Publications by authors named "Reza Malekzadeh"

546 Publications

Cost-effectiveness analysis of two routine therapeutic methods for eradication: a Persian cohort-based study.

Gastroenterol Hepatol Bed Bench 2021 ;14(3):250-259

Digestive Diseases Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.

Aim: This study aimed to analyze the cost-effectiveness of two routine therapeutic methods for eradication in Iran.

Background: Because of the importance of eradication on gastric cancer prevalence and costs, an economic analysis of the eradication methods is essential for health systems.

Methods: This cross-sectional study was conducted on 7,496 participants with positive Hepadnaviridae (HPsAg) test results for ; 6,163 of them were treated with furazolidone (group A), and 1,333 participants were treated with clarithromycin (group B). Data on GP visits, medications, and HPsAg costs as direct costs and absence from work and transportation as indirect costs was collected by researcher-made questionnaire. Indirect costs were calculated based on face-to-face interviews with 365 patients of the Persian Cohort Center. Successful eradication of infection (negative HPsAg) was defined as the effectiveness of the interventions. Incremental cost-effectiveness ratio (ICER) was used to compare the overall results.

Results: The total direct cost of for groups A and B were estimated at 13.7 and 5.83 billion IRR, respectively. The highest and lowest percentages of total costs were the cost of diagnostic services and the time cost, respectively. There was a significant difference between the two groups in drug costs (<0.001). The effect ratio for groups A and B was 85.93% and 96.54%, respectively. Cost per effectiveness was higher for clarithromycin (CE=3,250,170 IRR) than for furazolidone (CE=2,988,488 IRR), and ICER showed that 5.1 Million IRR per participant is needed to eradicate .

Conclusion: Based on the results, furazolidone was more cost-effective than clarithromycin for treatment. Therefore, due to the high prevalence of and the economic conditions of the health system in Iran, furazolidone can be a cost-effective choice between the two conventional treatment methods considering the results of further research and possible side effects.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245840PMC
January 2021

Levels and Trends of BMI, Obesity, and Overweight at National and Sub-national Levels in Iran from 1990 to 2016; A Comprehensive Pooled Analysis of Half a Million Individuals.

Arch Iran Med 2021 May 1;24(5):344-353. Epub 2021 May 1.

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

Background: In developing countries like Iran, the burden of obesity increases through comorbid diseases. We estimated the mean body mass index (BMI) and prevalence of overweight/obesity by components of sex, age, province, and year in Iran from 1990 to 2016.

Methods: Through a comprehensive systematic review, all relevant data sources pooled results with individual level national and sub-national population-based studies. Two stages of age-spatio-temporal modeling and Gaussian process regression were used to estimate mean BMI, followed by estimation of obesity and overweight prevalence through the crosswalk modeling.

Results: In 2016, the age-standardized mean BMI was 27.9 (27.2-28.7) kg/m² in women and 25.9 (25.2-26.5) kg/m² in men. At the same time, the prevalence rates of overweight and obesity were 71.7% (67.9-75.8), and 36.8% (34.1-39.7) in females, and 57.1% (53.7-60.6), and 18.4% (16.9-20) in men. This shows a considerable increase from 1990 when the figures were respectively 24.4 (23.3-25.5) , 36.6% (32.2-41.5), and 8.2% (95% UI: 6.9-9.7) in women, and 23.5 (22.5-24.5), 30% (26.4-34), and 4.7% (4.0-5.5) in men, with 66% attributed to population growth.

Conclusion: Considering the increasing trends of BMI, Sustainable Development Goals (SDGs) seem far out of reach. We need to call for action, aiming for both weight loss strategies and controlling the comorbidities that mediate high BMI risk.
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http://dx.doi.org/10.34172/aim.2021.51DOI Listing
May 2021

Levels and Trends of Hypertension at National and Subnational Scale in Iran from 1990 to 2016: A Systematic Review and Pooled Analysis.

Arch Iran Med 2021 Apr 1;24(4):306-316. Epub 2021 Apr 1.

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

Background: Raised blood pressure is a serious risk factor for several non-communicable diseases (NCDs) in Iran. In this study, we aimed to estimate the mean of systolic blood pressure (SBP) and diastolic blood pressure (DBP) and subsequently, the prevalence of hypertension by sex, age, province, and year in Iran.

Methods: We conducted a systematic review using PubMed, Web of Science, and Scopus databases through December 2017. We also used individual level data from eight national surveys, aggregated data from seven subnational population-based studies, and extracted data reported in 52 published studies. We used a two-stage model including Age-Spatio-Temporal and Gaussian process regression (GPR) to estimate mean systolic and diastolic blood pressure and used a crosswalk model to estimate the prevalence of hypertension by sex, age, province, and year.

Results: The number of hypertensive adults increased in Iran from 1.8 million (882 thousand in women) in 1990 to 13.6 million (7.2 million in women) in 2016. The national age-standardized prevalence of hypertension increased from 8.7% (7.8-9.7) to 28.8% (27.7-30.0) in women and from 8.0% (7.2-8.9) to 24.2% (23.1-25.3) in men from 1990 to 2016. Mean systolic and diastolic blood pressures show a similar increasing trend.

Conclusion: During the past 27 years, we observed an increase in the age-standardized prevalence and mean levels of blood pressure. If the current trend in levels of blood pressure and prevalence of hypertension continue in the coming years, Iran will not achieve the sixth target of the Global Action Plan by 2020 and the Sustainable Development Goals (SDGs) by 2030.
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http://dx.doi.org/10.34172/aim.2021.43DOI Listing
April 2021

Oral Health Status in the Pars Cohort Study.

Arch Iran Med 2021 Apr 1;24(4):273-279. Epub 2021 Apr 1.

Non-Communicable Disease Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Poor oral health is common in the world, especially in low-income and developing countries. We evaluated oral health status and its association with sociodemographic and economic variables in one of the largest cohort studies in Iran.

Methods: This cross-sectional study was conducted using data from the Pars Cohort Study which is conducted in a rural area in southern Iran. A total of 9264 individuals were enrolled in the initial registry. Data on sociodemographic and clinical characteristics were collected. Oral assessment was completed by trained physicians. Generalized negative binomial regression modeling was applied.

Results: Overall, data from 9264 participants entered the final analysis. The participants' mean age was 52.6 ± 9.7 years. In total, 8975 participants (96.8%) had at least one tooth loss and 1790 participants (19.3%) were edentulous. Female gender (incidence rate ratio [IRR]: 1.05, 95% CI: 1.02, 1.08) (IRR: 1.12, 95% CI: 1.07, 1.16), opium consumption (IRR: 1.17, 95% CI: 1.12, 1.22) (IRR: 1.23, 95% CI: 1.16 1.30), lower socioeconomic status (SES) (IRR: 1.07, 95% CI: 1.03, 1.10) (IRR: 1.10, 95% CI: 1.06, 1.15) and being illiterate (IRR: 1.23, 95% CI: 1.20, 1.26) (IRR: 1.36, 95% CI: 1.32, 1.41) were associated with higher decayed, missing and filled teeth (DMFT) and more tooth loss.

Conclusion: Oral health was poor in our study sample, especially among older individuals, people with lower SES, illiterate participants, smokers and opiate consumers, which shows the need for improvement in oral health care.
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http://dx.doi.org/10.34172/aim.2021.38DOI Listing
April 2021

Targeted Deep Sequencing of Cell-Free DNA in Esophageal Squamous Cell Carcinoma Using Low-Quality Serum: Concordance with Tumor Mutation.

Int J Mol Sci 2021 May 26;22(11). Epub 2021 May 26.

Genomic Epidemiology Branch, International Agency for Research on Cancer/World Health Organization (IARC/WHO), 69000 Lyon, France.

Circulating cell-free DNA (cfDNA) is emerging as a potential tumor biomarker. CfDNA-based biomarkers may be applicable in tumors without an available non-invasive screening method among at-risk populations. Esophageal squamous cell carcinoma (ESCC) and residents of the Asian cancer belt are examples of those malignancies and populations. Previous epidemiological studies using cfDNA have pointed to the need for high volumes of good quality plasma (i.e., >1 mL plasma with 0 or 1 cycles of freeze-thaw) rather than archival serum, which is often the main available source of cfDNA in retrospective studies. Here, we have investigated the concordance of mutations in tumor tissue and cfDNA extracted from archival serum left-over from 42 cases and 39 matched controls (age, gender, residence) in a high-risk area of Northern Iran (Golestan). Deep sequencing of coding regions was complemented with a specialized variant caller (Needlestack). Overall, 23% to 31% of mutations were concordantly detected in tumor and serum cfDNA (based on two false discovery rate thresholds). Concordance was positively correlated with high cfDNA concentration, smoking history (-value = 0.02) and mutations with a high potential of neoantigen formation (OR; 95%CI = 1.9 (1.11-3.29)), suggesting that tumor DNA release in the bloodstream might reflect the effects of immune and inflammatory context on tumor cell turnover. We identified mutations in five controls, one of whom was subsequently diagnosed with ESCC. Overall, the results showed that cfDNA mutations can be reliably identified by deep sequencing of archival serum, with a rate of success comparable to plasma. Nonetheless, 70% non-identifiable mutations among cancer patients and 12% mutation detection in controls are the main challenges in applying cfDNA to detect tumor-related variants when blindly targeting whole coding regions of the gene in ESCC.
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http://dx.doi.org/10.3390/ijms22115627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197963PMC
May 2021

International Scientific Collaboration Is Needed to Bridge Science to Society: USERN2020 Consensus Statement.

SN Compr Clin Med 2021 May 11:1-5. Epub 2021 May 11.

http://usern.org.

Scientific collaboration has been a critical aspect of the development of all fields of science, particularly clinical medicine. It is well understood that myriads of benefits can be yielded by interdisciplinary and international collaboration. For instance, our rapidly growing knowledge on COVID-19 and vaccine development could not be attained without expanded collaborative activities. However, achieving fruitful results requires mastering specific tactics in collaborative efforts. These activities can enhance our knowledge, which ultimately benefits society. In addition to tackling the issue of the invisible border between different countries, institutes, and disciplines, the border between the scientific community and society needs to be addressed as well. International and transdisciplinary approaches can potentially be the best solution for bridging science and society. The Universal Scientific Education and Research Network (USERN) is a non-governmental, non-profit organization and network to promote professional, scientific research and education worldwide. The fifth annual congress of USERN was held in Tehran, Iran, in a hybrid manner on November 7-10, 2020, with key aims of bridging science to society and facilitating borderless science. Among speakers of the congress, a group of top scientists unanimously agreed on The USERN 2020 consensus, which is drafted with the goal of connecting society with scientific scholars and facilitating international and interdisciplinary scientific activities in all fields, including clinical medicine.
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http://dx.doi.org/10.1007/s42399-021-00896-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111052PMC
May 2021

An intervention to increase hepatitis C virus diagnosis and treatment uptake among people in custody in Iran.

Int J Drug Policy 2021 May 12;95:103269. Epub 2021 May 12.

Digestive Oncology Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background: Iran is among countries with high opioid agonist therapy (OAT) coverage in prisons, which provides an infrastructure to increase feasibility of HCV programs. We aimed to evaluate the impact of an intervention to improve HCV screening, diagnosis, and treatment, including alongside the provision of OAT, in an Iranian prison.

Methods: During July-December 2018, in the Gorgan prison, all incarcerated adults (>18 years) received HCV antibody rapid testing and, if positive, provided a venepuncture sample for HCV RNA testing. Participants with positive RNA received direct-acting antiviral (DAA) therapy [(Sofosbuvir/Daclatasvir) for 24 or 12 weeks, respectively, for those with and without cirrhosis]. Response to treatment was measured by the sustained virological response at 12 weeks post-treatment (SVR12).

Results: Among 2015 incarcerated people with a median age of 35 years (IQR:29-41), the majority were male (97%), had not finished high school (68%), and had a history of drug use (71%), of whom 15% had ever injected drugs. A third of participants were receiving OAT, including 54% of those who had ever injected. HCV antibody prevalence was 6.7%, and RNA was detected in 4.6% of all participants; this prevalence was 32.6% and 24.7% among those with a history of injection, respectively. Treatment uptake was 82% (75/92) and was similar among people on OAT and those with a history of injection (81%). The majority completed treatment in prison and were available for SVR12 assessment (71%, 53/75). Achieved SVR12 was 100% (53/53) based on the available case analysis; those who did not have available SVR12 were released either prior to treatment initiation or completion (n = 39).

Conclusion: The availability of OAT infrastructure should be considered as an opportunity for enhancing HCV care in prisons. Where resources are limited, the prison harm reduction network could be used to design targeted HCV programs among people who are at higher risk of infection.
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http://dx.doi.org/10.1016/j.drugpo.2021.103269DOI Listing
May 2021

Exploring the interactions between Helicobacter pylori (Hp) infection and other risk factors of gastric cancer: A pooled analysis in the Stomach cancer Pooling (StoP) Project.

Int J Cancer 2021 Sep 24;149(6):1228-1238. Epub 2021 May 24.

Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

Helicobacter pylori (Hp) is crucial in gastric carcinogenesis, but infection alone is not a sufficient cause, and the interaction between Hp infection and other risk factors has not been adequately studied. We conducted a pooled analysis of seven case-control studies from the Stomach cancer Pooling (StoP) Project, comprising 1377 cases and 2470 controls, to explore the interaction among Hp infection and tobacco smoking, alcohol drinking, socioeconomic status (SES) and dietary salt intake on the risk of gastric cancer. We estimated summary odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) by multivariate unconditional logistic regression. The analysis showed no consistent interaction between Hp infection and cigarette smoking, while interaction was more than multiplicative for alcohol drinking (OR = 1.38, 95% CI: 1.07-1.77, P-interaction 0.02) and high intake of salt (OR = 2.62, 95% CI: 1.88-3.65, P-interaction = 0.04). The interaction with SES followed the multiplicative model (P = 0.49), resulting in a weakening among infected individuals of the protective effect of high SES among observed Hp-negative individuals. The interactions found were more pronounced in subjects with history of peptic ulcer. The interactions with Hp infection were stronger for cigarette smoking and dietary salt in the case of noncardia cancer, and for alcohol and SES in the case of cardia cancer. No differences were found when stratifying for histologic type. This large-scale study aimed to quantify the interaction between Hp infection and other modifiable risk factors of gastric cancer revealed that the benefit of combined Hp eradication and lifestyle modification on gastric cancer prevention may be larger than commonly appreciated.
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http://dx.doi.org/10.1002/ijc.33678DOI Listing
September 2021

Single-pill sofosbuvir and daclatasvir for treating hepatis C in patients co-infected with human immunodeficiency virus.

Int J Clin Pract 2021 Aug 17;75(8):e14304. Epub 2021 May 17.

Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: The current recommendation for treating hepatitis C virus (HCV) in HIV patients includes the combination of sofosbuvir (SOF) and daclatasvir (DCV). DCV should be used at different doses to compensate for interactions with antiretroviral therapy (ART). Up to three pills a day might be required which will significantly add to the pill burden of these patients. In this study, we have used a single-tablet approach to treating HCV-HIV coinfection.

Methods: Patients coinfected with HIV and HCV were prospectively enrolled from 10 centers throughout the country. Patients received a single once-daily fixed dose combination (FDC) pill containing 400 mg SOF and 30, 60 or 90 mg DCV depending on the type of ART they were receiving for 12 or 24 weeks. (ClinicalTrials.gov ID: NCT03369327).

Results: Two hundred thirty-three patients were enrolled from 10 centers. Twenty-three patients were lost to follow-up and two patients died from causes unrelated to treatment. Two hundred eight patients completed the treatment course of which 201 achieved SVR (96.6%).

Conclusion: Single-tablet combination of DCV and SOF is an effective and safe treatment for patients coinfected with HIV and HCV. The combination works well in patients on ART in which dose adjustment is required. Patients with cirrhosis, previous treatment failure and various genotypes respond identically. The expenses of genotyping can be saved.
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http://dx.doi.org/10.1111/ijcp.14304DOI Listing
August 2021

Heterogeneity of Associations between Total and Types of Fish Intake and the Incidence of Type 2 Diabetes: Federated Meta-Analysis of 28 Prospective Studies Including 956,122 Participants.

Nutrients 2021 Apr 7;13(4). Epub 2021 Apr 7.

Postgraduate Program in Epidemiology Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil.

The association between fish consumption and new-onset type 2 diabetes is inconsistent and differs according to geographical location. We examined the association between the total and types of fish consumption and type 2 diabetes using individual participant data from 28 prospective cohort studies from the Americas (6), Europe (15), the Western Pacific (6), and the Eastern Mediterranean (1) comprising 956,122 participants and 48,084 cases of incident type 2 diabetes. Incidence rate ratios (IRRs) for associations of total fish, shellfish, fatty, lean, fried, freshwater, and saltwater fish intake and type 2 diabetes were derived for each study, adjusting for a consistent set of confounders and combined across studies using random-effects meta-analysis. We stratified all analyses by sex due to observed interaction ( = 0.002) on the association between fish and type 2 diabetes. In women, for each 100 g/week higher intake the IRRs (95% CIs) of type 2 diabetes were 1.02 (1.01-1.03, = 61%) for total fish, 1.04 (1.01-1.07, = 46%) for fatty fish, and 1.02 (1.00-1.04, = 33%) for lean fish. In men, all associations were null. In women, we observed variation by geographical location: IRRs for total fish were 1.03 (1.02-1.04, = 0%) in the Americas and null in other regions. In conclusion, we found evidence of a neutral association between total fish intake and type 2 diabetes in men, but there was a modest positive association among women with heterogeneity across studies, which was partly explained by geographical location and types of fish intake. Future research should investigate the role of cooking methods, accompanying foods and environmental pollutants, but meanwhile, existing dietary regional, national, or international guidelines should continue to guide fish consumption within overall healthy dietary patterns.
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http://dx.doi.org/10.3390/nu13041223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068031PMC
April 2021

Cancer in Iran 2008 to 2025: Recent incidence trends and short-term predictions of the future burden.

Int J Cancer 2021 Aug 21;149(3):594-605. Epub 2021 Apr 21.

Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran.

Policymakers require estimates of the future number of cancer patients in order to allocate finite resources to cancer prevention, treatment and palliative care. We examine recent cancer incidence trends in Iran and present predicted incidence rates and new cases for the entire country for the year 2025. We developed a method for approximating population-based incidence from the pathology-based data series available nationally for the years 2008 to 2013, and augmented this with data from the Iranian National Population-based Cancer Registry (INPCR) for the years 2014 to 2016. We fitted time-linear age-period models to the recent incidence trends to quantify the future cancer incidence burden to the year 2025, delineating the contribution of changes due to risk and those due to demographic change. The number of new cancer cases is predicted to increase in Iran from 112 000 recorded cases in 2016 to an estimated 160 000 in 2025, a 42.6% increase, of which 13.9% and 28.7% were attributed to changes in risk and population structure, respectively. In terms of specific cancers, the greatest increases in cases are predicted for thyroid (113.8%), prostate (66.7%), female breast (63.0%) and colorectal cancer (54.1%). Breast, colorectal and stomach cancers were the most common cancers in Iran in 2016 and are predicted to remain the leading cancers nationally in 2025. The increasing trends in incidence of most common cancers in Iran reinforce the need for the tailored design and implementation of effective national cancer control programs across the country.
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http://dx.doi.org/10.1002/ijc.33574DOI Listing
August 2021

Main Approaches to Enhance Radiosensitization in Cancer Cells by Nanoparticles: A Systematic Review.

Adv Pharm Bull 2021 Feb 13;11(2):212-223. Epub 2020 Jul 13.

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

In recent years, high atomic number nanoparticles (NPs) have emerged as promising radio-enhancer agents for cancer radiation therapy due to their unique properties. Multi-disciplinary studies have demonstrated the potential of NPs-based radio-sensitizers to improve cancer therapy and tumor control at cellular and molecular levels. However, studies have shown that the dose enhancement effect of the NPs depends on the beam energy, NPs type, NPs size, NPs concentration, cell lines, and NPs delivery system. It has been believed that radiation dose enhancement of NPs is due to the three main mechanisms, but the results of some simulation studies failed to comply well with the experimental findings. Thus, this study aimed to quantitatively evaluate the physical, chemical, and biological factors of the NPs. An organized search of PubMed/Medline, Embase, ProQuest, Scopus, Cochrane and Google Scholar was performed. In total, 77 articles were thoroughly reviewed and analyzed. The studies investigated 44 different cell lines through 70 and 4 studies. A total of 32 different types of single or core-shell NPs in different sizes and concentrations have been used in the studies.
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http://dx.doi.org/10.34172/apb.2021.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046397PMC
February 2021

SARS-CoV-2 outbreak in Iran: The dynamics of the epidemic and evidence on two independent introductions.

Transbound Emerg Dis 2021 Apr 9. Epub 2021 Apr 9.

Department of Laboratory Sciences, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

The SARS-CoV-2 virus has been rapidly spreading globally since December 2019, triggering a pandemic, soon after its emergence. While Iran was among the first countries confronted with rapid spread of virus in February 2020, no real-time SARS-CoV-2 whole-genome tracking in early phase of outbreak was performed in the country. To address this issue, we provided 50 whole-genome sequences of viral isolates ascertained from different geographical locations in Iran during March-July 2020. The corresponding analysis on origins, transmission dynamics and genetic diversity of SARS-CoV-2 virus, represented at least two introductions of the virus into the country, constructing two major clusters defined as B.4 and B.1*. The first entry of the virus might have occurred around very late 2019/early 2020, as suggested by the time to the most recent common ancestor, followed by a rapid community transmission that led to dominancy of B.4 lineage in early epidemic till the end of June. Gradually, reduction in dominancy of B.4 occurred possibly as a result of other entries of the virus, followed by surge of B.1* lineages, as of mid-May. Remarkably, variation tracking of the virus indicated the increase in frequency of D614G mutation, along with B.1* lineages, which showed continuity till October 2020. The increase in frequency of D614G mutation and B.1* lineages from mid-May onwards predicts a rapid viral transmission that may push the country into a critical health situation followed by a considerable change in composition of viral lineages circulating in the country.
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http://dx.doi.org/10.1111/tbed.14104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251331PMC
April 2021

Obesity and incident gastrointestinal cancers: overall body size or central obesity measures, which factor matters?

Eur J Cancer Prev 2021 May;30(3):267-274

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

BMI does not reflect the location or amount of body fat. We aimed to investigate the role of general and central obesity measures in the prediction of incident gastrointestinal cancers. In this analysis of the Golestan Cohort Study, we included 47 586 cancer-free individuals followed for 12.3 years (IQR: 10.5-13.2). We investigated the association of obesity measures including BMI, waist circumference and waist-to-hip ratio (WHR) at enrollment and the incidence of esophageal, gastric, colorectal and pancreatic cancers. Cox proportional hazard models were used to estimate the association between covariates and gastrointestinal cancer risk. We observed no significant associations between obesity measures and incidence of the above-mentioned gastrointestinal cancers in men. In women, BMI, waist circumference and WHR were associated with significant reductions in the risk of esophageal squamous cell carcinoma (ESCC): hazard ratio (HR): 0.67 [95% confidence interval (CI): 0.56-0.81], HR: 0.71 (95% CI: 0.60-0.84) and HR: 0.80 (95% CI: 0.68- 0.94), respectively. In addition, WHR was associated with significantly increased risks for colorectal cancer (HR: 1.39, 95% CI: 1.08-1.78) and gastric cancer (HR: 1.24, 95% CI: 1.01-1.51) in women. In this study, statistically significant associations between obesity measures and incident esophageal, gastric and colorectal cancers were seen in women.
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http://dx.doi.org/10.1097/CEJ.0000000000000657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015184PMC
May 2021

Red Meat Consumption and Risk of Nonalcoholic Fatty Liver Disease in a Population With Low Meat Consumption: The Golestan Cohort Study.

Am J Gastroenterol 2021 Mar 24. Epub 2021 Mar 24.

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Departments of Biology, School of Art and Sciences, Utica College, Utica, New York, USA; Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Department of Radiology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran; Department of Biology, School of Computer, Mathematical, and Natural Sciences, Morgan State University, Baltimore, Maryland, USA; Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA; Departments of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Genetic Epidemiology Group, Section of Genetics, International Agency for Research on Cancer, the World Health Organization, Lyon, France; Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York, USA; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

Introduction: Nonalcoholic fatty liver disease (NAFLD), as the most common liver disease in the world, can range from simple steatosis to steatohepatitis. We evaluated the association between meat consumption and risk of NAFLD in the Golestan Cohort Study (GCS).

Methods: The GCS enrolled 50,045 participants, aged 40-75 years in Iran. Dietary information was collected using a 116-item semiquantitative food frequency questionnaire at baseline (2004-2008). A random sample of 1,612 cohort members participated in a liver-focused study in 2011. NAFLD was ascertained through ultrasound. Total red meat consumption and total white meat consumption were categorized into quartiles based on the GCS population, with the first quartile as the referent group. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Results: The median intake of total red meat was 17 and total white meat was 53 g/d. During follow-up, 505 individuals (37.7%) were diagnosed with NAFLD, and 124 of them (9.2%) had elevated alanine transaminase. High total red meat consumption (ORQ4 vs Q1 = 1.59, 95% CI = 1.06-2.38, P trend = 0.03) and organ meat consumption (ORQ4 vs Q1 = 1.70, 95% CI = 1.19-2.44, P trend = 0.003) were associated with NAFLD. Total white meat, chicken, or fish consumption did not show significant associations with NAFLD.

Discussion: In this population with low consumption of red meat, individuals in the highest group of red meat intake were at increased odds of NAFLD. Furthermore, this is the first study to show an association between organ meat consumption and NAFLD (see Visual Abstract, http://links.lww.com/AJG/B944).
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http://dx.doi.org/10.14309/ajg.0000000000001229DOI Listing
March 2021

Genome-Wide DNA Methylation Profiling of Esophageal Squamous Cell Carcinoma from Global High-Incidence Regions Identifies Crucial Genes and Potential Cancer Markers.

Cancer Res 2021 May 19;81(10):2612-2624. Epub 2021 Mar 19.

International Agency for Research on Cancer, Lyon, France.

Epigenetic mechanisms such as aberrant DNA methylation (DNAme) are known to drive esophageal squamous cell carcinoma (ESCC), yet they remain poorly understood. Here, we studied tumor-specific DNAme in ESCC cases from nine high-incidence countries of Africa, Asia, and South America. Infinium MethylationEPIC array was performed on 108 tumors and 51 normal tissues adjacent to the tumors (NAT) in the discovery phase, and targeted pyrosequencing was performed on 132 tumors and 36 NAT in the replication phase. Top genes for replication were prioritized by weighting methylation results using RNA-sequencing data from The Cancer Genome Atlas and GTEx and validated by qPCR. Methylome analysis comparing tumor and NAT identified 6,796 differentially methylated positions (DMP) and 866 differential methylated regions (DMR), with a 30% methylation (Δβ) difference. The majority of identified DMPs and DMRs were hypermethylated in tumors, particularly in promoters and gene-body regions of genes involved in transcription activation. The top three prioritized genes for replication, , and , had similar methylation differences in the discovery and replication sets. These genes were exclusively expressed in normal esophageal tissues in GTEx and downregulated in tumors. The specificity and sensitivity of these DNAme events in discriminating tumors from NAT were assessed. Our study identified novel, robust, and crucial tumor-specific DNAme events in ESCC tumors across several high-incidence populations of the world. Methylome changes identified in this study may serve as potential targets for biomarker discovery and warrant further functional characterization. SIGNIFICANCE: This largest genome-wide DNA methylation study on ESCC from high-incidence populations of the world identifies functionally relevant and robust DNAme events that could serve as potential tumor-specific markers. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/10/2612/F1.large.jpg.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-3445DOI Listing
May 2021

Oral Health and Risk of Upper Gastrointestinal Cancers in a Large Prospective Study from a High-risk Region: Golestan Cohort Study.

Cancer Prev Res (Phila) 2021 Jul 17;14(7):709-718. Epub 2021 Mar 17.

Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.

Tooth loss and periodontal disease have been associated with several cancers, and poor oral health may be an important risk factor for upper gastrointestinal (UGI, i.e., esophageal and gastric) cancers. We assessed the relationship between oral health and UGI cancers using a large prospective study of over 50,000 adults living in Golestan Province, Iran, a high-incidence area for these cancers. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated for the association between three different measures of oral health [frequency of tooth brushing; number of missing teeth; and the sum of decayed, missing, and filled teeth (DMFT)] and UGI cancers. During a median follow-up duration of 13 years, there were 794 incident UGI cancers (396 esophageal and 398 gastric cancers). Daily tooth brushing was associated with a decreased risk of developing both esophageal (HR = 0.670; 95% CI: 0.486-0.924) and gastric (HR = 0.741; 95% CI: 0.544-1.01) cancers (combined UGI cancer HR = 0.697; 95% CI: 0.558-0.871) compared with never brushing. Tooth loss in excess of the loess smoothed, age- and sex-specific median number of teeth lost was significantly associated with esophageal (HR = 1.64; 95% CI: 1.08-2.47) and gastric cancers (HR = 1.58; 95% CI: 1.05-2.38). There were some adverse associations between DMFT and UGI cancers but most were not statistically significant. These results suggest increased risk of developing UGI cancers among individuals with poor oral health, and those who do not perform regular oral hygiene. PREVENTION RELEVANCE: Poor oral health is associated with the risk of upper gastrointestinal cancers, and oral hygiene practices may help prevent these cancers.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295188PMC
July 2021

Associations of Total Legume, Pulse, and Soy Consumption with Incident Type 2 Diabetes: Federated Meta-Analysis of 27 Studies from Diverse World Regions.

J Nutr 2021 May;151(5):1231-1240

School of Public Health, Physiotherapy & Sports Science, University College Dublin, Dublin, Ireland.

Background: The consumption of legumes is promoted as part of a healthy diet in many countries but associations of total and types of legume consumption with type 2 diabetes (T2D) are not well established. Analyses across diverse populations are lacking despite the availability of unpublished legume consumption data in prospective cohort studies.

Objective: To examine the prospective associations of total and types of legume intake with the risk of incident T2D.

Methods: Meta-analyses of associations between total legume, pulse, and soy consumption and T2D were conducted using a federated approach without physical data-pooling. Prospective cohorts were included if legume exposure and T2D outcome data were available and the cohort investigators agreed to participate. We estimated incidence rate ratios (IRRs) and CIs of associations using individual participant data including ≤42,473 incident cases among 807,785 adults without diabetes in 27 cohorts across the Americas, Eastern Mediterranean, Europe, and Western Pacific. Random-effects meta-analysis was used to combine effect estimates and estimate heterogeneity.

Results: Median total legume intake ranged from 0-140 g/d across cohorts. We observed a weak positive association between total legume consumption and T2D (IRR = 1.02, 95% CI: 1.01 to 1.04) per 20 g/d higher intake, with moderately high heterogeneity (I2 = 74%). Analysis by region showed no evidence of associations in the Americas, Eastern Mediterranean, and Western Pacific. The positive association in Europe (IRR = 1.05, 95% CI: 1.01 to 1.10, I2 = 82%) was mainly driven by studies from Germany, UK, and Sweden. No evidence of associations was observed for the consumption of pulses or soy.

Conclusions: These findings suggest no evidence of an association of legume intakes with T2D in several world regions. The positive association observed in some European studies warrants further investigation relating to overall dietary contexts in which legumes are consumed, including accompanying foods which may be positively associated with T2D.
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http://dx.doi.org/10.1093/jn/nxaa447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112771PMC
May 2021

Correction: Effectiveness of Polypill for Prevention of Cardiovascular Disease (PolyPars): Protocol of a Randomized Controlled Trial.

Arch Iran Med 2021 02 1;24(2):166. Epub 2021 Feb 1.

Digestive Disease Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Teheran, Iran.

This corrects the article "Effectiveness of polypill for prevention of cardiovascular disease (PolyPars): protocol of a randomized controlled trial" published on 2020: Volume 23, Issue 08, Pages 548-556. Correction to: Arch Iran Med. 2020;23(8):548-556. doi: 10.34172/aim.2020.58. In the original version of this article, the recruitment period was wrongly reported to last from December 2014 to December 2015 in abstract and methods sections of the article. This is corrected into "from December 2015 to December 2016" in the PDF and HTML versions of the article. Also the "PolyIran" is changed to "PolyPars" in the last paragraph of the discussion section in the PDF and HTML versions of the article.
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http://dx.doi.org/10.34172/aim.2021.26DOI Listing
February 2021

Long-term opiate use and risk of cardiovascular mortality: results from the Golestan Cohort Study.

Eur J Prev Cardiol 2021 Mar;28(1):98-106

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Shariati Hospital, North Kargar Avenue, Tehran 14117-13135, Iran.

Aims: Tens of millions of people worldwide use opiates but little is known about their potential role in causing cardiovascular diseases. We aimed to study the association of long-term opiate use with cardiovascular mortality and whether this association is independent of the known risk factors.

Methods And Results: In the population-based Golestan Cohort Study-50 045 Iranian participants, 40-75 years, 58% women-we used Cox regression to estimate hazard ratios and 95% confidence intervals (HRs, 95% CIs) for the association of opiate use (at least once a week for a period of 6 months) with cardiovascular mortality, adjusting for potential confounders-i.e. age, sex, education, wealth, residential place, marital status, ethnicity, and tobacco and alcohol use. To show independent association, the models were further adjusted for hypertension, diabetes, waist and hip circumferences, physical activity, fruit/vegetable intake, aspirin and statin use, and history of cardiovascular diseases and cancers. In total, 8487 participants (72.2% men) were opiate users for a median (IQR) of 10 (4-20) years. During 548 940 person-years-median of 11.3 years, >99% success follow-up-3079 cardiovascular deaths occurred, with substantially higher rates in opiate users than non-users (1005 vs. 478 deaths/100 000 person-years). Opiate use was associated with increased cardiovascular mortality, with adjusted HR (95% CI) of 1.63 (1.49-1.79). Overall 10.9% of cardiovascular deaths were attributable to opiate use. The association was independent of the traditional cardiovascular risk factors.

Conclusion: Long-term opiate use was associated with an increased cardiovascular mortality independent of the traditional risk factors. Further research, particularly on mechanisms of action, is recommended.
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http://dx.doi.org/10.1093/eurjpc/zwaa006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133380PMC
March 2021

A Report on Statistics of an Online Self-screening Platform for COVID-19 and Its Effectiveness in Iran.

Int J Health Policy Manag 2021 Jan 16. Epub 2021 Jan 16.

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

Background: The most recent emerging infectious disease, coronavirus disease 2019 (COVID-19), is pandemic now. Iran is a country with community transmission of the disease. Telehealth tools have been proved to be useful in controlling public health disasters. We developed an online self-screening platform to offer a population-wide strategy to control the massive influx to medical centers.

Methods: We developed a platform operating based on given history by participants, including sex, age, weight, height, location, primary symptoms and signs, and high risk past medical histories. Based on a decision-making algorithm, participants were categorized into four levels of suspected cases, requiring diagnostic tests, supportive care, not suspected cases. We made comparisons with Iran STEPs (STEPwise approach to Surveillance) 2016 study and data from the Statistical Centre of Iran to assess population representativeness of data. Also, we made a comparison with officially confirmed cases to investigate the effectiveness of the platform. A multilevel mixed-effects Poisson regression was used to check the association of visiting platform and deaths caused by COVID-19.

Results: About 310 000 individuals participated in the online self-screening platform in 33 days. The majority of participants were in younger age groups, and males involved more. A significant number of participants were screened not to be suspected or needing supportive care, and only 10.4% of males and 12.0% of females had suspected results of COVID-19. The penetration of the platform was assessed to be acceptable. A correlation coefficient of 0.51 was calculated between suspected results and confirmed cases of the disease, expressing the platform's effectiveness.

Conclusion: Implementation of a proper online self-screening tool can mitigate population panic during wide-spread epidemics and relieve massive influx to medical centers. Also, an evidence-based education platform can help fighting infodemic. Noticeable utilization and verified effectiveness of such platform validate the potency of telehealth tools in controlling epidemics and pandemics.
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http://dx.doi.org/10.34172/ijhpm.2020.252DOI Listing
January 2021

Dietary quality using four dietary indices and lung cancer risk: the Golestan Cohort Study (GCS).

Cancer Causes Control 2021 May 21;32(5):493-503. Epub 2021 Feb 21.

Stony Brook Cancer Center, New York, NY, USA.

Purpose: The lung cancer incidence in Iran has increased almost ten times over the past three decades. In addition to the known causes such as smoking and certain occupational exposure, dietary quality has been suggested to play a role in lung cancer. We aim to explore the association between dietary pattern and lung cancer risk among a Middle East population.

Methods: Data came from Golestan Cohort Study which included 48,421 participants with 136 lung cancer cases diagnosed during a median follow-up of 12 years. Multivariable Cox proportional hazards regression models were used to calculate the HRs and 95% CI of lung cancer risk by tertile of the four dietary index scores-the Health Eating Index (HEI)-2015, the Alternative Health Eating Index (AHEI)-2010, the Alternative Mediterranean Diet (AMED), and the Dietary Approach to Stop Hypertension (DASH)-Fung.

Results: A higher DASH-Fung score was inversely associated with risk of lung cancer after adjusting for potential confounders (tertile three vs. tertile one: HR = 0.59 (0.38-0.93); p for trend = 0.07), and p with smoking was 0.46. Similar findings were observed among current smokers with the HEI-2015 score (tertile three vs. tertile one: HR = 0.22 (0.08-0.60): p for trend < 0.01), and p between smoking and the HEI-2015 score was 0.03.

Conclusion: In the GCS, consuming a diet more closely aligned with the DASH diet was associated with a reduced risk of lung cancer, which appeared to be independent of smoking status. There was also an inverse link between the HEI-2015 score and lung cancer risk among current smokers. Our finding is particularly important for the Middle East population, as diet may play an important role in cancer prevention and overall health.
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http://dx.doi.org/10.1007/s10552-021-01400-wDOI Listing
May 2021

CovidCTNet: an open-source deep learning approach to diagnose covid-19 using small cohort of CT images.

NPJ Digit Med 2021 Feb 18;4(1):29. Epub 2021 Feb 18.

Health Informatics Lab, Metropolitan College, Boston University, Boston, USA.

Coronavirus disease 2019 (Covid-19) is highly contagious with limited treatment options. Early and accurate diagnosis of Covid-19 is crucial in reducing the spread of the disease and its accompanied mortality. Currently, detection by reverse transcriptase-polymerase chain reaction (RT-PCR) is the gold standard of outpatient and inpatient detection of Covid-19. RT-PCR is a rapid method; however, its accuracy in detection is only ~70-75%. Another approved strategy is computed tomography (CT) imaging. CT imaging has a much higher sensitivity of ~80-98%, but similar accuracy of 70%. To enhance the accuracy of CT imaging detection, we developed an open-source framework, CovidCTNet, composed of a set of deep learning algorithms that accurately differentiates Covid-19 from community-acquired pneumonia (CAP) and other lung diseases. CovidCTNet increases the accuracy of CT imaging detection to 95% compared to radiologists (70%). CovidCTNet is designed to work with heterogeneous and small sample sizes independent of the CT imaging hardware. To facilitate the detection of Covid-19 globally and assist radiologists and physicians in the screening process, we are releasing all algorithms and model parameter details as open-source. Open-source sharing of CovidCTNet enables developers to rapidly improve and optimize services while preserving user privacy and data ownership.
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http://dx.doi.org/10.1038/s41746-021-00399-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893172PMC
February 2021

Estimates of anti-SARS-CoV-2 antibody seroprevalence in Iran - Authors' reply.

Lancet Infect Dis 2021 05 15;21(5):604-605. Epub 2021 Feb 15.

Digestive Oncology Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran 14117-13135, Iran; Digestive Disease Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran 14117-13135, Iran. Electronic address:

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http://dx.doi.org/10.1016/S1473-3099(21)00058-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906679PMC
May 2021

A Supporting System for Management of Patients with Inflammatory Bowel Disease during COVID-19 Outbreak: Iranian Experience-Study Protocol.

Middle East J Dig Dis 2020 Oct;12(4):238-245

Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

BACKGROUND The COVID-19 pandemic has affected the health care infrastructure dramatically, with abundant resources necessarily being redirected to COVID-19 patients and their care. Also, patients with chronic diseases like inflammatory bowel disease (IBD) may be affected in several ways during this pandemic. METHODS We used the Iranian registry of Crohn's and colitis (IRCC) infrastructure. We called and sent messages to follow-up and support the care of all registered patients. Besides, we prepared and distributed educational materials for these patients and physicians to reduce the risk of COVID-19 infection. We risk-stratified them and prepared outpatient clinics and hospitalization guidance for IBD patients. RESULTS Of 13165 Iranian patients with IBD, 51 have been diagnosed as having COVID-19. IBD patients made 1920 hotline calls. Among the patients with suspicious presentations, 14 COVID-19 infections were diagnosed. Additionally, 1782 patients with IBD from five provinces actively phone-called among whom 28 definite cases were diagnosed. CONCLUSION IBD patients' follow-up could help in diagnosing the affected IBD patients with COVID-19. Additionally, the performance of protective actions and preparing the patients and physicians for decisive proceedings are the principles of protection of IBD patients.
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http://dx.doi.org/10.34172/mejdd.2020.188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859612PMC
October 2020

Transethnic analysis of the human leukocyte antigen region for ulcerative colitis reveals not only shared but also ethnicity-specific disease associations.

Hum Mol Genet 2021 Apr;30(5):356-369

Schools of Mathematics and Statistics and BioSciences and Melbourne Integrative Genomics, University of Melbourne, Victoria 3010, Australia.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gut. Genetic association studies have identified the highly variable human leukocyte antigen (HLA) region as the strongest susceptibility locus for IBD and specifically DRB1*01:03 as a determining factor for ulcerative colitis (UC). However, for most of the association signal such as delineation could not be made because of tight structures of linkage disequilibrium within the HLA. The aim of this study was therefore to further characterize the HLA signal using a transethnic approach. We performed a comprehensive fine mapping of single HLA alleles in UC in a cohort of 9272 individuals with African American, East Asian, Puerto Rican, Indian and Iranian descent and 40 691 previously analyzed Caucasians, additionally analyzing whole HLA haplotypes. We computationally characterized the binding of associated HLA alleles to human self-peptides and analyzed the physicochemical properties of the HLA proteins and predicted self-peptidomes. Highlighting alleles of the HLA-DRB1*15 group and their correlated HLA-DQ-DR haplotypes, we not only identified consistent associations (regarding effects directions/magnitudes) across different ethnicities but also identified population-specific signals (regarding differences in allele frequencies). We observed that DRB1*01:03 is mostly present in individuals of Western European descent and hardly present in non-Caucasian individuals. We found peptides predicted to bind to risk HLA alleles to be rich in positively charged amino acids. We conclude that the HLA plays an important role for UC susceptibility across different ethnicities. This research further implicates specific features of peptides that are predicted to bind risk and protective HLA proteins.
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http://dx.doi.org/10.1093/hmg/ddab017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098114PMC
April 2021

Metabolomics reveals biomarkers of opioid use disorder.

Transl Psychiatry 2021 02 4;11(1):103. Epub 2021 Feb 4.

Department of Nutrition, Nutrition Research Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Opioid use disorder (OUD) is diagnosed using the qualitative criteria defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Diagnostic biomarkers for OUD do not currently exist. Our study focused on developing objective biological markers to differentiate chronic opiate users with OUD from chronic opiate users without OUD. Using biospecimens from the Golestan Cohort Study, we compared the metabolomics profiles of high opium users who were diagnosed as OUD positive with high opium users who were diagnosed as OUD negative. High opium use was defined as maximum weekly opium usage greater than or equal to the median usage (2.4 g per week), and OUD was defined as having 2 or more DSM-5 criteria in any 12-month period. Among the 218 high opium users in this study, 80 were diagnosed as OUD negative, while 138 were diagnosed as OUD positive. Seven hundred and twelve peaks differentiated high opium users diagnosed as OUD positive from high opium users diagnosed as OUD negative. Stepwise logistic regression modeling of subject characteristics data together with the 712 differentiating peaks revealed a signature that is 95% predictive of an OUD positive diagnosis, a significant (p < 0.0001) improvement over a 63% accurate prediction based on subject characteristic data for these samples. These results suggest that a metabolic profile can be used to predict an OUD positive diagnosis.
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http://dx.doi.org/10.1038/s41398-021-01228-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862627PMC
February 2021

Untargeted Metabolomics: Biochemical Perturbations in Golestan Cohort Study Opium Users Inform Intervention Strategies.

Front Nutr 2020 22;7:584585. Epub 2020 Dec 22.

Department of Nutrition, Nutrition Research Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.

Over 50 million people worldwide are estimated to use opioids, of which ~30 million use opiates (opium and its derivatives). Use of opiates has been associated with a variety of adverse complications such as neurological and behavioral outcomes, addiction, cancers, diabetes, and cardiovascular disease. While it is well known that opiates exert their neurobiological effects through binding with mu, kappa, and delta receptors to exert analgesic and sedative effects, mechanistic links to other health effects are not well understood. Our study focuses on the identification of biochemical perturbations in Golestan Cohort Study (GCS) opium users. We used untargeted metabolomics to evaluate the metabolic profiles of 218 opium users and 80 non-users participating in the GCS. Urine samples were obtained from adult (age 40-75) opium users living in the Golestan Province of Iran. Untargeted analysis of urine was conducted using a UPLC-Q-Exactive HFx Mass Spectrometry and a 700 MHz NMR Spectrometry. These GCS opium users had a significantly higher intake of tobacco and alcohol and a significantly decreased BMI compared with non-users. Metabolites derived from opium (codeine, morphine, and related glucuronides), nicotine, and curing or combustion of plant material were increased in opium users compared with non-users. Endogenous compounds which differentiated the opium users and non-users largely included vitamins and co-factors, metabolites involved in neurotransmission, Kreb's cycle, purine metabolism, central carbon metabolism, histone modification, and acetylation. Our study reveals biochemical perturbations in GCS opium users that are important to the development of intervention strategies to mitigate against the development of adverse effects of substance abuse.
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http://dx.doi.org/10.3389/fnut.2020.584585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783045PMC
December 2020