Adsorption of Natural Gas in Metal-Organic Frameworks: Selectivity, Cyclability, and Comparison to Methane Adsorption.

Evaluation of metal-organic frameworks (MOFs) for adsorbed natural gas (ANG) technology employs pure methane as a surrogate for natural gas (NG). This approximation is problematic, as it ignores the impact of other heavier hydrocarbons present in NG, such as ethane and propane, which generally have more favorable adsorption interactions with MOFs compared to methane. Herein, using quantitative Raman spectroscopic analysis and Monte Carlo calculations, we demonstrate the adsorption selectivity of high-performing MOFs, such as MOF-5, MOF-177, and SNU-70, for a methane and ethane mixture (95:5) that mimics the composition of NG. The impact of selectivity on the storage and deliverable capacities of these adsorbents during successive cycles of adsorption and desorption, simulating the filling and emptying of an ANG tank, is also demonstrated. The study reveals a gradual reduction in the storage performance of MOFs, particularly with smaller pore volumes, due to ethane accumulation over long-term cycling, until a steady state is reached with substantially degraded storage performance.

Returning personal genetic information on susceptibility to arsenic toxicity to research participants in Bangladesh.

BACKGROUND: There is growing consensus that researchers should offer to return genetic results to participants, but returning results in lower-resource countries has received little attention. In this study, we return results on genetic susceptibility to arsenic toxicity to participants in a Bangladeshi cohort exposed to arsenic through naturally-contaminated drinking water. We examine the impact on behavioral changes related to exposure reduction. METHODS: We enrolled participants from the Health Effects of Arsenic Longitudinal Study who had (1) high arsenic (≥150 µg/g creatinine) in a recent urine sample and (2) existing data on genetic variants impacting arsenic metabolism efficiency (AS3MT and FTCD). We used genetic data to recruit three study groups, each with n = 103: (1) efficient metabolizers (low-risk), (2) inefficient metabolizers (high-risk), and (3) a randomly-selected control group (NCT05072132). At baseline, all participants received information on the effects of arsenic and how to reduce exposure by switching to a low arsenic well. The two intervention groups also received their arsenic metabolism efficiency status (based on their genetic results). Changes in behavior and arsenic exposure were assessed using questionnaires and urine arsenic measures after six months. RESULTS: Clear decreases in urine arsenic after six months were observed for all three groups. The inefficient group self-reported higher levels of attempted switching to lower arsenic wells than the other groups; however, there was no detectable difference in urine arsenic reduction among the three groups. Participants showed strong interest in receiving genetic results and found them useful. The inefficient group experienced higher levels of anxiety than the other groups. Among the efficient group, that receiving genetic results did not appear to hinder behavioral change. CONCLUSION: Returning genetic results increased self-reported exposure-reducing behaviors but did not have a detectable impact on reducing urine arsenic over and above a one-on-one educational intervention.

Microscale Determination of Binary Gas Adsorption Isotherms in MOFs.

The experimental determination of mixed gas isotherms is challenging and thus rarely performed. Nevertheless, characterizing the performance of adsorbents toward mixtures of gases is critical in most adsorptive separations. Here, the utility of Raman spectroscopy in determining binary gas adsorption isotherms on the microscale with metal-organic framework (MOF) single crystals is demonstrated for quantifying C2H6/CH4 selectivity. The influence of pore size on sorption selectivity is determined experimentally. The technique also allows determination of kinetics of methane adsorption in MOFs, which is critical for refueling times in adsorbed natural gas storage.

Arsenic exposure from drinking water and endothelial dysfunction in Bangladeshi adolescents.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, with ∼80% of CVD-related deaths occurring in low- and middle-income countries. Growing evidence suggests that chronic arsenic exposure may contribute to CVD through its effect on endothelial function in adults. However, few studies have examined the influence of arsenic exposure on cardiovascular health in children and adolescents. To examine arsenic's relation to preclinical markers of endothelial dysfunction, we enrolled 200 adolescent children (ages 15-19 years; median 17) of adult participants in the Health Effects of Arsenic Longitudinal Study (HEALS), in Araihazar, Bangladesh. Participants' arsenic exposure was determined by recall of lifetime well usage for drinking water. As part of HEALS, wells were color-coded to indicate arsenic level (<10 µg/L, 10-50 µg/L, >50 µg/L). Endothelial function was measured by recording fingertip arterial pulsatile volume change and reactive hyperemia index (RHI) score, an independent CVD risk factor, was calculated from these measurements. In linear regression models adjusted for participant's sex, age, education, maternal education, land ownership and body weight, individuals who reported always drinking water from wells with >50 µg/L arsenic had a 11.75% lower level of RHI (95% CI: -21.26, -1.09, p = 0.03), as compared to participants who drank exclusively from wells with ≤50 µg/L arsenic. Sex-stratified analyses suggest that these associations were stronger in female participants. As compared to individuals who drank exclusively from wells with ≤50 µg/L arsenic, the use of wells with >50 µg/L arsenic was associated with 14.36% lower RHI (95% CI: -25.69, -1.29, p = 0.03) in females, as compared to 5.35% lower RHI (95% CI: -22.28, 15.37, p = 0.58) in males for the same comparison. Our results suggest that chronic arsenic exposure may be related to endothelial dysfunction in adolescents, especially among females. Further work is needed to confirm these findings and examine whether these changes may increase risk of later adverse cardiovascular health events.

Computational Identification and Experimental Demonstration of High-Performance Methane Sorbents.

Remarkable methane uptake is demonstrated experimentally in three metal-organic frameworks (MOFs) identified by computational screening: UTSA-76, UMCM-152 and DUT-23-Cu. These MOFs outperform the benchmark sorbent, HKUST-1, both volumetrically and gravimetrically, under a pressure swing of 80 to 5 bar at 298 K. Although high uptake at elevated pressure is critical for achieving this performance, a low density of high-affinity sites (coordinatively unsaturated metal centers) also contributes to a more complete release of stored gas at low pressure. The identification of these MOFs facilitates the efficient storage of natural gas via adsorption and provides further evidence of the utility of computational screening in identifying overlooked sorbents.

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.

The contribution of parent-to-offspring transmission of telomeres to the heritability of telomere length in humans.

Leukocyte telomere length (LTL) is a heritable trait with two potential sources of heritability (h2): inherited variation in non-telomeric regions (e.g., SNPs that influence telomere maintenance) and variability in the lengths of telomeres in gametes that produce offspring zygotes (i.e., "direct" inheritance). Prior studies of LTL h2 have not attempted to disentangle these two sources. Here, we use a novel approach for detecting the direct inheritance of telomeres by studying the association between identity-by-descent (IBD) sharing at chromosome ends and phenotypic similarity in LTL. We measured genome-wide SNPs and LTL for a sample of 5069 Bangladeshi adults with substantial relatedness. For each of the 6318 relative pairs identified, we used SNPs near the telomeres to estimate the number of chromosome ends shared IBD, a proxy for the number of telomeres shared IBD (Tshared). We then estimated the association between Tshared and the squared pairwise difference in LTL ((ΔLTL)2) within various classes of relatives (siblings, avuncular, cousins, and distant), adjusting for overall genetic relatedness (ϕ). The association between Tshared and (ΔLTL)2 was inverse among all relative pair types. In a meta-analysis including all relative pairs (ϕ > 0.05), the association between Tshared and (ΔLTL)2 (P = 0.01) was stronger than the association between ϕ and (ΔLTL)2 (P = 0.43). Our results provide strong evidence that telomere length (TL) in parental germ cells impacts TL in offspring cells and contributes to LTL h2 despite telomere "reprogramming" during embryonic development. Applying our method to larger studies will enable robust estimation of LTL h2 attributable to direct transmission of telomeres.

An increase in circulating B cells and B cell activation markers in peripheral blood is associated with cigarette smoking in a male cohort in Bangladesh.

In a cohort of approximately 200 Bangladeshi men, equally divided into smokers and non-smokers and equally divided by exposure to high and low levels of drinking water arsenic, we examined ex vivo a series of immune markers and immune function tests in peripheral blood mononuclear cells (PBMC). These immune parameters included PBMC cell surface markers (CSM) for B, T, monocytes, and NK cells, activated T and B cell markers, cytokine production in vitro, and analysis of CD4 subsets (Th1, Th2, Treg, and Th17 cells). We found that the effects of cigarette smoke were quite different than those associated with arsenic or polycyclic aromatic hydrocarbon (PAH)-DNA adducts. Cigarette smoking was associated with a significant increase in the number of PAH-DNA adducts as well as an increase in urinary levels of 1-hydropxypyrene (1-OHP). After correcting for arsenic exposure and PAH-DNA adducts, we found that cigarette smoking was associated with an increase in the percentage of CD19+ B cells, as well as the percentage of activated B cells (CD19+, HLA-DRbright cells) found in PBMC. These findings demonstrate activation of the immune system during chronic exposure to cigarette smoke, which is a known risk factor for autoimmune diseases.

Genome-wide association study of telomere length among South Asians identifies a second RTEL1 association signal.

BACKGROUND: Leucocyte telomere length (TL) is a potential biomarker of ageing and risk for age-related disease. Leucocyte TL is heritable and shows substantial differences by race/ethnicity. Recent genome-wide association studies (GWAS) report ~10 loci harbouring SNPs associated with leucocyte TL, but these studies focus primarily on populations of European ancestry. OBJECTIVE: This study aims to enhance our understanding of genetic determinants of TL across populations. METHODS: We performed a GWAS of TL using data on 5075 Bangladeshi adults. We measured TL using one of two technologies (qPCR or a Luminex-based method) and used standardised variables as TL phenotypes. RESULTS: Our results replicate previously reported associations in the TERC and TERT regions (P=2.2×10-8 and P=6.4×10-6, respectively). We observed a novel association signal in the RTEL1 gene (intronic SNP rs2297439; P=2.82×10-7) that is independent of previously reported TL-associated SNPs in this region. The minor allele for rs2297439 is common in South Asian populations (≥0.25) but at lower frequencies in other populations (eg, 0.07 in Northern Europeans). Among the eight other previously reported association signals, all were directionally consistent with our study, but only rs8105767 (ZNF208) was nominally significant (P=0.003). SNP-based heritability estimates were as high as 44% when analysing close relatives but much lower when analysing distant relatives only. CONCLUSIONS: In this first GWAS of TL in a South Asian population, we replicate some, but not all, of the loci reported in prior GWAS of individuals of European ancestry, and we identify a novel second association signal at the RTEL1 locus.

Screening for gene-environment (G×E) interaction using omics data from exposed individuals: an application to gene-arsenic interaction.

Identifying gene-environment interactions is a central challenge in the quest to understand susceptibility to complex, multi-factorial diseases. Developing an understanding of how inter-individual variability in inherited genetic variation alters the effects of environmental exposures will enhance our knowledge of disease mechanisms and improve our ability to predict disease and target interventions to high-risk sub-populations. Limited progress has been made identifying gene-environment interactions in the epidemiological setting using existing statistical approaches for genome-wide searches for interaction. In this paper, we describe a novel two-step approach using omics data to conduct genome-wide searches for gene-environment interactions. Using existing genome-wide SNP data from a large Bangladeshi cohort study specifically designed to assess the effect of arsenic exposure on health, we evaluated gene-arsenic interactions by first conducting genome-wide searches for SNPs that modify the effect of arsenic on molecular phenotypes (gene expression and DNA methylation features). Using this set of SNPs showing evidence of interaction with arsenic in relation to molecular phenotypes, we then tested SNP-arsenic interactions in relation to skin lesions, a hallmark characteristic of arsenic toxicity. With the emergence of additional omics data in the epidemiologic setting, our approach may have the potential to boost power for genome-wide interaction research, enabling the identification of interactions that will enhance our understanding of disease etiology and our ability to develop interventions targeted at susceptible sub-populations.

A study of telomere length, arsenic exposure, and arsenic toxicity in a Bangladeshi cohort.

BACKGROUND: Chronic arsenic exposure is associated with increased risk for arsenical skin lesions, cancer, and other adverse health outcomes. One potential mechanism of arsenic toxicity is telomere dysfunction. However, prior epidemiological studies of arsenic exposure, telomere length (TL), and skin lesion are small and cross-sectional. We investigated the associations between arsenic exposure and TL and between baseline TL and incident skin lesion risk among individuals participating in the Health Effects of Arsenic Longitudinal Study in Bangladesh (2000-2009). METHODS: Quantitative PCR was used to measure the average TL of peripheral blood DNA collected at baseline. The association between baseline arsenic exposure (well water and urine) and TL was estimated in a randomly-selected subcohort (n = 1469). A nested case-control study (466 cases and 464 age- and sex-matched controls) was used to estimate the association between baseline TL and incident skin lesion risk (diagnosed < 8 years after baseline). RESULTS: No association was observed between arsenic exposure (water or urine) and TL. Among incident skin lesion cases and matched controls, we observed higher skin lesion risk among individuals with shorter TL (Ptrend = 1.5 × 10-5) with odds ratios of 2.60, 1.59, and 1.10 for the first (shortest), second, and third TL quartiles compared to the fourth (longest). CONCLUSIONS: Arsenic exposure was not associated with TL among Bangladeshi adults, suggesting that leukocyte TL may not reflect a primary mode of action for arsenic's toxicity. However, short TL was associated with increased skin lesion risk, and may be a biomarker of arsenic susceptibility modifying arsenic's effect on skin lesion risk.

Comparison of Fecal Collection Methods for Microbiota Studies in Bangladesh.

To our knowledge, fecal microbiota collection methods have not been evaluated in low- and middle-income countries. Therefore, we evaluated five different fecal sample collection methods for technical reproducibility, stability, and accuracy within the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh. Fifty participants from the HEALS provided fecal samples in the clinic which were aliquoted into no solution, 95% ethanol, RNAlater, postdevelopment fecal occult blood test (FOBT) cards, and fecal immunochemical test (FIT) tubes. Half of the aliquots were frozen immediately at -80°C (day 0) and the remaining samples were left at ambient temperature for 96 h and then frozen (day 4). Intraclass correlation coefficients (ICC) were calculated for the relative abundances of the top three phyla, for two alpha diversity measures, and for four beta diversity measures. The duplicate samples had relatively high ICCs for technical reproducibility at day 0 and day 4 (range, 0.79 to 0.99). The FOBT card and samples preserved in RNAlater and 95% ethanol had the highest ICCs for stability over 4 days. The FIT tube had lower stability measures overall. In comparison to the "gold standard" method using immediately frozen fecal samples with no solution, the ICCs for many of the microbial metrics were low, but the rank order appeared to be preserved as seen by the Spearman correlation. The FOBT cards, 95% ethanol, and RNAlater were effective fecal preservatives. These fecal collection methods are optimal for future cohort studies, particularly in low- and middle-income countries.IMPORTANCE The collection of fecal samples in prospective cohort studies is essential to provide the opportunity to study the effect of the human microbiota on numerous health conditions. However, these collection methods have not been adequately tested in low- and middle-income countries. We present estimates of technical reproducibility, stability at ambient temperature for 4 days, and accuracy comparing a "gold standard" for fecal samples in no solution, 95% ethanol, RNAlater, postdevelopment fecal occult blood test cards, and fecal immunochemical test tubes in a study conducted in Bangladesh. Fecal occult blood test cards and fecal samples stored in 95% ethanol or RNAlater adequately preserve fecal samples in this setting. Therefore, new studies in low- and middle-income countries should include collection of fecal samples using fecal occult blood test cards, 95% ethanol, or RNAlater for prospective cohort studies.

The association between socioeconomic status and subclinical atherosclerosis in a rural Bangladesh population.

BACKGROUND: In Bangladesh, CVD accounts for the majority of non-communicable mortality. The purpose of this study was to determine the role of socioeconomic status (SES) on subclinical atherosclerosis measured as carotid intima-media thickness (IMT) in a rural Bangladesh population. METHODS: Carotid IMT was measured between 2010 and 2011 in 1022 participants (average age 46, 40% male) randomly selected from the Health Effects of Arsenic Longitudinal Study (HEALS), a population-based prospective cohort study based in rural Bangladesh. SES was measured as occupation type, land ownership, educational attainment, and television ownership. RESULTS: Half of the participants received formal education (53%) and under half owned land (48%) and a television (44%). Women were primarily homemakers (95%) and men worked as factory workers (24%), laborers (18%), or in business (55%). In univariate analysis, those owning greater than one acre of land (p=0.03), owning a television (p=0.02), or laborers and business owners compared to factory workers had higher levels of carotid IMT (p<0.01). In multivariate analysis after adjustment for confounders, only men employed in the business sector had elevated carotid IMT compared to factory workers. The association was strongest in older men (58.7µm, 95% CI 17.2-100.0, ≥50years old) compared to younger men (13.7µm, 95% CI -7.8-35.2, <50years old). CONCLUSION: Business sector employment was positively associated with subclinical atherosclerosis after adjustment for confounders. This finding is consistent with evidence from other developing nations suggesting that certain SES factors are independent predictors of CVD.

Association between genome-wide copy number variation and arsenic-induced skin lesions: a prospective study.

BACKGROUND: Exposure to arsenic in drinking water is a global health problem and arsenic-induced skin lesions are hallmark of chronic arsenic toxicity. We and others have reported germline genetic variations as risk factors for such skin lesions. The role of copy number variation (CNV) in the germline DNA in this regard is unknown. METHODS: From a large prospectively followed-up cohort, exposed to arsenic, we randomly selected 2171 subjects without arsenic-induced skin lesions at enrollment and genotyped their whole blood DNA samples on Illumina Cyto12v2.1 SNP chips to generate DNA copy number. Participants were followed up every 2 years for a total of 8 years, especially for the development of skin lesions. In Cox regression models, each CNV segment was used as a predictor, accounting for other potential covariates, for incidence of skin lesions. RESULT: The presence of genomic deletion(s) in a number of genes (OR5J2, GOLGA6L7P, APBA2, GALNTL5, VN1R31P, PHKG1P2, SGCZ, ZNF658) and lincRNA genes (RP11-76I14.1, CTC-535 M15.2, RP11-73B2.2) were associated with higher risk [HR between 1.67 (CI 1.3-2.1) and 2.15 (CI 1.5-2.9) for different CNVs] for development of skin lesions independent of gender, age, and arsenic exposure. Some deletions had stronger effect in a specific gender (ZNF658 in males, SGCZ in females) and some had stronger effect in higher arsenic exposure (lincRNA CTD-3179P9.1) suggesting a possible gene-environment interaction. CONCLUSION: This first genome-wide CNV study in a prospectively followed-up large cohort, exposed to arsenic, suggests that DNA deletion in several genes and lincRNA genes may predispose an individual to a higher risk of development of arsenic-induced skin lesions.

Predictions of the physicochemical properties of amino acid side chain analogs using molecular simulation.

A candidate drug compound is released for clinical trails (in vivo activity) only if its physicochemical properties meet desirable bioavailability and partitioning criteria. Amino acid side chain analogs play vital role in the functionalities of protein and peptides and as such are important in drug discovery. We demonstrate here that the predictions of solvation free energies in water, in 1-octanol, and self-solvation free energies computed using force field-based expanded ensemble molecular dynamics simulation provide good accuracy compared to existing empirical and semi-empirical methods. These solvation free energies are then, as shown here, used for the prediction of a wide range of physicochemical properties important in the assessment of bioavailability and partitioning of compounds. In particular, we consider here the vapor pressure, the solubility in both water and 1-octanol, and the air-water, air-octanol, and octanol-water partition coefficients of amino acid side chain analogs computed from the solvation free energies. The calculated solvation free energies using different force fields are compared against each other and with available experimental data. The protocol here can also be used for a newly designed drug and other molecules where force field parameters and charges are obtained from density functional theory.

Periodontal diseases and carotid intima-media thickness in Bangladesh.

AIM: To evaluate the relationship between periodontal diseases and subclinical atherosclerosis in a younger and lean South Asian population. METHODS: We conducted a cross-sectional study in 917 subjects (mean age 46 years and mean body mass index 21.1 kg/m2 ) from the Health Effects of Arsenic Longitudinal Study in Bangladesh. Multivariate linear regression models were used to assess the associations between multiple clinical measures of periodontal diseases and carotid intima-media thickness (IMT). RESULTS: Mean attachment loss (AL) and percentage of sites with AL ≥ 4 mm (% AL ≥ 4) were associated with increased IMT. The IMT was 20.0-µm (95% CI: 2.2, 37.8) and 26.5-µm (95% CI: 8.9, 44.1) higher in subjects in the top quartile of mean AL (>3.72 mm) and % AL ≥ 4 (>58.4%), respectively, compared to those in the bottom quartile. In a subset of 366 subjects, mean AL was positively associated with plasma levels of matrix metalloproteinase-9 (p < 0.05) and soluble intercellular adhesion molecule-1 (p < 0.01). CONCLUSIONS: Attachment loss was associated with subclinical atherosclerosis in this young and lean Bangladeshi population. Future prospective studies are needed to confirm this association.

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.

Gene-arsenic interaction in longitudinal changes of blood pressure: Findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide and mounting evidence indicates that toxicant exposures can profoundly impact on CVD risk. Epidemiologic studies have suggested that arsenic (As) exposure is positively related to increases in blood pressure (BP), a primary CVD risk factor. However, evidence of whether genetic susceptibility can modify the association between As and BP is lacking. In this study, we used mixed effect models adjusted for potential confounders to examine the interaction between As exposure from well water and potential genetic modifiers on longitudinal change in BP over approximately 7years of follow-up in 1137 subjects selected from the Health Effects of Arsenic Longitudinal Study (HEALS) cohort in Bangladesh. Genotyping was conducted for 235 SNPs in 18 genes related to As metabolism, oxidative stress and endothelial function. We observed interactions between 44 SNPs with well water As for one or more BP outcome measures (systolic, diastolic, or pulse pressure (PP)) over the course of follow-up. The interaction between CYBA rs3794624 and well water As on annual PP remained statistically significant after correction for multiple comparisons (FDR-adjusted p for interaction=0.05). Among individuals with the rs3794624 variant genotype, well water As was associated with a 2.23mmHg (95% CI: 1.14-3.32) greater annual increase in PP, while among those with the wild type, well water As was associated with a 0.13mmHg (95% CI: 0.02-0.23) greater annual increase in PP. Our results suggest that genetic variability may contribute to As-associated increases in BP over time.

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.