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The objective of this study was to design and evaluate a household-level arsenic education and well water arsenic testing intervention to increase arsenic awareness in Bangladesh. The authors randomly selected 1,000 study respondents located in 20 villages in Singair, Bangladesh. The main outcome was the change in knowledge of arsenic from baseline to follow-up 4 to 6 months after the household received the intervention. This was assessed through a pre- and post-intervention quiz concerning knowledge of arsenic. Respondents were between 18 and 102 years of age, with an average age of 37 years; 99.9% were female. The knowledge of arsenic quiz scores for study participants were significantly higher at follow-up compared with baseline. The intervention was effective in increasing awareness of the safe uses of arsenic-contaminated water and dispelling the misconception that boiling water removes arsenic. At follow-up, nearly all respondents were able to correctly identify the meaning of a red (contaminated) and green (arsenic safe) well relative to arsenic (99%). The educational program also significantly increased the proportion of respondents who were able to correctly identify the health implications of arsenic exposure. However, the intervention was not effective in dispelling the misconceptions in the population that arsenicosis is contagious and that illnesses such as cholera, diarrhea, and vomiting could be caused by arsenic. Further research is needed to develop effective communication strategies to dispel these misconceptions. This study demonstrates that a household-level arsenic educational program can be used to significantly increase arsenic awareness in Bangladesh. (Contains 4 tables.)

BackgroundA number of cohort studies have collected Scope mouthwash samples by mail, which are being used for microbiota measurements. We evaluated the stability of Scope mouthwash samples at ambient temperature and determined the comparability of Scope mouthwash with saliva collection using the OMNIgene ORAL Kit.MethodsFifty-three healthy volunteers from Mayo Clinic and 50 cohort members from Bangladesh provided oral samples. One aliquot of the OMNIgene ORAL and Scope mouthwash were frozen immediately and one aliquot of the Scope mouthwash remained at ambient temperature for 4 days and was then frozen. DNA was extracted and the V4 region of the 16S rRNA gene was PCR amplified and sequenced using the HiSeq. Intraclass correlation coefficients (ICC) were calculated.ResultsThe overall stability of the Scope mouthwash samples was relatively high for alpha and beta diversity. For example, the meta-analyzed ICC for the Shannon index was 0.86 (95% confidence interval, 0.76-0.96). Similarly, the ICCs for the relative abundance of the top 25 genera were generally high. The comparability of the two sample types was relatively low when measured using ICCs, but were increased by using a Spearman correlation coefficient (SCC) to compare the rank order of individuals.ConclusionsOverall, the Scope mouthwash samples appear to be stable at ambient temperature, which suggests that oral rinse samples received by the mail can be used for microbial analyses. However, Scope mouthwash samples were distinct compared with OMNIgene ORAL samples.ImpactStudies should try to compare oral microbial metrics within one sample collection type.

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.

BACKGROUND: Readymade garment workers globally experience distinctive vulnerabilities at the workplace. The situation is worse in many developing countries. However, there is a lack of scientific evidence about the health and safety of garment workers in the workplace. OBJECTIVE: The objective of this study was to examine the patterns of illness and injury of garment workers, factory level health safety policies and programs, and views and perception of management staff at factories in Bangladesh. METHODS: This mixed-method study was conducted among garment workers and management level staff between January 2018 and April 2019. We extracted 4000 health records of the workers who attended primary health care centers of the factories and conducted 11 key informant interviews using qualitative method from different management-level staff. RESULTS: Half of the workers (51.0%) were working in the sewing section following 12.8% in quality control and 12.3% in the laundry section. A review of the medical records showed that peptic ulcer diseases (PUDs) (19.2%), fever (11.7%), loose motion (10.3%), and headache (9.4%). Needle injury was uncommon for taking medical care. Occupational safety and health management, safe drinking water, access to maternity leave and other facilities were better in large and medium factories compared with those in small factories. CONCLUSIONS: Although the readymade garments sector is one of the largest sources of foreign currency revenue earnings in Bangladesh, occupational health and safety issues of workers remain a big concern. Thus, support from the government needs more focus on the health and safety of workers. [ABSTRACT FROM AUTHOR]

BackgroundBetel quid is chewed by 600 million people worldwide and it has been linked to obesity and cardiovascular disease. The purpose of our study was to examine the prevalence and predictors of betel quid chewing in a rural area of Bangladesh, and determine its effects on body mass index (BMI) and blood pressure.MethodsIn this population-based prospective study, we analysed data on 19 934 Bangladeshi adults. Linear and multivariate logistic regression was used to determine the socio-demographic predictors of betel quid chewing and the effect of betel quid on change in BMI and on systolic and diastolic blood pressure, pulse pressure, arterial pressure, overweight or obesity, and hypertension.ResultsAt baseline, betel quid was chewed by 33.2% of the cohort (35.5% of men, 31.6% of women). In a subsample in which we collected methods of use, 17.5% chewed it without tobacco and 82.5% chewed it with tobacco. In multivariate analysis, betel quid chewing was associated with female sex, older age, tobacco smoking and lower socio-economic status, as measured by fewer years of formal education and not owning land. Betel quid was chewed more times per day among women and older persons. At follow-up, persons who chewed betel quid without tobacco had higher systolic blood pressure, diastolic blood pressure and arterial pressure in comparison with never users. After controlling for other explanatory variables, chewing betel quid without tobacco was associated with general hypertension [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.04-2.10] and systolic hypertension (OR 1.55, 95% CI 1.01-2.37). We did not observe associations of betel quid chewing with BMI or overweight.ConclusionsBetel quid chewing is likely contributing to high blood pressure in Bangladesh, particularly among women.

The study aimed to find a demographic correlation between emotional intelligence and life satisfaction of students of the Chattogram district in Bangladesh. The sample consisted of 160 (80 males and 80 females) students who were selected purposively from the Chottrogram district in Bangladesh. Their age ranges were from 18 years to 25 years. The Bangla version of the Emotional Intelligence Scale (EIS) (Hossain and Uddin, 2008) and the Satisfaction with Life Scale (SWLS) (Ilyas, 2001) were used to measure emotional intelligence and life satisfaction. The findings of the present study showed that female students were significantly more emotional intelligence (t = -4.99, df = 158, p <.001) and life satisfaction (t = -6.24, df = 158, p <.001) than male students. The MS students showed more emotional intelligence (F = 8.18, df = 4, p <.001) and life satisfaction (F = 7.00, df = 4, p <.001) than first, second, third, and fourth-year undergraduate student. Findings also showed that students whose family income was above 30000 taka showed more emotional intelligence (F = 6.84, df = 2, p <.001) and life satisfaction (F = 3.40, df = 2, p <.04) than students whose family income was lower. Finally, a positive correlation (r = .85**, p <.01) was found between emotional intelligence and the life satisfaction. The findings are used to recommend that university authorities should provide, scholarship programs, counseling, and guidance service for a student especially for poor undergraduate students, so that they will be productive citizens. [ABSTRACT FROM AUTHOR]

Abstract Objective To reduce arsenic (As) exposure, we evaluated the effectiveness of training community members to perform water arsenic (WAs) testing and provide As education compared to sending representatives from outside communities to conduct these tasks. Methods We conducted a cluster based randomized controlled trial of 20 villages in Singair, Bangladesh. Fifty eligible respondents were randomly selected in each village. In 10 villages, a community member provided As education and WAs testing. In a second set of 10 villages an outside representative performed these tasks. Results Overall, 53% of respondents using As contaminated wells, relative to the Bangladesh As standard of 50 μg/L, at baseline switched after receiving the intervention. Further, when there was less than 60% arsenic contaminated wells in a village, the classification used by the Bangladeshi and UNICEF, 74% of study households in the community tester villages, and 72% of households in the outside tester villages reported switching to an As safe drinking water source . Switching was more common in the outside-tester (63%) versus community-tester villages (44%). However, after adjusting for the availability of arsenic safe drinking water sources, well switching did not differ significantly by type of As tester (Odds ratio =0.86[95% confidence interval 0.42-1.77). At follow-up, among those using As contaminated wells who switched to safe wells, average urinary As concentrations significantly decreased. Conclusion The overall intervention was effective in reducing As exposure provided there were As-safe drinking water sources available. However, there was not a significant difference observed in the ability of the community and outside testers to encourage study households to use As-safe water sources. The findings of this study suggest that As education and WAs testing programs provided by As testers, irrespective of their residence, could be used as an effective, low cost approach to reduce As exposure in many As-affected areas of Bangladesh.

Heavy metal contamination is widespread in Bangladesh. Previous studies have observed lead increases blood pressure over time. However, the role of other metal contaminants and essential micronutrients, which could also adversely affect blood pressure or act as protective factors, is understudied. We therefore evaluated the associations of lead, manganese, and selenium with blood and pulse pressure trajectories. We prospectively followed placebo-assigned participants nested within a randomized trial for the prevention of arsenic-related skin cancer (n = 255). Blood lead, manganese, and selenium were measured at baseline; blood pressure was measured at baseline and at 3 biennial follow-up examinations. Mixed-effect linear regression models were used to estimate associations with average annual changes in systolic, diastolic, and pulse pressure. In models simultaneously adjusted for baseline blood lead, manganese, and selenium concentrations in addition to other potential confounders, lead was linearly associated with increases in systolic blood pressure, but not with diastolic blood pressure or pulse pressure. A non-linear association was observed for manganese, such that mid-range concentrations were associated with decreases in systolic, diastolic, and pulse pressure. Baseline selenium concentrations in the highest quartile were also associated with longitudinal decreases in both systolic and diastolic blood pressure, while null associations were observed with pulse pressure. In exploratory analyses, the combination of mid-range manganese and high selenium concentrations completely offset lead-associated increases in blood and pulse pressure. The results indicate a direct, linear association of lead exposure with systolic blood pressure, and manganese and selenium exposures within certain ranges may have a blood pressure-lowering effect in this population. • Metal contamination is endemic in Bangladesh where elevated exposure to certain toxic metals can result in hypertension. • Epidemiologic research on other metals, including essential nutrients, in relation to blood pressure has been sparse. • ILead was related to higher blood pressure, whereas manganese and selenium within certain ranges were associated with declines. • This study highlights the potential for manganese and selenium as anti-hypertensive agents in a lead-exposed population. The findings of this study suggest toxic lead exposures remain a significant public health problem in Bangladesh where high levels are associated with high blood pressure; however, the nutritionally essential micronutrients manganese and selenium appear to confer protection from the hypertensive effects of lead. [ABSTRACT FROM AUTHOR]

Background: Arsenic exposure through drinking water persists in many regions. Inorganic As (InAs) is methylated to monomethylarsenical species (MMAs) and dimethyl-arsenical species (DMAs), facilitating urinary excretion. Arsenic methylation is dependent on one-carbon metabolism, which is influenced by nutritional factors such as folate and creatine. Objective: This study investigated the effects of folic acid (FA) and/or creatine supplementation on the proportion of As metabolites in urine. Design: In a 24-wk randomized, double-blinded, placebo-controlled trial, 622 participants were assigned to receive FA (400 or 800 μg per day), 3 g creatine per day, 400 μg FA + 3 g creatine per day, or placebo. The majority of participants were folate sufficient; all received As-removal water filters. From wk 12–24, half of the participants receiving FA received placebo. Results: Among groups receiving FA, the mean decrease in ln(%InAs) and %MMAs and increase in %DMAs exceeded those of the placebo group at wk 6 and 12 (P < 0.05). In the creatine group, the mean decrease in %MMAs exceeded that of the placebo group at wk 6 and 12 (P < 0.05); creatine supplementation did not affect change in %InAs or %DMAs. The decrease in %MMAs at wk 6 and 12 was larger in the 800 μg FA than in the 400 μg FA group (P = 0.034). There were no differences in treatment effects between the 400 μg FA and creatine + FA groups. Data suggest a rebound in As metabolite proportions after FA cessation; at wk 24, log(%InAs) and %DMAs were not significantly different than baseline levels among participants who discontinued FA supplementation. Conclusions: The results of this study confirm that FA supplementation rapidly and significantly increases methylation of InAs to DMAs. Further research is needed to understand the strong cross-sectional associations between urinary creatinine and As methylation in previous studies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ObjectiveCarotid 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.DesignCross-sectional analysis. Dietary intakes were measured using a validated, thirty-nine-item FFQ at baseline cohort recruitment. IMT measurements were obtained from 2010–2011.SettingRural Bangladesh.SubjectsParticipants (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.ResultsPrincipal 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).ConclusionsA gourd/root vegetable diet in this Bangladeshi population positively correlated with carotid IMT, while a balanced diet was associated with decreased IMT. [ABSTRACT FROM PUBLISHER]

Background: Creatine synthesis from guanidinoacetate consumes ~50% of s-adenosylmethionine (SAM)-derived methyl groups, accounting for an equivalent proportion of s-adenosylhomocysteine (SAH) and total homocysteine (tHcys) synthesis. Dietary creatine inhibits the synthesis of guanidinoacetate, thereby lowering plasma tHcys in rats.Objective: We tested the hypotheses that creatine supplementation lowers plasma guanidinoacetate, increases blood SAM, lowers blood SAH, and lowers plasma tHcys.Methods: Bangladeshi adults were randomly assigned to receive 1 of 4 treatments for 12 wk: placebo (n = 101), 3 g/d creatine (Cr; n = 101), 400 μg/d folic acid (FA; n = 153), or 3 g/d creatine plus 400 μg/d folic acid (Cr+FA; n = 103). The outcomes of plasma guanidinoacetate and tHcys, as well as whole blood SAM and SAH, were analyzed at baseline and week 12 by HPLC. Treatment effects of creatine supplementation were examined with the use of the group comparisons of Cr vs. placebo and Cr+FA vs. FA.Results: Plasma guanidinoacetate declined by 10.6% (95% CI: 4.9, 15.9) in the Cr group while increasing nonsignificantly in the placebo group (3.7%; 95% CI: -0.8, 8.5) (Pgroup difference = 0.0002). Similarly, plasma guanidinoacetate declined by 9.0% (95% CI: 3.4, 14.2) in the Cr+FA group while increasing in the FA group (7.0%; 95% CI: 2.0, 12.2) (Pgroup difference < 0.0001). Plasma tHcys declined by 23.4% (95% CI: 19.5, 27.1) and 21.0% (95% CI: 16.4, 25.2) in the FA and Cr+FA groups, respectively (Pgroup difference = 0.41), with no significant changes in the placebo or Cr groups (Pgroup difference = 0.35). A decrease in guanidinoacetate over time was associated with a decrease in tHcys over time in the Cr+FA group (β = 0.30; 95% CI: 0.17, 0.43; P < 0.0001).Conclusions: Our findings indicate that whereas creatine supplementation downregulates endogenous creatine synthesis, this may not on average lower plasma tHcys in humans. However, tHcys did decrease in those participants who experienced a decline in plasma guanidinoacetate while receiving creatine plus folic acid supplementation. This trial was registered at clinicaltrials.gov as NCT01050556. [ABSTRACT FROM AUTHOR]

Microplastics are omnipresent in the terrestrial and aquatic environment, and are considered as a potentially serious threat to the biodiversity and ecosystem. Pollution of plastic debris and microplastics in the inland and marine environment has raised concerns in Bangladesh, which is one of the most densely populated countries in the world. This review summarizes the research progress on separation and characterization of microplastics, as well as their occurrence and sources in Bangladesh. Despite of the first total ban on plastic bags in the world introduced back in 2002, microplastics have been ubiquitously detected in the country's inland and marine environment, with the majority of them coming from secondary sources. The microplastics observed in Bangladesh were dominated by fibers, which were derived mainly from textile sources. Polyethylene (PE), polyethylene terephthalate (PET), polypropylene (PP), and polyvinylchloride (PVC) were the most abundant polymers found for microplastics in the marine and freshwater environment of Bangladesh. Along with the identified research priorities to improve the understanding on the ecotoxicological effect and fate of microplastics, extensive and in-depth studies are required to bridge the knowledge gaps to enable comprehensive risk assessment of microplastic pollution on local ecosystems and human health, while effective management of plastic wastes and their recycling are necessary to alleviate this problem in the country. [Display omitted] • Bangladesh has significant plastic pollution despite the ban on plastic bags in 2002. • Fibers were the predominant type of microplastics found in the country's environment. • The microplastics originated primarily from the breakdown of discarded plastic wastes. • Key knowledge gaps on microplastic pollution and research priorities are identified. • The mis-management of plastic wastes should be tackled to curb microplastic pollution. [ABSTRACT FROM AUTHOR]

We conducted a cross-sectional study to evaluate the interrelationships between past arsenic exposure, biomarkers specific for susceptibility to arsenic exposure, and carotid intima-media thickness (cIMT) in 959 subjects from the Health Effects of Arsenic Longitudinal Study in Bangladesh. We measured cIMT levels on average 7.2 years after baseline during 2010–2011. Arsenic exposure was measured in well water at baseline and in urine samples collected at baseline and during follow-up. Every 1-standard-deviation increase in urinary arsenic (357.9 µg/g creatinine) and well-water arsenic (102.0 µg/L) concentration was related to a 11.7-µm (95% confidence interval (CI): 1.8, 21.6) and 5.1-µm (95% CI: −0.2, 10.3) increase in cIMT, respectively. For every 10% increase in monomethylarsonic acid (MMA) percentage, there was an increase of 12.1 µm (95% CI: 0.4, 23.8) in cIMT. Among participants with a higher urinary MMA percentage, a higher ratio of urinary MMA to inorganic arsenic, and a lower ratio of dimethylarsinic acid to MMA, the association between well-water arsenic and cIMT was stronger. The findings indicate an effect of past long-term arsenic exposure on cIMT, which may be potentiated by suboptimal or incomplete arsenic methylation capacity. Future prospective studies are needed to confirm the association between arsenic methylation capacity and atherosclerosis-related outcomes. [ABSTRACT FROM PUBLISHER]

Background: Few prospective studies have evaluated the influence of arsenic methylation capacity on cardiovascular disease (CVD) risk. Objective: We evaluated the association of arsenic exposure from drinking water and arsenic methylation capacity with CVD risk. Method: We conducted a case-cohort study of 369 incident fatal and nonfatal cases of CVD, including 211 cases of heart disease and 148 cases of stroke, and a subcohort of 1,109 subjects randomly selected from the 11,224 participants in the Health Effects of Arsenic Longitudinal Study (HEALS). Results: The adjusted hazard ratios (aHRs) for all CVD, heart disease, and stroke in association with a 1-SD increase in baseline well-water arsenic (112 µg/L) were 1.15 (95% CI: 1.01, 1.30), 1.20 (95% CI: 1.04, 1.38), and 1.08 (95% CI: 0.90, 1.30), respectively. aHRs for the second and third tertiles of percentage urinary monomethylarsonic acid (MMA%) relative to the lowest tertile, respectively, were 1.27 (95% CI: 0.85, 1.90) and 1.55 (95% CI: 1.08, 2.23) for all CVD, and 1.65 (95% CI: 1.05, 2.60) and 1.61 (95% CI: 1.04, 2.49) for heart disease specifically. The highest versus lowest ratio of urinary dimethylarsinic acid (DMA) to MMA was associated with a significantly decreased risk of CVD (aHR = 0.54; 95% CI: 0.34, 0.85) and heart disease (aHR = 0.54; 95% CI: 0.33, 0.88). There was no significant association between arsenic metabolite indices and stroke risk. The effects of incomplete arsenic methylation capacity--indicated by higher urinary MMA% or lower urinary DMA%-- with higher levels of well-water arsenic on heart disease risk were additive. There was some evidence of a synergy of incomplete methylation capacity with older age and cigarette smoking. Conclusions: Arsenic exposure from drinking water and the incomplete methylation capacity of arsenic were adversely associated with heart disease risk. [ABSTRACT FROM AUTHOR]

Background Epidemiologic research suggests that increased cancer risk due to chronic arsenic exposure persists for several decades even after the exposure has terminated. Observational studies suggest that antioxidants exert a protective effect on arsenical skin lesions and cancers among those chronically exposed to arsenic through drinking water. This study reports on the design, methods and baseline analyses from the Bangladesh Vitamin E and Selenium Trial ( BEST), a population-based chemoprevention study conducted among adults in Bangladesh with visible arsenic toxicity. Materials and methods Bangladesh Vitamin E and Selenium Trial is a 2×2 full factorial, double-blind, randomized controlled trial of 7000 adults having manifest arsenical skin lesions evaluating the efficacy of 6-year supplementation with alpha-tocopherol (100 mg daily) and L-selenomethionine (200 μg daily) for the prevention of nonmelanoma skin cancer. Results In cross-sectional analyses, we observed significant associations of skin lesion severity with male gender (female prevalence odds ratio ( POR) = 0·87; 95% CI = 0·79-0·96), older age (aged 36-45 years, POR = 1·27; 95% CI = 1·13-1·42; aged 46-55 years, POR = 1·44; 95% CI = 1·27-1·64 and aged 56-65 years, POR = 1·50; 95% CI = 1·26-1·78 compared with aged 25-35 years), hypertension ( POR = 1·29; 95% CI = 1·08-1·55), diabetes ( POR = 2·13; 95% CI = 1·32-3·46), asthma ( POR = 1·55; 95% CI = 1·03-2·32) and peptic ulcer disease ( POR = 1·20; 95% CI = 1·07-1·35). Conclusions We report novel associations between arsenical skin lesions with several common chronic diseases. With the rapidly increasing burden of preventable cancers in developing countries, efficient and feasible chemoprevention study designs and approaches, such as employed in BEST, may prove both timely and potentially beneficial in conceiving cancer chemoprevention trials in Bangladesh and beyond. [ABSTRACT FROM AUTHOR]

Background: Arsenic exposure from drinking water has been associated with heart disease; however, underlying mechanisms are uncertain. Objective: We evaluated the association between a history of arsenic exposure from drinking water and the prolongation of heart rate-corrected QT (QTc), PR, and QRS intervals. Method: We conducted a study of 1,715 participants enrolled at baseline from the Health Effects of Arsenic Longitudinal Study. We assessed the relationship of arsenic exposure in well water and urine samples at baseline with parameters of electrocardiogram (ECG) performed during 2005--2010, 5.9 years on average since baseline. Results: The adjusted odds ratio (OR) for QTc prolongation, defined as a QTc ≥ 450 msec in men and ≥460 msec in women, was 1.17 (95% CI: 1.01, 1.35) for a 1-SD increase in well-water arsenic (108.7 μg/L). The positive association appeared to be limited to women, with adjusted ORs of 1.24 (95% CI: 1.05, 1.47) and 1.24 (95% CI: 1.01, 1.53) for a 1-SD increase in baseline well-water and urinary arsenic, respectively, compared with 0.99 (95% CI: 0.73, 1.33) and 0.86 (95% CI: 0.49, 1.51) in men. There were no apparent associations of baseline well-water arsenic or urinary arsenic with PR or QRS prolongation in women or men. Conclusions: Long-term arsenic exposure from drinking water (average 95 μg/L; range, 0.1 --790 μg/L) was associated with subsequent QT-interval prolongation in women. Future longitudinal studies with repeated ECG measurements would be valuable in assessing the influence of changes in exposure. [ABSTRACT FROM AUTHOR]

The authors conducted a cross-sectional study to assess the relation between arsenic exposure from drinking water and plasma levels of markers of systemic inflammation and endothelial dysfunction (matrix metalloproteinase-9, myeloperoxidase, plasminogen activator inhibitor-1, soluble E-selectin, soluble intercellular adhesion molecule-1 (ICAM-1), and soluble vascular adhesion molecule-1 (VCAM-1)) using baseline data from 668 participants (age, >30 years) in the Health Effects of Arsenic Longitudinal Study in Bangladesh (2007–2008). Both well water arsenic and urinary arsenic were positively associated with plasma levels of soluble VCAM-1. For every 1-unit increase in log-transformed well water arsenic (ln μg/L) and urinary arsenic (ln μg/g creatinine), plasma soluble VCAM-1 was 1.02 (95% confidence interval: 1.01, 1.03) and 1.04 (95% confidence interval: 1.01, 1.07) times greater, respectively. There was a significant interaction between arsenic exposure and higher body mass index, such that the increased levels of plasminogen activator inhibitor-1 and soluble VCAM-1 associated with arsenic exposure were stronger among people with higher body mass index. The findings indicate an effect of chronic arsenic exposure from drinking water on vascular inflammation and endothelial dysfunction that could be modified by body mass index and also suggest a potential mechanism underlying the association between arsenic exposure and cardiovascular disease. [ABSTRACT FROM PUBLISHER]

Background: Several reports indicate that drinking water arsenic (WAs) and manganese (WMn) are associated with children's intellectual function. Very little is known, however, about possible associations with other neurologic outcomes such as motor function. Methods: We investigated the associations of WAs and WMn with motor function in 304 children in Bangladesh, 8-11 years of age. We measured As and Mn concentrations in drinking water, blood,urine, and toenails. We assessed motor function with the Bruininks-Oseretsky test, version 2, in four subscales-fine manual control (FMC), manual coordination (MC), body coordination (BC), and strength and agility-which can be summarized with a total motor composite score (TMC). Results: Log-transformed blood As was associated with decreases in TMC [β = -3.63; 95% confidence interval (CI): -6.72, -0.54; p < 0.01], FMC (β = -1.68; 95% CI: -3.19, -0.18; p < 0.05), and BC (β = -1.61; 95% CI: -2.72, -0.51; p < 0.01), with adjustment for sex, school attendance, head circumference, mother's intelligence, plasma ferritin, and blood Mn, lead, and selenium. Other measures of As exposure (WAs, urinary As, and toenail As) also were inversely associated with motor function scores, particularly TMC and BC. Square-transformed blood selenium was positively associated with TMC (β = 3.54; 95% CI: 1.10, 6.0; p < 0.01), FMC (β = 1.55; 95% CI: 0.40, 2.70; p < 0.005), and MC (β= 1.57; 95% CI: 0.60, 2.75; p < 0.005) in the unadjusted models. Mn exposure was not significantly associated with motor function. Conclusion: Our research demonstrates an adverse association of As exposure and a protective association of Se on motor function in children. [ABSTRACT FROM AUTHOR]

Elevated concentrations of arsenic in groundwater pose a public health threat to millions of people worldwide. The authors aimed to evaluate the association between arsenic exposure and skin lesion incidence among participants in the Health Effects of Arsenic Longitudinal Study (HEALS). The analyses used data on 10,182 adults free of skin lesions at baseline through the third biennial follow-up of the cohort (2000–2009). Discrete-time hazard regression models were used to estimate hazard ratios and 95% confidence intervals for incident skin lesions. Multivariate-adjusted hazard ratios for incident skin lesions comparing 10.1–50.0, 50.1–100.0, 100.1–200.0, and ≥200.1 μg/L with ≤10.0 μg/L of well water arsenic exposure were 1.17 (95% confidence interval (CI): 0.92, 1.49), 1.69 (95% CI: 1.33, 2.14), 1.97 (95% CI: 1.58, 2.46), and 2.98 (95% CI: 2.40, 3.71), respectively (Ptrend = 0.0001). Results were similar for the other measures of arsenic exposure, and the increased risks remained unchanged with changes in exposure in recent years. Dose-dependent associations were more pronounced in females, but the incidence of skin lesions was greater in males and older individuals. Chronic arsenic exposure from drinking water was associated with increased incidence of skin lesions, even at low levels of arsenic exposure (<100 μg/L). [ABSTRACT FROM PUBLISHER]

Background Proteinuria has been recognized as a marker for an increased risk of chronic renal disease. It is unclear whether arsenic (As) exposure from drinking water is associated with proteinuria.Methods We evaluated the association between As exposure from drinking water and proteinuria in 11 122 participants in the Health Effects of Arsenic Longitudinal Study (HEALS). Proteinuria was detected by urinary dipstick tests at baseline and at 2-year intervals. As exposure variables included baseline well As and changes in urinary As during follow-up modelled as time-dependent variables in the analyses.Results At baseline, well As was positively related to prevalence of proteinuria; prevalence odds ratios (PORs) for proteinuria in increasing quintiles of well As (&leq;7, 8–39, 40–91, 92–179 and 180–864 µg/l) were 1.00 (ref), POR 0.99 [95% confidence interval (CI) 0.77–1.27], POR 1.23 (95% CI 0.97–1.57), POR 1.50 (95% CI 1.18–1.89) and POR 1.59 (95% CI 1.26–2.00) (P for trend <0.01). Hazard ratios for incidence of proteinuria were POR 0.83 (95% CI 0.67–1.03) and POR 0.91 (95% CI 0.74–1.12) for participants with a decreasing level of >70 and 17–70 µg/l in urinary As over time, respectively, and were POR 1.17 (95% CI 0.97–1.42) and POR 1.42 (95% CI 1.16–1.73) for participants with an increasing level of 16–68 and >68 µg/l in urinary As over time, respectively, compared with the group with relatively little changes in urinary As as the reference group (urinary As −16 to 15 µg/l).Conclusion The findings suggest that there are adverse effects of As exposure on the risk of proteinuria and the effects are modifiable by recent changes in As exposure. [ABSTRACT FROM PUBLISHER]

Background: Essential tremor (ET) is one of the most common neurological diseases. Few prevalence studies have been conducted in South Asia, and none in Bangladesh, one of the most populated countries in the world. We estimated the prevalence of ET in a population-based study in Araihazar, Bangladesh. Methods: As part of an in-person evaluation in a health outcomes study, each study participant produced 2 handwriting samples, from which ET diagnoses were assigned by 2 independent movement disorder neurologists. Results: The crude prevalence of ET (age ≥18 years) was 19/1,229 [1.5%, 95% confidence interval (CI) = 1.0-2.4], and was similar in men and women. The crude prevalence was 2.5% in participants aged ≥40 years and was one half that (1.3%) among younger participants (<40 years), although the difference did not reach statistical significance (p = 0.18). The age-adjusted prevalence (United States 2000 census) was 2.0% (95% CI = 1.2-2.8). Conclusion: The crude prevalence of ET in Araihazar, Bangladesh, was 1.5%. There is 1 other population-based study in a developing country (Turkey) which, like ours, did not restrict enrollment to middle-aged or elderly individuals and did not rely on screening questionnaires; the crude prevalence in the 2 studies is very similar. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Dietary factors are believed to modulate arsenic toxicity, potentially influencing risk of arsenical skin lesions. The authors evaluated associations among dietary patterns, arsenic exposure, and skin lesion risk using baseline food frequency questionnaire data collected in the Health Effects of Arsenic Longitudinal Study (HEALS) in Araihazar, Bangladesh (2000–2009). They identified dietary patterns and estimated dietary pattern scores using factor analysis. Scores were tested for association with incident skin lesion risk and interaction with water arsenic exposure by using ∼6 years of follow-up data (814 events among 9,677 individuals) and discrete time hazards models (adjusting for key covariates). The authors identified 3 clear dietary patterns: the “gourd and root,” “vegetable,” and “animal protein” patterns. The gourd and root pattern score was inversely associated with skin lesion risk (Ptrend = 0.001), with hazard ratios of 0.86, 0.73, and 0.69 for the second, third, and fourth highest quartiles. Furthermore, the association between water arsenic and skin lesion incidence was stronger among participants with low gourd and root scores (multiplicative Pinteraction < 0.001; additive Pinteraction = 0.05). The vegetable pattern and animal protein pattern showed similar but weaker associations and interactions. Eating a diet rich in gourds and root vegetables and increasing dietary diversity may reduce arsenical skin lesion risk in Bangladesh. [ABSTRACT FROM PUBLISHER]

Skin lesions are classic clinical signs of toxicity due to long-term exposure to arsenic, and they are considered precursors to arsenic-related skin cancer. The authors prospectively evaluated synergisms between effects of arsenic exposure and those of tobacco use, sun exposure, and pesticide and fertilizer use on incident skin lesions using risk factor data from 5,042 men from the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh, which recruited participants from October 2000 to May 2002. Discrete time hazard models were used to estimate measures of synergistic interactions on the additive scale. The authors observed significant synergistic effects between various measures of arsenic exposure and smoking and fertilizer use. The relative excess risks for the interactions between smoking status and arsenic exposure were 0.12 (95% confidence interval: 0.06, 0.19) for water arsenic and 0.11 (95% confidence interval: 0.05, 0.15) for urinary arsenic measures, respectively. Significant synergistic effects were also observed between fertilizer use and water arsenic (relative excess risk for the interaction = 0.06, 95% confidence interval: 0.01, 0.12). This is the first prospective study based on individual-level data that supports a role for smoking and certain occupational risk factors in modification of the effect of long-term arsenic exposure on skin lesions. Understanding differential arsenic susceptibility allows researchers to develop interventions to prevent the health consequences of this massive problem in the Bangladeshi population and beyond. [ABSTRACT FROM PUBLISHER]

Background: Body mass index (BMI) (kg/m(2)) has a U- or J-shaped relationship with all-cause mortality in Western and East Asian populations. However, this relationship is not well characterized in Bangladesh, where the BMI distribution is shifted towards lower values.Methods: Using data on 11,445 individuals (aged 18-75 years) participating in the Health Effects of Arsenic Longitudinal Study (HEALS) in Araihazar, Bangladesh, we prospectively examined associations of BMI (measured at baseline) with all-cause mortality during approximately 6 years of follow-up. We also examined this relationship within strata of key covariates (sex, age, smoking, education and arsenic exposure). Cox proportional hazards models adjusted for these covariates and BMI-related illnesses were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for BMI categories defined by the World Health Organization.Results: Low BMI was strongly associated with increased mortality in this cohort (P-trend < 0.0001). Severe underweight (BMI < 16 kg/m(2); HR 2.06, CI 1.53-2.77) and moderate underweight (16.0-16.9 kg/m(2); HR 1.39, CI 1.01-2.90) were associated with increased all-cause mortality compared with normal BMI (18.6-22.9 kg/m(2)). The highest BMI category (> or =23.0 kg/m(2)) did not show a clear association with mortality (HR 1.10, CI 0.77-1.53). The BMI-mortality association was stronger among individuals with <5 years of formal education (interaction P = 0.02).Conclusions: Underweight (presumably due to malnutrition) is a major determinant of mortality in the rural Bangladeshi population. [ABSTRACT FROM AUTHOR]

This study investigated the relationship between near-surface lithology and the spatial variability of As concentrations using sediment grain-size analysis and electromagnetic induction survey in the southeast Bangladesh. It has been observed that the aquifers overlain by finer sediments have higher concentrations of As in groundwater, whereas As concentrations are remarkably low in aquifers having permeable sandy materials or thinner silt/clay layer at the surface. The near-surface lithology acts as a controlling factor for spatial distributions of groundwater As within the very shallow depths (<15 m). Shallow alluvial aquifers can provide low-As drinking water in many areas of the country when tube wells are properly installed after investigation of the overlying near-surface sediment attributes and hydraulic properties. [ABSTRACT FROM AUTHOR]

BACKGROUND: There is a need to identify and evaluate an effective mitigation program for arsenic exposure from drinking water in Bangladesh. OBJECTIVE: We evaluated the effectiveness of a multifaceted mitigation program to reduce As exposure among 11,746 individuals in a prospective cohort study initiated in 2000 in Araihazar, Bangladesh, by interviewing participants and measuring changes in urinary As levels. METHODS: The interventions included a) person-to-person reporting of well test results and health education; b) well labeling and village-level health education; and c) installations of 50 deep, low-As community wells in villages with the highest As exposure. RESULTS: Two years after these interventions, 58% of the 6,512 participants with unsafe wells (As = 50 µg) at baseline had responded by switching to other wells. Well labeling and village-level health education was positively related to switching to safe wells (As < 50 µg/L) among participants with unsafe wells [rate ratio (RR) = 1.84; 95% confidence interval (CI), 1.60-2.11] and inversely related to any well switching among those with safe wells (RR = 0.80; 95% CI, 0.66-0.98). The urinary As level in participants who switched to a well identified as safe (< 50 µg As/L) dropped from an average of 375 µg As/g creatinine to 200 µg As/g creatinine, a 46% reduction toward the average urinary As content of 136 µg As/g creatinine for participants that used safe wells throughout. Urinary As reduction was positively related to educational attainment, body mass index, never-smoking, absence of skin lesions, and time since switching (p for trend < 0.05). CONCLUSIONS: Our study shows that testing of wells and informing households of the consequences of As exposure, combined with installation of deep community wells where most needed, can effectively address the continuing public health emergency from arsenic in drinking water in Bangladesh. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. • Demonstrates the feasibility of returning results in lower resource settings. • Participants responded positively to genetic information and its utility. • A one-on-one informational intervention reduced arsenic exposure. • No additional exposure reduction was detected for returning genetic results. • Impact of returning results may be masked by effective informational intervention. [ABSTRACT FROM AUTHOR]

Chronic arsenic exposures are associated with multiple hematologic disturbances, including anemia. The goal of this study was to evaluate associations between arsenic exposures and hematological parameters among men and women who are chronically exposed to elevated levels of arsenic from drinking water. Hematologic analyses were performed on blood collected from 755 participants (45% male and 54% female) in the Health Effects of Arsenic Longitudinal Study (HEALS) cohort, Bangladesh. Herein, we used linear regression models to estimate associations between red blood cell (RBC) parameters (i.e., RBC counts, hematocrit (HCT), hemoglobin (Hgb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC)) and measurements of arsenic exposure (urinary arsenic and urinary arsenic metabolites). Arsenic exposures showed trending associations with decreased RBC counts in both men and women, a positive association with MCV in males, and an inverse association with MCHC among males, but not among non-smoking females. Among men, those who smoked had stronger associations between arsenic exposures and MCHC than non-smoking males. Collectively, our results show that arsenic exposures affect multiple RBC parameters and highlight potentially important sex differences in arsenic-induced hematotoxicity. • Arsenic exposures showed trending associations with decreased RBC counts in both men and women. • Arsenic exposures were positively associated with MCV and MCH among male participants. • Arsenic exposures were inversely associated with MCHC in smoking males but not in non-smoking males or females. • Associations between arsenic exposures and RBC parameters were stronger in men vs women. [ABSTRACT FROM AUTHOR]

Abstract Background Emerging data suggest that inorganic arsenic exposure and gut microbiome are associated with the risk of cardiovascular disease. The gut microbiome may modify disease risk associated with arsenic exposure. Our aim was to examine the inter-relationships between arsenic exposure, the gut microbiome, and carotid intima-media thickness (IMT)—a surrogate marker for atherosclerosis. Methods We recruited 250 participants from the Health Effects of Arsenic Longitudinal Study in Bangladesh, measured IMT and collected fecal samples in year 2015–2016. 16S rRNA gene sequencing was conducted on microbial DNA extracted from the fecal samples. Arsenic exposure was measured using data on arsenic concentration in drinking water wells over time to derive a time-weighted water arsenic index. Multivariable linear regression models were used to test the inter-relationships between arsenic exposure, relative abundance of selected bacterial taxa from phylum to genus levels, and IMT. Results We identified nominally significant associations between arsenic exposure, measured using either time-weighted water arsenic or urinary arsenic, and the relative abundances of several bacterial taxa from the phylum Tenericutes , Proteobacteria , and Firmicutes. However, none of the associations retained significance after correction for multiple testing. The relative abundances of the family Aeromonadaceae and genus Citrobacter were significantly associated with IMT after correction for multiple testing (P -value = 0.02 and 0.03, respectively). Every 1% increase in the relative abundance of Aeromonadaceae and Citrobacter was related to an 18.2-μm (95% CI: 7.8, 28.5) and 97.3-μm (95% CI: 42.3, 152.3) difference in IMT, respectively. These two taxa were also the only selected family and genus using the LASSO variable selection method. There was a significant interaction between Citrobacter and time-weighted water arsenic in IMT (P for interaction = 0.04). Conclusions Our findings suggest a role of Citrobacter in the development of atherosclerosis, especially among individuals with higher levels of arsenic exposure. Highlights • We identified nominally significant associations between arsenic exposure and the relative abundances of several bacterial taxa in the phylum Tenericutes , Proteobacteria , and Firmicutes. However, none of the associations retained significance after correction for multiple comparisons with FDR ≤ 5%. • The relative abundances of the family Aeromonadaceae and genus Citrobacter were significantly associated with carotid IMT after adjustment for multiple comparisons with FDR ≤ 5%. • There was a significant interaction between Citrobacter and time-weighted water arsenic in IMT (P -value = 0.04). • The data suggest that the gut microbiome may play an important role in the development of atherosclerosis, especially among individuals with higher levels of arsenic exposure. [ABSTRACT FROM AUTHOR]

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 ( P trend = 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. [ABSTRACT FROM AUTHOR]

Background Arsenic (As) methylation capacity in epidemiologic studies is typically indicated by the proportions of inorganic As (%InAs), monomethylarsonic acid (%MMA), and dimethylarsinic acid (%DMA) in urine as a fraction of total urinary As. The relationship between renal function and indicators of As methylation capacity has not been thoroughly investigated. Objectives Our two aims were to examine (1) associations between estimated glomerular filtration rate (eGFR) and %As metabolites in blood and urine, and (2) whether renal function modifies the relationship of blood %As metabolites with respective urinary %As metabolites. Methods In a cross-sectional study of 375 As-exposed Bangladeshi adults, we measured blood and urinary As metabolites, and calculated eGFR from plasma cystatin C. Results In covariate-adjusted linear models, a 1 ml/min/1.73 m 2 increase in eGFR was associated with a 0.39% increase in urinary %InAs ( p <0.0001) and a mean decrease in urinary %DMA of 0.07 ( p =0.0005). In the 292 participants with measurable blood As metabolites, the associations of eGFR with increased blood %InAs and decreased blood %DMA did not reach statistical significance. eGFR was not associated with urinary or blood %MMA in covariate-adjusted models. For a given increase in blood %InAs, the increase in urinary %InAs was smaller in those with reduced eGFR, compared to those with normal eGFR ( p =0.06); this effect modification was not observed for %MMA or %DMA. Conclusions Urinary excretion of InAs may be impaired in individuals with reduced renal function. Alternatively, increased As methylation capacity (as indicated by decreased urinary %InAs) may be detrimental to renal function. [ABSTRACT FROM AUTHOR]

Exposure to arsenic (As) in drinking water is a widespread public health problem leading to increased risk for multiple outcomes such as cancer, cardiovascular disease, and possibly renal disease; potential mechanisms include inflammation and oxidative stress. We tested the hypothesis that As exposure is associated with increased inflammation and decreased estimated glomerular filtration rate (eGFR) and examined whether the effects of As were modified by plasma glutathione (GSH), glutathione disulfide (GSSG), or the reduction potential of the GSSG/2GSH pair ( E h GSH). In a cross-sectional study of N = 374 Bangladeshi adults having a wide range of As exposure, we measured markers of inflammation (plasma C-reactive protein (CRP), α-1 acid glycoprotein (AGP)), renal function (eGFR), GSH, and GSSG. In covariate-adjusted models, a 10% increase in water As, urinary As adjusted for specific gravity (uAs), or blood As (bAs) was associated with a 0.74% ( p = 0.01), 0.90% ( p = 0.16), and 1.39% ( p = 0.07) increase in CRP, respectively; there was no association with AGP. A 10% increase in uAs or bAs was associated with an average reduction in eGFR of 0.16 ( p = 0.12) and 0.21 ml/min/1.73 m 2 ( p = 0.08), respectively. In stratified analyses, the effect of As exposure on CRP was observed only in participants having E h GSH > median (uAs p Wald = 0.03; bAs p Wald = 0.05). This was primarily driven by stronger effects of As exposure on CRP in participants with lower plasma GSH. The effects of As exposure on eGFR were not modified significantly by E h GSH, GSH, or GSSG. These data suggest that participants having lower plasma GSH and a more oxidized plasma E h GSH are at increased risk for As-induced inflammation. Future studies should evaluate whether antioxidant treatment lowers plasma E h GSH and reduces risk for As-induced diseases. [ABSTRACT FROM AUTHOR]

Abstract: Epidemiologic studies that evaluated genetic susceptibility for the effects of arsenic exposure from drinking water on subclinical atherosclerosis are limited. We conducted a cross-sectional study of 1078 participants randomly selected from the Health Effects of Arsenic Longitudinal Study in Bangladesh to evaluate whether the association between arsenic exposure and carotid artery intima–media thickness (cIMT) differs by 207 single-nucleotide polymorphisms (SNPs) in 18 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction. Although not statistically significant after correcting for multiple testing, nine SNPs in APOE, AS3MT, PNP, and TNF genes had a nominally statistically significant interaction with well-water arsenic in cIMT. For instance, the joint presence of a higher level of well-water arsenic (≥40.4μg/L) and the GG genotype of AS3MT rs3740392 was associated with a difference of 40.9μm (95% CI=14.4, 67.5) in cIMT, much greater than the difference of cIMT associated with the genotype alone (β=−5.1μm, 95% CI=−31.6, 21.3) or arsenic exposure alone (β=7.2μm, 95% CI=−3.1, 17.5). The pattern and magnitude of the interactions were similar when urinary arsenic was used as the exposure variable. Additionally, the at-risk genotypes of the AS3MT SNPs were positively related to the proportion of monomethylarsonic acid (MMA) in urine, which is indicative of arsenic methylation capacity. The findings provide novel evidence that genetic variants related to arsenic metabolism may play an important role in arsenic-induced subclinical atherosclerosis. Future replication studies in diverse populations are needed to confirm the findings. [Copyright &y& Elsevier]

Abstract: Arsenic (As) exposure has been associated with both urologic malignancy and renal dysfunction; however, its association with hematuria is unknown. We evaluated the association between drinking water As exposure and hematuria in 7843 men enrolled in the Health Effects of Arsenic Longitudinal Study (HEALS). Cross-sectional analysis of baseline data was conducted with As exposure assessed in both well water and urinary As measurements, while hematuria was measured using urine dipstick. Prospective analyses with Cox proportional regression models were based on urinary As and dipstick measurements obtained biannually since baseline up to six years. At baseline, urinary As was significantly related to prevalence of hematuria (P-trend<0.01), with increasing quintiles of exposure corresponding with respective prevalence odds ratios of 1.00 (reference), 1.29 (95% CI: 1.04–1.59), 1.41 (95% CI: 1.15–1.74), 1.46 (95% CI: 1.19–1.79), and 1.56 (95% CI: 1.27–1.91). Compared to those with relatively little absolute urinary As change during follow-up (−10.40 to 41.17μg/l), hazard ratios for hematuria were 0.99 (95% CI: 0.80–1.22) and 0.80 (95% CI: 0.65–0.99) for those whose urinary As decreased by >47.49μg/l and 10.87 to 47.49μg/l since last visit, respectively, and 1.17 (95% CI: 0.94–1.45) and 1.36 (95% CI: 1.10–1.66) for those with between-visit increases of 10.40 to 41.17μg/l and >41.17μg/l, respectively. These data indicate a positive association of As exposure with both prevalence and incidence of dipstick hematuria. This exposure effect appears modifiable by relatively short-term changes in drinking water As. [Copyright &y& Elsevier]

Abstract: Background: Dietary pattern analysis is emerging as a practical, effective tool for relating comprehensive dietary intake to risk of cardiovascular disease mortality. However, no studies have applied this technique to a population outside of the developed world. Methods: We conducted prospective cohort analyses in 11,116 participants enrolled in the Health Effects of Arsenic Study in Araihazar, Bangladesh, measuring deaths attributable to disease of circulatory system, heart disease, and cerebrovascular disease. Participants were enrolled in 2000 and followed up for an average of 6.6years. Dietary information was obtained through a previously validated food-frequency questionnaire at baseline. Results: Principal component analysis based on our comprehensive, 39 item FFQ yielded 3 dietary patterns: (i) a “balanced” pattern, comprised of steamed rice, red meat, fish, fruit and vegetables; (ii) an “animal protein” diet, which was more heavily weighted towards eggs, milk, red meat, poultry, bread, and vegetables; and (iii) a “gourd and root vegetable” diet that heavily relied on a variety of gourds, radishes, pumpkin, sweet potato, and spinach. We observed a positive association between increasing adherence to the animal protein diet and risk of death from both disease of the circulatory system and heart disease; the hazard ratios were 1.13 (95% CI, 1.00–1.28, p =0.05) and 1.17 (95% CI, 0.99–1.38, p =0.07), respectively, in relation to one standard deviation increase in the factor scores for the animal protein diet pattern, after controlling for age, sex, body mass index, smoking status, and energy intake. The positive association was more significant among ever smokers; the hazard ratios (95% CI) for deaths from disease of the circulatory system and heart disease were 1.17 (1.02–1.34) and 1.20 (1.00–1.45), respectively, in relation to one standard deviation increase in the factor scores for the animal protein diet pattern. Conclusions: An animal protein-rich diet in rural Bangladesh may increase risk of heart disease mortality, especially among smokers. This emphasizes the need to further explore and address the impact of dietary patterns on cardiovascular disease in populations undergoing epidemiologic transition. [Copyright &y& Elsevier]

Abstract: Recently, epidemiologic studies of developmental neurotoxicology have been challenged to increase focus on co-exposure to multiple toxicants. Earlier reports, including our own work in Bangladesh, have demonstrated independent associations between neurobehavioral function and exposure to both arsenic (As) and manganese (Mn) in school-aged children. Our earlier studies, however, were not designed to examine possible interactive effects of exposure to both As and Mn. To allow investigation of possible synergistic impact of simultaneous exposures, we recruited a new sample of 299 8–11 year old children, stratified by design on As (above and below 10μg/L) and Mn (above and below 500μg/L) concentrations of household wells. When adjusted only for each other, both As and Mn in whole blood (BAs; BMn) were significantly negatively related to most WISC-IV subscale scores. With further adjustment for socio-demographic features and ferritin, BMn remained significantly associated with reduced Perceptual Reasoning and Working Memory scores; associations for BAs, and for other subscales, were expectably negative, significantly for Verbal Comprehension. Urinary As (per gram creatinine) was significantly negatively associated with Verbal Comprehension scores, even with adjustment for BMn and other contributors. Mn by As interactions were not significant in adjusted or unadjusted models (all p''s>0.25). Findings are consistent with other reports documenting adverse impact of both As and Mn exposure on child developmental outcomes, although associations appear muted at these relatively low exposure levels. [Copyright &y& Elsevier]

Abstract: The contamination of groundwater by arsenic in Bangladesh is a major public health concern affecting 35–75 million people. Although it is evident that high levels (>300 μg/L) of arsenic exposure from drinking water are related to adverse health outcomes, health effects of arsenic exposure at low-to-moderate levels (10–300 μg/L) are not well understood. We established the Health Effects of Arsenic Longitudinal Study (HEALS) with more than 20,000 men and women in Araihazar, Bangladesh, to prospectively investigate the health effects of arsenic predominately at low-to-moderate levels (0.1 to 864 μg/L, mean 99 μg/L) of arsenic exposure. Findings to date suggest adverse effects of low-to-moderate levels of arsenic exposure on the risk of pre-malignant skin lesions, high blood pressure, neurological dysfunctions, and all-cause and chronic disease mortality. In addition, the data also indicate that the risk of skin lesion due to arsenic exposure is modifiable by nutritional factors, such as folate and selenium status, lifestyle factors, including cigarette smoking and body mass index, and genetic polymorphisms in genes related to arsenic metabolism. The analyses of biomarkers for respiratory and cardiovascular functions support that there may be adverse effects of arsenic on these outcomes and call for confirmation in large studies. A unique strength of the HEALS is the availability of outcome data collected prospectively and data on detailed individual-level arsenic exposure estimated using water, blood and repeated urine samples. Future prospective analyses of clinical endpoints and related host susceptibility will enhance our knowledge on the health effects of low-to-moderate levels of arsenic exposure, elucidate disease mechanisms, and give directions for prevention. [Copyright &y& Elsevier]

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. • Arsenic exposure may contribute to CVD through its effect on endothelial function. • Few have examined the influence of arsenic on cardiovascular health in adolescents. • Higher lifetime As exposure was related to significantly reduced endothelial function. • Endothelial dysfunction in adolescence may be a risk factor for later life disease. [ABSTRACT FROM AUTHOR]

Summary Objectives: Very few studies have examined mental health morbidity in Bangladesh. This community-based study of rural Bangladesh in 2000-2001 estimated the burden of mental morbidity among rural people of working age. Study design and methods: Community surveys were conducted with one respondent from each household of three selected villages in the service provision area of a non-profit public health organization. General Health Questionnaire 60 (GHQ-60) was used as a screening tool in Stage I, and clinical examination by a Western-trained psychiatrist was undertaken for concurrent validation in Stage II. Results: The overall prevalence of psychiatric disorders in this rural area was 16.5%. Depressive disorders and anxiety disorders constituted about one-half and one-third of the total cases, respectively. A significantly higher prevalence of mental disorders was found in the economically poor respondents, those over 45 years of age, and women from large families. Conclusion: There is a high prevalence of psychiatric disorders in rural Bangladesh. These findings should aid the planning of locally relevant and appropriate mental healthcare programmes. There is an urgent need for a national mental healthcare policy that strengthens primary mental healthcare services. [ABSTRACT FROM AUTHOR]

• Higher BMI is associated with more efficient As methylation in Bangladeshi women. • The associations were attenuated after adjustment for choline. • Body fat influences estrogen, which stimulates choline synthesis. • Choline can indirectly serve as an alternative methyl donor for As methylation. Water-borne arsenic (As) exposure is a global health problem. Once ingested, inorganic As (iAs) is methylated to mono-methyl (MMA) and dimethyl (DMA) arsenicals via one-carbon metabolism (OCM). People with higher relative percentage of MMA (MMA%) in urine (inefficient As methylation), have been shown to have a higher risk of cardiovascular disease and several cancers but appear to have a lower risk of diabetes and obesity in populations from the US, Mexico, and Taiwan. It is unknown if this opposite pattern with obesity is present in Bangladesh, a country with lower adiposity and higher As exposure in drinking water. To characterize the association between body mass index (BMI) and As methylation in Bangladeshi adults and adolescents participating in the Folic Acid and Creatine Trial (FACT); Folate and Oxidative Stress (FOX) study; and Metals, Arsenic, and Nutrition in Adolescents Study (MANAS). Arsenic species (iAs, MMA, DMA) were measured in urine and blood. Height and weight were measured to calculate BMI. The associations between concurrent BMI with urine and blood As species were analyzed using linear regression models, adjusting for nutrients involved in OCM such as choline. In FACT, we also evaluated the prospective association between weight change and As species. Mean BMIs were 19.2/20.4, 19.8/21.0, and 17.7/18.7 kg/m2 in males/females in FACT, FOX, and MANAS, respectively. BMI was associated with As species in female but not in male participants. In females, after adjustment for total urine As, age, and plasma folate, the adjusted mean differences (95% confidence) in urinary MMA% and DMA% for a 5 kg/m2 difference in BMI were −1.21 (−1.96, −0.45) and 2.47 (1.13, 3.81), respectively in FACT, −0.66 (−1.56, 0.25) and 1.43 (−0.23, 3.09) in FOX, and −0.59 (−1.19, 0.02) and 1.58 (−0.15, 3.30) in MANAS. The associations were attenuated after adjustment for choline. Similar associations were observed with blood As species. In FACT, a 1-kg of weight increase over 2 to 10 (mean 5.4) years in males/females was prospectively associated with mean DMA% that was 0.16%/0.19% higher. BMI was negatively associated with MMA% and positively associated with %DMA in females but not males in Bangladesh; associations were attenuated after plasma choline adjustment. These findings may be related to the role of body fat on estrogen levels that can influence one-carbon metabolism, e.g. by increasing choline synthesis. Research is needed to determine whether the associations between BMI and As species are causal and their influence on As-related health outcomes. [ABSTRACT FROM AUTHOR]