Publications by authors named "Bagher Larijani"

811 Publications

Aminoimidazo[1,2-a]pyridine Bearing Different Pyrazole Moieties as the Structural Scaffold for the Development of BACE1 Inhibitor; Synthesis, Structural Characterization, In vitro and In silico Studies.

Curr Org Synth 2022 Jan 26. Epub 2022 Jan 26.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Regarding the critical role of amyloid-β plaques on the pathogenesis of Alzheimer's disease, a series of aminoimidazo[1,2-a]pyridine derivatives was designed and synthesized as potential anti-BACE1 agents targeting the production of amyloid-β plaques. In vitro, biological results demonstrated that compounds 7b and 7f exhibited the best inhibitory potency against BACE1 with IC50 values of 22.48 ± 2.06 and 30.61 ± 3.48 μM, respectively. Also, the ligand-protein docking evaluations revealed that compounds 7b and 7f could effectively bind with the different pockets of BACE1 through different interactions with the residue of the active site. The results of current studies underline the potential role of aminoimidazo[1,2-a] pyridine-containing pyrazole derivatives for developing novel BACE1 inhibitors.
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http://dx.doi.org/10.2174/1570179419666220126113014DOI Listing
January 2022

The Role of Gut Microbiota-Brain Axis in Pathophysiology of ADHD: A Systematic Review.

J Atten Disord 2022 Jan 20:10870547211073474. Epub 2022 Jan 20.

Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Objective: The main goal of this systematic review is to summarize evidences regarding alterations of microbial composition in ADHD cases and uncover underlying mechanisms.

Methods: A comprehensive search was conducted on PubMed, Web of Science, and Scopus databases up to March 2021. All the observational studies including case-control, cross-sectional, and cohorts investigating the correlations between the gut microbiota and ADHD in both adults and children were included.

Results: We found eight eligible studies. , , and were increased which may lead to impaired dopamine related functions in CNS. Moreover, decrease of frequency in ADHD could result in higher permeability and crossing of inflammatory cytokines. Regarding the short chain fatty acids-producing bacteria, family decreased and and species increased.

Conclusion: Gut microbiota correlation with ADHD and its underlying mechanisms could open new windows for developing novel therapies of ADHD by manipulating microbiota.
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http://dx.doi.org/10.1177/10870547211073474DOI Listing
January 2022

The association of cardio-metabolic risk factors and history of falling in men with osteosarcopenia: a cross-sectional analysis of Bushehr Elderly Health (BEH) program.

BMC Geriatr 2022 01 11;22(1):46. Epub 2022 Jan 11.

Osteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Osteosarcopenia, defined as sarcopenia plus osteopenia/osteoporosis, may increase the risk of fractures and affects morbidity and mortality in the older population. Falling is also common in the elderly and increases the risk of fractures and mortality. We examined the association of cardio-metabolic risk factors with a history of falling in osteosarcopenic men.

Methods: We used the baseline data of the Bushehr Elderly Health (BEH) program. Osteosarcopenia was defined as having both sarcopenia (reduced skeletal muscle mass plus low physical performance and/or low muscle strength) and osteopenia/osteoporosis (T-score ≤ - 1.0). Falling was defined as a self-reported history of an unintentional down on the ground during the previous year before the study. We used logistic regression analysis to estimate the adjusted odds ratio (AOR) with a 95% Confidence Interval (CI) to quantify the associations.

Results: All elderly men diagnosed with osteosarcopenia (n = 341), with a mean age of 73.3(±7.4) years, were included. Almost 50(14.7%) participants reported falling. Age showed a positive association with falling (AOR: 1.09, 95%CI: 1.04-1.14). An increase of 10 mmHg in systolic blood pressure(SBP), reduces the odds of falling by 26%(AOR:0.74, 95%CI:0.62-0.89), while a positive association was detected for fasting plasma glucose (FPG), as 10 mg/dl increase in the FPG, raises the chance of falling by 14%(AOR = 1.14, 95%CI:1.06,1.23). Hypertriglyceridemia was inversely associated with falling (AOR = 0.33, 95% CI: 0.12, 0.89).

Conclusions: Falling is a major public health problem in rapidly aging countries, especially in individuals with a higher risk of fragility fractures. Older age-raised fasting plasma glucose and low SBP are associated with falling in osteosarcopenic patients.  Considering the higher risk of fracture in osteosarcopenic men, comprehensive strategies are needed to prevent fall-related injuries in this high-risk population.
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http://dx.doi.org/10.1186/s12877-021-02657-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8753863PMC
January 2022

The ethical challenges in pharmacy practice in community Pharmacies: A qualitative study.

Saudi Pharm J 2021 Dec 11;29(12):1441-1448. Epub 2021 Nov 11.

Medical Ethics and History of Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: Pharmacists as a group of health care professionals, face different types of ethical challenges in their everyday routine that may impede pharmaceutical care.

Objectives: In this study, we aimed at evaluation and recognition of the ethical challenges of pharmacy practice in community pharmacies.

Methods: This exploratory study was conducted as a qualitative study consisting of open-ended in-depth interviews and focus group discussions followed by content analysis. The study participants were chosen from pharmacists with PharmD degree who had at least 4 years work experience and were the founders or technical managers of community pharmacies, either as governmental or private. Interviews continued until data saturation and transcribed verbatim. The content analysis was done by Graneheim and Lundman method. The codes were generated, and categorized. After assessment and final modifications, the results of the study were discussed and confirmed in a focus group discussion conducted by 7 experts who teach medical ethics and/or pharmacy ethics.

Results: Overall, 40 pharmacists were interviewed (mean age 46 ± 11.3 years). The extracted ethical challenges of pharmacy practice were categorized into 3 main themes, 11 subthemes and 102 codes. The themes were achieved as challenges related to professionalism and professional practice, challenges related to professional communications and challenges related to regulations and policies.

Conclusion: Taken together, it seems that most of the challenges of pharmacy practice are related to professionalism and professional commitment; however, the regulations and policies provide serious obstacles for pharmacy practice and pharmaceutical care. More efforts towards teaching professionalism and modification of regulations and policies are recommended.
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http://dx.doi.org/10.1016/j.jsps.2021.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8720823PMC
December 2021

Association between being metabolically healthy/unhealthy and metabolic syndrome in Iranian adults.

PLoS One 2022 6;17(1):e0262246. Epub 2022 Jan 6.

Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: The prevalence of metabolically healthy obesity (MHO) varies based on different criteria. We assessed the prevalence of MHO and metabolic unhealthiness based on body mass index (BMI) and their association with metabolic syndrome (MetS) in a nation-wide study.

Methods: Data were taken from the STEPs 2016 study, from 18,459 Iranians aged ≥25 years. Demographic, metabolic, and anthropometric data were collected. Subjects were stratified by BMI, metabolic unhealthiness, and having MetS. The latter was defined based on National Cholesterol Education Program Adult Treatment Panel III 2004 (NCEP ATP III), was then assessed.

Results: The prevalence of MHO and metabolic unhealthiness in obese subjects was 7.5% (about 3.6 million) and 18.3% (about 8.9 million), respectively. Most of the metabolic unhealthy individuals were female (53.5%) or urban residents (72.9%). Low physical activity was significantly and positively associated (Odds Ratio: 1.18, 95% CI: 1.04-1.35) with metabolic unhealthiness, while being a rural residence (0.83, 0.74-0.93), and having higher education (0.47, 0.39-0.58) significantly but negatively affected it. Dyslipidemia was the most frequent MetS component with a prevalence rate of 46.6% (42.1-51.1), 62.2% (60.8-63.6), 76.3% (75.1-77.5), and 83.4% (82.1-84.6) among underweight, normal weight, overweight and obese phenotypes, respectively.

Conclusion: BMI aside, an additional set of criteria such as metabolic markers should be taken into account to identify normal weight but metabolically unhealthy individuals. Given the highest prevalence of dyslipidemia among obese subjects, further interventions are required to raise public awareness, promote healthy lifestyles and establish lipid clinics.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0262246PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8735615PMC
January 2022

An Overview of Zebrafish Modeling Methods in Drug Discovery and Development.

Adv Exp Med Biol 2021 Dec 28. Epub 2021 Dec 28.

Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Animal studies are recognized as a significant step forward in the bridging between drug discovery and clinical applications. Animal models, due to their relative genetic, molecular, physiological, and even anatomical similarities to humans, can provide a suitable platform for unraveling the mechanisms underlying human diseases and discovering new therapeutic approaches as well. Recently, zebrafish has attracted attention as a valuable experimental and pharmacological model in drug discovery and development studies due to its prominent characteristics such as the high degree of genetic similarity with humans, genetic manipulability, and prominent clinical features. Since advancing a theory to a valid and reliable observation requires the manipulation of animals, it is, therefore, essential to use efficient modeling methods appropriate to the different aspects of experimental conditions. In this context, applying several various approaches such as using chemicals, pathogens, and genetic manipulation approaches allows zebrafish development into a preferable model that mimics some human disease pathophysiology. Thus, such modeling approaches not only can provide a framework for a comprehensive understanding of the human disease mechanisms that have a counterpart in zebrafish but also can pave the way for discovering new drugs that are accompanied by higher amelioration effects on different human diseases.
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http://dx.doi.org/10.1007/5584_2021_684DOI Listing
December 2021

The Association between Waterpipe Smoking and Metabolic Syndrome: A Cross-Sectional Study of the Bushehr Elderly Health Program.

Biomed Environ Sci 2021 Nov;34(11):910-915

Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

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http://dx.doi.org/10.3967/bes2021.125DOI Listing
November 2021

Global, regional, and national quality of care of gallbladder and biliary tract cancer: a systematic analysis for the global burden of disease study 1990-2017.

Int J Equity Health 2021 Dec 18;20(1):259. Epub 2021 Dec 18.

Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: To improve health outcomes to their maximum level, defining indices to measure healthcare quality and accessibility is crucial. In this study, we implemented the novel Quality of Care Index (QCI) to estimate the quality and accessibility of care for patients with gallbladder and biliary tract cancer (GBBTC) in 195 countries, 21 Global Burden of Disease (GBD) regions, Socio-demographic Index (SDI) quintiles, and sex groups.

Method: This cross-sectional study extracted estimates on GBBTC burden from the GBD 2017, which presents population-based estimates on GBBTC burden for higher than 15-year-old patients from 1990 to 2017. Four secondary indices indicating quality of care were chosen, comprising Mortality to incidence, Disability-Adjusted Life Year (DALY) to prevalence, prevalence to incidence, and years of life lost (YLL) to years lived with disability (YLD) ratios. Then, the whole dataset was analyzed using Principal Component Analysis to combine the four indices and create a single all-inclusive measure named QCI. The QCI was scaled to the 0-100 range, with 100 indicating the best quality of care among countries. Gender Disparity Ratio (GDR) was defined as the female to male QCI ratio to show gender inequity throughout the regions and countries.

Results: Global QCI score for GBBTC was 33.5 in 2017, which has increased by 29% since 1990. There was a considerable gender disparity in favor of men (GDR = 0.74) in 2017, showing QCI has moved toward gender inequity since 1990 (GDR = 0.85). Quality of care followed a heterogeneous pattern among regions and countries and was positively correlated with the countries' developmental status reflected in SDI (r = 0.7; CI 95%: 0.61-0.76; P value< 0.001). Accordingly, High-income North America (QCI = 72.4) had the highest QCI; whereas, Eastern Sub-Saharan Africa (QCI = 3) had the lowest QCI among regions. Patients aged 45 to 80 had lower QCI scores than younger and older adults. The highest QCI score was for the older than 95 age group (QCI = 54), and the lowest was for the 50-54 age group (QCI = 26.0).

Conclusions: QCI improved considerably from 1990 to 2017; however, it showed heterogeneous distribution and inequity between sex and age groups. In each regional context, plans from countries with the highest QCI and best gender equity should be disseminated and implemented in order to decrease the overall burden of GBBTC.
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http://dx.doi.org/10.1186/s12939-021-01596-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8684179PMC
December 2021

Dietary Quality Index and Cardiometabolic Risk Factors among Adult Women.

Iran J Public Health 2021 Aug;50(8):1713-1721

Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

Background: The prevalence of cardiovascular disease is dramatically increasing particularly in developing countries. Among the different factors, diet has an important role in the pathogenesis of these diseases. This study aimed to assess the relationship between dietary quality index-international (DQI-I) and cardiovascular risk factors in adult Iranian women.

Methods: This was a cross-sectional study of 371 participants, aged 20-50 yr, and recruited from 10 health centers from health centers affiliated with Tehran University of Medical Sciences (TUMS), Tehran, Iran in 2018. Usual dietary intake was evaluated by a validated and reliable 168-items food frequency questionnaire (FFQ). To assess overall quality of diet, the Dietary Quality Index-International (DQI) was used. Anthropometric measurements, blood pressure, and fasting blood of samples were taken to assess biochemical parameters related to cardiovascular disease.

Results: The results of linear regression showed that DQI-I score was inversely and directly associated with serum level of total cholesterol (TC) (0.27, confidence interval (CI): 0.13-0.58; <0.001) and high-density lipoprotein cholesterol (HDL-C) (2.53, CI: 1.42-4.52; =0.001), respectively. However, there was no significant association between DQI-I and other cardiovascular risk factors.

Conclusion: A greater DQI-I score was associated with preferable lipid profile including TC and HDL-C. Future large-scale, prospective cohort or clinical studies are required to confirm these findings.
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http://dx.doi.org/10.18502/ijph.v50i8.6819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8643538PMC
August 2021

Gut microbiota modulation as a possible mediating mechanism for fasting-induced alleviation of metabolic complications: a systematic review.

Nutr Metab (Lond) 2021 Dec 14;18(1):105. Epub 2021 Dec 14.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, North Kargar Ave, 1411413137, Tehran, Iran.

Background: Intermittent fasting has been reported to have positive effects on obesity, diabetes, cardiovascular diseases, hypertension, and several neurodegenerative diseases through different mechanisms such as alteration in the gut microbiota. This systematic review was conducted with the aim of providing an overview of the existing animal and human literature regarding the gut microbiota alterations in various fasting regimens.

Method: A systematic literature search was conducted on PubMed, Scopus and Web of Science databases up to May 2021 to find all relevant studies examining the gut microbiota alteration during the fasting. Original researches on animal models or human patients were included in this study.

Results: The search fulfilled 3072 documents from which 31 studies (20 animal and 11 human studies) were included. Upon fasting, abundance of several beneficial bacteria including Lactobacillus and Bifidobacterium shifted significantly. Moreover, some taxa, including Odoribacter which negatively associated with blood pressure bloomed during fasting. Ramadan fasting, as a kind of intermittent fasting, improves health parameters through positive changes in gut microbiota including upregulation of A. muciniphila, B. fragilis, Bacteroides and butyric acid-producing Lachnospiraceae.

Conclusion: The findings suggest that different fasting regimens including alternate-day fasting, calorie- and time-restricted fasting programs and Ramadan fasting could promote health maybe through the modulation of gut microbiome. However, further studies are needed to explore properly the connection between gut microbiota and meal frequency and timing.
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http://dx.doi.org/10.1186/s12986-021-00635-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8670288PMC
December 2021

Targeting dyslipidemia with antioxidative vitamins C, D, and E; a systematic review of meta-analysis studies: Dyslipidemia and antioxidative vitamins.

J Diabetes Metab Disord 2021 Dec 21;20(2):2037-2047. Epub 2021 Oct 21.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: There is controversial evidence for the beneficial effects of antioxidative vitamins (vits) on dyslipidemia. In this regard, we aimed to systematically review all meta-analyses of trials on this topic.

Methods: We comprehensively searched PubMed, Web of Science, Scopus, and Cochrane Library databases until January 2021 to explore the published English meta-analyses of trials conducted to assess the effects of single or combined vits C, D and E consumption on lipid profile. The meta-analyses of observational, in vivo/in vitro or case-report studies were excluded. Search results were reported based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) flowchart.

Results: Overall, 25 meta-analyses including 32,177 individuals with different underlying disorders met our inclusion criteria. Numerous studies had assessed supplementation with Vit-D or its combination with other agents on lipid profile. Consumption of 400 IU/day (d) to 50,000 IU/week (w) Vit-D for at least eight weeks improved the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) in type 2 diabetes mellitus or polycystic ovary syndrome (PCOS) patients. This treatment reduced the levels of TC and TG in patients with chronic kidney disease. A significant increase in high-density lipoprotein cholesterol (HDL-C) levels was only observed in coronary artery disease patients. Sole intake of 500-2000 mg/d Vit-C for at least 3 weeks improved LDL-C and TG values in hypercholesterolemic patients. Nevertheless, sole intake of Vit-E had controversial effects on lipid profile. The combination of 400-1800 IU/d omega-3 free fatty acid (FFA) and 400 IU/d Vit-E significantly reduced the levels of LDL-C and TG in overweight individuals, without any significant effect on other components. A significant improvement of TG values was observed after consumption of 1000-2000 mg/d omega-3 FFA plus 400 IU/d Vit-E along with 50,000 IU/each 2w Vit-D for at least 6 weeks in diabetic patients.

Conclusion: The beneficial effects of antioxidative vitamins (C, D, E) or their combination with other agents on lipid profile varied based on their dosage, intake duration, and the health status of the individuals.

Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-021-00919-8.
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http://dx.doi.org/10.1007/s40200-021-00919-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630136PMC
December 2021

Nutrition and Diet Therapy in Diabetes Mellitus: A Roadmap based on available evidence.

J Diabetes Metab Disord 2021 Dec 11;20(2):1913-1918. Epub 2021 Sep 11.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, PO Box: 1411413137, Tehran, Iran.

Background: Nutrition is considered as a primary approach for diabetes management. It needs a comprehensive assessment of evidence to identify nutritional dimensions that should be explored in the future. We aimed to provide a roadmap on diabetes and nutrition and clarify research gaps in this field.

Methods: In the present review, we searched Scopus and PubMed electronic databases to collect eligible publications with English and Farsi languages from 2015 to December 2019 in the field of nutrition and diabetes. Relevant papers were classified into six subgroups including biochemistry/ animal studies, clinical nutrition, food industry, genetic, public health, and dietary supplements. Based on evidence-based pyramid, publications were categorized as well. Publications trend from 2015 to 2019 and frequency of publications in each category were provided.

Results: Finally, we reached 438 eligible papers. Most studies (40.86%) were clinical trials and in most human studies ( = 224) patients with type 2 diabetes were considered. Probiotic/prebiotic/ symbiotic, vitamin D, and omega-3/fish oil were the most frequent studied dietary supplements. Low portions of studies were dedicated to diabetic children ( = 3), type 1 diabetes ( = 6), diabetes complications ( = 23) and GDM ( = 25).

Conclusion: An increasing trend in nutrition publications in the field of diabetes was observed. Publications were mostly dedicated to clinical trials with a focus on dietary supplements. Low portion of studies have been dedicated to children with diabetes, diabetes complications, and GDM. More attention to high quality basic research, product-based projects, and interdisciplinary studies in the field of nutrition and diabetes are needed.
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http://dx.doi.org/10.1007/s40200-021-00876-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630236PMC
December 2021

Diabetic Foot scientific activities in Endocrinology and Metabolism Research Institute.

J Diabetes Metab Disord 2021 Dec 15;20(2):1767-1772. Epub 2021 Jun 15.

Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: Diabetic Foot (DF) as a common complication of Diabetes should be intensive intervention for prevention, management and rehabilitation. In this regard, Diabetes Research Center of Endocrinology and Metabolism Research Institute (EMRI) of Tehran University of Medical Sciences (TUMS) considered DF as a priority research area to investigate multidimensional aspects of DF care. We are intended to summarize DF research studies affiliated to the EMRI for over the last two decades.

Methods: Three Electronic databases including Web of Science, PubMed, and Scopus were searched until January 2020 to find articles about DF published affiliated to EMRI. The main concepts of search strategies were "diabetes", "Foot". 115 documents retrieved from these databases which screened for inclusion and exclusion criteria. The visualization of the network of co-authorship of authors and co-occurrence of keywords was illustrated and documents were analyzed for content according to the Main areas of DF Research studies.

Result: 64 related documents including original articles, reviews, letters, notes, and book chapter have included to this study. According to the objectives of the retrieved studies, DF documents and research studies categorized in the two main groups including DF prevention, classification and risk stratification in addition management of DF.

Conclusion: Despite conducted research and educational activities in DF prevention and management, the following topics would be considered as well: effective offloading treatment, correcting the nutritional status for improving wound healing and novel educational strategies for diabetic foot multi-disciplinary team.
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http://dx.doi.org/10.1007/s40200-021-00823-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630246PMC
December 2021

Comparison of anthro-metabolic indicators for predicting the risk of metabolic syndrome in the elderly population: Bushehr Elderly Health (BEH) program.

J Diabetes Metab Disord 2021 Dec 28;20(2):1439-1447. Epub 2021 Aug 28.

Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Metabolic syndrome (MetS) is a cluster metabolic disorder that includes central obesity, insulin resistance, hypertension, and dyslipidemia, and is highly associated with an increased risk of developing non-communicable diseases (NCDs). This study aimed to compare the reliability of anthro-metabolic indices [visceral adiposity index (VAI), body roundness index (BRI), and a body shape index (BSI), body adiposity index (BAI), lipid accumulation product (LAP), waist to hip ratio, and waist to height ratio] in predicting MetS in Iranian older people.

Methods: This cross-sectional study was conducted based on the data of 2426 adults aged ≥60 years that participated in the second stage of the Bushehr Elderly Health (BEH) program, a population-based prospective cohort study being conducted in Bushehr, Iran. MetS was defined based on the revised National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria. The receiver operating characteristic (ROC) curve analysis was used to assess predictive performance of anthro-metabolic indices and determine optimal cutoff values. Logistic regression analysis was applied to determine the associations between MetS and indices.

Results: 2426 subjects (48.1% men) with mean ± SD age of 69.34 ± 6.40 years were included in the study. According to ATP III criteria, 34.8% of men and 65.2% of women had MetS (P < 0.001). Of the seven examined indices, the AUCs of VAI and LAP in both genders were higher than AUCs of other anthro-metabolic indices. Also, in general population, VAI and LAP had the greatest predictive power for MetS with AUC 0.87(0.86-0.89) and 0.87(0.85-0.88), respectively. The lowest AUC in total population belonged to BSI with the area under the curve of 0.60(0.58-0.62). After adjusting for potential confounders (e.g. age, sex, education, physical activity, current smoking) in the logistic regression model, the highest OR in the total population was observed for VAI and LAP, which was 16.63 (13.31-20.79) and 12.56 (10.23-15.43) respectively. The lowest OR for MetS was 1.93(1.61-2.30) for BSI.

Conclusion: This study indicated that both VAI and LAP are the most valuable indices among the anthro-metabolic indices to identify MetS among the elderly in both genders. So, they could be used as proper assessment tools for MetS in clinical practice. However, the cost-benefit of these indices compared to the ATP III criteria need further studies.
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http://dx.doi.org/10.1007/s40200-021-00882-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630247PMC
December 2021

The association between muscle indicators and bone mass density and related risk factors in the diabetic elderly population: Bushehr Elderly Health (BEH) Program.

J Diabetes Metab Disord 2021 Dec 25;20(2):1429-1438. Epub 2021 Aug 25.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, NO 10, Jalale-Al-Ahmad Ave, Chamran Highway, Tehran, Iran.

Background: Loss of muscle mass and strength and bone mass density are complications of the aging process. Studies show that the prevalence of sarcopenia and osteoporosis may be higher in patients with diabetes. Therefore, this study was aimed to investigate the relationship between muscle mass and strength indices and bone mass density in diabetic elderly.

Materials And Methods: This cross-sectional study was conducted based on the data collected during the Bushehr Elderly Health (BEH) Program, stage II. Diabetes was defined as FPG ≥ 126 mg/dl or HbA1C ≥ 6.5 or taking anti-diabetic medication. Dual x-ray absorptiometry (DXA, Discovery WI, Hologic Inc, USA) was used to measure bone mineral density, fat mass, trabecular bone score (TBS) and muscle mass. Muscle strength was measured by grip strength.Osteoporosis was defined as the bone mineral density of ≥ 2.5 standard deviations (SD) below the average value of young normal adults (T-score of ≤ -2.5 SD) in the femoral neck, or lumbar spine (L1-L4) or total hip. To determine the relationship between skeletal muscle index (SMI) and muscle strength on bone status in a continuous scale was used from linear regression. To estimate the effect of SMI and muscle strength on osteoporosis was used from modified Poisson regression for analysis.

Results: This study included 759 diabetic elderly with a mean age of 68.6 years and 56.9% of them were women. Skeletal muscle index (SMI) was related to all sites of BMDs and TBS L1-L4 after adjusted in full models (P-value < 0.001). The largest coefficients were observed for BMD L1-L4 in all models (β: 0.043 g/cm; 95% CI: 0.030-0.057 in full model). Muscle strength was also associated with BMDs and TBS. Only, in model 2 (adjustments for age and sex effect), there was no significant relationship between muscle strength and BMD L1-L4 and TBS L1-L4. The strongest associations were observed for the total hip BMD and muscle strength (β: 0.034 g/cm; 95% CI: 0.022- 0.046 in full model). Also, increased SMI and muscle strength was associated with decreased osteoporosis in crude and adjusted models (P < 0.001).

Conclusions: In this study, it was revealed that the reduction of SMI in elderly patients with diabetes was significantly associated with decreased BMD and TBS. The muscle strength was also associated with BMD and TBS. So, muscle strength and muscle mass should be measured separately ever since both are independently associated with BMD and TBS. Muscle strength and muscle mass were negatively associated with osteoporosis in older people with diabetes. Thus, we should pay more attention to muscle strength training in older people with diabetes, particularly in osteoporotic patients.
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http://dx.doi.org/10.1007/s40200-021-00881-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630123PMC
December 2021

Pilot study in pharmacogenomic management of empagliflozin in type 2 diabetes mellitus patients.

J Diabetes Metab Disord 2021 Dec 10;20(2):1407-1413. Epub 2021 Aug 10.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, No.10-Jalal-e-Ale-Ahmad Street, Chamran Highway, 1411713119 Tehran, Iran.

Background: Type 2 diabetes mellitus (T2DM) is a metabolic disorder in which the patients with high blood sugar develop insufficient insulin secretion or insulin resistance. The gene is a member of sodium/glucose transporter family which can reduce heart and kidney problems. The current study aims to look into any association between rs11646054 variant in gene and the anti-diabetic efficacy and safety of empagliflozin.

Methods: 14 T2DM who failed to respond to previous treatments empagliflozin 10 mg was added for 6 months Genotyping of the rs11646054 variant of gene was performed by polymerase chain reaction (PCR) followed by Sanger sequencing.

Results: Although hemoglobin A1c (HbA1c) and low-density lipoprotein (LDL) were not significantly different, but the mean fasting blood sugar (FBS), 2-h post prandial (2hpp), albumin-to-creatinine ratio (ACR), and total cholesterol (TC) were significantly decreased after 6 months empagliflozin treatment. There was a significant difference in the mean final reductions in FBS level among genotypes. It's important to mention that those who were GG homozygotes had a tendency to have more decrements.

Conclusions: The study results indicate that effects of variation in (rs11646054) on the clinical efficacy of empagliflozin were negligible.
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http://dx.doi.org/10.1007/s40200-021-00874-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630276PMC
December 2021

Association of vitamin D receptor gene polymorphism with the occurrence of low bone density, osteopenia, and osteoporosis in patients with type 2 diabetes.

J Diabetes Metab Disord 2021 Dec 23;20(2):1375-1383. Epub 2021 Aug 23.

Endocrinology and Metabolism Research Center (EMRC), Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences (TUMS), Tehran, Iran.

Purpose: This study aims to analyze the association between VDR gene polymorphism and the occurrence of "low bone density (LBD)/osteopenia/osteoporosis" or LBDOO in type 2 diabetes (T2D) patients among a clustered population in northwest of Iran. The studied VDR gene polymorphism included (rs7975232), (rs1544410), (rs2228570), (rs4516035) and, (rs731236).

Methods: In this population-based cross-sectional study, patients with T2D were identified within a group of 1266 participants based on self-report of diabetes, history of diabetes medication, and recorded laboratory data. Separately for each polymorphism and gender, crude and adjusted (age, BMI) odds ratios (ORs) were calculated for participants with T2D through logistic regression analysis.

Results: The prevalence of T2D was 16.41% in people residing in the city of Sanandaj in 2011. Of the participants with T2D, 13.92% and 81.29% had osteoporosis and vitamin D deficiency, respectively. In women, the genotype of the gene significantly decreased the risk of LBDOO versus the genotype, after adjusting for BMI and age (adjusted OR:0.18, CI: 0.03-0.97). Conversely, the genotype of the gene enhanced the risk of LBDOO versus the genotype (adjusted OR:7.64, CI: 2.03-28.72).

Conclusion: The polymorphism of both and genes was associated with the risk of LBDOO in women with T2D. This is the first time a study has highlighted this effect for the polymorphism of the gene; we believe that this study would serve as a basis for future studies.
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http://dx.doi.org/10.1007/s40200-021-00871-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630208PMC
December 2021

Studying the relationship between cognitive impairment and frailty phenotype: a cross-sectional analysis of the Bushehr Elderly Health (BEH) program.

J Diabetes Metab Disord 2021 Dec 6;20(2):1229-1237. Epub 2021 Jul 6.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, NO. 10, Jalale-Al- Ahmad Ave, Chamran Highway, Tehran, Iran.

Background: Some pathophysiological effects of physical frailty and cognitive impairment might be similar; therefore, finding the associations in epidemiologic studies could guide clinicians and researchers to recognize effective strategies for each type of frailty such as frailty phenotype and frailty index, which in turn will result in a preventive approach. The study aimed to reveal which components of frailty phenotype are more associated with cognitive impairment. The findings of this study may help other researchers clarify the related pathways.

Methods: This is a cross-sectional analysis of the results of the second phase of Bushehr Elderly Health Program; a community-based elderly prospective cohort study conducted in 2015-2016. The participants were selected through a multistage stratified cluster random sampling method. Frailty was assessed based on the Fried frailty phenotype criteria. Cognitive impairment was assessed by the Mini-Mental State Examination (MMSE), the Mini-Cog, and the Category Fluency Test (CFT). Multiple logistic regression models were applied to determine the association between frailty and cognitive impairment. Depression trait was assessed using the Patient Health Questionnaire-9 (PHQ-9). Activities of daily living were assessed using the Barthel Index and Instrumental Activities of Daily Living (IADLs) using Lawton's IADL.

Results: The studyp conducted among people ≥ 60 years old (N = 2336) with women consisting 51.44% of the sample group. The mean age of the participants was 69.26 years old. The prevalence of pre-frailty and frailty were 42.59% and 7.66%, respectively. In the fully adjusted model, the odds ratio of the association between pre-frailty and frailty with cognitive impairment was 1.239, 95% CI: 1.011 - 1.519 and 1.765, 95% CI: 1.071 - 2.908, respectively (adjusted for age, sex, education, body mass index, smoking, diabetes mellitus, PHQ- 9, Barthel Index, and IADLs). In the fully adjusted multiple logistic regression models, all of the components of Fried frailty phenotype were significantly related to cognitive impairment except weight loss.

Conclusion: Cognitive impairment may be associated with frailty phenotype. Moreover, low strength and function of muscles had a stronger association with cognitive impairment. It seems that a consideration of cognitive impairment assessment in older people along with frailty and vice versa in clinical settings is reasonable.
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http://dx.doi.org/10.1007/s40200-021-00847-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630203PMC
December 2021

Placenta derived Mesenchymal Stem Cells transplantation in Type 1 diabetes: preliminary report of phase 1 clinical trial.

J Diabetes Metab Disord 2021 Dec 9;20(2):1179-1189. Epub 2021 Jul 9.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute , Tehran University of Medical Sciences , Tehran, Iran.

Introduction: Type 1 Diabetes Mellitus (T1DM) is an auto immune reaction against insulin secreting beta cells. Exogenous insulin administration is the only standard treatment for T1DM. However, despite tight glycemic control many patients will develop chronic life-threatening complications. Recently, stem cell transplantation has been suggested as a novel treatment for eliminating the beta cell damage and promoting their regeneration by modulating auto-immunity. To our knowledge; this is the first preliminary report of placenta derived MSCs (PLMSCs) transplantation in juvenile T1DM.

Method: An Open label non-randomized phase 1 clinical trial was designed to evaluate the safety of PLMSCs transplantation in new onset juvenile T1DM (IRCT20171021036903N2). PLMSCs were manufactured in our clean room facility using a Xeno-free/GMP compliant protocol. The first series of patients (n = 4) received one dose of1 × 10 PLMSCs/kg intravenously. Diabetic clinical and laboratory parameters and side effects were evaluated weekly for the first month, monthly for 6 months, and then every 3 month till 1 year.

Results: Serious adverse events were not seen during 1 year follow-up. Partial remission and hypoglycemic attacks were happened one month after transplantation in two patients. ZnT8-Ab decreased till month 3 and then increased again in all patients. Anti Gad-Ab decreased till month 3 of follow up then increased.

Discussion: This preliminary report of our phase I clinical trial demonstrated the short term safety of PLMSCs transplantation in juvenile T1DM. To prove the long term safety and probable efficacy of this treatment more investigations are needed.

Trial Registration: Iranian Registry of Clinical Trials: IRCT20171021036903N2.
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http://dx.doi.org/10.1007/s40200-021-00837-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630319PMC
December 2021

Complications of illegal abortion in the suburbs of Tehran: A 9-year cross-sectional study.

J Res Med Sci 2021 18;26:89. Epub 2021 Oct 18.

Department of Medical Ethics, Tehran University of Medical Science, Tehran, Iran.

Background: Illegal abortion is a common way to terminate unintended pregnancy. It may be associated with severe complications and may raise maternal mortality and morbidity rate. Illegal abortion is one of the important concerns in health system. In our study, we consider illegal abortion claims in Medical Council court in the suburbs of Tehran.

Materials And Methods: A retrospective study was conducted. Data were extracted from registered judicial complainant cases of illegal abortion in Shahriyar medical court, Iran, during 2009-2017.

Results: There were 751 registered claims during 2009-2017. Among them, a total of 95 gynecological claims were included in the study. Four (4.2%) registered claims were illegal abortion with severe complications such as peritonitis, rupture of uterine, small intestine, rectum, and mesentery perforation. Three cases had consumed misoprostol (prostaglandin E2) and one case had used prostaglandin E1 before curettage. Misoprostol was also used significantly more frequently than other methods for abortion before curettage ( < 0.05). Minor and short-term complications did not registered.

Conclusion: The feature of claims showed that only severe morbidity and complications were registered in medical court. The definition of illegal abortion as a criminal act can be one of the factors of decreasing of abortion's complication claims.
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http://dx.doi.org/10.4103/jrms.JRMS_141_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607174PMC
October 2021

Global, regional, and national burden and quality of care index of endocarditis: the global burden of disease study 1990-2019.

Eur J Prev Cardiol 2021 Dec 13. Epub 2021 Dec 13.

Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Second floor, No. 10, Al-e-Ahmad and Chamran Highway Intersection, Tehran 1411713137, Iran.

Aims: Endocarditis accounts for significant morbidity and mortality. Timely diagnosis and prompt treatment are of paramount importance for optimal patient outcome. However, only few studies have assessed quality of care (QoC) in endocarditis. We aimed to describe QoC and changes in epidemiological features of endocarditis from 1990 to 2019.

Methods And Results: Using primary indices of mortality, incidence, years of life lost, years lived with disability, and disability-adjusted life year, obtained from the Global Burden of Disease Study 2019, we calculated four secondary measures. Principal component analysis was performed to calculate QoC index (QCI), scored on a scale of 0-100 with higher values indicating better QoC, for different locations, age groups, and genders from 1990 to 2019. The all-ages incidence rate of endocarditis was estimated to increase significantly from 1990 to 2019, while mortality rate did not change. The age-standardized QCI was 73.6% globally, with higher values in high-income countries than in low-income countries. High-income North America (82.0%) and Asia Pacific (81.1%) had the highest QCI, whereas Eastern Europe (43.3%) had the lowest. Globally, the 30-49 and 95+ age groups had the highest (91.3%) and the lowest (71.7%) QCI, respectively. In most countries, particularly those with lower socio-demographic index, women had better QCI.

Conclusion: This is the first global assessment of QCI, shedding light on the current trends and highlighting the necessity of improving the endocarditis QoC, mainly by timely case detection, adherence to antibiotic prophylaxis guidelines, utilizing targeted antibiotics and advanced treatments, in the African region and resolving gender inequality in selected countries.
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http://dx.doi.org/10.1093/eurjpc/zwab211DOI Listing
December 2021

Red flags of poor prognosis in pediatric cases of COVID-19: the first 6610 hospitalized children in Iran.

BMC Pediatr 2021 12 10;21(1):563. Epub 2021 Dec 10.

Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: COVID-19 clinical course, effective therapeutic regimen, and poor prognosis risk factors in pediatric cases are still under investigation and no approved vaccinehas been introduced for them.

Methods: This cross-sectional study evaluated different aspect of COVID-19 infection in hospitalized COVID-19 positive children (≺18 years oldwith laboratory confirmed COVID-19 infection, using the national COVID-19 registry for all admitted COVID-19 positive cases from February 19 until November 13,2020, in Iran.

Results: We evaluated 6610 hospitalized children. Fifty-four percent (3268) were male and one third of them were infants younger than 1 year. Mortality rate in total hospitalized children was 5.3% and in children with underlying co-morbidities (14.4%) was significantly higher (OR: 3.6 [2.7-4.7]). Chronic kidney disease (OR: 3.42 [1.75-6.67]), Cardiovascular diseases (OR: 3.2 [2.09-5.11]), chronic pulmonary diseases (OR: 3.21 [1.59-6.47]), and diabetes mellitus (OR: 2.5 [1.38-4.55]), resulted in higher mortality rates in hospitalized COVID-19 children. Fever (41%), cough (36%), and dyspnea (27%) were the most frequent symptoms in hospitalized children and dyspnea was associated with near three times higher mortality rate among children with COVID-19 infection (OR: 2.65 [2.13-3.29]).

Conclusion: Iran has relatively high COVID-19 mortality in hospitalized children. Pediatricians should consider children presenting with dyspnea, infants≺ 1 year and children with underlying co-morbidities, as high-risk groups for hospitalization, ICU admission, and death.
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http://dx.doi.org/10.1186/s12887-021-03030-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8660655PMC
December 2021

Annual incidence of osteoporotic hip fractures in Iran: a systematic review and meta-analysis.

BMC Geriatr 2021 11 30;21(1):668. Epub 2021 Nov 30.

Osteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Osteoporosis (OP) is progressively becoming a global concern with the aging of the world's populations. Osteoporotic fractures are associated with significantly increased mortality rates and a financial burden to health systems. This Meta-analysis aims to estimate the annual incidence of osteoporotic fractures in Iran.

Methods: A comprehensive systematic literature search was performed through Medline (PubMed), Embase, Scopus, Web of Science, and Google Scholar to identify studies which contain an investigation of the incidence of osteoporotic fractures in Iran up to December 3rd 2020, with no time and language restriction. For the risk of bias assessments of studies, the Joanna Briggs Institute (JBI) critical appraisal checklist for studies reporting prevalence data was used. The pooled estimation of the incidence of osteoporotic fractures in population aged≥50 years was calculated using random-effects meta-analysis, and the heterogeneity of included studies was quantified with the I statistic.

Results: In all, 6708 papers were initially retrieved from the electronic databases, among which seven studies were included in the meta-analysis. The pooled standardized annual cumulative incidence of hip fractures was estimated as 138.26 (95% CI: 98.71-193.65) per 100,000 population and 157.52 (95% CI: 124.29-199.64) per 100,000 population in men and women, respectively.

Conclusion: This study showed a high incidence rate of osteoporotic hip fractures in Iran. Early detection and treatment of individuals with higher risks of primary fragility fractures at primary health care as well as implementing fracture liaison services to prevent secondary fractures are highly recommended. The results suffer from the following limitations: first, a low number of studies that were eligible for inclusion; second, the lack of population-based studies; and presence of highly heterogeneous studies despite the use of a random effect model.
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http://dx.doi.org/10.1186/s12877-021-02603-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638533PMC
November 2021

Proto-Oncogene Mutational Analysis in 45 Iranian Patients Affected with Medullary Thyroid Carcinoma: Report of a New Variant.

J Thyroid Res 2021 3;2021:7250870. Epub 2021 Nov 3.

Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background: The aim of this study was to identify germline mutation of the (rearranged during transfection) gene in patients with medullary thyroid carcinoma (MTC) and their first-degree relatives to find presymptomatic carriers for possible prophylactic thyroidectomy. . We examined all six hot spot exons (exons 10, 11, 13, and 14-16) of the gene by PCR and bidirectional Sanger sequencing in 45 Iranian patients with MTC (either sporadic or familial form) from 7 unrelated kindred and 38 apparently sporadic cases. First-degree relatives of positive cases were also genotyped for index mutation. Moreover, presymptomatic carriers were referred to the endocrinologist for further clinical management and prophylactic thyroidectomy if needed.

Results: Overall, the genetic status of all of the participants was determined by mutation screening, including 61 affected individuals, 22 presymptomatic carriers, and 29 genetically healthy subjects. In 37.5% (17 of 45) of the MTC referral index patients, 8 distinct germline mutations were found, including p.C634R (35.3%), p.M918T (17.6%), p.C634Y (11.8%), p.C634F (5.9%), p.C611Y (5.9%), p.C618R (5.9%), p.C630R (5.9%), p.L790F (5.9%), and one uncertain variant p.V648I (5.9%). Also, we found a novel variant p.H648R in one of our apparently sporadic patients.

Conclusion: mutation detection is a promising/golden screening test and provides an accurate presymptomatic diagnostic test for at-risk carriers (the siblings and offspring of the patients) to consider prophylactic thyroidectomy. Thus, according to the ATA recommendations, the screening of the proto-oncogene is indicated for patients with MTC.
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http://dx.doi.org/10.1155/2021/7250870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580628PMC
November 2021

Characteristics of published/registered clinical trials on COVID-19 treatment: A systematic review.

Daru 2021 Dec 11;29(2):449-467. Epub 2021 Nov 11.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Objectives: Due to the rapid spread of COVID-19 worldwide, many countries have designed clinical trials to find efficient treatments. We aimed to critically report the characteristics of all the registered and published randomized clinical trials (RCTs) conducted on COVID-19, and summarize the evaluation of potential therapies developed in various regions.

Evidence Acquisition: We comprehensively searched PubMed, Cochrane Library, Web of Science, Scopus, and Clinicaltrial.gov databases to retrieve all the relevant studies up to July 19, 2021, in conformity with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart. We included all English-language published/registered RCTs on COVID-19, and excluded non-RCT, in-vitro/in-vivo, editorials, and review studies. Two reviewers independently evaluated all the records, and then analyzed by using SPSS 17.

Results: Within 3018 included studies, 2801 (92.8%) and 217 (7.2%) were registered or published RCTs consisting of about 600 synthetic drugs. Herbal medicines have been studied in 23 trials (10.6%) among the published RCTs and in 357 registered RCTs (12.7%). Hydroxychloroquine 23 (10.6%) and convalescent plasma 194 (6.9%) alone or in combination with other agents were the most frequently used interventions in published and registered RCTs, respectively. Most published RCTs have been conducted in Western Pacific Region (WPRO) (50 trials, 23.0%) including 45 trials from China. Also, a greater proportion of registered RCTs have been conducted in the Region of the Americas (PAHO) (885 trials, 31.6%) including 596 RCTs from the United States (U.S). Globally, 283 registered trials have been conducted to assess new developed vaccines for COVID or previously established for other disorders.

Conclusion: The present study highlighted the wide range of potential therapeutic agents in published and registered COVID-19 clinical trials across a wide range of regions. However, it is urgently required to global coordination in order to conduct more well-designed trials and progress in discovering safe and effective treatments.
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http://dx.doi.org/10.1007/s40199-021-00422-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581284PMC
December 2021

Recent Advances of COVID-19 Modeling Based on Regenerative Medicine.

Front Cell Dev Biol 2021 25;9:683619. Epub 2021 Oct 25.

Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has caused a pandemic since December 2019 that originated in Wuhan, China. Soon after that, the world health organization declared Coronavirus disease-2019 a global health concern. SARS-CoV-2 is responsible for a lethal respiratory infection as well as the involvement of other organs due to its large tropism spectrum such as neurologic, cardiovascular, endocrine, gastrointestinal, and renal systems. Since the behavior of the virus is not fully understood, a new manifestation of the infection is revealed every day. In order to be able to design more efficient drugs and vaccines to treat the infection, finding out the exact mechanism of pathogenicity would be necessary. Although there have been some big steps toward understanding the relevant process, there are still some deficiencies in this field. Accordingly, regenerative medicine (RM), can offer promising opportunities in discovering the exact mechanisms and specific treatments. For instance, since it is not always possible to catch the pathophysiology mechanisms in human beings, several modeling methods have been introduced in this field that can be studied in three main groups: stem cell-based models, organoids, and animal models. Regarding stem cell-based models, induced pluripotent stem cells are the major study subjects, which are generated by reprogramming the somatic stem cells and then directing them into different adult cell populations to study their behavior toward the infection. In organoid models, different cell lines can be guided to produce a 3D structure including liver, heart, and brain-like platforms. Among animal models, mice are the most common species in this field. However, in order for mice models to be permissive to the virus, angiotensin-converting enzyme 2 receptors, the main receptor involved in the pathogenicity of the virus, should be introduced to the host cells through different methods. Here, the current known mechanism of SARS-CoV-2 infection, different suggested models, the specific response toward different manipulation as well as challenges and shortcomings in each case have been reviewed. Finally, we have tried to provide a quick summary of the present available RM-based models for SARS-CoV-2 infection, as an essential part of developing drugs, for future therapeutic goals.
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http://dx.doi.org/10.3389/fcell.2021.683619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573217PMC
October 2021

Potential for Stem Cell-Based Therapy in the Road of Treatment for Neurological Disorders Secondary to COVID-19.

Regen Eng Transl Med 2021 Oct 29:1-15. Epub 2021 Oct 29.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Abstract: The severe acute respiratory syndrome coronavirus 2 has led to the worldwide pandemic named coronavirus disease 2019 (COVID-19). It has caused a significant increase in the number of cases and mortalities since its first diagnosis in December 2019. Although COVID-19 primarily affects the respiratory system, neurological involvement of the central and peripheral nervous system has been also reported. Herein, the higher risk of neurodegenerative diseases in COVID-19 patients in future is also imaginable. Neurological complications of COVID-19 infection are more commonly seen in severely ill individuals; but, earlier diagnosis and treatment can lead to better long-lasting results. In this respect, stem cell biotechnologies with considerable self-renewal and differentiation capacities have experienced great progress in the field of neurological disorders whether in finding out their underlying processes or proving them promising therapeutic approaches. Herein, many neurological disorders have been found to benefit from stem cell medicine strategies. Accordingly, in the present review, the authors are trying to discuss stem cell-based biotechnologies as promising therapeutic options for neurological disorders secondary to COVID-19 infection through reviewing neurological manifestations of COVID-19 and current stem cell-based biotechnologies for neurological disorders.

Lay Summary: Due to the substantial burden of neurological disorders in the health, economic, and social system of society, the emergence of neurological manifestations following COVID-19 (as a life-threatening pandemic) creates the need to use efficient and modern methods of treatment. Since stem cell-based methods have been efficient for a large number of neurological diseases, it seems that the use of mentioned methods is also effective in the process of improving neurological disorders caused by COVID-19. Hereupon, the current review aims to address stem cell-based approaches as treatments showing promise to neurological disorders related to COVID-19.
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http://dx.doi.org/10.1007/s40883-021-00234-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555723PMC
October 2021

Metabolomics Signatures of SARS-CoV-2 Infection.

Adv Exp Med Biol 2021 Nov 5. Epub 2021 Nov 5.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical sciences, Tehran, Iran.

For a very long time, viral infections have been considered as one of the most important causes of death and disability around the world. Through the viral infection, viruses as small pathogens enter the host cells and use hosts' biosynthesis machinery to replicate and collect infectious lineages. Moreover, they can modify hosts' metabolic pathways in order to their own purposes. Nowadays (in 2019-2020), the most famous type of viral infection which was caused by a novel type of coronavirus is called COVID-19 disease. It has claimed the lives of many people around the world and is a very serious threat to health. Since investigations of the effects of viruses on host metabolism using metabolomics tools may have given focuses on novel appropriate treatments, in the current review the authors highlighted the virus-host metabolic interactions and metabolomics perspective in COVID-19.
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http://dx.doi.org/10.1007/5584_2021_674DOI Listing
November 2021

COVID-19 in patients with diabetes: factors associated with worse outcomes.

J Diabetes Metab Disord 2021 Oct 28:1-10. Epub 2021 Oct 28.

Present Address: Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Purpose: Diabetes is one of the major comorbidities associated with COVID-19. We aimed to determine the clinical and epidemiological factors associated with the mortality of COVID-19 in diabetic patients in Iran, and also the impact of prescribed antiviral and antibiotics on patients' status.

Methods: In this study, we used the national registry of hospitalized patients with Severe Acute Respiratory Syndrome (SARS) Symptoms with diabetes from February 18, 2020, to December 22, 2020. Demographic, clinical features, treatments, concurrent comorbidities, and their associations with mortality and severity outcomes were assessed using logistic regression.

Results: 78,554 diabetic in-patients with SARS symptoms were included from 31 provinces of whom 37,338 were PCR positive for COVID-19. Older age and male gender are associated with COVID-19 mortality in diabetic patients. CVD is the most frequent comorbidity (42%). CVD, kidney disease, liver disease, and COPD are associated comorbidities which increased the risk of mortality. The mortality rate is higher in diabetic patients comparing to patients with no comorbidities, particularly in younger age groups. The frequency of antiviral, and antibiotics in COVID-19 positive patients was 34%, and 31%, respectively. Antibiotic treatment has no association with mortality in COVID-19 patients.

Conclusions: Diabetic patients indicate higher mortality comparing to patients without any underlying comorbidities. Restrict strategies on increasing effective health care utilization must be considered in diabetic patients, especially in those with parallel underlying comorbidities. Regarding the antibiotic resistance issue and the noticeable use of antibiotics in diabetic patients, it is recommended to prioritize an antibiotic guideline prescription in COVID-19 patients for better stewardship by countries.
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http://dx.doi.org/10.1007/s40200-021-00910-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553287PMC
October 2021

The effect of walnut consumption on cardiometabolic profiles of individuals with abnormal glucose homoeostasis: a systematic review and meta-analysis of clinical trials.

Br J Nutr 2021 Nov 2:1-13. Epub 2021 Nov 2.

Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

Findings on the effect of walnut consumption on cardiometabolic profiles in individuals with abnormal glucose homoeostasis are conflicting. We summarised earlier data in this regard. A systematic literature search of relevant reports published in Medline/PubMed, ISI web of Science, EMBASE, SCOPUS and Google Scholar up to October 2020 was conducted. Randomised trials that enrolled individuals with abnormal glucose homoeostasis in which the main intervention was walnut consumption were included. Abnormal glucose homoeostasis was defined as a spectrum of impaired glucose tolerance or pre-diabetic status that is associated with insulin resistance. Twelve studies were included in systematic review and eight in meta-analysis. No significant effect of walnut consumption on anthropometric measures, including weighted mean difference (WMD: -0·13; 95 % CI -0·64, 0·39 kg), BMI (-0·08; 95 % CI -0·47, 0·32 kg/m2) and waist circumference (0·01; 95 % CI -0·50, 0·52 cm) was observed. Although walnut intake did not influence on lipid profiles (including TAG, total- and HDL-cholesterol levels), individuals in the intervention group tended to have lower levels of LDL-cholesterol than those in the control group (-0·10; 95 % CI -0·20, 0·01 mmol/l; P = 0·06). Other cardiometabolic factors including markers of glycaemic control (fasting blood glucose and HbA1C levels), blood pressure and stimulus-adjusted response measure (a parameter of endothelial function) were not significantly affected. However, walnut consumption resulted in a significant increase in flow-mediated dilation (FMD) (0·93 %; 95 % CI 0·16, 1·71 %). Summarising earlier evidence, we found that walnut consumption might influence FMD and LDL-cholesterol levels in individuals with abnormal glucose homoeostasis. It did not affect other cardiometabolic profiles in these individuals.
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http://dx.doi.org/10.1017/S0007114521004414DOI Listing
November 2021
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