevent tissue breakdown. more recently, an analysis by (makhsous et al., 2007). chemical debriding agents achieve removal of necrotic tissue, escher and slough by topical treatment of proteolytic enzymes on chronic wounds. their mechanism of action relate to their enzymatic degradation of collagen and liquefaction of necrotic debris without damaging granulation tissue (salcido et al., 2012). methods: the study was conducted by quantative study design that was undertaken characteristics of pressure sore of spinal cord injury patients of a selected hospital in crp, bangladesh with 30 samples included with the inclusion criteria. data were collected by face to face interviewed method. data analysis the data analysis was performed in the program „statistical package for social science‟ (spss) version 20. the presentation was performed in spss and in microsoft office word 2010. every questionnaire was rechecked for missing information or unclear information. at first put the name of variables in the variable 22 views of spss and the types, values, decimal, label alignment and measurement level of data. result and discussion this chapter provides an overview of the findings and the results from the analysis were presented. the statistical package for the social science (spss) and msexcel spreadsheets were used to assist in the statistical analysis of the data from 30 participants from centre for the rehabilitation of paralyzed (crp) & hospital. to avoid any bias in the data caused by discussion between the participants, the investigator was present at all times during the data collection. the data obtained from the study were analysed using descriptive statistics. according to the appropriate scales of measurement, measures of central tendency, frequency distribution and measures of dispersion were used to analyse and describe the data. the most significant results are discussed. percentage analysis had appeared to be the most effective method for providing the greatest amount of information about how the participants answered these questions. table 1: individual characteristics of the subject variables variable (%) n sex male (93%) 28 female (7%) 2 educational qualification under ssc (80%) 24 ssc (17%) 5 cmi 03 (02), 312−317 manuscript central 313 central hsc (3%) 1 cause of pressure sore same position (40%) 12 surgery (17%) 5 wound (43%) 13 place of pressure sore sacral region (26%) 8 coccyx region (17%)5 buttock (43%)13 leg (13%)4 measurement of pressure sore 1-2cm (17%)5 2-3cm (50%)15 3-4cm (23%)7 4cm or more (10%)3 stage of pressure sore stage-1 (13%)4 stage-2 (30%)9 stage-3 (40%)12 stage-4 (17%)5 number of pressure sore one (67%) 20 two (30%) 9 three (3%) 1 urinary incontinence yes (100%) 30 no (0%) 0 urinary infection yes (13%) 4 no (87 %) 26 spasticity yes (53 % )16 no (47% )14 tale 2: the between-subject analysis for association association between measurement of pressure sore and stage of pressure sore. chi-square pvalue 0.521 0.413 this observed chi-square value was .521 and p value was .413. so the result was not significant that indicate there was association between measurement of pressure sore and stage of pressure sore. this observed chi-square value was 0.053 and p value was 0.043. so the result was significant that indicate there was association between urinary infection and convulsion of the participants. some important result showed in different chart: educational level of the participants: among the 30 participant who had pressure sore 80% (n=24) participants were under s.sc, 17%% (n=5) participants had ssc and 3% (n=1) participants hsc of educational status. association between urinary infection and convulsion of the participants. chi-square pvalue 0.053 0.043 cmi 03 (02), 312−317 manuscript central 314 manuscript central md. mahbub hossain et al. central information about educational level. information about causes of pressure sore: among the 30 participants who had pressure sore due to 40% (n=12) participants were same position, 17% (n=5) participants had surgery and 43% (n=13) participants had wound. causes of pressure sore of the participant place of pressure sore of the participants: the place of pressure sore were 26% (n=8) participants got pressure sore in sacral region, 17% (n=5) participants got pressure sore in coccyx region & 43% (n=13) participants got pressure sore in buttock &13% (n=4) participants got pressure sore in leg. 0% 20% 40% 60% 80% under s.sc s.sc h.sc under s.sc s.sc h.sc 0% 5% 10% 15% 20% 25% 30% 35% 40% same position surgery wound same position surgery wound 0.00% 5.00% 10.00% 15.00% 20.00% 25.00% 30.00% 35.00% 40.00% 45.00% secral region coccyx region buttock leg secral region coccyx region buttock leg cmi 03 (02), 312−317 manuscript central 315 manuscript central md. mahbub hossain et al. central place of pressure sore of the participants measurement of pressure sore of the participants among 30 participants, 17% (n=5) participants had 1-2cm of pressure sore, 50% (n=15) participants had 2-3cm of pressure sore , 23% (n=7) participants had 3-4cm of pressure sore and 10% (n=3) participants had 4cm or more of pressure sore. measurement of pressure sore of the participants stage of pressure sore of the participants among 30 participants, 13% (n=4) participants had one degree of pressure sore, 30% (n=9) participants had two degree of pressure sore, 40% (n=12) participants had three degree of pressure sore and 17% (n=5) participants had four degree of pressure sore. stage of pressure sore of the participants conclusion the researcher explored the characteristics of pressure sore of spinal cord injury patients attended at crp. the study was conducted on 30 participants who was admitted in centre for the rehabilitation of paralysed & hospital where most of the participants had pressure sore 43% (n=13) participants were buttocks, 17 %( n=5) participants had pressure sore in coccyx region, 26% (n=8) participants had pressure sore in sacral region and 13 %( n=4) participants had pressure 17% 50% 23% 10% 1-2cm 2-3cm 3-4cm 4cm or more masurement of pressure sore 13% 30% 40% 17% stage 1 stage 2 stage 3 stage 4 stage of pressure sore cmi 03 (02), 312−317 manuscript central 316 manuscript central md. mahbub hossain et al. central sore in leg. among 30 participants, according to the degree of pressure sore, 13% (n=4) participants had one degree of pressure sore, 30% (n=9) participants had two degree of pressure sore, 40% (n=12) participants had three degree of pressure sore and 17% (n=5) participants had four degree of pressure sore. pressure sore is a serious complicated among sci patients for which a lot of patients are dying every year. we must prevent pressure sore in order to improve rehab serious of sci at institutional setting. hospitals admit neurological impaired patients including sci must administered appropriate measure to prevent ulcer. references 1. t. kroll, m. t. neri, and p. s. ho, “secondary conditions in spinal cord injury: results from a prospective survey,” disability and rehabilitation, vol. 29, no. 15, pp. 1229–1237, 2007. 2. y. chen, m. j. devivo, and a. b. jackson, “pressure ulcer prevalence in people with spinal cord injury: age-period-duration effects,” archives of physical medicine & rehabilitation, vol. 86, no. 6, pp. 1208–1213, 2005. 3. y. s. yang, g. l. chang, m. j. hsu, and j. j. chang, “remote monitoring of sitting behaviors for community-dwelling manual wheelchair users with spinal cord injury,” spinal cord, vol. 47, no. 1, pp. 67–71, 2009. 4. salcido r, popescu a, potter a, talavera f, kolaski k, allen k, et al. pressure ulcers and wound care. [accessed 2012 february 14. 5. bauer j, phillips lg. moc-pssm cme article: pressure sores. plast reconstr surg 2008;1211 suppl:1–10. 6. makhsous m, priebe m, bankard j, rowles d, zeigler m, chen d, et al. measuring tissue perfusion during pressure relief maneuvers: insights into preventing pressure ulcers. j spinal cord med 2007;30(5):497–507. cmi 03 (02), 312−317 manuscript central 317 manuscript central md. mahbub hossain et al. how to cite this article: hossain, m. m. ., khatun, m. ., & habiba, u. . (2022). charecteristics of pressure sore of spinal cord injury patients attentded at crp. clinical medicine insights, 3(2), 312–317. https://doi.org/10.52845/ cmi/2022-3-2-5 cmi 04 (03), 415−429 cmi journal 415 clinical medicine insights doi:https://doi.org/10.52845/cmi/2023-4-3-3 cmi 04 (03), 415-429 (2023) issn (o) 2694-4626 original article efficacy of highand low-dose, highly bioavailable curcumin (curcurouge ® ) for treating knee osteoarthritis: a randomized, doubleblind, placebo-controlled prospective study yasuaki nakagawa m.d. 1,2 , shigeru yamada m.d. 3 ,shogo mukai m.d. 3 ,kaori akiyoshi 4 ,yasuhiro katsuura 5 ,tadashi hashimoto 5 1 clinical research center, national hospital organization kyoto medical center, japan 2 department of orthopaedic surgery, japan baptist medical foundation, japan 3 department of orthopaedic surgery, national hospital organization 4 department of medical infomatics, national hospital organization 5 therabiopharma incorporation, japan *corresponding author: yasuaki nakagawa, md abstract: purposes : to evaluate the clinical effects of orally administered curcurouge○r in patients with knee osteoarthritis (oa) after 12 weeks of treatment. methods: in this randomized, double-blind, placebo-controlled, prospective clinical study. 90 patients over the age 40 with knee oa of kellgren-lawrence (kl) grade ii or iii were enrolled. a placebo or curcurouge○r containing 60 mg or 180 mg/day of curcumin was administered orally every day for 12 weeks. to monitor adverse events, blood biochemical analyses were performed before and after 12 weeks of each intervention. the patients’ knee symptoms were evaluated for 12 weeks using the japanese knee osteoarthritis measure (jkom) criteria, a knee pain visual analog scale (vas), the japanese orthopedic association (joa) knee scoring system, the need for nonsteroidal anti-inflammatory drugs (nsaids) and a timed up-and-go test (tug). results: the declining trend in nsaids needs was significantly greater in high-dose curcurouge ○r group than in placebo group. the decrease of highly sensitive crp was significantly greater in high-dose of curcurouge ® than placebo group. in patients with kl grade ii, joa and vas scores improved significantly more in the high-dose curcurouge ○r group than in the placebo group. we didn’t find curcurouge ® related adverse event during the study period. conclusion: curcurouge○r has succeeded in proofing a potential for treating human knee oa, particularly at an early stage. trial registration: jrcts 051200058 keywords: knee osteoarthritis, treatment, safety, highly bioavailable curcumin, curcurouge○r level of evidence: level i, a randomized, double-blind, placebo-controlled prospective study copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/lic enses/bync-nd/4.0/). https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ cmi 04 (03), 415−429 cmi journal 416 cmi journal yasuaki nakagawa, md introduction osteoarthritis (oa) is a common degenerative disease that causes disability and poor quality of life. it affects approximately 240 million people worldwide, with 10% of men and 18% of women affected [1]. hip or knee oa is a chronic condition mostly treated with analgesics and nonsteroidal anti-inflammatory drugs (nsaids), but these medications can cause serious gastrointestinal and cardiovascular adverse events, especially with longterm use [2,3]. thus, disease-modifying agents that not only alleviate joint pain but also slow the progression of the condition are required. curcumin is a polyphenol extracted from turmeric, that has long been used safely in foods like curry [4]. curcumin, a promising therapeutic food material with anti-inflammatory and anti-oxidative properties; has long been used as an antiinflammatory treatment in traditional chinese and ayurvedic medicine [4]. it regulates various biochemical and molecular pathways by modulating several molecular targets, including transcription factors, cytokines, enzymes, and genes, that regulate cell proliferation or apoptosis [5]. it appears to have anti-inflammatory effects comparable to steroidal drugs and nsaids such as indomethacin and phenylbutazone [6]. some studies have linked curcumin’s anti-inflammatory properties to the suppression of prostaglandin synthesis by its effect on cyclooxygenase [7], a key enzyme responsible for the conversion of arachidonic acid to prostaglandins. it has also been shown to inhibit proteasome activity and induce apoptosis in human colon cancer cells, both in vitro and in vivo [8]. furthermore, it inhibits nuclear factor-kappa b (nf-kb) activation [9], which is a key event in the chronic inflammatory process. based on these findings, curcumin is expected to be effective for a wide range of diseases related to chronic inflammation, including cancer, cardiovascular disease, metabolic syndrome, alzheimer’s disease, oa, and other common diseases and aging conditions [4,5,10,11]. furthermore, it has been shown to be a potent inhibitor of the chondrocyte production of inflammatory and catabolic mediators [10]. however, curcumin has a very low bioavailability. theracurmin○r , which is a submicron-particle colloidal dispersion of curcumin [12], has better oral bioavailability in humans [13]. in a randomized, double-blind, placebo-controlled, prospective clinical trial in patients with oa to evaluate the efficacy of theracurmin ○r, , nakagawa showed that theracurmin○r improved the knee pain visual analog scale (vas) scores [14]. to further improve bioavailability, sunagawa developed curcurouge○r(therabiopharma, kanagawa, japan), a novel amorphous formulation of curcumin. they confirmed that curcurouge○r was 3.4-fold higher bioavailable than theacurmin○r in a single-dose, double-blind, two-way crossover study in 12 volunteers [15]. the purpose of the current study was to determine the clinical efficacy of orally administered curcurouge○r in patients with knee oa after 12 weeks of treatment. we hypothesized that consuming curcurouge○r ingestion for 12 weeks would improve the symptoms and functional abilities of patients with knee oa. materials and methods to test our hypothesis, we conducted a randomized, double-blind, placebo-controlled, prospective clinical study with three treatment groups: high dose (180 mg/day curcumin) and low dose (60 mg/day curcumin) curcurouge○r and placebo. at the start of the treatment period, randomization was cmi 04 (03), 415−429 cmi journal 417 cmi journal yasuaki nakagawa, md performed after baseline tests and using a computer-generated numbers table without stratification. based on randomization, the allocation was performed by someone who was not involved in the current project. from september 2020 to october 2022, 90 patients over the age of 40 with knee oa confirmed by the radiographic analysis were selected and enrolled in the study. they were divided into three groups of 30 patients each. before participating, all subjects provided written informed consent. all procedures were reviewed and approved by the nara medical university certified review board (nara0017), and this study was performed in accordance with the world medical association’s declaration of helsinki. this study was registered at japan registry for clinical trials (jrcts051200058). in this study, patients over the age of 40 with primary medial knee oa and kl grades of ii or iii with radiographic classification were eligible. however, patients with severe renal dysfunction or on dialysis, severe liver dysfunction or cirrhosis, severe cardiovascular diseases, severe cerebrovascular dysfunction, severe diabetes mellitus, curcumin abuse, or pregnancy were excluded from this study. furthermore, those who had received more than two types of anticoagulants, previous knee surgeries, knee injection treatment including hyaluronic acid during the study, knee steroid injections two months before the study, or other steroids four weeks before the study were excluded. if patients required nsaids during the study, oral celecoxib two pills per day (100 mg per pill) were prescribed. the other combined therapy we allowed was pain relief patches. a high or low-dose of curcurouge○r or placebo was administered orally twice a day, for 12 weeks. patients in the high-dose curcurouge○r group took two capsules containing 90 mg of curcumin per capsule, while those in the low-dose curcurouge○r group took two capsules containing 30 mg of curcumin per capsule per day. similarly, patients in the placebo group took two placebo capsules per day that were similar in shape and color to those of curcurouge○r . the placebo was primarily made of crystalline cellulose, silicon dioxide, calcium stearate and food colorings. for the compliance check, the patients were asked to report the number of remaining capsules and the prescribed celecoxib pills at their 2, 4, 6, 8, 10 and 12-week visits at our outpatient clinic. the study’s flow chart is depicted in figure 1. the highand low-dose curcurouge○r and placebo groups included 30 patients. the drop-out cases due to adverse events were two in the high-dose group (due to severe lumbago and buttock pain in one case and vertigo and nausea in one case), four in the low-dose group (due to dermatitis in one case, consent withdrawal in one case, severe knee pain in one case and un-wellness in one case), and none in the placebo group. the study’s safety committee decided that all of the aforementioned adverse events were unrelated to curcurouge○r . one case in the high-dose group was excluded due to poor drug intake compliance. finally, 83 patients (27 in the high-dose curcurouge○r group, 26 in the low-dose curcurouge○r group, and 30 in the placebo group) were included for further analysis. blood biochemical analyses were performed before the study and after 12 weeks of each intervention, and blood curcumin concentrations were analyzed after 12 weeks using a previously described analytical method [15]. the patients’ knee symptoms were assessed at 0, 2, 4, 6, 8, 10 and 12 weeks according to the japanese knee cmi 04 (03), 415−429 cmi journal 418 cmi journal yasuaki nakagawa, md osteoarthritis measure (jkom) criteria [16], the jkom knee pain vas, and the knee scoring system of the japanese orthopedic association (joa) knee scoring system [17]. the jkom consists of 25 questions divided into four subcategories for patient self-assessment (pain and stiffness, condition in daily life, general activities, and health conditions) and is based on the world health organization’s international classification of functioning, disability, and health, validated in the same way as the western ontario and mcmaster universities’ arthritis index. the joa scale assesses four functions: the ability to walk (30 points), the ability to climb up and down stairs (25 points), the range of motion (rom; 35 points), and joint swelling (10 points). each knee joint can achieve a maximum score of 100 points on the joa scale. the improved jkom, vas, and joa scores (the differences between the scores at each time point and before the study) were calculated. furthermore, adverse events and the number of celecoxib pills taken during the 12-week period were recorded. we also calculated nsaids necessity in 3 groups. a timed up-and-go test (tug) and the rom of their knee joints were measured before the study and after 12 weeks of each intervention. these performance-based measures are recommended as validated outcome measures by the osteoarthritis research society international to assess physical function in adults with knee oa [18,19]. in tug, participants were asked to stand up, walk around a cone three meters away, and then return to their chairs at their regular pace. the chair had no arms, and a height of 50 cm from the seated position. the time and number of gaits required to complete this task were recorded. the primary endpoints were jkom, vas, and joa knee score, as well as nsaid necessities. the secondary endpoints were tug, knee rom, blood biochemistry analyses, and adverse events. the primary analysis was performed following the full-analysis-set principal. data were expressed as mean and standard deviation (sd) and compared among groups using a three-factor analysis of variance for parametric variables or the kruskalwallis test for non-parametric variables. a paired student’s t-test was used to compare data at 0 and 12 weeks of treatment in each group. categorical data were compared using the chi-squared test. the level of statistical significance was set to a p value of less than 0.05. all statistical analyses were performed using ezr, a modified version of the r commander designed to include statistical functions frequently used in biostatistics. results the baseline characteristics of the study patients in each of the three groups are summarized in table 1. the majority of patients were female, accounting for 77.8% in the high-dose of curcurouge○r group, 88.5% in the low-dose of curcurouge○r group, and 70.0% in the placebo group. the patient ages were also comparable across the three groups. the kl grading system was used to quantify disease severity in order to effectively randomize disease status upon study entry between groups. for kl grade ii, there were nine cases in the high-dose curcurouge○r group, eight cases in the low-dose curcurouge○r group, and 10 cases in the placebo group. for kl grade iii, there were 18 cases in the high-dose group, 18 cases in the low-dose group, and 20 cases in the placebo group. there were no statistical differences in the baseline characteristics, as well as compliance, among the three groups. cmi 04 (03), 415−429 cmi journal 419 cmi journal yasuaki nakagawa, md figure1. patient flowchart for the study table 1. baseline characteristics of the studied groups. curcurouge® 90 mg curcurouge® 30 mg placebo p-value number of patients 27 26 30 male/female 6/21 3/23 9/21 0.251 age (mean ± sd) 71.1 ± 6.5 71.4 ± 10.3 70.1 ± 9.5 0.837 kellgren-lawrence classification (ⅱ/ⅲ) 9/18 8/18 10/20 0.999 osteoarthritis lesion (one knee/both) 19/8 18/8 19/11 0.875 joa score (mean ± sd) 72.3 ± 11.1 73.4 ± 9.2 73.2 ± 12.1 0.933 jkom score (mean ± sd) 30.2 ± 19.0 31.3 ± 19.8 32.3 ± 16.6 0.911 vas score (mean ± sd) 0.46 ± 0.24 0.39 ± 0.24 0.49 ± 0.23 0.283 cmi 04 (03), 415−429 cmi journal 420 cmi journal yasuaki nakagawa, md joa, the japanese orthopedic association knee scoring system; jkom, the japanese knee osteoarthritis measure; vas, the knee pain visual analogue scale. figure 2 depicts the blood curcumin concentrations, with mean curcumin concentration in the high-dose and low-dose curcurouge ○r groups, as well as the placebo group, at 12 weeks of treatment being 199.6, 79.1, and 0 ng/ml respectively. the highdose curcurouge ○r group had significantly higher blood curcumin concentrations than the low-dose group. figure 2. blood curcumin concentrations 12 weeks after treatment. in each group, the joa knee oa scores at 12 weeks were significantly higher than those at 0 weeks. the changes in joa knee oa scores from 0 to 12 weeks are depicted in figure 3a. at 8 weeks, the joa score was significantly higher in the high-dose curcurouge ○r group than in the placebo group, with no significant differences among the three groups at 12 weeks. in addition, jkom scores at 12 weeks were significantly lower than those at 0 weeks in the high-dose curcurouge ○r and placebo groups, with no significant differences among the three groups. furthermore, vas scores at 12 weeks were significantly lower than those at 0 weeks in all groups (fig. 3b), with no significant differences among the three groups. the nsaid need ratio in the three groups is depicted in figure 3c. the declining trend in the high-dose curcurouge ○r group was significantly greater than that in the placebo group (p<0.05), with respect to the approximate regression line slope. cmi 04 (03), 415−429 cmi journal 421 cmi journal yasuaki nakagawa, md points figure 3a. improvement of japanese orthopedic association (joa) scores in the studied groups over weeks. points figure. 3b improvement of visual analogue scale (vas) scores in the studied groups over weeks. -0.2 0 0.2 0.4 0.6 0.8 0 week 2 weeks 4 weeks 6 weeks 8 weeks 10 weeks 12 weeks improved vas scores 90mg 30mg placebo cmi 04 (03), 415−429 cmi journal 422 cmi journal yasuaki nakagawa, md % figure. 3c nonsteroidal anti-inflammatory drug (nsaid) need ratio changes in the studied groups over weeks. the number of gaits in tug in the three groups is depicted in figure 4. the number of gaits at 12 weeks of treatment was significantly lower than that at 0 weeks in the high-dose curcurouge ○r group, with no significant differences among the three groups. in terms of knee rom and gait time changes in tug, there were no significant differences among three groups. figure 4. the number of gaits in the timed up-and-go test (tug) in the studied groups. cmi 04 (03), 415−429 cmi journal 423 cmi journal yasuaki nakagawa, md in patients with kl grade ii, joa score significantly improved from 0 to 12 weeks in the high-dose curcurouge ○r group (19.2±14.7 points) more than in the placebo group (4.5±8.9 points) (fig. 5a), while vas score was significantly reduced (high-dose -0.36±0.18, placebo -0.01±0.22) (fig. 5b). in terms of jkom scores, rom of knee joints, and tug gait time, there were no significant differences among three groups. the number of gaits at 12 weeks of treatment was significantly lower than that at 0 weeks in the high-dose curcurouge ○r group, with no significant differences in the other two groups (fig. 5c). figure 5a. improvement of japanese orthopedic association (joa) scores in patients with kellgrenlawrence (kl) grade ii in the studied groups. figure 5b. improvement of visual analogue scale (vas) scores in patients with kellgren-lawrence (kl) grade ii in the studied groups. cmi 04 (03), 415−429 cmi journal 424 cmi journal yasuaki nakagawa, md figure 5c. timed up-and-go test (tug) gait number in patients with kellgren-lawrence (kl) grade ii in the studied groups. in patients with kl grade iii, there were no significant differences in joa, jkom, or vas scores, as well as rom of knee joints, and tug gait time and number, among the three groups. at 12 weeks of treatment, all laboratory results were comparable to baseline values in each groups, except in some patients in each group for slight increases in triglyceride (four cases in the high-dose group, three in the low-dose group, and three in the placebo group), blood urea nitrogen (two cases in the high-dose group, seven in the low-dose group, and four in the placebo group), uric acid (three cases in the low-dose group and one in the placebo group), and slight decreases in hematocrit (three cases in the high-dose group, two in the low-dose group, and three in the placebo group), and albumin (five cases in the high-dose group, two in the lowdose group, and four in the placebo group) levels. these were all minor changes. on comparing the laboratory results at 12 weeks of treatment to those at 0 weeks, only highly sensitive c-reactive protein (hs-crp) levels significantly differed, with a greater reduction in the high-dose group than in the placebo group (p=0.0432) (fig. 6). table 2 summarizes the adverse events that occurred in all groups during this study. according to the study’s safety committee, all of the aforementioned adverse events were unrelated to curcurouge○r or the placebo. cmi 04 (03), 415−429 cmi journal 425 cmi journal yasuaki nakagawa, md figure 6. reduction of highly sensitive c-reactive protein levels at three months in the studied groups. table 2. adverse events in the studied groups occuring during the study period. curcurouge® 90 mg curcurouge® 30 mg placebo gastrointestinal disorders 1 case 2 cases 1 case vertigo 2 cases 1 case 0 cases diarrhea 2 cases 0 cases 1 case lower limb edema 2 cases 1 case 1 case itching 1 case 1 case 1 case radial nerve palsy 0 cases 0 cases 1 case discussion in this study, we revealed that blood curcumin concentrations were significantly higher in the high-dose curcurouge ○r than in the low-dose curcurouge ○r group. in each group, joa knee oa scores 12 weeks after treatment were significantly higher and vas scores were significantly lower than at 0 weeks. the declining trend of nsaid needs in the high-dose group was significantly greater than that in the placebo group (p<0.05), with respect to the approximate regression lineslope. only in the high-dose group, tug gait number at 12 weeks decreased significantly compared with 0 weeks. in patients with kl grade ii, joa and vas scores significantly improved from 0 to 12 weeks in the high-dose group more than in the placebo group. the reduction of hscrp levels was significantly greater in the highdose group than in the placebo group (p=0.0432). several adverse events occurred in all groups during this study, but the study’s safety committee determined that all of them were unrelated to curcurouge○r or the placebo. these results indicate that curcurouge ® can be an effective and safe treatment for patients with oa, especially those with kl grade ii. cmi 04 (03), 415−429 cmi journal 426 cmi journal yasuaki nakagawa, md curcumin has anti-inflammatory as well as antioxidative activities and is expected as a treatment of osteoarticular diseases. a high dose of standardized curcumin extract (500 mg twice daily) was reported to associate with the improvements on the tug, six-minute walk test, and joa total score in oa patients [20]. but the doubts have been raised about the ability of oral curcumin to reach pharmacologically active concentrations in synovial fluid or joint tissues [21] because its oral bioavailability is only 1% [22]. in the present study, we were able to prove that super-absorbable curcumin formulation, curcurouge ® , improved symptoms including pain in patients with kl grade ii. according to the basic research or animal models for the relationship between curcumin and oa, zeng reported that curcumin could reduce synovial cell viability, inhibit cell proliferation, increase cell apoptosis, and eventually alleviate oa-related inflammation by inhibiting matrix metalloproteinase (mmp)-3 expression [23]. nicoliche demonstrated that curcumin treatment has a protective effect on cartilage by increasing ihh, col2, and sox-5 expressions and the number of chondrocytes, without affecting cartilage thickness or mmp-8 and mmp-13 expressions [24]. in addition, curcuminoid delivery via hyaluronic acids/chitosan nanoparticles suppressed chondrocyte apoptosis by inactivating the nuclear factor-kappa b (nf-kb) pathway [25]. curcumin might have the potential to inhibit oa development via suppressing nf-kb/hypoxia-inducible factor 2α pathway activation [26]. moreover, in the oa rats model, nakahata demonstrated that curcumin monoglucuronide sodium salt (tbp1901) injections significantly reduced synovial inflammation at weeks 1 and 2 as well as tumor necrosis factor-α expression in the articular cartilage at week 6. tbp1901 injections also suppressed articular cartilage damage, subchondral bone plate thickening, subchondral bone plate perforation, and osteophyte formation at week 10 [27]. tbp1901 intra-articular injections suppressed synovial inflammation in the acute phase of posttraumatic oa in destabilized medial meniscus rats. in the chronic phase, tbp1901 suppressed articular cartilage damage and regulated subchondral bone plate changes [27]. therefore, curcumin is thought to have anti-inflammatory and chondroprotective effects in the oa model. in clinical study using curcurouge ® in elderly volunteers, kishimoto demonstrated that curcurouge ® administration significantly reduces the neutrophil-to-lymphocyte ratio, an indicator of prognosis in cardiovascular disease, cancer, infectious diseases, and aging [28]. curcumin's safety has been reported in several studies. in this regard, bannuru found no differences between patients receiving curcuminoids and those receiving placebo in the incidence of treatment withdrawal due to adverse events [29]. according to hsiao's meta-analysis, low-dose (daily dose <1,000mg) and high-dose (daily dose ≧1,000mg) curcuminoids had less adverse event rate than nsaids in knee oa [30]. the limitations of our study were the small number of patients (n=90) and the short treatment duration (12 weeks) for knee oa. this was a pilot study to determine the effect of curcurouge○r on knee oa, but we were able to observe significant improvements in joa and vas scores, nsaid (celecoxib) needs, and tug. future studies may on a larger number of patients with knee oa over a longer duration are required to validate our findings. cmi 04 (03), 415−429 cmi journal 427 cmi journal yasuaki nakagawa, md in conclusion, curcurouge○r has succeeded in proofing a potential for treating human knee oa, particularly at an early stage. acknowledgments we thank mr. atsushi imaizumi and mr. atsuhiro kishimoto for technical assistance. conflict of interests financial support and potential conflicts of interest of our article is in the following: this research was financially supported by therabiopharma corporation (kanagawa, japan). the authors declare that there is no conflict of interest except the above. references 1. grazio s, balen d. obesity: risk factor and predictor of osteoarthritis. lijec vjest. 2009; 131: 22-26 2. smalley we, ray wa, daugherty jr, griffin mr. nonsteroidal anti-inflammatory drugs and the incidence of hospitalizations for peptic ulcer diseases in elderly persons. am j epidemiol 1995;141:539-45 3. felson dt, lawrence rc, hochberg mc, mcalindon t, dieppe pa, minor ma et al. osteoarthritis: new insights, part 2: treatment approaches. ann intern med 2000;133:726-37 4. goel 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https://doi.org/10.52845/cmi/2022-3-2-2 cmi 03 (02), 287−296 (2022) issn (o) 2694-4626 research article clinical outcome of corona virus disease-19 patients in an infectious disease center, olodo, ibadan, oyo state, nigeria oluwagbenga alonge1,2, fowotade adeola3, folasade bamidele2, toyosi omotosho2, moradeyo aboluwoye2, stephen olulana2, nayim fashina4, fisayo famuyiwa5, anifat eegunjobi6, ganiyu arinola7 1department of surgery, college of medicine, university of ibadan, ibadan, nigeria 2lnfectious disease centre, olodo, lbadan, nigeria 3department of medical microbiology, university of ibadan, nigeria 4department of medical microbiology, university college hospital, lbadan, nigeria 5department of chemical pathology, university college hospital, lbadan, nigeria 6department of chemical pathology, lautech, ogbomosho, nigeria 7department of immunology, university of ibadan, ibadan, nigeria. abstract introduction: corona virus disease (covid-19) is a severe respiratory infection caused by the newly emerged severe acute respiratory syndrome-corona virus-2 (sars-cov-2). globally, mortality from this disease is high and infection sequelae can result in long-term illness. covid-19 is a new disease and the best way to manage patients remains uncertain, particularly in resource-limited settings. an evaluation of the clinical outcome of covid-19 cases managed at the infectious disease center (idc), olodo in ibadan, oyo state, nigeria over a period of eighteen weeks was carried out. this center (idc), olodo was designated by the oyo state covid-19 task force to manage mild to severe cases of covid-19 in oyo state. materials and methods: a treatment protocol designed by the case management team of the oyo state covid-19 task force was adopted. the protocol included classifying patients based on clinical signs and symptoms and qpcr cycle threshold (ct) values, treating with a cocktail that included chloroquine or hydroxychloroquine, zinc, vitamins c and d and or antibiotic(s) as indicated. physiotherapy and nutritional support for these patients were also considered as priority. results: during the period of study, 3,119 individuals tested for sarscov-2 infection in oyo state received a positive result and 310 (9.9%) were admitted to the idc, olodo, ibadan. the average duration of admission was 10.22 3.48 days, with 22(7.1%) patients requiring respiratory support by way of supplemental oxygen using re-breather bags and continuous positive airway pressure (cpap)was used on one patient. no mortality was recorded among the 310 patients managed according to the protocol at the idc,olodo, ibadan during the study period. conclusion: this clinical outcome suggests that the management protocol used in our center is effective and thus deserves evaluation for use in resource poor settings. keywords: covid-19 pandemic, management protocol, oyo state. manuscript central used to avoid complications of hemodialysis manifested in uremic state including anorexia, nausea, vomiting leading to malnutrition, fluid and electrolyte imbalance leading to volume overload, hyperkalemia, metabolic acidosis, and hyperphosphatemia, as well as abnormalities related to hormonal or systemic dysfunction such as hypertension, anemia, hyperlipidemia, and bone disease, timely diagnosis of proteinenergy-wasting (pew) is important for early initiation of nutritional intervention and treatment. in addition, education plans should be prepared to mediate the nutrient intakes and identify the patient’s difficulties and provide practical help. keywords: renal dialysis, nutritional status, hemodialysis, malnutrition copyright : © 2022 the authors. published by publisher. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/licenses/by-nc-nd/4.0/). cmi 03 (02), 287−296 287 https://doi.org/10.52845/cmi/2022-3-1-4 https://creativecommons.org/licenses/by-nc-nd/4.0/ http://medicineinsights.info/index.php/cmi/index 1 introduction t he severe acute respiratory syndromecorona virus-2 (sars-cov-2) responsible for the coronavirus disease 19 (covid-19) pandemic is a new virus of the coronaviridae family in the nidovirales order. this group of virus, including the severe acute respiratory syndrome coronavirus (sars-cov) and the middle east respiratory syndrome (mers) coronavirus, has been shown to cause acute lung injury (ali) and acute respiratory distress syndrome (ards) resulting in respiratory failure and death in some patients. the signs and symptoms of sars-cov-2 viral infection may be similar to those of influenza and seasonal allergies and in the tropical setting may mimic common ailments including malaria (yang et al., 2020 and shereen et al., 2020). human to human transmission of coronavirus occurs via droplets or aerosol and the virus uses spike proteins to attach to the angiotensinconverting enzyme 2 (ace-2) on the surface of normal cells. conformational change in the spike protein facilitates viral envelope fusion with the cell membrane. once within the cell, the virus initiates replication, ultimately producing more viruses that infect other cells (shereen et al., 2020). sarscov-2 viral infection activates antiviral immune responses that are often accompanied by marked and uncontrolled pro-inflammatory cytokines overdrive also referred to as cytokine storm (yang et al., 2020). severe sars-cov-2 infection has been found to cause lymphopenia which can arise because of ace-2 receptor expression on lymphocytes permitting viral entry and consequent lymphocyte cell death. sars-cov-2 infection is also accompanied by increase serum lactic acidaemia, a condition that is also known to inhibit lymphocyte proliferation. subsequently, there is associated lymphocyte, granulocyte and monocyte dysfunction, and a high neutrophil-to-lymphocyte ratio, in severe sars-cov-2 infection (yang et al., 2020). severe and critically illcovid-19 cases exhibits severe pneumonia and metabolic disorders developing into acute respiratory distress syndrome, multiple organ dysfunctions, septic shock and death (huang et al., 2020). some studies suggested that the immunopathogenesis after sars-cov-2 infection has been linked to the development of the disease into severe cases (qin et al., 2020). no known specific and effective drugs or vaccines have been developed to manage or prevent covid-19 (wu et al., 2020) thus many drugs have been evaluated in its management and further search contunues. national institute of health (nih) and food and drug administration (fda) recommended, remdesivir and convalescent blood products as promising potentials for covid-19 treatment apart from the uses of chloroquine, hydroxychloroquine, favipiravir, ivermectin, and colchicines (hossen et al., 2020). usage of another antihelminthic drug (apart from ivermectin) was also proposed (onifade and arinola, 2020). tocilizumab was deemed as adjunctive therapy for patients with cytokine release syndrome while baricitinib and ruxolitinib were reported to have additive immunosuppressive effect (hossen et al., 2020). santos et al (2020) reported that therapeutics for covid-19 includes camostatmesylate, remdesivir, favipiravir, tocilizumab, baricitinib, convalescent plasma, and humanized monoclonal antibodies. oyo state, in the south western region of nigeria, has a population of about seven million people. the index case of coronavirus infection in the state was reported in ibadan, the state capital on 21st march 2020 and the patient was temporarily isolated and managed at the agbami chest clinic in jericho, ibadan, nigeria. three other patients who tested positive for the viral infection were subsequently transferred to the infectious disease center (idc) at olodo, ibadan on 27th april 2020 when this designated center was commissioned. this fully furnished center was established by the oyo state government to provide clinical care for residents of the state who test positive for sars-cov-2 virus and were symptomatic enough to warrant institutional care as well as some asymptomatic supplementary information the online version of this article (10.52845/cmi/2022-3-2-2) contains supplementary material, which is available to authorized users. cmi 03 (02), 287−296 manuscript central 288 manuscript central dr. bushra mohsen abdulla et al. patients whose home environments were not conducive for the approved self isolation policy of the nigerian center for disease control (ncdc). oyo state has two ncdc-approved laboratories that conduct qpcr testing and release results of testing within 48 hours as mandated by the oyo state task force on covid-19. at the time of reporting these clinical outcomes, oyo state, nigeria had conducted 15,733 tests of which 3,119 were positive for the virus with 1,952 recoveries and 37 deaths. none of the deaths was recorded at the idc, olodo and this may be a pointer to the relative effectiveness of management protocol being practiced in this center and this may be worth reviewing particularly in other resourcelimited settings. parallel flow was established for the staff as part of the infection prevention and control protocols. whilst on admission, patients were commenced on a cocktail of medications; oral chloroquine or hydroxychloroquine for three days; oral zinc for three weeks; azithromycin for three days; vitamin c for three weeks and vitamin d was added to the protocol in patients with respiratory symptoms along with those whose oxygen saturation falls below 95% in room air. chest physiotherapy was commenced and antibiotics listed in the antibiogram for community pneumonia in nigeria was administered via the intravenous route for a minimum of 48 hours (and later changed to oral medications) if patients had clinical features of chest infection. subcutaneous enoxaparin (clexane) 40 mg daily or twice daily and dexamethasone with doses ranging from 6mg daily to 10mg depending on the weight of the patient were added to the regime of medications in patients with lung infiltration on plain radiograph or on computerized tomography of the chest. all the patients were well hydrated and served high protein diet except when contraindicated. in addition, the physiotherapist carried out breathing exercises, conducted physical workout and aerobic exercises for patients twice weekly whilst indoor games were provided as the needs arose. twenty two patients requiring supplemental oxygen were managed with rebreather bags and cpap mask but no patient required mechanical ventilation although the center currently has two mechanical ventilators and three cpap machines. medical staff at the center had pre-exposure prophylaxis comprising oral chloroquine for three days or hydroxychloroquine for three days; zinc tablet for three weeks; azithromycin three days and vitamin c tablet for three weeks. the medical staffs were also required to work on a one-week-on and one-week-off shift duty and were accommodated in designated hotels without contact with their families during the time that they were on duty and two weeks after completing their shifts. manuscript central cmi 03 (02), 287−296 (2022) 289 methodology over a period of 18 weeks, three hundred and ten (310) consecutive covid-19 patients were managed as in-patients at the infectious disease center, olodo in ibadan. on admission, their sars-cov-2 qpcr cycle threshold (ct) values were documented based on assays for the n-gene and orflab genes, baseline laboratory investigations were carried out including electrolytes and urea, liver function test and blood film (thick and thin films) for malaria parasite. co-morbidities were also documented and patients with severe respiratory difficulties as defined by oxygen saturation (spo2) of less than 90% were managed in the 10-bed intensive care unit (icu). for all other patients, disease severity classification was a determinant of ct values, clinical signs and symptoms, rather than symptoms alone. as the clinical conditions of the icu patients improved, and the ct values increased, these patients were weaned from the icu to a high dependency unit (hdu) and finally the general male and female wards, from where patients were discharged. during the study period, the protocol for discharge as laid by the ncdc was that the patients should have two negative qpcr results. this has since changed in line with best global practices and international consensus. a unilateral flow was maintained for patients and another results cmi 03 (02), 287−296 (2022) manuscript central 290 a total of three hundred and ten (310) patients with a median age of 36 years with ages ranging from 2 years to 95 years were managed at the center over an eighteen-week period. more than half of the patients (53.9%) were aged 21 to 40 years with 1% of the cases aged >80 years. there were more males (66.1%) among the patients than females (33.9%) (table 1). the dosage of vitamin d (1000 iu), vitamin c (1000 iu), zn (20mg), azithromycin, hydroxychloroquine or chloroquine as given to covid-19 patients and medical staff at the center is presented in table 2. in table 3, 60.5% of the patients had symptoms especially among the 21-40years age group (50.3%). only 35 (17.9%) patients presented with only one symptom whilst 20.5% had three symptoms. the five commonest symptoms in descending order were; fever (18.4%), headache (18.1%), anosmia (10.9%), agenuia (10.1%) and cough (9.1%) in table 4. one hundred and three (103) patients had co-morbidities as follows: only hypertension in 69(53.9%), only peptic ulcer disease in 23(18.0%) whilst 11(8.6%) had only diabetes mellitus. combinations of at least two of these conditions were present in 25 out of 103 patients (table 5). the mean length of stay at the isolation center was 10.22 3.48 days whilst the mean ct value on admission was 30.42 5.49. there was a significant negative association between the length of stay and the ct value on admission (table 6). in addition, patients with comorbidities stayed on admission longer even if they were admitted with lower ct values (table 7). table 1: socio-demographic presentation of covid-19 patients at idc, olodo, ibadan, nigeria. table 2: medication used among covid-19 patients and pre-exposure prophylaxis for un-infected medical staff at idc, ibadan, nigeria. manuscript central dr. bushra mohsen abdulla et al. manuscript central cmi 03 (02), 287−296 (2022) 291 table: 3 relationship between symptoms and age of covid-19 patients at the idc, olodo, ibadan, nigeria. table 4: percentages of symptoms number and types among covid-19 patients at the idc, olodo, ibadan, nigeria table 5: frequencies and percentages of co-morbidity types among covid-19 patients at the idc, olodo, ibadan, nigeria. table 6: correlation of length of stay and ct value among covid-19 patients in idc, olodo, ibadan, nigeria. discussion inflammation, renal dysfunction, respiratory burst, immune dysregulation and accumulation of immune complexes are common in nigerian covid-19 patients (arinola, 2021; arinola et al., 2021a-d; arinola et al., 2020; akinwumi et al., 2021; arinola et al., 2022). the present study shows that covid-19 patients in idc, olodo were mostly males, mainly between the 21-40years age range, spent between 2-21days on admission with few comorbid conditions. also, there was no mortality recorded during the eighteen week period spanning 27th april 2020 and 24th august 2020. these corroborates our earlier reports (arinola et al., 2020) which emphasised the impact of age, occupation and gender on incidence or case fatality of covid-19 and that low mortality of covid-19 patients in the idc may be related to effective management, nonfatal nature of sar-cov-2 among idc patients or mild to severe form of covid-19 disease when admitted (arinola et al., 2020). the treatment options for covid-19 are largely supportive as there is no universally agreed protocol of care. therapeutics targeting the spike protein attachment to human cells and replication of sarscov-2 has generated a lot of interest and this is the mechanism of action of remdesivir either used singly or in combination with chloroquine. monoclonal antibodies targeting the spike protein receptor binding domain (rbd) are undergoing trials as well as other therapeutics (yang et al., 2020 and shereen et al., 2020). it is important to note that, with the exception of the repurposed drugs, most of these experimental therapies will be out of reach of nigerian patients even when they receive approval. therefore, careful evaluation of repurposed drugs, including chloroquine or hydroxychloroquine and vitamins and zinc manuscript centralcmi 03 (02), 287−296 (2022) 292 table 6: correlation of length of stay and ct value among covid-19 patients in idc, olodo, ibadan, nigeria. supplementation used at the oyo state idc is important. unfortunately, few clinical trials are currently underway in nigeria and most facilities are yet to share observational data such as we present in this report. the repurposing of chloroquine and hydroxychloroquine for treatment of sars-cov-2 infection was premised on the anti-inflammatory properties of these antimalarial which may be beneficial to the patients if there is underlying malaria parasitaemia and also to reduce pre-empted occurrence of inflammatory cytokine storm which is associated with sars-cov-2 infection (yang et al., 2020). various reports in the early phase of the pandemic showed that a number of existing drugs could inhibit sars-cov-2 replication in vitro, including chloroquine and hydroxychloroquine (two established anti-malarial drugs which share similar chemical structures and mechanisms of action), as well as azithromycin and ivermectin spawned interest in repurposing these drugs at various treatment centers including the idc, olodo, ibadan. whilst initial clinical trial data has not revealed a role for these compounds in preventing or treating covid-19, other trials remain in progress and very few trials are being conducted in africa where the pandemic’s trajectory is markedly different. these medications were not used in the context of a trial and the positive outcomes in this high-risk disease, encouraged their continued use during the 18-week period. the fact that the patients tolerated these medications without a risk of bacterial and malarial super-infection needs further evaluation. meo et al (2020) proposed that chloroquine and hydroxychloroquine are beneficial in the management of covid-19 and highlighted specific mechanisms of action, viz: inhibition of manuscript central dr. bushra mohsen abdulla et al. manuscript central cmi 03 (02), 287−296 (2022) 293 the receptor binding by the virus, inhibition of membrane fusion by the virus and immune modulation leading to a decrease in cytokine release. the use of vitamin d in the management of covid-19 patients hinged on the autocrine function and has been supported by a single center, retrospective cohort study which found that persons who are deficient in vitamin d at the time of testing were more likely to test positive for covid-19 (onifade and arinola, 2020). a recent study concluded that vitamin d intoxication is common among nigerian patients with covid-19 and the vitamin d intoxication is associated with low plasma hscrp level. there is the need for public enlightenment on the dangers inherent in vitamin d supplement abuse in nigerians (onifade et al, 2022). immuno-modulatory function of vitamin c depends on its requirement for collagen biosynthesis, maintenance of epithelial integrity, chemotaxis and phagocytosis (arinola and edem, 2020; sureda et al., 2013). vitamin c has a highly effective antioxidant capacity, thus protecting important biomolecules from damage by oxidants generated during normal cell metabolism (alvarado et al., 2006). zinc affect the number and function of immune cells (macrophages, neutrophils, dendritic cells, mast cells, t cells and b cells) (haase and rink, 2007). zinc also play essential roles in the signaling and inflammatory output of monocytes and macrophages, including activation of mitogenactivated protein kinase and nf-κb (haase and rink, 2007), reduction of lysosomes integrity (siebenlist et al., 1994), activation of nlrp3 inflammasome (brieger et al., 2013), induction of il-1β secretion by macrophages (summersgill et al., 2014), reduction of il-6 and tnf-α in human monocytes (mayer et al., 2014). activation of the immune system results in increased generation of reactive oxygen species which is neutralized by zn (arinola and edem, 2020b). immunomodulatory and anti-inflammatory functions of vitamin d, vitamin c and zn makes them appropriately supportive in the management of covid-19 patients. in a resource poor settings lacking access to novel therapies and local pharmaceutical industries engaged in drug discovery, exhaustive evaluation of well-tolerated repurposed drugs is probably justified. this is particularly true in the case of chloroquine, hydroxychloroquine and azithromycin for which clinical trial data suggesting a lack of effectiveness in very dissimilar settings and modes of use contrasts with our experience of notably good outcomes and other lines of evidence pointing to the contrary (yang et al., 2020; chowdhury et al., 2020; boulware et al., 2020). as many trials that could be informative are still in progress, the case management team of the oyo state covid-19 task force maintained its consensus for continued use of these two anti-malarial medications for persons with the coronavirus infection along with other medications aimed at improving the immune systems of the patients, pending further review. while there is lack of clinical trial or comparator data, the use of a cocktail of chloroquine or hydroxychloroquine, zinc, vitamin c and vitamin d along with azithromycin, clexane, dexamethasone and the appropriate antibiotic choice made in line with the antibiotic ladder for community pneumonia when required has been associated with full recovery of all patients without any mortality over an eighteen-week period (joshua et al., 2019; meltzer et al., 2020). the consensus is therefore that strong evidence will be required to justify altering this affordable cocktail of medication during the pandemic in a resource poor setting while effective and acceptable covid-19 vaccine is sourced by the government of nigeria. conclusion a treatment protocol based on prevailing scientific knowledge designed by the case management team of the oyo state covid-19 task force was adopted in the management of patients with mild and severe diseases at the first oyo state infectious disease center at olodo, ibadan from april, 2020. the outcome of care over the initial 18 weeks is impressively strong. in a resource poor setting, this protocol of supportive care may be considered along with the other preventive measures until such time when accessible therapies backed by strong evidence are available for treating 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(2020). efficacy of chloroquine and hydroxychloroquine in the treatment of covid-19. european review for medical and pharmacological sciences. 24:4539-4547 23. onifade aa and arinola og (2020). albendazole reduces serum levels of inflammatory cytokines: potential strategy for the management of cytokine storm”. saudi journal of biomedical research. 5 (11): 320-324. doi : 10.36348/sjbr.2020.v05i11.006 manuscript central dr. bushra mohsen abdulla et al. how to cite this article: alonge, o. ., adeol, f. ., bamidele, f. ., omotosho, t. ., aboluwoye, m. ., olulana, s. ., fashina, n. ., famuyiwa, f. ., eegunjobi, a. ., & arinola, g. . (2022). clinical outcome of corona virus disease-19 patients in an infectious disease center, olodo, ibadan, oyo state, nigeria. clinical medicine insights, 3(2), 287– 296. https://doi.org/10.52845/cmi/20 22-3-2-2 24. onifade aa, sheu kadiri rahamon, olatunbosun ganiyu arinola. (2022). plasma levels of vitamin d and c-reactive protein in adult nigerians with covid-19. afr. j. biomed. research. in press. 25. qin, c. et al. (2020). dysregulation of immune response in patients with covid-19 in wuhan, china. clin infect dis. 248 https:// doi.org/10.1093/cid/ciaa. 26. santos j, brierley s, gandhi mj, cohen ma, moschella pc, declan abl. (2020). viruses. 30. 12(7):705. doi: 10.3390/v12070705. 27. shereen ma, khna s, kazmi a, bashir n, siddique r. (2020). covid-19 infection: origin, transmission and characteristics of human coronaviruses. journal of advanced research. 24: 91-98 28. siebenlist u, g. franzoso, and k. brown. (1994). structure, regulation and function of nf-kappa b. annual review of cell biology. 10(1): 405–455. 29. summersgill h, h. england, g. lopezcastejon et al. (2014). zinc depletion regulates the processing and secretion of il-1β. cell death & disease. 5(1): article e1040. doi: 10.1038/ cddis.2013.547. 30. sureda a, ferrer md, mestre a, tur ja, pons a. (2013). prevention of neutrophil protein oxidation with vitamins c and e diet supplementation without affecting the adaptive response to exercise. intl j sport nutr exerc metab. 23(1):31-39. 31. wu r, wang l, kuo hd, shannar a, peter r, chou pj, li s, hudlikar r, liu x, liu z, poiani gj, amorosa l, brunetti l, kong an. (2020). an update on current therapeutic drugs treating covid-19. curr pharmacol rep. 11:1-15. doi: 10.1007/s40495-020-00216 32. yang l, liu s, liu j, zhang z, wan x, huang b, chen y and zhang y. (2020). covid-19: immunopathogenesis and immunotherapeutics. signal transduction and targeted therapy. 128:1-8. cmi 03 (02), 287−296 manuscript central 296 introduction causes of nutritional disorder in hd inadequate food intake abnormal nutrient metabolism aim and objectives methodology result assessment of nutritional status of hd. patients prevalence of malnutrition using subjective global assessment body mass index in the study patients bmi and sga score laboratory investigation association between nutrient intake and sga discussion conclusions references blank page blank page blank page cmi 05 (02), 600−618 cmi journal 600 clinical medicine insights doi:https://doi.org/10.52845/cmi/2023-5-2-1 cmi 05 (02), 600-618 (2023) issn (o) 2694-4626 original article carbon negative gasoline and diesel fuel replacements dr. michael vladislavovich tyurin *corresponding author: dr. michael vladislavovich tyurin introduction recent changes at the top of the us executive administration have been combined with the not very wise decisions to cut down the petroleum imports from the russian federation. the free market economy of the us immediately reacted by skyrocketing of the gasoline and the diesel fuels prices at the gas stations to the levels affecting all other prices nationwide. for instance the cost of the tx dl skyrocketed from $11 usd to $33 usd (the coefficient of recalculation all the prices this year vs. year of 2021 and below ghat year is up to 3 and above the rule of the market economy). that coefficient 3 and above 3 is typical for the increase of other prices nationwide as the major price-wise rule of the free market economy [21]. subsequently, the proper running of the us economy is possible only with the very wise decisions of the top of governmental administration. we offer herein the carbon negative replacements of the gasoline and of the diesel fuel manufactured from petroleum by the same fuels manufactured from the air co2. nationwide replacement of the technologies based on the use of petroleum as the source of chemicals or the fuels manufactured by the carbon negative technologies is absolutely essential since the earth has passed the level of the air co2 400 ppm, the “point of no return” per the nasa discoveries of 2010 [21]. now the air co2 exceeds 450 ppm 51.and goes up based of the wide distribution of the intensive transportation based on the use of petroleum-derived gasoline and diesel fuel [21]. the author has written much about the carbon negative replacements of gasoline or diesel fuel manufactured by international petroleum corporations from petroleum via its distillation at the refineries the number of which is around 80 in the continental us and each of them operating produces a lot of air co2 [5-16,19]. now there is the time to elaborate this topic. abstract: petroleum recovery from the ground and its distillation to get gasoline and diesel fuel burned in gasoline and diesel cars / trucks, airjets, etc. leads to the global environmental catastrophe in 10-15 years from now which the humankind will not survive. the author plans to save the earth’s fresh water by developing nationwide manufacture of the carbon negative replacements of gasoline and diesel fuel and add additional distilled water and the genetically engineered foods to help the humankind pass said .environmental crisis. the author plans to raise additional investor’s money to organize nationwide network of the new type of gas stations selling not only carbon negative fuels but additionally to that the foods for home cooking and essential household items to save time to the valued customers preventing them to drive additionally to walmart and grocery stores. the ordering system to provide additional goods is also planned. the environmental problem outlined has the solution: elimination of international petroleum corporations and their change to carbon negative corporations. key words: carbon negative fuels; additional distilled water from sea water; genetically engineered carbon negative foods; new type of the gas stations; the ordering system for the new type of gas stations. copyright : © 2021 the authors. published by medical editor and educational research publishers ltd. this is an open access article under the cc by-nc-nd license (https://creativecommons.org/lic enses/bync-nd/4.0/). received 25 jan 2024 | revised 10 feb 2024 | accepted 25 mar 2024 | published online 15 apr 2024 https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ https://creativecommons.org/lic%20enses/by-nc-nd/4.0/ cmi 05 (02), 600−618 cmi journal 601 cmi journal dr. michael vladislavovich tyurin the combustion energy of fuel butanol is represented by the following numbers for the isomers of fuel n-butanol shown below as indicated in [6,7]: 1-butanol: −2.671 kj/mol, 2butanol: −2.661.1 kj/mol, 62.isobutanol: −2.662.6 kj/mol, tert-butyl alcohol: −2.644.8 kj/mol. the combustion energy of gasoline is slightly higher. it is around -3.200kj/mol 64.[6]. the combustion energy of daa or mesityl oxide is -3.600 kj/mol [6]. in addition to that the octane number of the most prosperous fuel isobutanol is 98 [1,2]. therefore, adding the fuel isobutanol [18] to the mixture of other carbon negative fuels as above will substantially increase the overall summary octane number of said mixture. besides that the viscosity of pure fuel isobutanol and other isomers of fuel n-butanol prevents it safe use at outside temperatures below 34 o f [21]. that is why we offer this carbon negative mixture comprising 40% of fuel isobutanol, 10% fuel nbutanol, 72.30% mesityl oxide [24,34,35] and 20% fuel diacetyl alcohol (daa) [15-17, 73.29]. this will eventually compete with the products of the international petroleum corporations originated from petroleum as we discuss below its causing the outlined environmental crisis related to the increase of the air co2 content [24]. the mesityl oxide chemical formula is give in fig. 1. fig. 1. mesityl oxide [24,34,35]. therefore, we have decided to sacrifice both corporate cars for the test driving them on the highway and in the city of brownsville, texas, to see if any damage could possibly happen to the cars, and especially their engines operated with the fuel isobutanol and other carbon negative fuels as above. the manufacturing price of the acetone manufactured from the air co2 is approximately $0.35 per gallon [3]. the condensation of the two acetone molecules over the alkaline catalyst per [4] gives fuel diacetyl alcohol at the manufacturing cost of $0.02 per gallon. the combustion energy of the fuel diacetyl alcohol is approximately -3.473 kj/mol as compared to the combustion energy of the diesel fuel of -808 kj/mol which substantially exceeds the typical for the diesel fuel combustion engine energy release as the mechanical energy of driving and corresponds to the higher engine power under the given engine mechanical dimensions, probably because of the increase of the combustion mixture explosive pressure. mesityl oxide combustion energy elevates that of the diesel fuel, and we have decided to test the said mixture of the carbon negative fuels comprising as above 40% of fuel isobutanol, 10% fuel n-butanol, 30% mesityl oxide [24,34,35] and 20% fuel diacetyl alcohol (daa) and that 98.mixture has been tested on the diesel truck 2022 ram 3500. however, we are not the explosion experts to discuss this herein [5]. indicated elevation of the explosive pressure in the case of using diacetyl alcohol (daa) and metsityl oxide happens in the purchased manufactured diesel vehicles. this note is to keep checking the engine combustion chamber gaskets often to notice any damage by the qualified dealership mechanic or to notice sudden loss of engine power with the need to get the engine to the qualified dealership mechanic for repairs of damaged combustion chamber gaskets [6]. biocatalysts used to manufacture the carbon negative fuels have different synthetic genes introduced by the means of genome tailoring using the unique electrotrasformation / electrofusion generator developed by the author when he still was in the russian federation [18,19]. four carbon alcohol fuel n-butanol and its isomers are widely recommended to replace gasoline manufacture by the international cmi 05 (02), 600−618 cmi journal 602 cmi journal dr. michael vladislavovich tyurin petroleum corporations from petroleum. said isomers of fuel n-butanol are shown in fig. 2. fig. 2. fuel n-butanol and its isomers sec-butanol, tert-butanol and isobutanol [20]. our biocatalyst making fuel isobutanol has several genetically engineered genes for that purpose [18,20]. the fuel isobutanol bioisynthesis by this strain is shown in fig. 3 fig. 3. genetically engineered fuel isobutanol pathway in our biocatalyst [18,20]. cmi 05 (02), 600−618 cmi journal 603 cmi journal dr. michael vladislavovich tyurin 124.fuel isobutanol has elevated viscosity and at lower temperatures near o o c and below that forms gels [21]. it is obvious that any gel structure in the fuel line at said low outside temperatures will be the obstacle for the proper internal combustion engine operations. therefore we offer the blends of 80 % (vol/vol) carbon negative isobutanol manufactured by our carbon negative corporations and 20% (vol/vol) of diacetone alcohol manufactured by our carbon negative corporations, etc. said mixture of the carbon negative fuels as above survives the negative temperatures without the increase of the viscosity in the fuel line and therefore, this mixture is totally compatible with the diesel and gasoline using trucks nationwide, including the territories where the low winter and spring / autum temperatures exist nationwide. said mixture of carbon negative fuels maintains liquid state even at very low negative (much below 0 o c) temperatures and does not form any gel structures in the fuel line ensuring the normal operation of the engine. fuel isobutanol, the perfect carbon negative fuel, has a shortcoming bringing it to the zero use: high viscosity, tendency to form gel at temperatures below 0 o c (or 34 o f) [22,23]. the fuel isobutanol has viscosity cp or mpa•s @ 20°c 3.102 [24]. forming gel in the fuel line is absolutely not acceptable. the engines have to run perfectly at any reasonable temperatures. if in the state of tx the low temperatures are typical for only a few months, then in the northern states the winter has low air temperatures for a much longer time. therefore, there has to be the tool to eliminate the gasoline viscosity to the levels acceptable at the low air temperatures below 0 o c. this remedy is found already. mixing of 80 % (vol/vol) of carbon negative fuel isobutanol with 20 % (vol/vol) of diacetyl alcohol (daa), which we produce carbon negative from condensing of the two carbon negative acetone molecules over the alkalyne catalyst [25,26]. let me go to the carbon negative fuels carbon negative replacements of gasoline and diesel fuel manufactured from petroleum by the international petroleum corporations. earlier we have published the diacetone alcohol (daa) as the carbon negative replacement of the gasoline and diesel fuel. daa might be produced by the condensation of the two acetone molecules over the alkaline catalyst [4]. the explosion energy of daa is way above the explosion energy of the diesel fuel manufactured by the major international petroleum corporations from the petroleum [27,28]. therefore, we have to pray that our customers will check their engines regularly with the qualified mechanics for the damages which potentially might be caused by the use of daa in the existing trucks. therefore the manufacturers of the diesel trucks will have to make certain changes to the design of their trucks to accommodate much higher explosion energy of added part of daa. this might be unnecessary however their manufacturers have to acknowledge the massive use of the carbon negative gasoline replacement and make certain changes improving the mechanical resistance of the gaskets in the engine compartment. not to mention herein that the international petroleum corporations now spend $1.75 to manufacture 1 gallon of gasoline or 1 gallon of the diesel fuel. that eventually affects the prices [of the gasoline and the diesel fuel manufactured from petroleum [6]. fig. 4 explains how our acetogen biocatalyst synthesized carbon negative fuel acetone from the air co2 [29]. resulting carbon negative fuel acetone is used for the manufacture of daa by the condensation of the two acetone molecules over the alkaline catalyst [4]. cmi 05 (02), 600−618 cmi journal 604 cmi journal dr. michael vladislavovich tyurin fig. 4. biosynthesis of fuel carbon negative acetone from the air co2 [29]. the following chemical reaction allows us make certain calculations per the acetone yield [29]: 12 co2 + 56 h2 = 3.6 acetone + 0.06 cell carbon again, we have to note, that our manufacturing facility is the grid-independent, getting all the electric energy solely from the solar panels covering all the area over our bioreactors. we used our original not having any world’s analogs gas blend fermentation vessels [1,3,5,7-18]. the bottom of each vessel was covered with the gas pall spargers providing the size of gas blend bells of around 0.5 micrometers. the overall fermentation work went extremely well with the high microbial densities of the genetically engineered strains of clostridium sp. mt896 and of clostridium sp. macet113 [29]. when the acetone reached the concentration of about 8 9 g/l in each fermentation block of our fermentation plant, the fermentation was deceased and the acetone was collected from the fermentation fluid. evaporated acetone was collected and then subjected to the treatment under the alkaline catalyst per the us patent 1550792a [4] to reach the production of the diacetyl alcohol. at the concentration of the diacetyl alcohol 97% it was collected, dehydrated from the trace amounts of water and used as the diesel engine fuel. so, now we are ready to offer to the customers the replacement of the diesel fuel, manufactured in the us solely from the air co2. materials and methods in this article we describe the bioreactors used to manufacture our carbon negative fuels. the image reflecting one of said bioreactors is shown in fig. 5. cmi 05 (02), 600−618 cmi journal 605 cmi journal dr. michael vladislavovich tyurin fig.5. our horizontal bioreactor design [30]. this is the modification of the known already horizontal bioreactor of beckman coulter life sciences [11]. the idea is the same: the feed is gaseous like for growing of algae cells [11]. however we grow the acetogen biocatalysts in one set of bioreactor modules producing from the gas blend of h2 and co2 (the gas blend we use has 80 % vol/vol of h2 .and 20 % vol/vol co2 fuel isobutanol [7-10, 2-16,19] and in the other set of said bioreactor modules to manufacture acetone [29]. as fig. 5 shows, in our system we used 14 impellers causing random distribution of the gaseous blend over the bioreactor volume we have used. said gas blend was composed of 80% vol/vol h2 and 20% vol/vol of co2. this is very important that said co2 was extracted from the surrounding air. the process of said c02 extraction is proprietary and we will describe it in our subsequent publication since we do not have enough money for the us patenting process and trust that the publications in the peer-reviewed journals totally replace the related patents and have to be always overcome by the patents of competitors if any. the horizontal bioreactor shown in fig. 5 has been filled by the nutrient medium by 6768%. the rest of the bioreactor space was for the used by us gas blend as above. it is important to note that each impellers used were composed of the properly balanced for the rotation three polished stainless 316s steel blades at the speed of 450 rpm. the pressure of the gas blend used in the horizontal bioreactor shown in fig. 5 was 15 psi. the total number of said diffusion stones was 39 per each bioreactor we have used. fuel isobutanol was manufactured using the genetically engineered biocatalysts per [18]. diacetone alcohol (daa) was created from the carbon negative acetone manufactured before using the technology we have already described [29] by the condensation of the two carbon negative acetone molecules over the alkaline catalyst as described [29]. said carbon negative fuel isobutanol and daa were used as the carbon negative fuels sold to the customers. in case of fuel isobutanol its known high viscosity causing problems in fuel lines of the cars at low air temperatures if fuel isobutanol was used pure were resolved as discussed before [6] by mixing of 80% vol/vol of fuel isobutanol with 20% vol/vol of carbon negative daa as described herein above. said problem with elevated viscosity does not exist for the said mixture of the cmi 05 (02), 600−618 cmi journal 606 cmi journal dr. michael vladislavovich tyurin carbon negative fuels as above: 40% of fuel isobutanol, 10% fuel n-butanol, 30% mesityl oxide [24,34,35] and 20% fuel diacetyl alcohol (daa). it is important to note that the impeller blades were placed on a 316s stainless teal shift fixed in the horizontal bioreactor by the podshipniks [31]. these are the specially designed and properly manufactured for handling and rotation elements providing long and productive life for shift with the impellers shown in fig. 4 and used in the bioreactor. podshipniks are shown in fig. 4 and in fig. 5. fig. 6. podshipnik used in our horizontal bioreactor [30]. it is important to note that the author was assassinated by shell after offering shell commercialization of his proprietary technology of gasoline manufacturing from the air co2 (the declaration of interests statement section of this original article). as the response the author has came up with the proposition to displace the existing petroleum corporations operating in the usa by the corporations manufacturing carbon negative fuels from the air co2 in sincere author’s intent to bring the air co2 content to the level of the year 1900 or just before the active petroleum fields discovery and exploration followed by the distillation of petroleum in the refineries itself producing the air co2 [6]. it is also important to mention herein that the carbon negative fuels were sold at the new type of the gas stations shown in fig 3. below. we have tested our carbon negative fuels of the set of corporate vehicles we have sacrificed for that purpose even without knowing the results of the testing performed but with the great hope that all said vehicles will survive said testing and will be used again but with only the carbon negative fuels. for said testing we have sacrificed corporate 270.2020 toyota camry, peugeout 3008 and the diesel truck 2020 chevrolet silverado 1500 duramax diesel. the gas mileage in the town of brownsville and on the highways was meticulously recorded by the respective chauffeurs certified mechanics from the toyota, peugeot and chevrolet dealerships were invited to the corporate garage of our corporations to meticulously check 1)stated cars driving and 2) any mechanical damages, especially in the engine compartments, like gaskets on the engines anticipating damage of some of them after at least 10,000 miles of testing. the testing was performed for 20,000 miles for each test vehicle. the records on the gas mileage for all types of 280.tested cars are discussed herein. we have mentioned that we sell our carbon negative fuels at the new type of the gas stations, combining 1) the sales of the carbon negative fuels and 2) the sales of the certain goods for which the valued customers had to drive cmi 05 (02), 600−618 cmi journal 607 cmi journal dr. michael vladislavovich tyurin additionally to walmart and the grocery stores along with ordering (includes also the on-line ordering) of the goods the customers could not find at the new type of the gas stations but needed and had to drive to the next to the gas stations store to purchase them. in addition to that the new type of the gas stations was selling the bottled distilled water manufactured at our new type of business activity the sea based set of solar panels powered boats for the distillation of the sea water. the new type of the gas stations was also used to sell to the valued customers consumers of the carbon negative fuels the food for home cooking, not the prepared at the gas stations or ready to eat food sold at the old type of the gas stations. our intent was to ensure the valued customers will find the new type of the carbon negative gas stations a valuable option to save their time for not visiting on their cars the walmart and the grocery stores. certain foods were prepared using the genetically engineered fungi (to be approved for the nationwide use). we used the ordering option for the goods not currently sold bu had to be added to save the time for our valuable customers. for that purpose the sales people took the orders and there was also the on-line ordering system. development of carbon negative foods. the genetic engineering of the fungi was performed as described before for the genetic engineering of the acetogens-biocatalysts at the first step the author has eliminated fungi genes not essential for the fungi maintenance and propagation [4]. at the second step of 308.genetic engineering of fungi is the cloning in fungi of the recombinant genes of lamb and other animals (not listed herein) or tomatoes, potatoes, cabbage, bread and spice. said genetically engineered fungi will be cultivated in the sterile evironment at the corporate site. the special care will be taken about the contracting capabilities of the genetically engineered muscle tissues allowing the muscle tissues of said genetically engineered creatures to grow as the natural muscle tissue has to grow with the training of the muscle owners. genetically engineered meats. the author trusts that his energy and cell components carbon negative system developed recently for the engineered acetogen biocatalysts should work well without any complications in genetically engineered fungi (the species has to be determined yet) containing the genes of lamb structures as thought originally should work without any problems in genetically engineered fungi (the species has to be .determined yet) containing the genes of meat production. original thinking of the author was about the lamb originated genes, but that might change at the level of operations. a variety of genes encoding various meat structures must be engineered to add the smell and the feeling at the teeth during chowing the exact feeling of the meat structures consumed. like the sensation of cracking the rib, cartilage, etc. the special care will be taken about the contracting capabilities of the genetically engineered muscle tissues allowing the muscle tissues of said genetically engineered creatures to grow as the natural muscle tissue has to grow with the training of the genetically engineered said 333.muscle owners genetically engineered muscle fibers. genetically engineered tomatoes, potatoes, cabbage, etc. the author trusts that the energy generation and cell components structures creation could be produced by the carbon negative system developed recently for the engineered acetogen biocatalysts [6-18] should work well without any complications in genetically engineered fungi (the species has to be determined yet) containing the genes of respective vegetables production. the author eventually will not be able to provide the exposure to the sun light and the fresh air of said genetically engineered tomatoes, potatoes, cabbage and other vegetables which have to be maintained under the sterile conditions over the lifetime of the genetically engineered fungi-based systems. genetically engineered bread and bread-based products the author trusts that the energy and cell components carbon negative system developed recently for the engineered acetogen biocatalysts should work well without any complications in genetically engineered fungi (the species has to be cmi 05 (02), 600−618 cmi journal 608 cmi journal dr. michael vladislavovich tyurin determined yet) containing the genes of respective bread and bread-based products production. the author has to engineer and design the system for baking of said genetically engineered bread and bread-based products. eventually there will be certain problems with not properly cooked genetically engineered bread and bread-based products. genetically engineered spices the author has given great thought about spices. any food especially genetically engineered one has to have salt and spices. the author did not think about the genetic engineering of salt, it has to be available with no limitations. but genetically engineered spices based on pepper and other components used to produce spices have to be engineered. the author trusts that the energy and cell components carbon negative system developed recently for the engineered acetogen biocatalyst should work well without any complications in genetically engineered fungi (the species has to be determined yet) containing the genes of respective genetically engineered pepper and other components giving the taste of spices. the salt will be added to such genetically engineered spices as the powder which can be sterilized as usually to get into the sterile genetically engineered environment, or there will not be any need for that. results the author was really surprised when all his planned herein in this original article experimental parts worked well as described before [7-10, 1214] with the carbon negative replacement of gasoline and diesel fuel. data on testing of the carbon negative fuel using real gasoline and diesel fuels vehicles. results on no any visible defects or vehicles misbehavior while driving the certified mechanics from the respective car dealerships meticulously tested the respective corporate cars at the corporate manufacturing site and drove said cars on the roads nearby the manufacturing site meticulously to reveal any damages caused by the replacement of the gasoline or the diesel fuel by the suggested mixture of fuel diacetyl alcohol (80% v./v.) and fuel isobutanol (20% v./v.). the 40% of fuel isobutanol, 10% fuel n-butanol, 30% mesityl oxide [24,34,35] and 20% fuel diacetyl alcohol (daa) to power the diesel truck 2022 ram 3500. the cars were placed on the treadmill with the device to check the engine emissions. no unusual exhaust gas emissions were ever tested and discovered in the exhaust gas of all tested vehicles. no unusual emissions in the cars exhausts no unusual engine emissions were noted by said mechanics for all tested corporate cars. then the mechanics made the test drives of the each said vehicle. no any mechanical or any other damages to the engines of the all said cars were ever revealed upon said thorough testing. test drives of each said vehicle by the certified mechanics did not reveal any abnormal driving behavior in any of said cars. the mechanics still did not make any further recommendations on the following use of the gasoline and the diesel fuel replacement leaving for the author the possibility of reporting this very good news to the general public. the gas mileages of the cars used to test the mixture of fuel diacetyl alcohol (80% v./v.) and fuel isobutanol (20% v./v.) or the mixture as we stated above40% of fuel isobutanol, 10% fuel n-butanol, 30% mesityl oxide [24,34,35] and 20% fuel diacetyl alcohol (daa) as the replacement of gasoline were 37 mpg on the highway and 31 mpg in the city of brownsville. you can easily calculate the average gas mileage from said numbers. but the overall picture looks to us very promising since the gas mileage even slightly exceeded the gasoline from petroleum use mileage in toyota camry and porshe cayenne turbo. due to the limited number of the tested cars we cannot make any predictions for the other car makes and the cars made before the year of 2020. this will become the risk of the other car owners, who will decide to replace their gasoline with the produced from the air co2 mixture of fuel diacetyl alcohol (80% v./v.) and fuel isobutanol (20% v./v.). if you remember our corporate goal is to replace all the petroleum use by the use of the air co2, initially to resolve the issue of the transportation problems, substantially increasing the air co2 content via the air co2 accumulation and eventually to decrease the air co2 content causing the fresh water loss to the outer space vacuum as stated before. the similar cmi 05 (02), 600−618 cmi journal 609 cmi journal dr. michael vladislavovich tyurin picture was seen if we used said mixture 40% of fuel isobutanol, 10% fuel n-butanol, 30% mesityl oxide [24,34,35] and 20% fuel diacetyl alcohol (daa) to fuel the diesel truck 2022 ram 3500: highway mileage 37 mpg, town mileage 35 mpg for the long testing time of 20,000. fuel efficiency of the new carbon negative replacement of the gasoline and diesel fuel for the use of said mixture of fuel diacetyl alcohol (80% v./v.) and fuel isobutanol (20% v./v.) as the diesel fuel replacement for over the 20,000 miles runs, the 10,000 miles old 2020 shevrolet silverado1500 truck was used for test runs on our carbon negative diesel fuel for 20,000 miles.. the diesel fuel mileage was achieved on the highway at the average diesel fuel mileage ~38 mpg, and at ~32 mpg driving in the city. the calculated the combined driving efficiency was about ~36 mpg. the author does not take any risk in forecasting the diesel fuel mileage behavior of the other diesel cars/trucks makes and per the mileage forecasting for the diesel cars/trucks makes older than the year of 2020. discussion nasa has stated in 2010 after measuring the air co2 content above 400 ppm that that was the “point of no return” to healthy environment on the earth. now the air co2 level exceeds 450 ppm. what that means and how do we pan to reduce the air co2 content to the level we have in our dreams the air co2 level of the year 1900 or just before the active discovery of the oil wells and fields and the massive petroleum production and use fore distillation to manufacture gasoline and diesel fuel by the international petroleum corporations. the air co2 is the heaviest gas of the air gas blend having density of 1.22 g/m 3. air co2 density exceeds 1.97 g/m 3. therefore by the gravity force the air co2 is covering the ground. the ground is the natural refuge for all kinds of fresh water: fresh water from rains, snow/ice melting, etc. the ground is the place where from the creeks, rivers start from to go to the sea, lakes and ponds. with the air co2 excessively covering the ground it produces much more fresh water vapors as that was in the year of 1900. in the southern states of the us the temperature of the ground reaches 100 o c and up. the fresh water trapped in the ground might even boil increasing the evaporation of the fresh water vapors to the air. the air is attached to the ground by the gravity force. the average thickness of the air layer above the ground is only 400 miles. the other end of said air layer is the outer space vacuum. in 2010 nasa has found a lot of ice on the dark surface of the moon. nasa has concluded that ice was captured by the dark surface of the moon (-293 o c) and the fresh water vapors came form earth. the moon worked as the “cold trap” for said vapors. compare diameters of earth and the moon, thinking that the moon is located in 200,000 miles distance from earth. what that means? earth is wasting its fresh water to the outer space. how to stop it? this might be stopped by the stopping the air co2 production. for that purpose we have developed our carbon negative fuel and food corporations and manufacture the carbon negative fuels. therefore we are offering the carbon negative fuels instead of the widely used gasoline and diesel fuel manufactured by the international petroleum corporations from petroleum on the over 80 in the continental us refineries and sold to customers nationwide. the described for the acetogen biocatalysts new type of the horizontal bioreactor design has the three gas blend diffusion stones per the perimeter of the bioreactor to ensure the even distribution of the feeding acetogen biocatalysts with the gas blend components. the total number of said diffusion stones was per each bioreactor. they are located evenly with three inches apart from each other solely in the liquid part of the horizontal bioreactor. fig. 1 has the only one of said diffusion stones, but the horizontal bioreactor for the manufacture of the carbon negative fuels has three at the perimeter of the immersed to the medium part three inches apart from each other with the total number of said stones thirty nine [30]. the author suggests his own carbon negative fuels sold at the new type of gas stations shown in fig. 7. cmi 05 (02), 600−618 cmi journal 610 cmi journal dr. michael vladislavovich tyurin fig. 7. new type of the carbon negative fuels gas station offered herein. the new gas stations (fig. 7) selling carbon negative daa and the carbon negative mixture as we noted above: 40% of fuel isobutanol, 10% fuel n-butanol, 30% mesityl oxide [24,34,35] and 20% fuel diacetyl alcohol (daa) [15-17, 29] along with the genetically engineered foods and normal foods for home cooking of the customers showed pretty much promising tendencies of the improved sales of both the carbon negative fuel and the foods for the home cooking and consumption. additionally said gas stations will sell to the customers the chemicals widely used by the household and this all just to save the valuable time for the valuable customers. apparently customers really appreciated the opportunity to save their time while visiting said new version of the gas stations selling also foods for the households. saving of the customers time was our primary priority and the new route to improve sales of the carbon negative fuels. basically we have reached our goal; the new kind of the gas stations will probably replace the existing gas station selling only snacks and gasoline and diesel fuel manufactured from petroleum. actually, said above the new type of the gas stations along with the offered there carbon negative fuels is the delicate response of the author to shell with its attempted murder of the author of this original article in response to the author’s offer to shell go start the manufacture of the carbon negative fuels. we are concerned about the amount of the fresh water reserves on earth. fig. 8 shows the governmental data on that [33]. fig. 9 elaborates these data. cmi 05 (02), 600−618 cmi journal 611 cmi journal dr. michael vladislavovich tyurin fig. 8. fresh water reserves of earth [33]. fig. 9. loss of fresh water from earth to the space vacuum due to the elevated air co2 concentrations [6,21]. cmi 05 (02), 600−618 cmi journal 612 cmi journal dr. michael vladislavovich tyurin the author came to houston in 1998. he was pleased by the houston warm weather and always blue bottomless sky. just in passed from that 26 years the houston weather has changed. there is rain almost every day now. rain is good as more fresh water comes to the ground. however we need to realize that the earth atmosphere which is only 400 miles thick above the ground and ends up with the outer space vacuum sucking the fresh water vapors from earth’s atmosphere if the air co2 exceeds certain levels. said atmosphere structure is not even. rains are at the atmosphere’s bottom. above that there are different events and above that is the space vacuum. therefore, the rainy now weather in houston reflects the substantially increased amount of the fresh water vapors in the air gas blend blend. specifically, with the changes in houston weather you can easily see that over accumulated air co2 boils sea water in the mexican gulf. most part of mexican gulf is in the equator area where the sun gives for free to us up to 1,330 wt/m 2 of the solar panels. the same happens with the air co2 which selectively absorbs the solar light infra red energy converting it to heat. that heat boils sea water on the surface of mexican gulf causing changes in houston weather. south winds bring evaporated from mexican gulf fresh water condensed in the clouds often offering rain these days. only 25 years from the author’s arrival to houston and such a dramatic weather change. so, you can easily see that the changes to the fresh water evaporation to the space vacuum are coming as we now project in the next 10-25 years from now. fresh water shortage will mean the shortage of the crops and the livestock production. the ecological crisis is coming and it will be the worst in the history of the humankind. the author plans to prevent that from happening. fig. 10 explains the thoughts of the author. fig. 10. the intelligent response of the author to the attempt of shell to kill him after his visit and proposition to shell to commercialize the proprietary technology of gasoline manufacture from the air co2 for just $0.35 per gallon of product while shell and other international petroleum corporations spend over $1.75 to manufacture gallon of gasoline or diesel fuel from petroleum. replacement of petroleum corporations by the carbon negative corporations offering carbon negative fuels and carbon negative genetically engineered foods for the humankind consumption during the time of the proposed fresh water shortage. cmi 05 (02), 600−618 cmi journal 613 cmi journal dr. michael vladislavovich tyurin the planned price for the gasoline and diesel fuel replacements is planned at the level of $2.65$2.87 per gallon regardless if the fuel will be used for the gasoline or diesel fuel powered cars / trucks. we have not had a chance to investigate the suitability of this new carbon negative mixture use for powering of the air jet turbines yet [36]. we are confident it will work even there, but we have to check it thoroughly and meticulously there like we did with the gasoline or diesel fuel powered cars in this article. therefore we are gong to save the earth’s fresh water escaping to the outer space. what fresh water shortage mean? no crops and no livestock production. global starvation is coming to earth. and we are going to revert it by noted herein means. the author claims he will save this world, he will save the earth’s fresh water. declaration of interests statement ethics approval and consent to participate. the author has received all the proper documents granting the ethical approval and the consent to participate from the state of texas officials. the author has made sure that the ethical approval and his consent to participate in preparation and submission for publication of this article were properly approved by the respective authorities of the state of texas. consent for publication. the author has expressed his complete consent to participate in work with this article and its publication in this journal. availability of data and materials. the author makes all his data and materials herein available for any third party. the data and materials might be obtained from the author at po box 300230, houston, tx, 77340. email drmtyurin64@gmail.com. if any third party needs any materials used to publish this article, please, do contact the author. competing interests. this article is another step in the war which has started by shell international petroleum corporation some time back by attempted murder of the author. the people hired by shell has totaled the author’s corporate car and did some other illegal things to the author which have concluded the author that the war with the international petroleum corporations has started already. no houston fbi or houston police investigation of said attempted murder has happened and this is behind the responsibility of the texas governor with all the legal remedies the author might use in his fight to sue the state and its governor gregory abbott. the attempted murder has the statute of limitations 20 years, and there are jurisdictions above the level of the state of texas. the author had certain legal problems with the at that time attorney general of the state of texas in 2013, now texas governor, greg abbott and the author is going to resolve all the legal problems with the texas governor, regardless would he be dismissed or not. the corporate author’s website http://syngasbiofuelsenergy.com was destroyed by the person, the attorney of hirsch and westheimer law firm, pc by the last name levy. she belongs to the same family which owned or owns the grocery stores chain named “fiesta” in houston texas. the author was unable to find a lawyer in texas to file the respective federal law suit and recover his corporate website, but the author has the us constitutional right to recite this website in the references herein. therefore the author has multiple legal problems with the state of texas and the author is going to resolve said legal problems at the respective court level in the us. the author was already involved into the war which has been started by the international petroleum corporation shell. the author has approached shell offering them for the commercialization the proprietary technology of gasoline or diesel fuel manufacture from the air co2, not from petroleum which shell and other international petroleum corporations use. shell representative met the author, got his draft of the at that time in publication article on creation gasoline from the air co2 [2]. shell hired two mexicans to kill the author in the car accident, paying the possibly around $6,000 for this dirty job, which has been done in houston texas at the us59 down south (9494 southwest fwy). the houston fbi and the houston police were contacted by the author multiple times over his mobile phone however there was no any detailed and thorough police or the fbi investigation of said attempted murder of the author since as the http://syngasbiofuelsenergy.com/ cmi 04 (03), 396−414 cmi journal 614 cmi journal dr. michael vladislavovich tyurin author trusts, both houston fbi and houston police are totally corrupted by the international petroleum corporations. therefore any law is not used in the state of texas to hurt said corporations. therefore the author has to look for the law enforcement outside of the state of texas, at the national level and he will do that to affect the texas governor abbott for his actions of 2013 and have him resign from his position. therefore the author has conflict of interests with the state of texas, texas governor gregg abbott, texas fbi and texas police. since that time more scientific publications by the author on the gasoline and diesel fuel production from the air co2 came out [11-47]. the us patents are extremely expensive, therefore the author uses instead of patents scientific publications. publications are as good as the us patents, each the us patent has to claim something better than the author already did in his scientific publications. the author working on the acetogens-biocatalysts has no any competition in the world because of his prior invention, the electroporation / electrofusion generator, already sold as a sample (with no right for reproduction) to the us corporation btx, inc. / genetronics, inc. (san-diego, ca). said generator and the invented by the authorgenome tailoring technology make him with no any competition in the whole world. the author has conflict of interest with his ph. d. supervisor, professor boris a. shenderov, who apparently worked for the kgb in the former soviet union. in 1992, when the author has applied form the first international passport of the ussr, we went to the local police department and set in line much before the international passport department started working . when the author has entered said local police department he immediately was arrested and jailed in the local prison without any announcement of his fault why he was arrested. the author has recently changed his job leaving professor shenderov and joining the ussr research institute gniigenetica. therfore prof. shenderov started making every possible efforts to harm the author with the use of kgb. therefore the author instead of getting his first international passport of the ussr was arrested and without any notification of the crime he has committed he was arrested and forwarded with the machine guns armed police workers to the local jail. in the local jail the author was placed with another five persons, criminals, who knew what for they were arrested and jailed and smoked tobacco heavily right in the prison jail cell with the size of about 5.5 x 5.5 x 5.5 meters (about 10 x 10 x 10 feet). because of said tobacco smoke the author became very sick and in five hours after being jailed he asked the god he never prayed to (the author is the ateist) to take the author to haven. the author wanted to die at said moment. his blood pressure and heart pulse were astonishingly high, and the author was really sick at said time. he started knocking inside the jail cell to the cell entrance door trying to get attention of the policemen on duty. but that was not effective and no medical help was rendered by the police to the author at the author’s requests. he asked the god to make him dead, he asked god to take him to haven. suddenly the author has heard the god’s voice right in the author’s head. the god said in english: “this is not your time to die yet . you have not done your major business yet. calm down, try to relax and wait till the police understands that they were mistaken with you and will release you”. indeed in a few days the author was released and has received his first international passport of the ussr. in 2001 the author has recovered that he has being doing wrong things at his work and started working on the carbon negative fuels and genetically engineered foods on the base of acetogens. that was the major business the russian god told to the author in 1992 at the jail cell when the author has asked his god to take him to haven and die. therefore the author has the conflict of interest with his former ph. d. supervisor prof. b. a. shenderov. the author states herein that certain articles in the reference section cited berzin v. berzin vg was the business partner of the author during his time at syngas biofuels energy. inc (2007-2013). he even paid his own $300 to start said business and spoke to his personal attorney to start said business registering it with the state of tx. however berzin v did not participate in no actual work at said corporation and obviously did not do any contributions to the articles listed in the reference section herein. his authorship was included as such as he paid for said business. that is all the readers want to know. berzin v. retired at the age of 65 and went to the retirement house which name is kept by him strictly cmi 05 (02), 600−618 cmi journal 615 cmi journal dr. michael vladislavovich tyurin confidential to avoid the author of contacting him at any time. the author recites publications where the authors were drs. m. kiriukhin and e. gak. said authors were paid significant amounts of cash by the author for doing their research when the author has hired them in the russian federation to do said r & d projects on the acetogens when the author was the ceo, executive chairman, president of tyurin enterprises, llc. funding. the author has received no funding. the investors of the author has read this article draft to his investors and they have decided not to include no funding information as they have stated to the author. they stated the author should write “no funding” per this original article. no funding. no funding was used to prepare and publish this original article. the available investors have declined to provide their information for this publication. they have suggested to note that the article was prepared and published with no any funding source. authors' contributions. the author has conducted all the experiments himself. the author has planned, wrote this original article and edited the written text, including proper placement of the illustrations mentioned. the author read, edited and approved the final manuscript. the author is the only owner of all materials disclosed in this original article. the author has plans to distribute his proprietary products after their approval as needed. the author might be contacted for the data and materials at po box 300230, houston, tx, 77230, drmtyurin64@gmail.com. the author contributed to the study conception and design. material preparation, data collection and analysis were performed by the author. the first draft of the manuscript was written by the author. the author read and approved the final manuscript. acknowledgements. the author does have the other parties to acknowledge. ms. joany kerr, the international sales director of btx, inc./ genetronics, inc., and the ceo of btx, inc./ genetronics, inc. dr. gunter a. hoffman for giving to the author his copy of the electrofusion / electrotransformation generator prior to that sold to btx, inc./ genetronics, inc. the author confirms herein the help of the third secretary of the us embassy in moscow at that time (1995) mr. james winkelman for his help to receive funds for the transportation of said generator from moscow to san-diego via ups in 1995. the author herein confirms help of dr. nikita tamm from the moscow state university for his help in receiving cash in $ in moscow, the russian federation, from san-diego, ca in 1995. authors' information. the author has the b. sci. in biological engineering (1984), m. sci. in biology (1985), m. d. in internal medicine (1986) (all from saratov state medical university, the ussr) in addition to the ph. d. in molecular biology, molecular pharmacology, microbiology (1990) from the ussr research institute for antibiotics (moscow, the ussr). the author dr. tyurin michael vladislavovich has changed his second name from “vladimirovich” to “vladislavovich” after his father, professor, dr. tyurin vladimir iljich has changed his first name from “vladimir” to “vladislav” in 2017. the author at his corporations can be reached at po box 300230 .in houston tx 77230 and via email drmtyurin64gmail.com. originality-significance statement the author has wrote this original article based on his originality of the business approach and the existing resistance of the international petroleum corporation to the technology of manufacturing carbon negative fuels to replace their production of fuels originating from petroleum. the reduction of the air co2 levels towards the prepetroleum era of the year 1900 is paramount,since our planet looses fresh water to the outer space vacuum. nasa has confirmed that in 2010 sating that the earth has reached the “point of no return” to the healthy environmental conditions suitable for life on our planet. the new family of the gas stations selling not only carbon negative fuels but also foods for cooking at home and commodity chemicals for the households will save a lot of time for the customers of said new gas stations. cmi 05 (02), 600−618 cmi journal 616 cmi journal dr. michael vladislavovich tyurin references 1. kiriukhin m, tyurin m, gak e (2014) genome tailoring powered production of isobutanol in continuous co2/h2 blend fermentation using engineered acetogen biocatalyst. j ind microbiol biotechnol. 41(5):763-781. 2. morrison rt, boyd rn (1992). organic chemistry (6th ed.). new jersey: prentice hall. 3. tyurin m. 2013. gene replacement and elimination using λredand flp-based tool to re-direct carbon flux in acetogen biocatalyst during continuous co₂/h₂ blend fermentation. j ind microbiol biotechnol. 2013, 712.40(7):749-58. doi: 10.1007/s10295-0131279-1. 4. us patent us1550792a. https://patents. google.com/patent/us1550792a/en. 5. tyurin mv (2022) diacetone alcohol instead of diesel fuel https://pubhtml5.com/pobs/ twbs/diacetone_alcohol_as_the_diesel_fuel/ 16 6. tyuirn mv (2007) http:// syngasbiofuelsener gy.com. 7. 7 tyurin mv (2023) gasoline replacements carbon negative diacetyl aclohol and isobutanol. space science journal. v 1, issue 1, 1-7. 8. tyurin mv (2023) carbon negative replacements of gasoline and 719.diesel fuel. journal of infrastructure preservation and resilience. 720.submitted for publication 03/23/2023. 9. tyurin mv (2022) new gasoline or diesel fuel replacement. adv. j. sci. eng. tech. v.7(03) 126-140. issn: 2330 – 1744. 10. tyurin mv (2022) carbon negative gasoline replacement. advance journal of science, engineering and technology. v.7 (3),1-7. 11. tyurin mv (2022) air co2 for the manufacture of fuels. diesel fuel diacetyl alcohol. irish international journal of engineering and applied sciences irish j. eng. a. sci. v.6(02),12-24. 12. tyurin mv (2022) diesel fuel or gasoline raplacement diacetyl alcohol. gasoline replacement fuel isobutanol or diacetyl alcohol. air co2 for the manufacture of the fuels. oil and gas research. 96, v.3 (12), 234-248. 13. tyurin mv (2022) air co2 for the manufacture of the commodity fuels; diesel fuel replacement and gasoline replacement carbon negative diacetyl alcohol breakdown of gasoline and diesel fuel prices at the gas stations. fuel. 82, 388-392. 14. tyurin mv (20220 air co2 for manufacture of the fuels: diesel fuel or gasoline replacement diacetyl alcohol gasoline replacement fuel isobutanol or diacetyl alcohol:: 9786204749587: amazon.com: books. 15. tyurin mv (2021) gasoline and diesel fuel replacement fuel diacetyl alcohol. international journal of automotive technology. volume 23(1), 23-46. 16. tyurin mv (2021) air co2 for the manufacture of the commodity fuels. atmospheric pollution research. .13(4), 7794. 17. tyurin mv (2021) diacetone alcohol as the diesel. alternative energies efficiency evaluation. ed.: dr. muhammad wakil shahzad. intechopen. rijeka: janeza trdine 9, 51000 rijeka, croatia. london: 5 princess gate court, london, sw7 2qj, uk. https:// www.intechopen.com/books/10687. 18. tyurin mv, padda rs. (2019) nitrogen gas reducing commercial acetogen biocatalyst suitable for direct and selective reduction of co2 inorganic carbon to organic carbon and atmospheric nitrogen to fuel isobutanol during continuous fermentation of co2 + h2 + n2 gas blend. international research journal of applied sciences, engineering and technology. v.3, # 4, 1 10. 19. tyurin mv (1992) russian patent ru 2005776. generator for electrotransformation https://pubhtml5.com/pobs/%20twbs/diacetone_alcohol_as_the_diesel_fuel/16 https://pubhtml5.com/pobs/%20twbs/diacetone_alcohol_as_the_diesel_fuel/16 https://pubhtml5.com/pobs/%20twbs/diacetone_alcohol_as_the_diesel_fuel/16 https://www.amazon.com/air-co2-manufacture-fuels-alcoholgasoline/dp/6204749587 https://www.amazon.com/air-co2-manufacture-fuels-alcoholgasoline/dp/6204749587 https://www.amazon.com/air-co2-manufacture-fuels-alcoholgasoline/dp/6204749587 https://www.amazon.com/air-co2-manufacture-fuels-alcoholgasoline/dp/6204749587 https://www.amazon.com/air-co2-manufacture-fuels-alcoholgasoline/dp/6204749587 https://www.amazon.com/air-co2-manufacture-fuels-alcoholgasoline/dp/6204749587 cmi 05 (02), 600−618 cmi journal 617 cmi journal dr. michael vladislavovich tyurin and electrofusion/electrodistruction of various cells: microbial, animal, plant and the process of its manufacture, and the set of plate-parallel polished electrodes and the process of their manufacture from the titanium-based metal alloy vk-2. 20. tyurin mv (1992). russian patent ru 2005776-2. plate-parallel polished electrodes and the process of their manufacture from the titanium-based metal alloy vk-2. 21. tyurin mv (2022) air co2 for the manufacture of the fuels. diesel fuel diacetyl alcohol. irish international journal of engineering and applied sciences. v.6 (02) 12-24. 22. tyurin mv (2007) http://syngasbiofuel senergy.com. 23. dow chemicals. technical data sheet. isopbutanol. oecd sids. isobutanol.cas n°: 78-83-1. 24. dow chemicals. isobutanol. technical datasheet. https://www.google.com/search ?q=dow+chemicals.+isobutanol.+techni76 8.cal+datasheet&rlz=1c1gceu_enus1054 us1054&oq=dow+chemicals.+isobutanol. ++technical+datasheet&aqs=chrome..69i5 7.1053j0j4&sourceid=chrome&ie=utf8#bsht=cgrmynntegqibdab. 25. tyurin mv (2022) environmental problem solution. clinical medicine insights. cmi 039010, 256-261. (fuel isobutanol gasoline replacement, fuel diacetyl alcohol diesel fuel replacement, fresh water shortness). 26. gak e, tyurin mv, kiriukhin m (2014) genome tailoring powered production of isobutanol in continuous co2/h2 blend fermentation using engineered acetogen biocatalyst. j ind microbiol biotechnol. 41(5):763-781 http://www.ncbi.nlm.nih.gov /pubmed/24659176. 27. kiriukhin m, tyurin mv, gak e (2014) uvinduced mutagenesis in acetogens: resistance to methanol, ethanol, acetone, or n-butanol in recombinants with reduced genomes during continuous co2 / h2 gas blend fermentation. world journal of microbiology and biotechnology. 30(5):1559-1574. https://pub med.ncbi.nlm.nih.gov/24415498/. 28. tyurin mv (2022) environmental problem solution. clinical medicine insights. cmi 039010, 256-261. (fuel isobutanol gasoline replacement, fuel diacetyl alcohol diesel fuel replacement, fresh water shortness). 29. tyurin mv (2016) (invited) direct and selective syngas biocatalysis for manufacture of fuels and commodity chemicals. in: syngas: production, emerging technologies and ecological impacts. r. myers, ed. nova publishers, ny, 2016. https://www.nova publishers.com/catalog/product_info.php?prod ucts_id=5791. 30. berzin v, kiriukhin m, tyurin mv (2012) selective production of acetone during continuous synthesis gas fermentation by engineered 794.biocatalyst clostridium sp. macet113. letters of appl microbiol. 795.55(2):149-54. doi: 10.1111/j.1472-765x. 2012.03272.x. 31. tyurin mv (2023) bioreactor for carbon negative gasoline and diesel fuel replacements. letters in microbiology. v. 75 (34) 86-90. 32. https://bearing-service.ru/en/about-ourcompany/. 33. berzin v, kiriukhin m, tyurin m (2013) crelox66/lox71-based elimination of phosphotransacetylase or acetaldehyde dehydrogenase shifted carbon flux in acetogen rendering selective overproduction of ethanol or acetate. appl biochem biotechnol. 195(3):181-8. https://link.springer.com/article /10.1007/s12010-012-9864-8. 34. http://ga.water.usds.gov/edu/earthwherewater. html. 35. us patent 1232897 preparation of isophorone and mesityl oxide from acetone. filed 198412-03, issued 1988-02-16. https://www.google.com/search%20?q=dow+chemicals.+isobutanol.+techni768.cal+datasheet&rlz=1c1gceu_enus1054us1054&oq=dow+chemicals.+isobutanol.++technical+datasheet&aqs=chrome..69i57.1053j0j4&sourceid=chrome&ie=utf-8#bsht=cgrmynntegqibdab https://www.google.com/search%20?q=dow+chemicals.+isobutanol.+techni768.cal+datasheet&rlz=1c1gceu_enus1054us1054&oq=dow+chemicals.+isobutanol.++technical+datasheet&aqs=chrome..69i57.1053j0j4&sourceid=chrome&ie=utf-8#bsht=cgrmynntegqibdab https://www.google.com/search%20?q=dow+chemicals.+isobutanol.+techni768.cal+datasheet&rlz=1c1gceu_enus1054us1054&oq=dow+chemicals.+isobutanol.++technical+datasheet&aqs=chrome..69i57.1053j0j4&sourceid=chrome&ie=utf-8#bsht=cgrmynntegqibdab https://www.google.com/search%20?q=dow+chemicals.+isobutanol.+techni768.cal+datasheet&rlz=1c1gceu_enus1054us1054&oq=dow+chemicals.+isobutanol.++technical+datasheet&aqs=chrome..69i57.1053j0j4&sourceid=chrome&ie=utf-8#bsht=cgrmynntegqibdab https://www.google.com/search%20?q=dow+chemicals.+isobutanol.+techni768.cal+datasheet&rlz=1c1gceu_enus1054us1054&oq=dow+chemicals.+isobutanol.++technical+datasheet&aqs=chrome..69i57.1053j0j4&sourceid=chrome&ie=utf-8#bsht=cgrmynntegqibdab https://www.google.com/search%20?q=dow+chemicals.+isobutanol.+techni768.cal+datasheet&rlz=1c1gceu_enus1054us1054&oq=dow+chemicals.+isobutanol.++technical+datasheet&aqs=chrome..69i57.1053j0j4&sourceid=chrome&ie=utf-8#bsht=cgrmynntegqibdab https://www.google.com/search%20?q=dow+chemicals.+isobutanol.+techni768.cal+datasheet&rlz=1c1gceu_enus1054us1054&oq=dow+chemicals.+isobutanol.++technical+datasheet&aqs=chrome..69i57.1053j0j4&sourceid=chrome&ie=utf-8#bsht=cgrmynntegqibdab https://bearing-service.ru/en/about-our-company/ https://bearing-service.ru/en/about-our-company/ https://link.springer.com/article%20/10.1007/s12010-012-9864-8 https://link.springer.com/article%20/10.1007/s12010-012-9864-8 http://ga.water.usds.gov/edu/earthwherewater.html. http://ga.water.usds.gov/edu/earthwherewater.html. cmi 05 (02), 600−618 cmi journal 618 cmi journal dr. michael vladislavovich tyurin 36. us patent 3,413,372. process for the synthesis of mesitylene. filed 1966-09-29. expired 1985-11-26 (lifetime). 37. jet fuel: biofuels are slowly coming to business jets aopa. https://www.aopa.org/news-and-media/all-news/2020/february/pilot/turbine-pilot-biofuel https://www.aopa.org/news-and-media/all-news/2020/february/pilot/turbine-pilot-biofuel 