Faculty Bibliography

PURPOSE: The objective of this analysis was to evaluate the effects of dietary B vitamin intakes on creatinine-adjusted urinary total arsenic concentration among individuals participating in the Health Effects of Arsenic Longitudinal Study (HEALS) cohort in Araihazar, Bangladesh. Arsenic exposure is a major public health problem in Bangladesh, where nearly 77 million people have been chronically exposed to arsenic through the consumption of naturally contaminated groundwater. Dietary factors influencing the metabolism of ingested arsenic may potentially be important modifiers of the health effects of arsenic in this population. METHODS: Daily average B vitamin intakes from a validated food frequency questionnaire and laboratory data on drinking water and urinary arsenic concentrations among 9,833 HEALS cohort participants were utilized. Statistical analyses were conducted using generalized estimating equations incorporating knotted spline linear regression. RESULTS: Increasing dietary intakes of thiamin, niacin, pantothenic acid, and pyridoxine were found to significantly increase urinary total arsenic excretion, adjusted for daily arsenic intake from drinking water and other potential confounders. CONCLUSIONS: These results suggest that higher intakes of certain B vitamins may enhance the excretion of arsenic from the body. This study offers new insights into modifiable dietary factors that relate to arsenic excretion and thus provides potential avenues for the prevention of arsenic-related health effects

Because the human skin microbiota may play roles in the causation or modification of skin diseases, we sought to provide initial quantitative analysis from different cutaneous locations. We developed quantitative PCRs to enumerate the total bacterial and fungal populations, as well as the most common bacterial and fungal genera present in six locales, in eight healthy subjects. We used a set of primers and TaqMan MGB probes based on the bacterial 16S rRNA and fungal internally transcribed spacer region, as well as bacterial genus-specific probes for Propionibacterium, Corynebacterium, Streptococcus, and Staphylococcus and a fungal genus-specific probe for Malassezia. The extent of human DNA contamination of the specimen was determined by quantitating the human housekeeping GAPDH gene. The highest level of 16S rRNA copies of bacteria was present in the axilla (4.44 +/- 0.18 log(10) copies/mul [mean +/- standard error of the mean]), with normalization based on GAPDH levels, but the other five locations were similar to one another (range, 2.48 to 2.89 log(10) copies/mul). There was strong symmetry between the left and right sides. The four bacterial genera accounted for 31% to 59% of total bacteria, with the highest percent composition in the axilla and the lowest in the forearm. Streptococcus was the most common genus present on the forehead and behind the ear. Corynebacterium spp. were predominant in the axilla. Fungal levels were 1 to 2 log(10) lower than for bacteria, with Malassezia spp. accounting for the majority of fungal gene copies. These results provide the first quantitation of the site and host specificities of major bacterial and fungal populations in human skin and present simple methods for their assessment in studies of disease

BACKGROUND: The long-term effects of arsenic exposure from drinking water at levels < 300 microg/L and the risk of diabetes mellitus remains a controversial topic. METHOD: We conducted a population-based cross-sectional study using baseline data from 11,319 participants in the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh, to evaluate the associations of well water arsenic and total urinary arsenic concentration and the prevalence of diabetes mellitus and glucosuria. We also assessed the concentrations of well water arsenic, total urinary arsenic, and urinary arsenic metabolites in relation to blood glycosylated hemoglobin (HbA1c) levels in subsets of the study population. RESULTS: More than 90% of the cohort members were exposed to drinking water with arsenic concentration < 300 microg/L. We found no association between arsenic exposure and the prevalence of diabetes. The adjusted odds ratios for diabetes were 1.00 (referent), 1.35 [95% confidence interval (CI), 0.90-2.02], 1.24 (0.82-1.87), 0.96 (0.62-1.49), and 1.11 (0.73-1.69) in relation to quintiles of time-weighted water arsenic concentrations of 0.1-8, 8-41, 41-91, 92-176, and > or = 177 microg/L, respectively, and 1.00 (referent), 1.29 (0.87-1.91), 1.05 (0.69-1.59), 0.94 (0.61-1.44), and 0.93 (0.59-1.45) in relation to quintiles of urinary arsenic concentrations of 1-36, 37-66, 67-114, 115-204, and > or = 205 microg/L, respectively. We observed no association between arsenic exposure and prevalence of glucosuria and no evidence of an association between well water arsenic, total urinary arsenic, or the composition of urinary arsenic metabolites and HbA1c level. CONCLUSIONS: Our findings do not support an association of arsenic exposure from drinking water and a significantly increased risk of diabetes mellitus in the range of levels observed. Further prospective studies would be valuable in confirming the findings

Animal studies and small clinical trials have shown that taurine (2-aminoethanesulphonic acid), a sulphur-containing molecule mainly obtained from the diet in human subjects, has a variety of biological actions that are related to atherosclerosis and cardiovascular functions. However, epidemiological studies of taurine and CHD risk are lacking. We evaluated whether a single measurement of serum taurine could serve as an estimate for long-term serum levels. Serum taurine was measured using HPLC in three annual samples from thirty postmenopausal women selected from the New York University Women's Health Study. Overall, serum taurine values ranged from 62.8 to 245.3 nmol/ml, with a mean of 140 nmol/ml. The intraclass correlation coefficient of a single measurement of serum taurine was 0.48 (95 % CI 0.26, 0.68), which can be improved to 0.65 by using the mean of two annual measurements. The CV was 7 %. These results indicate that the mean of two or more annual measurements of serum taurine is a sufficiently reliable measure of long-term serum levels that can be used in epidemiological studies

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

BACKGROUND: Millions of people worldwide are chronically exposed to arsenic through drinking water, including 35-77 million people in Bangladesh. The association between arsenic exposure and mortality rate has not been prospectively investigated by use of individual-level data. We therefore prospectively assessed whether chronic and recent changes in arsenic exposure are associated with all-cause and chronic-disease mortalities in a Bangladeshi population. METHODS: In the prospective cohort Health Effects of Arsenic Longitudinal Study (HEALS), trained physicians unaware of arsenic exposure interviewed in person and clinically assessed 11 746 population-based participants (aged 18-75 years) from Araihazar, Bangladesh. Participants were recruited from October, 2000, to May, 2002, and followed-up biennially. Data for mortality rates were available throughout February, 2009. We used Cox proportional hazards model to estimate hazard ratios (HRs) of mortality, with adjustment for potential confounders, at different doses of arsenic exposure. FINDINGS: 407 deaths were ascertained between October, 2000, and February, 2009. Multivariate adjusted HRs for all-cause mortality in a comparison of arsenic at concentrations of 10.1-50.0 microg/L, 50.1-150.0 microg/L, and 150.1-864.0 microg/L with at least 10.0 microg/L in well water were 1.34 (95% CI 0.99-1.82), 1.09 (0.81-1.47), and 1.68 (1.26-2.23), respectively. Results were similar with daily arsenic dose and total arsenic concentration in urine. Recent change in exposure, measurement of total arsenic concentrations in urine repeated biennially, did not have much effect on the mortality rate. INTERPRETATION: Chronic arsenic exposure through drinking water was associated with an increase in the mortality rate. Follow-up data from this cohort will be used to assess the long-term effects of arsenic exposure and how they might be affected by changes in exposure. However, solutions and resources are urgently needed to mitigate the resulting health effects of arsenic exposure. FUNDING: US National Institutes of Health.

Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geographic area. Demographic and lifestyle characteristics were examined in relation to 25(OH)D using stepwise linear regression and polytomous logistic regression. The prevalence of 25(OH)D concentrations less than 25 nmol/L ranged from 3% to 36% across cohorts, and the prevalence of 25(OH)D concentrations less than 50 nmol/L ranged from 29% to 82%. Seasonal differences in circulating 25(OH)D were most marked among whites from northern latitudes. Statistically significant positive correlates of 25(OH)D included male sex, summer blood draw, vigorous physical activity, vitamin D intake, fish intake, multivitamin use, and calcium supplement use. Significant inverse correlates were body mass index, winter and spring blood draw, history of diabetes, sedentary behavior, smoking, and black race/ethnicity. Correlates varied somewhat within season, race/ethnicity, and sex. These findings help identify persons at risk for low vitamin D status for both clinical and research purposes

Upper gastrointestinal (GI) cancers of the stomach and esophagus have high incidence and mortality worldwide, but they are uncommon in Western countries. Little information exists on the association between vitamin D and risk of upper GI cancers. This study examined the association between circulating 25-hydroxyvitamin D (25(OH)D) and upper GI cancer risk in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Concentrations of 25(OH)D were measured from 1,065 upper GI cancer cases and 1,066 age-, sex-, race-, and season-of blood draw-matched controls from 8 prospective cohort studies. In multivariate-adjusted models, circulating 25(OH)D concentration was not significantly associated with upper GI cancer risk. Subgroup analysis by race showed that among Asians, but not Caucasians, lower concentrations of 25(OH)D (<25 nmol/L) were associated with a statistically significant decreased risk of upper GI cancer (reference: 50-<75 nmol/L) (odds ratio = 0.53, 95% confidence interval: 0.31, 0.91; P trend = 0.003). Never smokers with concentrations of <25 nmol/L showed a lower risk of upper GI cancers (odds ratio = 0.55, 95% confidence interval: 0.31, 0.96). Subgroup analyses by alcohol consumption produced opposing trends. Results do not support the hypothesis that interventions aimed at increasing vitamin D status would lead to a lower risk of these highly fatal cancers

Although the kidney is a major organ for vitamin D metabolism, activity, and calcium-related homeostasis, little is known about whether this nutrient plays a role in the development or the inhibition of kidney cancer. To address this gap in knowledge, the authors examined the association between circulating 25-hydroxyvitamin D (25(OH)D) and kidney cancer within a large, nested case-control study developed as part of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Concentrations of 25(OH)D were measured from 775 kidney cancer cases and 775 age-, sex-, race-, and season-matched controls from 8 prospective cohort studies. Overall, neither low nor high concentrations of circulating 25(OH)D were significantly associated with kidney cancer risk. Although the data showed a statistically significant decreased risk for females (odds ratio = 0.31, 95% confidence interval: 0.12, 0.85) with 25(OH)D concentrations of > or =75 nmol/L, the linear trend was not statistically significant and the number of cases in this category was small (n = 14). The findings from this consortium-based study do not support the hypothesis that vitamin D is inversely associated with the risk of kidney cancer overall or with renal cell carcinoma specifically