Association of Water Arsenic With Incident Diabetes in U.S. Adults: The Multi-Ethnic Study of Atherosclerosis and the Strong Heart Study.

OBJECTIVE: We examined the association of arsenic in federally regulated community water systems (CWSs) and unregulated private wells with type 2 diabetes (T2D) incidence in the Strong Heart Family Study (SHFS), a prospective study of American Indian communities, and the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective study of racially and ethnically diverse urban U.S. communities. RESEARCH DESIGN AND METHODS: We evaluated 1,791 participants from SHFS and 5,777 participants from MESA who had water arsenic estimates available and were free of T2D at baseline (2001-2003 and 2000-2002, respectively). Participants were followed for incident T2D until 2010 (SHFS cohort) or 2019 (MESA cohort). We used Cox proportional hazards mixed-effects models to account for clustering by family and residential zip code, with adjustment for sex, baseline age, BMI, smoking status, and education. RESULTS: T2D incidence was 24.4 cases per 1,000 person-years (mean follow-up, 5.6 years) in SHFS and 11.2 per 1,000 person-years (mean follow-up, 14.0 years) in MESA. In a meta-analysis across the SHFS and MESA cohorts, the hazard ratio (95% CI) per doubling in CWS arsenic was 1.10 (1.02, 1.18). The corresponding hazard ratio was 1.09 (0.95, 1.26) in the SHFS group and 1.10 (1.01, 1.20) in the MESA group. The corresponding hazard ratio (95% CI) for arsenic in private wells and incident T2D in SHFS was 1.05 (0.95, 1.16). We observed statistical interaction and larger magnitude hazard ratios for participants with BMI <25 kg/m2 and female participants. CONCLUSIONS: Low to moderate water arsenic levels (<10 µg/L) were associated with T2D incidence in the SHFS and MESA cohorts.

Arsenic exposure is associated with alterations to multiple red blood cell parameters among adults in rural Bangladesh.

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.

Cumulative Stress Across the Life Course and Biological Aging in Adulthood.

OBJECTIVE: Psychosocial stressors have been linked with accelerated biological aging in adults; however, few studies have examined stressors across the life course in relation to biological aging. METHODS: In 359 individuals (57% White, 34% Black) from the Child Health and Development Studies Disparities study, economic (income, education, financial strain), social (parent-child relations, caretaker responsibilities) and traumatic (death of a sibling or child, violence exposure) stressors were assessed at multiple time points (birth and ages 9, 15, and 50 years). Experiences of major discrimination were assessed at age 50. Life period stress scores were then assessed as childhood (birth-age 15 years) and adulthood (age 50 years). At age 50 years, participants provided blood samples, and DNA methylation was assessed with the EPIC BeadChip. Epigenetic age was estimated using six epigenetic clocks (Horvath, Hannum, Skin and Blood age, PhenoAge, GrimAge, Dunedin Pace of Aging). Age acceleration was determined using residuals from regressing chronologic age on each of the epigenetic age metrics. Telomere length was assessed using the quantitative polymerase chain reaction-based methods. RESULTS: In linear regression models adjusted for race and gender, total life stress, and childhood and adult stress independently predicted accelerated aging based on GrimAge and faster pace of aging based on the DunedinPace. Associations were attenuated after adjusting for smoking status. In sex-stratified analyses, greater childhood stress was associated with accelerated epigenetic aging among women but not men. No associations were noted with telomere length. CONCLUSIONS: We found that cumulative stressors across the life course were associated with accelerated epigenetic age, with differences by sex (e.g., accelerated among women). Further research of this association in large and diverse samples is needed.

Impact of lowering the US maximum contaminant level on arsenic exposure: Differences by race, region, and water arsenic in NHANES 2003-2014.

Our objective was to evaluate regional and sociodemographic inequalities in water arsenic exposure reductions associated with the US Environmental Protection Agency's Final Arsenic Rule, which lowered the arsenic maximum contaminant level to 10 µg/L in public water systems. We analyzed 8544 participants from the 2003-14 National Health and Nutrition Examination Survey (NHANES) reliant on community water systems (CWSs). We estimated arsenic exposure from water by recalibrating urinary dimethylarsinate (rDMA) to remove smoking and dietary contributions. We evaluated mean differences and corresponding percent reductions of urinary rDMA comparing subsequent survey cycles to 2003-04 (baseline), stratified by region, race/ethnicity, educational attainment, and tertile of CWS arsenic assigned at the county level. The overall difference (percent reduction) in urine rDMA was 0.32 µg/L (9%) among participants with the highest tertile of CWS arsenic, comparing 2013-14 to 2003-04. Declines in urinary rDMA were largest in regions with the highest water arsenic: the South [0.57 µg/L (16%)] and West [0.46 µg/L, (14%)]. Declines in urinary rDMA levels were significant and largest among Mexican American [0.99 µg/L (26%)] and Non-Hispanic White [0.25 µg/L (10%)] participants. Reductions in rDMA following the Final Arsenic Rule were highest among participants with the highest CWS arsenic concentrations, supporting legislation can benefit those who need it the most, although additional efforts are still needed to address remaining inequalities in CWS arsenic exposure.

Buildup from birth onward of short telomeres in human hematopoietic cells.

Telomere length (TL) limits somatic cell replication. However, the shortest among the telomeres in each nucleus, not mean TL, is thought to induce replicative senescence. Researchers have relied on Southern blotting (SB), and techniques calibrated by SB, for precise measurements of TL in epidemiological studies. However, SB provides little information on the shortest telomeres among the 92 telomeres in the nucleus of human somatic cells. Therefore, little is known about the accumulation of short telomeres with age, or whether it limits the human lifespan. To fill this knowledge void, we used the Telomere-Shortest-Length-Assay (TeSLA), a method that tallies and measures single telomeres of all chromosomes. We charted the age-dependent buildup of short telomeres (<3 kb) in human hematopoietic cells from 334 individuals (birth-89 years) from the general population, and 18 patients with dyskeratosis congenita-telomere biology disorders (DC/TBDs), whose hematopoietic cells have presumably reached or are close to their replicative limit. For comparison, we also measured TL with SB. We found that in hematopoietic cells, the buildup of short telomeres occurs in parallel with the shortening with age of mean TL. However, the proportion of short telomeres was lower in octogenarians from the general population than in patients with DC/TBDs. At any age, mean TL was longer and the proportion of short telomeres lower in females than in males. We conclude that though converging to the TL-mediated replicative limit, hematopoietic cell telomeres are unlikely to reach this limit during the lifespan of most contemporary humans.

A systematic evidence map for the evaluation of noncancer health effects and exposures to polychlorinated biphenyl mixtures.

Assessing health outcomes associated with exposure to polychlorinated biphenyls (PCBs) is important given their persistent and ubiquitous nature. PCBs are classified as a Group 1 carcinogen, but the full range of potential noncancer health effects from exposure to PCBs has not been systematically summarized and evaluated. We used systematic review methods to identify and screen the literature using combined manual review and machine learning approaches. A protocol was developed that describes the literature search strategy and Populations, Exposures, Comparators, and Outcomes (PECO) criteria used to facilitate subsequent screening and categorization of literature into a systematic evidence map of PCB exposure and noncancer health endpoints across 15 organs/systems. A comprehensive literature search yielded 62,599 records. After electronic prioritization steps, 17,037 studies were manually screened at the title and abstract level. An additional 900 studies identified by experts or supplemental searches were also included. After full-text screening of 3889 references, 1586 studies met the PECO criteria. Relevant study details such as the endpoints assessed, exposure duration, and species were extracted into literature summary tables. This review compiles and organizes the human and mammalian studies from these tables into an evidence map for noncancer health endpoints and PCB mixture exposure to identify areas of robust research as well as areas of uncertainty that would benefit from future investigation. Summary data are available online as interactive visuals with downloadable metadata. Sufficient research is available to inform PCB hazard assessments for most organs/systems, but the amount of data to inform associations with specific endpoints differs. Furthermore, despite many years of research, sparse data exist for inhalation and dermal exposures, which are highly relevant human exposure routes. This evidence map provides a foundation for future systematic reviews and noncancer hazard assessments of PCB mixtures and for strategic planning of research to inform areas of greater uncertainty.

Indoor and outdoor air pollution and couple fecundability: a systematic review.

BACKGROUND: Air pollution is both a sensory blight and a threat to human health. Inhaled environmental pollutants can be naturally occurring or human-made, and include traffic-related air pollution (TRAP), ozone, particulate matter (PM) and volatile organic compounds, among other substances, including those from secondhand smoking. Studies of air pollution on reproductive and endocrine systems have reported associations of TRAP, secondhand smoke (SHS), organic solvents and biomass fueled-cooking with adverse birth outcomes. While some evidence suggests that air pollution contributes to infertility, the extant literature is mixed, and varying effects of pollutants have been reported. OBJECTIVE AND RATIONALE: Although some reviews have studied the association between common outdoor air pollutants and time to pregnancy (TTP), there are no comprehensive reviews that also include exposure to indoor inhaled pollutants, such as airborne occupational toxicants and SHS. The current systematic review summarizes the strength of evidence for associations of outdoor air pollution, SHS and indoor inhaled air pollution with couple fecundability and identifies gaps and limitations in the literature to inform policy decisions and future research. SEARCH METHODS: We performed an electronic search of six databases for original research articles in English published since 1990 on TTP or fecundability and a number of chemicals in the context of air pollution, inhalation and aerosolization. Standardized forms for screening, data extraction and study quality were developed using DistillerSR software and completed in duplicate. We used the Newcastle-Ottawa Scale to assess risk of bias and devised additional quality metrics based on specific methodological features of both air pollution and fecundability studies. OUTCOMES: The search returned 5200 articles, 4994 of which were excluded at the level of title and abstract screening. After full-text screening, 35 papers remained for data extraction and synthesis. An additional 3 papers were identified independently that fit criteria, and 5 papers involving multiple routes of exposure were removed, yielding 33 articles from 28 studies for analysis. There were 8 papers that examined outdoor air quality, while 6 papers examined SHS exposure and 19 papers examined indoor air quality. The results indicated an association between outdoor air pollution and reduced fecundability, including TRAP and specifically nitrogen oxides and PM with a diameter of ≤2.5 µm, as well as exposure to SHS and formaldehyde. However, exposure windows differed greatly between studies as did the method of exposure assessment. There was little evidence that exposure to volatile solvents is associated with reduced fecundability. WIDER IMPLICATIONS: The evidence suggests that exposure to outdoor air pollutants, SHS and some occupational inhaled pollutants may reduce fecundability. Future studies of SHS should use indoor air monitors and biomarkers to improve exposure assessment. Air monitors that capture real-time exposure can provide valuable insight about the role of indoor air pollution and are helpful in assessing the short-term acute effects of pollutants on TTP.

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

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

Low-dose ionizing radiation and cancer mortality among enlisted men stationed on nuclear-powered submarines in the United States Navy.

BACKGROUND: Men stationed on nuclear-powered submarines are occupationally exposed to external ionizing radiation at very low levels and radiation dose for each individual is closely monitored. Little is known about ionizing radiation (IR) risks of cancer mortality for populations with levels of cumulative ionizing radiation exposure this low. MATERIALS AND METHODS: This historical cohort study followed 85,033 enlisted men who had served on a nuclear-powered submarine in the U.S. Navy between 1969 and 1982 to determine patterns of cancer mortality. Occupational radiation doses were measured by badge dosimeters for each individual for all periods of Navy service potentially involving radiation exposure. Deaths were ascertained through 1995 by searches of multiple national mortality databases. Within-cohort dose-response relationships for cancer mortality were estimated using linear Poisson regression models. Individual-level smoking status was not available so cancer risks were estimated separately for cancers with and without previously published evidence of consistently moderate or strong associations with smoking. RESULTS: A total of 584 cancer deaths occurred during a follow-up period of up to 27 years. The mean and median cumulative occupational radiation doses received while in the Navy were 5.7 and 1.1 milliSieverts (mSv), respectively, range 0-242 mSv. Mortality Excess Relative Risks (ERRs) per 10 mSv and 95% confidence intervals (CI) were 0.053 (CI -0.03, 0.17) for all cancers, 0.052 (CI -0.03, 0.18) for all solid cancers, and 0.003 (CI -0.29, 0.30) for leukemias excluding chronic lymphocytic leukemia. The ERRs per 10 mSv were 0.052 (CI -0.07, 0.17) for cancers previously associated with smoking and 0.012 (CI -0.10, 0.12) for cancers that were not. CONCLUSIONS: The ERR point estimates for solid cancers and leukemia were statistically compatible with those reported in previously published studies of other ionizing radiation-exposed and monitored cohorts, albeit with wide confidence intervals. This study, with high-quality measurements of in-Navy occupational external IR doses, high follow-up proportion, and detailed IR dose-response analyses, is consistent with the premise of small excess cancer risks from low-dose IR.

Mortality of Enlisted Men Who Served on Nuclear-Powered Submarines in the United States Navy.

OBJECTIVE: To describe the long-term mortality experience of a cohort of enlisted men who served on nuclear-powered submarines in the United States Navy and breathed recirculated filtered air for extended periods of time. METHODS: In this historical cohort study we estimated standardized mortality ratios (SMRs) and used within-cohort Poisson regression analyses to address healthy worker biases. RESULTS: Three thousand two hundred sixty three deaths occurred among 85,498 men during 1,926,875 person-years of follow-up from 1969 to 1995. SMRs were reduced for most cause-of-death categories, prostate cancer had a twofold elevation. In within-cohort comparisons, prostate cancer mortality did not increase with duration of submarine service, but ischemic heart disease mortality increased 26% per 5 years of submarine service. CONCLUSIONS: Long periods of submarine service do not increase mortality in most cause-of-death categories. Increased mortality from ischemic heart disease likely reflects the effects of tobacco smoke.

Associations of prenatal exposure to mixtures of organochlorine pesticides and smoking and drinking behaviors in adolescence.

It is important to identify the factors that influence the prevalence of disinhibitory behaviors, as tobacco and alcohol use in adolescence is a strong predictor of continued use and substance abuse into adulthood. Organochlorine pesticides (OCPs) are persistent organic pollutants that pose a potential risk to the developing fetus and offspring long-term health. We examined associations between prenatal exposure OCPs and their metabolites (i.e., p,p'-DDT, p,p'-DDE, o,p'-DDT, oxychlordane, and hexachlorobenzene (HCB)), both as a mixture and single compounds, and alcohol consumption and smoking at adolescence in a sample (n = 554) from the Child Health and Development Studies prospective birth cohort. Bayesian Kernel Machine Regression demonstrated a trend of higher risk of alcohol use and smoking with higher quartile mixture levels. Single-component analysis showed increased odds of smoking and drinking with increases in lipid-adjusted p,p'-DDE serum levels (aOR = 2.06, 95% CI 0.99-4.31, p = 0.05, per natural log unit increase). We found significant effect modification in these associations by sex with higher p,p'-DDT serum levels (aOR = 0.26, 95% CI 0.09-0.076, p = 0.01, per natural log unit increase) was associated with lower odds of smoking and drinking in female adolescents, while higher p,p'-DDE serum levels (aOR = 2.98, 95% CI 1.04-8.51, p = 0.04, per natural log unit increase) was associated with higher odds of the outcomes. Results of the mutually adjusted model were not significant for male adolescents. Further research to understand reasons for these sex-differences are warranted.

Could maternal thyroid function during pregnancy affect daughters' age at menarche through child growth? A mediation analysis.

Early menarche is associated with adverse health outcomes during adolescence as well as breast and other reproductive cancers later in adulthood. However, the causes of early menarche and the pathways through which they operate are not fully understood. Though maternal thyroid function during pregnancy affects child growth, and rapid childhood growth is associated with a decreased age at menarche, the relationship between prenatal maternal thyroid function and daughters' age at menarche has not been examined. We conducted a mediation analysis in a historical cohort of 260 mother-child pairs to estimate the total and indirect effects of maternal prenatal thyroid function on daughters' age at menarche. No association was observed between thyroid stimulating hormone (TSH) or anti-thyroid peroxidase antibodies (ATPO) and daughters' age at menarche. Using a sample-specific, a-priori cutoff at the 10th percentile, low levels of maternal free thyroxine (FT4) were associated with earlier daughter age at menarche, with a hazard ratio (95 % CI) of 1.70 (1.02, 2.84) comparing the bottom 10th percentile with the top 90th percentile of exposure levels. Higher maternal FT4 was associated with rapid child weight gain from ages 5-9, and rapid child weight gain from ages 5-9 was associated with earlier age at menarche; the estimated indirect effect of this pathway was null. While maternal FT4 is associated with earlier age at menarche in daughters, this is not mediated by rapid weight gain in our study population, suggesting that maternal FT4 is operating through a different pathway.

Metabolic Abnormalities, Dietary Risk Factors and Nutritional Management in Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a devastating progressive neurodegenerative disease that affects motor neurons, leading to a relentless paralysis of skeletal muscles and eventual respiratory failure. Although a small percentage of patients may have a longer survival time (up to 10 years), in most cases, the median survival time is from 20 to 48 months. The pathogenesis and risk factors for ALS are still unclear: among the various aspects taken into consideration, metabolic abnormalities and nutritional factors have been the focus of recent interests. Although there are no consistent findings regarding prior type-2 diabetes, hypercholesterolemia and ALS incidence, abnormalities in lipid and glucose metabolism may be linked to disease progression, leading to a relatively longer survival (probably as a result of counteract malnutrition and cachexia in the advanced stages of the disease). Among potential dietary risk factors, a higher risk of ALS has been associated with an increased intake of glutamate, while the consumption of antioxidant and anti-inflammatory compounds, such as vitamin E, n-3 polyunsaturated fatty acids, and carotenoids, has been related to lower incidence. Poor nutritional status and weight loss in ALS resulting from poor oral intake, progressive muscle atrophy, and the potential hypermetabolic state have been associated with rapid disease progression. It seems important to routinely perform a nutritional assessment of ALS patients at the earliest referral: weight maintenance (if adequate) or gain (if underweight) is suggested from the scientific literature; evidence of improved diet quality (in terms of nutrients and limits for pro-inflammatory dietary factors) and glucose and lipid control is yet to be confirmed, but it is advised. Further research is warranted to better understand the role of nutrition and the underlying metabolic abnormalities in ALS, and their contribution to the pathogenic mechanisms leading to ALS initiation and progression.

Explaining the Black-white depression paradox: Interrogating the Environmental Affordances Model.

The Environmental Affordances (EA) model posits that Black Americans' engagement with unhealthy behaviors (i.e. smoking, alcohol use, eating calorie-dense foods) to cope with stressor exposure may simultaneously account for their observed greater risk of chronic physical illness, and their observed equal or lesser prevalence of depression, relative to white Americans - the so-called "Black-white depression paradox." However, the specific mechanisms through which such effects might arise have been theorized and analyzed inconsistently across studies, raising concerns regarding the appropriateness of existing empirical tests of the model as well as the validity of the conclusions. We specify the two mechanisms most consistent with the EA model - 'Mediation-only' and 'Mediation and Modification' - and derive a priori predictions based on each. We systematically test these pathways using a subset of 559 participants of the Child Health and Development Study who were included in an adult follow-up study between 2010 and 2012 and self-identified as Black or white. Results failed to support either of the two mechanisms derived from the EA model, challenging the validity and utility of the model for explaining racial differences in depression; efforts to develop alternative hypotheses to explain the paradox are needed.

Arsenic exposure associated T cell proliferation, smoking, and vitamin D in Bangladeshi men and women.

There are limited data examining the consequences of environmental exposure to arsenic on the immune system in adults, particularly among smokers. Smoking has been shown to exacerbate or contribute to impaired immune function in men chronically exposed to arsenic. In contrast, vitamin D (VitD) is known to have a positive influence on innate and adaptive immune responses. The effect of circulating VitD on arsenic-associated immune dysfunction is not known. Here we examine the relationship of arsenic exposure and T cell proliferation (TCP), a measure of immune responsiveness, and circulating VitD among adult men and women in Bangladesh. Arsenic exposure was assessed using total urinary arsenic as well as urinary arsenic metabolites all adjusted for urinary creatinine. TCP was measured ex vivo in cryopreserved peripheral blood mononuclear cells from 614 adult participants enrolled in the Bangladesh Health Effects of Arsenic Longitudinal Study; serum VitD was also evaluated. The influence of cigarette smoking on arsenic-induced TCP modulation was assessed only in males as there was an inadequate number of female smokers. These studies show that arsenic suppressed TCP in males. The association was significantly strong in male smokers and to a lesser extent in male non-smokers. Interestingly, we found a strong protective effect of high/sufficient serum VitD levels on TCP among non-smoking males. Furthermore, among male smokers with low serum VitD (⊔20 ng/ml), we found a strong suppression of TCP by arsenic. On the other hand, high VitD (>20 ng/ml) was found to attenuate effects of arsenic on TCP among male-smokers. Overall, we found a strong protective effect of VitD, when serum levels were >20 ng/ml, on arsenic-induced inhibition of TCP in men, irrespective of smoking status. To our knowledge this is the first large study of immune function in healthy adult males and females with a history of chronic arsenic exposure.

Racial differences in alcohol and tobacco use in adolescence and mid-adulthood in a community-based sample.

PURPOSE: Smoking and alcohol use have been posited as possible contributors to racial health disparities, despite higher smoking and alcohol use among non-Hispanic White youth and young adults compared to Blacks. To further investigate this claim, we aim to assess variation in alcohol and cigarette use across two distinct points of the life course. METHOD: Data are from a subset of 559 (279 male, 280 female) self-identified Black and White participants of the Child Health and Development study. Self-report alcohol and cigarette use were collected between age 15-17 and at mean age 50. Logistic regressions were estimated; supplementary analyses adjusted for maternal age, prenatal smoking, household income, childhood SES, and education. RESULTS: White participants were more likely to drink regularly (Odds ratio (OR) 2.2; 95%CI 1.2, 4.0) and be intoxicated (OR 2.0; 95%CI 1.2, 3.2) in adolescence compared with Blacks. In mid-adulthood, Whites remained more likely to currently drink (OR 2.3; 95%CI 1.6, 3.4) but among drinkers, less likely to binge drink (OR 0.4; 95%CI 0.2, 0.8). White participants were less likely to smoke in mid-adulthood (OR 0.4; 95%CI 0.3, 0.6), but among smokers, were more likely to smoke ≥ ½ a pack per day (OR 3.4; 95%CI 1.5, 7.8). CONCLUSIONS: Blacks were less likely to engage in drinking across the life course, but, among drinkers, more likely to binge drink in mid-adulthood. Blacks were more likely to smoke in mid-adulthood, but smoked infrequently compared with Whites. These patterns suggest that a reframing of disparities mechanisms to focus on broader structural and social factors may benefit progress in understanding and ameliorating inequities.

Functional connectivity of the reading network is associated with prenatal polybrominated diphenyl ether concentrations in a community sample of 5 year-old children: A preliminary study.

Genetic factors explain 60 percent of variance in reading disorder. Exposure to neurotoxicants, including polybrominated diphenyl ethers (PBDEs), may be overlooked risk factors for reading problems. We used resting-state functional magnetic resonance imaging (rs-fMRI) to examine associations between prenatal PBDE concentrations and functional connectivity of a reading-related network (RN) in a community sample of 5-year-old children (N = 33). Maternal serum PBDE concentrations (∑PBDE) were measured at 12.2 ±â€¯2.8 weeks gestation (mean ±â€¯SD). The RN was defined by 12 regions identified in prior task-based fMRI meta-analyses; global efficiency (GE) was used to measure network integration. Linear regression evaluated associations between ∑PBDE, word reading, and GE of the RN and the default mode network (DMN); the latter to establish specificity of findings. Weighted quantile sum regression analyses evaluated the contributions of specific PBDE congeners to observed associations. Greater RN efficiency was associated with better word reading in these novice readers. Children with higher ∑PBDE showed reduced GE of the RN; ∑PBDE was not associated with DMN efficiency, demonstrating specificity of our results. Consistent with prior findings, ∑PBDE was not associated word reading at 5-years-old. Altered efficiency and integration of the RN may underlie associations between ∑PBDE concentrations and reading problems observed previously in older children.

Perinatal phthalates exposure decreases fine-motor functions in 11-year-old girls: Results from weighted Quantile sum regression.

INTRODUCTION: Phthalates are a group of high production chemicals, generally used as plasticizers and odor enhancers. Phthalates cross the blood-placenta barrier and are associated with deficits in cognitive functions and behavior problems in offspring. We previously reported sex-specific associations with motor function when phthalates are considered singly. Because exposure to phthalates usually occurs as mixtures, here we assess these associations between a mixture of phthalates and motor function at age 11 years. METHODS: Data come from the prospective cohort study of mothers and offspring who participated in the Columbia Center for Children's Environmental Health birth cohort (CCCEH). Seven phthalate metabolites were measured in maternal spot urine obtained during the third trimester and motor function was evaluated using the short form of the Bruininks-Oseretsky Test of Motor Proficiency, 2nd edition (BOT-2) at the age of 11 years. We used Weighted Quartile Sum (WQS) regression models to examine the effect of phthalate metabolites in males and females separately. The models were adjusted for child age in months, child BMI, maternal race (African-American vs. Dominican), prenatal alcohol consumption, maternal demoralization score, HOME score, and urine specific gravity. In a secondary analysis we used linear regression models to examine the association between the sum of molar concentrations of both DEHP and non-DEHP metabolites, and outcomes of gross and fine motor functions. RESULTS: 209 mother-child pairs were eligible for this analysis. A significant decrease in fine-motor functions was observed among females, but not among males, following exposure to high levels of weighted quartile sum of seven phthalate metabolites (Covariates-adjusted coefficient estimate B = -2.7, 95% Confidence Interval [CI] -4.64 to -0.75, p = 0.01 for females [n = 116] and B = -1.63, 95%CI -3.94 to 0.69, p = 0.16 for males [n = 93]). The most highly weighted phthalate metabolites, associated with fine-motor functions among females, were MBP, MBZP, and MIBP, all non-DEHP phthalates. No significant associations were found between the weighted quartile sum of seven phthalate metabolites and gross-motor functions at the age of 11 years for males (B = -0.81, 95%CI -1.17 to 1.96, p = 0.23). With the molar sum of four non-DEHP phthalates as main predictor of linear regression models, we found significant decrease in gross and fine motor functions among females prenatally exposed to non-DEHP phthalates B = -0.98, 95%CI -1.98 to 0.03, p = 0.05 and B = -0.85, 95%CI -1.49 to -0.20, p = 0.01, respectively). CONCLUSIONS: Phthalate exposure during pregnancy was associated with decreased motor functions among 11-year-old girls.

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.

Changes in human peripheral blood mononuclear cell (HPBMC) populations and T-cell subsets associated with arsenic and polycyclic aromatic hydrocarbon exposures in a Bangladesh cohort.

Exposures to environmental arsenic (As) and polycyclic aromatic hydrocarbons (PAH) have been shown to independently cause dysregulation of immune function. Little data exists on the associations between combined exposures to As and PAH with immunotoxicity in humans. In this work we examined associations between As and PAH exposures with lymphoid cell populations in human peripheral blood mononuclear cells (PBMC), as well as alterations in differentiation and activation of B and T cells. Two hundred men, participating in the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh, were selected for the present study based on their exposure to As from drinking water and their cigarette smoking status. Blood and urine samples were collected from study participants. We utilized multiparameter flow cytometry in PBMC to identify immune cells (B, T, monocytes, NK) as well as the T-helper (Th) cell subsets (Th1, Th2, Th17, and Tregs) following ex vivo activation. We did not find evidence of interactions between As and PAH exposures. However, individual exposures (As or PAH) were associated with changes to immune cell populations, including Th cell subsets. Arsenic exposure was associated with an increase in the percentage of Th cells, and dose dependent changes in monocytes, NKT cells and a monocyte subset. Within the Th cell subset we found that Arsenic exposure was also associated with a significant increase in the percentage of circulating proinflammatory Th17 cells. PAH exposure was associated with changes in T cells, monocytes and T memory (Tmem) cells and with changes in Th, Th1, Th2 and Th17 subsets all of which were non-monotonic (dose dependent). Alterations of immune cell populations caused by environmental exposures to As and PAH may result in adverse health outcomes, such as changes in systemic inflammation, immune suppression, or autoimmunity.