Reduction of household air pollution through clean fuel intervention and recovery of cellular immune balance.

BACKGROUND: We conducted a clean fuel intervention trial (Bangladesh Global Environmental and Occupational Health (GEOHealth) (NCT02824237) with liquefied petroleum gas (LPG) for 26 months among rural Bangladeshi women chronically exposed to household air pollution (HAP) from biomass fuel (BMF) use. We aimed to evaluate the effect of HAP reduction following LPG intervention on immune response outcome. METHODS: We supplied LPG cook stove and refills in cylinder in 200 households for 26 months. We measured personal exposure to HAP [particulate matter 2.5 (PM2·5), black carbon (BC) and carbon monoxide (CO)] in 200 women (main cook) by personal monitors at pre- and post-intervention. Immune function was assessed before and after intervention, in blood collected within 2 weeks of HAP measurements. Primary endpoints included reduction in HAP, lymphocyte proliferation and oxidative stress response, and alterations in T and B cell proportions. FINDINGS: Exclusive LPG use for 26 months resulted in significant reduction in PM2·5 (43.5%), BC (13%) and CO (48%) exposure in the women. For one unit decrease in BC, Treg cells and memory B cells increased by 7% and 34% respectively, in the peripheral circulation. One unit decrease in CO was significantly associated with increase in early B cells and plasmablasts by 66% and 5% respectively. For one unit decrease in BC, percent-dividing cells, proliferation and expansion indices increased by 2%, 0.4%, and 1%, respectively. INTERPRETATION: Reduced personal exposure to HAP through clean fuel intervention was related to a return towards cellular immune balance.

Establishing a surveillance system on sexual and reproductive health and rights (SRHR) of key populations (KPs) at risk of compromised outcome of SRHR- A protocol for a mixed-method study.

BACKGROUND: Key populations (KPs) who are at risk of compromised situation of sexual and reproductive health and rights in Bangladesh constitute including males having sex with males, male sex workers, transgender women (locally known as hijra) and female sex workers. Globally, these key populations experience various sexual and reproductive health and rights burdens and unmet needs for ailments such as sexually transmitted infections including Neisseria Gonorrhoea, Chlamydia Trachomatis and human papillomavirus. Most key population focused interventions around the world, including Bangladesh, primarily address human immune deficiency virus and sexually transmitted infections-related concerns and provide syndromic management of sexually transmitted infections, other sexual and reproductive health and rights issues are remained overlooked that creates a lack of information in the related areas. There is currently no systematic research in Bangladesh that can produce representative data on sexual and reproductive health and rights among key populations, investigates their sexual and reproductive health and rights needs, how their needs evolve, and investigate underlying factors of sexual and reproductive health and rights issues that is crucial for informing more sexual and reproductive health and rights-friendly interventions for key populations. Keeping all these issues in mind, we are proposing to establish a sexual and reproductive health and rights surveillance system for key populations in Bangladesh. METHOD: The sexual and reproductive health and rights surveillance system will be established in Dhaka for males having sex with males, male sex workers and transgender women, and the other in Jashore for female sex workers. The duration will be for 3 years and data will be collected twice, in year one and year two adopting a mixed method repeated cross-sectional design. All key populations 15 years and above will be sampled. Behavioural data will be collected adopting a face-to-face technique and then biological samples will be collected. Those who will be found positive for human papillomavirus, will be referred to a government hospital for treatment. Free treatment will be provided to those who will be found positive for other sexually transmitted infections. In total, 2,240 key populations will be sampled. Written assent/consent will be taken from everyone. Data will be entered by Epi-Info and analysed by Stata. Report will be produced in every year. DISCUSSION: This surveillance system will be the first of its kind to systematically assess the situation of sexual and reproductive health and rights among selected key populations in Bangladesh. It is expected that this study will provide insights needed for improving the existing sexual and reproductive health and rights intervention modalities for these vulnerable and marginalized key populations.

Prevalence, Clinical Severity, and Seasonality of Adenovirus 40/41, Astrovirus, Sapovirus, and Rotavirus Among Young Children With Moderate-to-Severe Diarrhea: Results From the Vaccine Impact on Diarrhea in Africa (VIDA) Study.

BACKGROUND: While rotavirus causes severe diarrheal disease in children aged <5 years, data on other viral causes in sub-Saharan Africa are limited. METHODS: In the Vaccine Impact on Diarrhea in Africa study (2015-2018), we analyzed stool from children aged 0-59 months with moderate-to-severe diarrhea (MSD) and without diarrhea (controls) in Kenya, Mali, and The Gambia using quantitative polymerase chain reaction. We derived the attributable fraction (AFe) based on the association between MSD and the pathogen, accounting for other pathogens, site, and age. A pathogen was attributable if the AFe was ≥0.5.The severity of attributable MSD was defined by a modified Vesikari score (mVS). Monthly cases were plotted against temperature and rainfall to assess seasonality. RESULTS: Among 4840 MSD cases, proportions attributed to rotavirus, adenovirus 40/41, astrovirus, and sapovirus were 12.6%, 2.7%, 2.9%, and 1.9%, respectively. Attributable rotavirus, adenovirus 40/41, and astrovirus MSD cases occurred at all sites, with mVS of 11, 10, and 7, respectively. MSD cases attributable to sapovirus occurred in Kenya, with mVS of 9. Astrovirus and adenovirus 40/41 peaked during the rainy season in The Gambia, while rotavirus peaked during the dry season in Mali and The Gambia. CONCLUSIONS: In sub-Saharan Africa, rotavirus was the most common cause of MSD; adenovirus 40/41, astrovirus, and sapovirus contributed to a lesser extent among children aged <5 years. Rotavirus- and adenovirus 40/41-attributable MSD were most severe. Seasonality varied by pathogen and location. Efforts to increase the coverage of rotavirus vaccines and to improve prevention and treatment for childhood diarrhea should continue.

Personal exposure to household air pollution and lung function in rural Bangladesh: A population-based cross-sectional study.

We assessed whether personal exposure to household air pollution [PM2.5 and black carbon (BC)] is associated with lung functions (FEV1, FVC, and their ratio) in non-smoking adults in rural Bangladesh. We measured personal exposure to PM2.5 using gravimetric analysis of PM2.5 mass and BC by reflectance measurement between April 2016 and June 2019. The average 24-hour PM2.5 and BC concentration was 141.0µgm-3 and 13.8µgm-3 for females, and 91.7 µgm-3 and 10.1 µgm-3 for males, respectively. A 1 µgm-3 increase in PM2.5 resulted in a 0.02 ml reduction in FEV1, 0.43 ml reduction in FVC, and 0.004% reduction in FEV1/FVC. We also found a similar inverse relationship between BC and lung functions (9.6 ml decrease in FEV1 and 18.5 ml decrease in FVC per 1µgm-3 increase in BC). A higher proportion of non-smoking biomass fuel users (50.1% of the females and 46.7% of the males) had restrictive patterns of lung function abnormalities, which need further exploration.

Exposure to arsenic and level of Vitamin D influence the number of Th17 cells and production of IL-17A in human peripheral blood mononuclear cells in adults.

There is limited evidence on the effects of environmental exposure to arsenic (As) on the immune system in adults. In a population-based study, we have found that urinary As (UAs), and its metabolites [inorganic As (InAs), monomethylated arsenicals (MMA+3/+5), and dimethylated arsenicals (DMA+3/+5)] modulate or influence the number of T-helper 17 (Th17) cells and IL-17A cytokine production. In non-smoking women, we observed that UAs and DMA+3/+5 were associated with changes in Th17 cell numbers in a nonlinear fashion. In smoking males, we found that UAs was associated with a significant decrease of Th17 cell numbers. Similar association was observed among non-smoking males. Likewise, UAs, DMA+3/+5 and MMA+3/+5 were associated with diminished production of IL-17A among non-smoking males. When stratified by Vitamin D levels defined as sufficient (≥20 ng/ml) and insufficient (<20 ng/ml), we found a substancial decrease in Th17 cell numbers among those with insufficient levels. Individuals with sufficient VitD levels demonstrated significant inhibition of IL-17A production in non-smoking males. Collectively, we find that exposure to As via drinking water is associated with alterations in Th17 numbers and IL-17A production, and that these associations may be modified by Vitamin D status. Our findings have significance for health outcomes associated with As exposure.

Association of household air pollution with cellular and humoral immune responses among women in rural Bangladesh.

Household air pollution (HAP) arising from combustion of biomass fuel (BMF) is a leading cause of morbidity and mortality in low-income countries. Air pollution may stimulate pro-inflammatory responses by activating diverse immune cells and cyto/chemokine expression, thereby contributing to diseases. We aimed to study cellular immune responses among women chronically exposed to HAP through use of BMF for domestic cooking. Among 200 healthy, non-smoking women in rural Bangladesh, we assessed exposure to HAP by measuring particulate matter 2.5 (PM2.5), black carbon (BC) and carbon monoxide (CO), through use of personal monitors RTI MicroPEM™ and Lascar CO logger respectively, for 48 h. Blood samples were collected following HAP exposure assessment and were analyzed for immunoprofiling by flow cytometry, plasma IgE by immunoassay analyzer and cyto/chemokine response from monocyte-derived-macrophages (MDM) and -dendritic cells (MDDC) by multiplex immunoassay. In multivariate linear regression model, a doubling of PM2.5 was associated with small increments in immature/early B cells (CD19+CD38+) and plasmablasts (CD19+CD38+CD27+). In contrast, a doubling of CO was associated with 1.20% reduction in CD19+ B lymphocytes (95% confidence interval (CI) = -2.36, -0.01). A doubling of PM2.5 and BC each was associated with 3.12% (95%CI = -5.85, -0.38) and 4.07% (95%CI = -7.96, -0.17) decrements in memory B cells (CD19+CD27+), respectively. Exposure to CO was associated with increased plasma IgE levels (beta(ß) = 240.4, 95%CI = 3.06, 477.8). PM2.5 and CO exposure was associated with increased MDM production of CXCL10 (ß = 12287, 95%CI = 1038, 23536) and CCL5 (ß = 835.7, 95%CI = 95.5, 1576), respectively. Conversely, BC exposure was associated with reduction in MDDC-produced CCL5 (ß = -3583, 95%CI = -6358, -807.8) and TNF-α (ß = -15521, 95%CI = -28968, -2074). Our findings suggest that chronic HAP exposure through BMF use adversely affects proportions of B lymphocytes, particularly memory B cells, plasma IgE levels and functions of antigen presenting cells in rural women.

Drug resistance pattern among ART-naive clients attending an HIV testing and counseling center in Dhaka, Bangladesh.

In Bangladesh, antiretroviral therapy (ART) is provided without screening drug resistance-associated mutations (DRM) among people living with HIV, while DRM might emerge and transmit to the newly infected individual. The present study was aimed to identify DRM among ART-naive clients from an HIV testing and counseling (HTC) center in the initial stages of ART programs. Randomly selected (n = 64) archived plasma samples were used for the pol gene amplification and sequencing by sanger technology. Recovered sequences (n = 10) were genotyped using HIV genotyping tools of NCBI and analyzed using the Stanford University HIV drug resistance database (hivdb.stanford.edu). Various genotypes with a number of DRM were identified in HTC clients, who belonged to different risk groups based on behavioral data. The drug resistance algorithm showed that all samples were fully resistant to tipranavir/ritonavir drugs except for one intermediate resistance. Despite the small sample size, our understanding from this study warrants an ART policy with a DRM monitoring system for the country.

The Association Between Smoking and Gut Microbiome in Bangladesh.

INTRODUCTION: Epidemiological studies that investigate alterations in the gut microbial composition associated with smoking are lacking. This study examined the composition of the gut microbiome in smokers compared with nonsmokers. AIMS AND METHODS: Stool samples were collected in a cross-sectional study of 249 participants selected from the Health Effects of Arsenic Longitudinal Study in Bangladesh. Microbial DNA was extracted from the fecal samples and sequenced by 16S rRNA gene sequencing. The associations of smoking status and intensity of smoking with the relative abundance or the absence and presence of individual bacterial taxon from phylum to genus levels were examined. RESULTS: The relative abundance of bacterial taxa along the Erysipelotrichi-to-Catenibacterium lineage was significantly higher in current smokers compared to never-smokers. The odds ratio comparing the mean relative abundance in current smokers with that in never-smokers was 1.91 (95% confidence interval = 1.36-2.69) for the genus Catenibacterium and 1.89 (95% confidence interval = 1.39-2.56) for the family Erysipelotrichaceae, the order Erysipelotrichale, and the class Erysipelotrichi (false discovery rate-adjusted p values = .0008-.01). A dose-response association was observed for each of these bacterial taxa. The presence of Alphaproteobacteria was significantly greater comparing current with never-smokers (odds ratio = 4.85, false discovery rate-adjusted p values = .04). CONCLUSIONS: Our data in a Bangladeshi population are consistent with evidence of an association between smoking status and dosage with change in the gut bacterial composition. IMPLICATIONS: This study for the first time examined the relationship between smoking and the gut microbiome composition. The data suggest that smoking status may play an important role in the composition of the gut microbiome, especially among individuals with higher levels of tobacco exposure.

Assessment of arsenic and polycyclic aromatic hydrocarbon (PAH) exposures on immune function among males in Bangladesh.

Arsenic and polycyclic aromatic hydrocarbons (PAH) are environmental pollutants to which people around the world are exposed through water, food and air. In mouse and in vitro studies of human cells, both of these chemicals have been shown to modulate the immune system. In some experimental studies, a synergistic disruption of immune function was observed by a combined exposure to arsenic and PAH. However, a joint effect of arsenic and PAH on immune function has not been studied in humans. We have conducted an epidemiological investigation to examine effects of chronic arsenic and PAH exposures on immune function. We assessed T-cell proliferation (TCP) and cytokine production of anti-CD3/anti-CD28 stimulated lymphocytes in human peripheral blood mononuclear cells (HPBMC) among 197 healthy men enrolled to the Health Effects of Arsenic Longitudinal (HEALS) cohort in Bangladesh. By design, approximately half were active smokers and the rest were never smokers. Our analyses demonstrated that IL-1b, IL-2, IL-4 and IL-6 were significantly stimulated as a function of urinary arsenic levels in models adjusted for age, body mass index (BMI), smoking status and PAH-DNA adducts. After correcting for false detection rate (FDR), only IL-1b remained statistically significant. We found a U-shaped dose response relationship between urinary arsenic and IL-1b. On the other hand, PAH-DNA adducts were associated with an inhibition of TCP and appeared as an inverted U-shape curve. Dose response curves were non-monotonic for PAH-DNA adduct exposures and suggested that cytokine secretion of IFNg, IL-1b, IL-2, IL-10 and IL17A followed a complex pattern. In the majority of donors, there was a trend towards a decrease in cytokine associated with PAH-DNA adducts. We did not observe any interaction between urinary arsenic and PAH-DNA adducts on immune parameters. Our results indicate that long-term exposures to arsenic and PAH have independent, non-monotonic associations with TCP and cytokine production.

Association of Arsenic Exposure with Whole Blood DNA Methylation: An Epigenome-Wide Study of Bangladeshi Adults.

BACKGROUND: Arsenic exposure affects [Formula: see text] people worldwide, including [Formula: see text] in Bangladesh. Arsenic exposure increases the risk of cancer and other chronic diseases, and one potential mechanism of arsenic toxicity is epigenetic dysregulation. OBJECTIVE: We assessed associations between arsenic exposure and genome-wide DNA methylation measured at baseline among 396 Bangladeshi adults participating in the Health Effects of Arsenic Longitudinal Study (HEALS) who were exposed by drinking naturally contaminated well water. METHODS: Methylation in whole blood DNA was measured at [Formula: see text] using the Illumina InfiniumMethylationEPIC (EPIC) array. To assess associations between arsenic exposure and CpG methylation, we used linear regression models adjusted for covariates and surrogate variables (SVs) (capturing unknown technical and biologic factors). We attempted replication and conducted a meta-analysis using an independent dataset of [Formula: see text] from 400 Bangladeshi individuals with arsenical skin lesions. RESULTS: We identified 34 CpGs associated with [Formula: see text] creatinine-adjusted urinary arsenic [[Formula: see text]]. Sixteen of these CpGs annotated to the [Formula: see text] array, and 10 associations were replicated ([Formula: see text]). The top two CpGs annotated upstream of the ABR gene (cg01912040, cg10003262 ). All urinary arsenic-associated CpGs were also associated with arsenic concentration measured in drinking water ([Formula: see text]). Meta-analysis ([Formula: see text] samples) identified 221 urinary arsenic-associated CpGs ([Formula: see text]). The arsenic-associated CpGs from the meta-analysis were enriched in non-CpG islands and shores ([Formula: see text]) and depleted in promoter regions ([Formula: see text]). Among the arsenic-associated CpGs ([Formula: see text]), we observed significant enrichment of genes annotating to the reactive oxygen species pathway, inflammatory response, and tumor necrosis factor [Formula: see text] ([Formula: see text]) signaling via nuclear factor kappa-B ([Formula: see text]) hallmarks ([Formula: see text]). CONCLUSIONS: The novel and replicable associations between arsenic exposure and DNA methylation at specific CpGs observed in this work suggest that epigenetic alterations should be further investigated as potential mediators in arsenic toxicity and as biomarkers of exposure and effect in exposed populations. https://doi.org/10.1289/EHP3849.

A missense variant in FTCD is associated with arsenic metabolism and toxicity phenotypes in Bangladesh.

Inorganic arsenic (iAs) is a carcinogen, and exposure to iAs via food and water is a global public health problem. iAs-contaminated drinking water alone affects >100 million people worldwide, including ~50 million in Bangladesh. Once absorbed into the blood stream, most iAs is converted to mono-methylated (MMA) and then di-methylated (DMA) forms, facilitating excretion in urine. Arsenic metabolism efficiency varies among individuals, in part due to genetic variation near AS3MT (arsenite methyltransferase; 10q24.32). To identify additional arsenic metabolism loci, we measured protein-coding variants across the human exome for 1,660 Bangladeshi individuals participating in the Health Effects of Arsenic Longitudinal Study (HEALS). Among the 19,992 coding variants analyzed exome-wide, the minor allele (A) of rs61735836 (p.Val101Met) in exon 3 of FTCD (formiminotransferase cyclodeaminase) was associated with increased urinary iAs% (P = 8x10-13), increased MMA% (P = 2x10-16) and decreased DMA% (P = 6x10-23). Among 2,401 individuals with arsenic-induced skin lesions (an indicator of arsenic toxicity and cancer risk) and 2,472 controls, carrying the low-efficiency A allele (frequency = 7%) was associated with increased skin lesion risk (odds ratio = 1.35; P = 1x10-5). rs61735836 is in weak linkage disequilibrium with all nearby variants. The high-efficiency/major allele (G/Valine) is human-specific and eliminates a start codon at the first 5´-proximal Kozak sequence in FTCD, suggesting selection against an alternative translation start site. FTCD is critical for catabolism of histidine, a process that generates one-carbon units that can enter the one-carbon/folate cycle, which provides methyl groups for arsenic metabolism. In our study population, FTCD and AS3MT SNPs together explain ~10% of the variation in DMA% and support a causal effect of arsenic metabolism efficiency on arsenic toxicity (i.e., skin lesions). In summary, this work identifies a coding variant in FTCD associated with arsenic metabolism efficiency, providing new evidence supporting the established link between one-carbon/folate metabolism and arsenic toxicity.

Association between number of children and carotid intima-media thickness in Bangladesh.

Previous studies on the association between number of children and carotid intima-media thickness (cIMT) were limited to Western populations. Pregnancy in women is associated with physiologic changes that may influence the risk of cardiovascular disease. Comparing the association between number of children and cIMT in men and women can provide insights on whether the association may be due to pregnancy. We investigated the association between number of children and cIMT among 718 female (mean age 37.5 years) and 417 male participants (mean age 41.3 years), randomly selected from the Health Effect of Arsenic Longitudinal Study (HEALS), a population-based cohort study in Bangladesh. Multivariate linear regression was used to assess the association and to control for education attainment, history of diabetes, age, smoking, betel use, BMI, systolic blood pressure, and diastolic blood pressure. The average number of children was 4.43 for women and 3.74 for men. There were no nulliparous women. We observed a positive association between number of children and cIMT in women. Mean cIMT increased by 4.5 µm (95% CI, 0.8-8.1) per increment of one birth (P = 0.02). Compared to women with two children, cIMT in women with 4 children and ≥5 children was 23.6µm (95%CI, 2.6-44.7; P = 0.03) and 25.1 µm (95%CI, 3.5-46.6; P = 0.02) greater, respectively. The association was not modified by BMI, SBP, betel use or age. Data in men showed no evidence of association (P = 0.4). The finding suggests a role of high parity in atherosclerosis in women of a low-income, high parity population.

Arsenic Exposure from Drinking Water and Urinary Metabolomics: Associations and Long-Term Reproducibility in Bangladesh Adults.

BACKGROUND: Chronic exposure to inorganic arsenic from drinking water has been associated with a host of cancer and noncancer diseases. The application of metabolomics in epidemiologic studies may allow researchers to identify biomarkers associated with arsenic exposure and its health effects. OBJECTIVE: Our goal was to evaluate the long-term reproducibility of urinary metabolites and associations between reproducible metabolites and arsenic exposure. METHODS: We studied samples and data from 112 nonsmoking participants (58 men and 54 women) who were free of any major chronic diseases and who were enrolled in the Health Effects of Arsenic Longitudinal Study (HEALS), a large prospective cohort study in Bangladesh. Using a global gas chromatography-mass spectrometry platform, we measured metabolites in their urine samples, which were collected at baseline and again 2 y apart, and estimated intraclass correlation coefficients (ICCs). Linear regression was used to assess the association between arsenic exposure at baseline and metabolite levels in baseline urine samples. RESULTS: We identified 2,519 molecular features that were present in all 224 urine samples from the 112 participants, of which 301 had an ICC of ≥0.60. Of the 301 molecular features, water arsenic was significantly related to 31 molecular features and urinary arsenic was significantly related to 74 molecular features after adjusting for multiple comparisons. Six metabolites with a confirmed identity were identified from the 82 molecular features that were significantly associated with either water arsenic or urinary arsenic after adjustment for multiple comparisons. CONCLUSIONS: Our study identified urinary metabolites with long-term reproducibility that were associated with arsenic exposure. The data established the feasibility of using metabolomics in future larger studies. https://doi.org/10.1289/EHP1992.

Associations between prenatal arsenic exposure with adverse pregnancy outcome and child mortality.

BACKGROUND: Chronic arsenic exposure is a public health concern in many parts of the world, with elevated concentrations in groundwater posing a threat to millions of people. Arsenic is associated with various cancers and an array of chronic diseases; however, the relationship with adverse pregnancy outcomes and child mortality is less established. OBJECTIVES: We evaluated associations between individual-level prenatal arsenic exposure with adverse pregnancy outcomes and child mortality in a pregnancy study among 498 women nested in a larger population-based cohort in rural Bangladesh. METHODS: Creatinine-adjusted urinary total arsenic concentration, a comprehensive measure of exposure from water, food, and air sources, reflective of the prenatal period was available for participants. Self-reported pregnancy outcomes (livebirth, stillbirth, spontaneous/elective abortion) were ascertained. Generalized estimating equations, accounting for multiple pregnancies of participants, were used to estimate odds ratios and 95% confidence intervals in relation to adverse pregnancy outcomes. Vital status of livebirths was subsequently ascertained through November 2015. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals in relation to child mortality. RESULTS: We observed a significant association between prenatal arsenic exposure and the risk of stillbirth (greater than median; adjusted OR = 2.50; 95% CI = 1.04, 6.01). We also observed elevated risk of child mortality (greater than median; adjusted HR = 1.92; 95% CI = 0.78, 4.68) in relation to prenatal arsenic exposure. CONCLUSIONS: Prospective studies should continue to evaluate prenatal and early life health effects of arsenic exposure and arsenic remediation strategies for women of child-bearing age.

The association between telomere length and mortality in Bangladesh.

Telomeres are tandem repeat sequences at the end of chromosomes that bind proteins to protect chromosome ends. Telomeres shorten with age, and shorter leukocyte telomere length (TL) has been associated with overall mortality in numerous studies. However, this association has not been tested in populations outside of Europe and the U.S. We assessed the association between TL and subsequent mortality using data on 744 mortality cases and 761 age-/sex-matched controls sampled from >27,000 participants from three longitudinal Bangladeshi cohorts: Health Effects of Arsenic Longitudinal Study (HEALS), HEALS Expansion (HEALS-E), and Bangladesh Vitamin E and Selenium Trial (BEST). We used conditional logistic regression to estimate odds ratios (ORs) for the association between a standardized TL variable and overall mortality, as well as mortality from chronic diseases, respiratory diseases, circulatory diseases, and cancer. In HEALS and BEST, we observed an association between shorter TL and increased overall mortality (P=0.03 and P=0.03), mortality from chronic disease (P=0.01 and P=0.03) and mortality from circulatory disease (P=0.03 and P=0.04). Results from pooled analyses of all cohorts were consistent with HEALS and BEST. This is the first study demonstrating an association between short TL and increased mortality in a population of non-European ancestry.

Major dietary patterns and carotid intima-media thickness in Bangladesh.

OBJECTIVE: Carotid intima-media thickness (IMT) is a validated surrogate marker of preclinical atherosclerosis and is predictive of cardiovascular morbidity and mortality. Research on the association between IMT and diet, however, is lacking, especially in low-income countries or low-BMI populations. DESIGN: Cross-sectional analysis. Dietary intakes were measured using a validated, thirty-nine-item FFQ at baseline cohort recruitment. IMT measurements were obtained from 2010-2011. SETTING: Rural Bangladesh. SUBJECTS: Participants (n 1149) randomly selected from the Health Effects of Arsenic Longitudinal Study, an ongoing, population-based, prospective cohort study established in 2000. Average age at IMT measurement was 45·5 years. RESULTS: Principal component analysis of reported food items yielded a 'balanced' diet, an 'animal protein' diet and a 'gourd and root vegetable' diet. We observed a positive association between the gourd/root vegetable diet and IMT, as each 1 sd increase in pattern adherence was related to a difference of 7·74 (95 % CI 2·86, 12·62) µm in IMT (P<0·01), controlling for age, sex, total energy intake, smoking status, BMI, systolic blood pressure and diabetes mellitus diagnoses. The balanced pattern was associated with lower IMT (-4·95 (95 % CI -9·78, -0·11) µm for each 1sd increase of adherence; P=0·045). CONCLUSIONS: A gourd/root vegetable diet in this Bangladeshi population positively correlated with carotid IMT, while a balanced diet was associated with decreased IMT.

Betel quid use and mortality in Bangladesh: a cohort study.

OBJECTIVE: To evaluate the potential effects of betel quid chewing on mortality. (A quid consists of betel nut, wrapped in betel leaves; tobacco is added to the quid by some users). METHODS: Prospective data were available on 20 033 individuals aged 18-75 years, living in Araihazar, Bangladesh. Demographic and exposure data were collected at baseline using a standardized questionnaire. Cause of death was defined by verbal autopsy questionnaires administered to next of kin. We estimated hazard ratios (HR) and their 95% confidence intervals (CI) for associations between betel use and mortality from all causes and from specific causes, using Cox proportional hazards models. We adjusted for age, sex, body mass index, educational attainment and tobacco smoking history. FINDINGS: There were 1072 deaths during an average of 10 years of follow-up. Participants who had ever used betel were significantly more likely to die from all causes (HR: 1.26; 95% CI: 1.09-1.44) and cancer (HR: 1.55; 95% CI: 1.09-2.22); but not cardiovascular disease (HR: 1.16; 95% CI: 0.93-1.43). These findings were robust to adjustment for potential confounders. There was a dose-response relationship between mortality from all causes and both the duration and the intensity of betel use. The population attributable fraction for betel use was 14.1% for deaths from all causes and 24.2% for cancer. CONCLUSION: Betel quid use was associated with mortality from all causes and from cancer in this cohort.

Dipstick proteinuria as a predictor of all-cause and cardiovascular disease mortality in Bangladesh: A prospective cohort study.

OBJECTIVE: Baseline, persistent, incident, and remittent dipstick proteinuria have never been tested as predictors of mortality in an undeveloped country. The goal of this study was to determine which of these four types of proteinuria (if any) predict mortality. METHODS: Baseline data was collected from 2000 to 2002 in Bangladesh from 11,121 adults. Vital status was ascertained over 11-12years. Cox models were used to evaluate proteinuria in relation to all-cause and cardiovascular disease (CVD) mortality. CVD mortality was evaluated only in those with baseline proteinuria. Persistent, remittent, and incident proteinuria were determined at the 2-year exam. RESULTS: Baseline proteinuria of 1+ or greater was significantly associated with all-cause (hazard ratio (HR) 2.87; 95% C.I., 1.71-4.80) and CVD mortality (HR: 3.55; 95% C.I., 1.81-6.95) compared to no proteinuria, adjusted for age, gender, arsenic well water concentration, education, hypertension, BMI, smoking, and diabetes mellitus. Persistent 1+ proteinuria had a stronger risk of death, 3.49 (1.64-7.41)-fold greater, than no proteinuria. Incident 1+ proteinuria had a 1.87 (0.92-3.78)-fold greater mortality over 9-10years. Remittent proteinuria revealed no increased mortality. CONCLUSIONS: Baseline, persistent, and incident dipstick proteinuria were predictors of all-cause mortality with persistent proteinuria having the greatest risk. In developing countries, those with 1+ dipstick proteinuria, particularly if persistent, should be targeted for definitive diagnosis and treatment. The two most common causes of proteinuria to search for are diabetes mellitus and hypertension.

Arsenic exposure, telomere length, and expression of telomere-related genes among Bangladeshi individuals.

BACKGROUND: Inorganic arsenic is a carcinogen whose mode of action may involve telomere dysfunction. Recent epidemiological studies suggest that chronic arsenic exposure is associated with longer telomeres and altered expression of telomere-related genes in peripheral blood. In this study, we evaluated the association of urinary arsenic concentration with expression of telomere-related genes and telomere length in Bangladeshi individuals with a wide range of arsenic exposure through naturally contaminated drinking water. METHODS: We used linear regression models to estimate associations between urinary arsenic and array-based expression measures for 69 telomere related genes using mononuclear cell RNA samples from 1799 individuals. Association between arsenic exposure and a qPCR-based telomere length measure was assessed among 167 individuals. RESULTS: Urinary arsenic was positively associated with expression of WRN, and negatively associated with TERF2, DKC1, TERF2IP and OBFC1 (all P<0.00035, Bonferroni-corrected threshold). We detected interaction between urinary arsenic and arsenic metabolism efficiency in relation to expression of WRN (P for interaction =0.00008). In addition, we observed that very high arsenic exposure was associated with longer telomeres compared to very low exposure (P=0.02). DISCUSSION: Our findings suggest that arsenic's carcinogenic mode of action may involve alteration of telomere maintenance and/or telomere damage. This study extends our knowledge regarding the effect of arsenic on telomere length and expression of telomere-related genes.

A prospective study of arm circumference and risk of death in Bangladesh.

BACKGROUND: Epidemiological studies have observed protective effects of mid-upper arm circumference (MUAC) against all-cause mortality mostly in Western populations. However, evidence on cause-specific mortality is limited. METHODS: The sample included 19 575 adults from a population-based cohort study in rural Bangladesh, who were followed up for an average of 7.9 years for mortality. Cox proportional hazards regression was used to evaluate the effect of MUAC, as well as the joint effect of body mass index (BMI) and MUAC, on the risk of death from any cause, cancer and cardiovascular disease (CVD). RESULTS: During 154 664 person-years of follow-up, 744 deaths including 312 deaths due to CVD and 125 deaths due to cancer were observed. There was a linear inverse relationship of MUAC with total and CVD mortality. Each 1-cm increase in MUAC was associated a reduced risk of death from any cause [hazard ratio (HR) = 0.85; 95% confidence interval (C), 0.81-0.89) and CVD (HR = 0.87; 95% CI, 0.80-0.94), after controlling for potential confounders. No apparent relationship between MUAC and the risk of death from cancer was observed. Among individuals with a low BMI (<18.5 kg/m(2)), a MUAC less than 24 cm was associated with increased risk for all-cause (HR = 1.81; 95% CI, 1.52-2.17) and CVD mortality (HR = 1.45; 95% CI, 1.11-1.91). CONCLUSIONS: MUAC may play a critical role on all-cause and CVD mortality in lean Asians.