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The incidence of esophageal squamous cell carcinoma (ESCC) is disproportionately high in the eastern corridor of Africa and parts of Asia. Emerging research has identified a potential association between poor oral health and ESCC. One possible link between poor oral health and ESCC involves the alteration of the microbiome. We performed an integrated analysis of four independent sequencing efforts of ESCC tumors from patients from high- and low-incidence regions of the world. Using whole genome sequencing (WGS) and RNA sequencing (RNAseq) of ESCC tumors from 61 patients in Tanzania, we identified a community of bacteria, including members of the genera Fusobacterium, Selenomonas, Prevotella, Streptococcus, Porphyromonas, Veillonella and Campylobacter, present at high abundance in ESCC tumors. We then characterized the microbiome of 238 ESCC tumor specimens collected in two additional independent sequencing efforts consisting of patients from other high-ESCC incidence regions (Tanzania, Malawi, Kenya, Iran, China). This analysis revealed similar ESCC-associated bacterial communities in these cancers. Because these genera are traditionally considered members of the oral microbiota, we next explored whether there was a relationship between the synchronous saliva and tumor microbiomes of ESCC patients in Tanzania. Comparative analyses revealed that paired saliva and tumor microbiomes were significantly similar with a specific enrichment of Fusobacterium and Prevotella in the tumor microbiome. Together, these data indicate that cancer-associated oral bacteria are associated with ESCC tumors at the time of diagnosis and support a model in which oral bacteria are present in high abundance in both saliva and tumors of some ESCC patients.

Background and objective: Two decades ago, an international initiative (GEMINI) was launched in a high-risk, low-resource region in Northeast Iran, aiming to investigate incidence, etiology, early detection, and treatment of esophageal squamous cell carcinoma (ESCC). An earlier report from this area, highlighted poor ESCC survival rates, with a 5-year survival probability of 3.3% and the median survival time of 7 months. Our study assesses whether ESCC survival has improved since the implementation of the GEMINI initiative in this region. Material and methods: 490 adult patients with histologically-confirmed ESCC were recruited from the Atrak clinic, Golestan, Iran, between 2007 and 2018. At recruitment, information on demographics and various exposures were collected. Active (telephone surveys) and passive (linkage to Golestan population-based cancer and death registries) follow-up methods were used to determine patients' vital status though March 2019. Survival estimates were obtained by Kaplan-Meier method and Cox proportional hazards regression models. Results: Over the study period 340 deaths were recorded. Five-year ESCC survival probability was 23% (95% Confidence Interval: 19% to 28%), and the median survival time was 19 months. Five-year survival probability was higher among individuals who were younger (35% in <60-year-olds vs. 12% for >70-year-olds, p<0.001), educated (34% vs. 21% for no formal education, p = 0.027), never used opium (28% vs. 15%, p = 0.0016), and received cancer treatment (37% vs. 4%, p<0.001). In the adjusted models, a higher hazard of death was associated with older age [HR for each 10-year increase = 1.36 (95% CI = 1.22 to 1.51)], Turkman ethnicity [HR = 1.35 (95%CI: 1.07 to 1.70)], opium use [HR = 1.53 (95%CI: 1.20 to 1.94)],and receiving no cancer treatment [HR = 5.81 (95%CI: 3.97 to 8.52)]. Conclusion: Over the last two decades, ESCC survival in this population has significantly improved, highlighting the potential of enhancing healthcare infrastructure and ensuring access to affordable medical care in resource-limited, high-risk regions. Older age at diagnosis, Turkman ethnicity, opium use, and untreated cases (indicative of advanced disease at diagnosis) were identified as the main ESCC prognostic factors in this population. [ABSTRACT FROM AUTHOR]

BackgroundThe burden of chronic kidney disease (CKD) is increasing globally in particular in fast emerging economies such as Iran. Population-based studies on prevalence of CKD in Iran are scarce. The objective of the current study was to explore the prevalence and determinants of CKD in the setting of Golestan Cohort Study (GCS), the largest prospective cohort in the Middle East.MethodsIn this observational study, 11,409 participants enrolled in the second phase of GCS were included. Sex, age, literacy, residence, anthropometric measurements, smoking, opium use, self-reported history of cardiovascular diseases (heart disease and/or stroke), hypertension, diabetes, and lipid profile were the predictors of interest. The outcomes of interest were eGFR and CKD defined as eGFR< 60 ml/min/1.73m2.ResultsMean (SD) of GFR was 70.0 ± 14.7 ml/min/1.73m2 among all participants, 68.2 ± 14.2 among women, and 72.0 ± 15.0 among men. Prevalence of CKD was 23.7% (26.6% in women, 20.6% in men). The prevalence of CKD stages 3a, 3b, 4, and 5 were 20.0%, 3.3%, 0.4% and 0.1%, respectively. Female sex, older age, urban residence, history of CVD, hypertension or diabetes, larger body mass and surrogates of body fat and opium use were all associated with CKD. Opium had a significant positive association with CKD in adjusted model. All anthropometric measurements had positive linear association with CKD. Being literate had inverse association. Sex had significant interaction with anthropometric indices, with higher odds ratios among men compared with women. A significantly high association was observed between the rate of change in waist circumference and systolic blood pressure with risk of CKD.ConclusionOne in four people in this cohort had low eGFR. Obesity and overweight, diabetes, hypertension, and dyslipidemia are major risk factors for CKD. Halting the increase in waist circumference and blood pressure may be as important as reducing the current levels.

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a rising global public health concern. It has been demonstrated that its prevalence and characteristics vary by region and racial/ethnicity. We aimed to investigate the prevalence of MAFLD and its characteristics among Turkmen and non-Turkmen ethnic groups in a multiethnic population region of Iran. Methods: In this cross-sectional study, we analyzed baseline data for 1614 participants, aged above 50 years, from the PolyIran- Liver trial who were randomly selected from Gonabad city and determined the prevalence of MAFLD and its demographic and metabolic disorders for both the Turkmen and non-Turkmen ethnic groups. Multivariate binary logistic regressions were applied to identify MAFLD-associated factors for men and women separately for the Turkmen and non-Turkmen populations. Results: The mean (SD) age of the participants was 59.1(6.7) years. Of the participants, 51.5% (n = 831) were men, and 52.9% (n = 854) were Turkmen. The prevalence of MAFLD among the overall study population was 39.8% (n = 614). It was more common among women (45.8% vs. 34.1% in men, P < 0.001), non-Turkmens (43.9% vs. 36.1% in Turkmens, P < 0.001), and at age 50-64 (41.5% vs.36.1% in age ≥ 65 P = 0.004). The fully adjusted multivariate analysis in sex strata exhibited an independent negative association between Turkmen ethnicity only among men but not among women. The increased waist circumference (WC) was the most common metabolic disorder, observed in more than 95.5% of patients with MAFLD (P < 0.001). Multivariate analysis in sex/ ethnic strata with adjustment for potential confounders revealed an independent association of MAFLD with increased WC, insulin resistance, impaired fasting glucose/diabetes type 2, and high alanine aminotransferase (ALT) among women in both ethnic groups while with elevated triglyceride (TG) only among Turkmen and high body mass index (BMI) only among non-Turkmen women. Increased WC had the strongest independent association with MAFLD among women and the highest odds ratio (OR) with MAFLD in Turkmen women (OR: 6.10; 95% CI 1.56-23.86 vs. 4.80 in non-Turkmen women). Among men, MAFLD was independently associated with insulin resistance, high BMI, and high ALT in both ethnic groups and elevated TG only in non-Turkmen men (all P < 0.001). Insulin resistance had the strongest independent OR with MAFLD among men with similar size in both ethnic groups (4.68 [95% CI 2.56-8.55]) in non-Turkmen men and 4.37 (95% CI 2.27-8.42 in Turkmen men). Conclusion: This study revealed the high prevalence of MAFLD with a sex and ethnic disparity in the middle-aged population of Gonabad city. Further research is needed to understand the factors contributing to the higher prevalence of MAFLD in this region, particularly in women. Furthermore, considering the diverse ethnic population of Iran, it is suggested that future investigations on the sex and ethnic aspects of MAFLD in the Iranian population be conducted to provide targeted prevention strategies better suited for the Iranian population. [ABSTRACT FROM AUTHOR]

Introduction. The role of progranulin in individuals with metabolic syndrome is not exactly clear.We aimed to assess the serum level of progranulin in type 2 diabetic patients with and without metabolic syndrome and compare them with healthy controls.

BACKGROUND: Three billion people burn nonclean fuels for household purposes. Limited evidence suggests a link between household fuel use and gastrointestinal (GI) cancers. OBJECTIVES: We investigated the relationship between indoor burning of biomass, kerosene, and natural gas with the subsequent risk of GI cancers. METHODS: During the period 2004-2008, a total of 50,045 Iranian individuals 40-75 years of age were recruited to this prospective population-based cohort. Upon enrollment, validated data were collected on demographics, lifestyle, and exposures, including detailed data on lifetime household use of different fuels and stoves. The participants were followed through August 2018 with RESULTS: During the follow-up, 962 participants developed GI cancers. In comparison with using predominantly gas in the recent 20-y period, using predominantly biomass was associated with higher risks of esophageal [hazard ratio (HR): 1.89; 95% confidence interval (CI): 1.02, 3.50], and gastric HR: 1.83; 95% CI: 1.01, 3.31) cancers, whereas using predominantly kerosene was associated with higher risk of esophageal cancer (HR: 1.84; 95% CI: 1.10, 3.10). Lifetime duration of biomass burning for both cooking and house heating (exclusive biomass usage) using heating-stoves without chimney was associated with higher risk of GI cancers combined (10-y HR: 1.14; 95% CI: 1.07, 1.21), esophageal (10-y HR: 1.19; 95% CI: 1.08, 1.30), gastric (10-y HR: 1.11; 95% CI: 1.00, 1.23), and colon (10-y HR: 1.26; 95% CI: 1.03, 1.54) cancers. The risks of GI cancers combined, esophageal cancer, and gastric cancer were lower when biomass was burned using chimney-equipped heating-stoves (strata difference p-values = 0.001, 0.003, and 0.094, respectively). Duration of exclusive kerosene burning using heating-stoves without chimney was associated with higher risk of GI cancers combined (10-y HR: 1.05; 95% CI: 1.00, 1.11), and esophageal cancer (10-y HR: 1.14; 95% CI: 1.04, 1.26). DISCUSSION: Household burning of biomass or kerosene, especially without a chimney, was associated with higher risk of some digestive cancers. Using chimney-equipped stoves and replacing these fuels with natural gas may be useful interventions to reduce the burden of GI cancers worldwide. https://doi.org/10.1289/EHP5907, Introduction An estimated 3 billion people still cook and heat their homes using open fires or leaky stoves fueled by kerosene, biomass, or coal (WHO 2018). Combustion of these fuels [...]

Purpose: We aimed to estimate the level and trend of plasma cholesterol and raised total cholesterol (TC > 200 mg/dl) prevalence at national and subnational level of Iran. Methods: Nine national surveys and 27 studies, encompassing 3,505 unique points on over 500,000 adults, aged > 25 years with a report of laboratory measurement of TC were found. Age-spatio-temporal model and Gaussian Process Regression were used to estimate mean TC for each sex, 5-year age groups, and 31 provinces from 1990 to 2016. Results: At national level, age-standardized prevalence of TC > 200 mg/dL has decreased from 57·2%(53·3–61·1) to 22·4%(20·5–24·3) in women and 53·2%(49·1–57·3) to 18·0%(16·4–19·6) in men. TC distribution presented a condensation between 170-200 mg/dL. At subnational level, decreasing and converging patterns of raised TC prevalence were detected. Conclusion: The decrease in raised TC is likely the result of statin widespread use, food industry improvements, and the expanded primary health care. [ABSTRACT FROM AUTHOR]

Background: Many diabetic individuals use prescription and non-prescription opioids and opiates. We aimed to investigate the joint effect of diabetes and opiate use on all-cause and cause-specific mortality.Methods: Golestan Cohort study is a prospective population-based study in Iran. A total of 50 045 people-aged 40-75, 28 811 women, 8487 opiate users, 3548 diabetic patients-were followed during a median of 11.1 years, with over 99% success follow-up. Hazard ratio and 95% confidence intervals (HRs, 95% CIs), and preventable death attributable to each risk factor, were calculated.Results: After 533 309 person-years, 7060 deaths occurred: 4178 (10.8%) of non-diabetic non-opiate users, 757 (25.3%) diabetic non-users, 1906 (24.0%) non-diabetic opiate users and 219 (39.8%) diabetic opiate users. Compared with non-diabetic non-users, HRs (95% CIs) for all-cause mortality were 2.17 (2.00-2.35) in diabetic non-opiate users, 1.63 (1.53-1.74) in non-diabetic opiate users and 2.76 (2.40-3.17) in diabetic opiate users. Among those who both had diabetes and used opiates, 63.8% (95% CI: 58.3%-68.5%) of all deaths were attributable to these risk factors, compared with 53.9% (95% CI: 50%-57.4%) in people who only had diabetes and 38.7% (95% CI: 34.6%-42.5%) in non-diabetic opiate users. Diabetes was more strongly associated with cardiovascular than cancer mortality. The risk of early mortality in known cases of diabetes did not depend on whether they started opiate use before or after their diagnosis.Conclusions: Using opiates is detrimental to the health of diabetic patients. Public awareness about the health effects of opiates, and improvement of diabetes care especially among individuals with or at risk of opiate use, are necessary. [ABSTRACT FROM AUTHOR]