Exposure to Polyfluoroalkyl Chemicals and Cholesterol, Body Weight, and Insulin Resistance in the General U.S. Population

BACKGROUND. Polyfluoroalkyl chemicals (PFCs) are used commonly in commercial applications and are detected in humans and the environment worldwide. Concern has been raised that they may disrupt lipid and weight regulation. OBJECTIVES. We investigated the relationship between PFC serum concentrations and lipid and weight outcomes in a large publicly available data set. METHODS. We analyzed data from the 2003-2004 National Health and Nutrition Examination Survey (NHANES) for participants 12-80 years of age. Using linear regression to control for covariates, we studied the association between serum concentrations of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorooctane sulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS) and measures of cholesterol, body size, and insulin resistance. RESULTS. We observed a positive association between concentrations of PFOS, PFOA, and PFNA and total and non-high-density cholesterol. We found the opposite for PFHxS. Those in the highest quartile of PFOS exposure had total cholesterol levels 13.4 mg/dL [95% confidence interval (CI), 3.8-23.0] higher than those in the lowest quartile. For PFOA, PFNA, and PFHxS, effect estimates were 9.8 (95% CI, -0.2 to 19.7), 13.9 (95% CI, 1.9-25.9), and -7.0 (95% CI, -13.2 to -0.8), respectively. A similar pattern emerged when exposures were modeled continuously. We saw little evidence of a consistent association with body size or insulin resistance. CONCLUSIONS. This exploratory cross-sectional study is consistent with other epidemiologic studies in finding a positive association between PFOS and PFOA and cholesterol, despite much lower exposures in NHANES. Results for PFNA and PFHxS are novel, emphasizing the need to study PFCs other than PFOS and PFOA.National Institute of Environmental Health Sciences (R21ES013724, T32ES014562

Is Greenness Associated with Dementia? A Systematic Review and Dose–Response Meta-analysis

Purpose of review: We assessed the relation between environmental greenness and risk of dementia and cognitive impairment, based on a systematic review and meta-analysis up to March 30, 2022, characterizing whenever possible the shape of the association using dose-response meta-analysis. Recent findings: Twelve studies were included in this review, either using normalized difference vegetation index (NDVI) or land use/cover (LU/LC) methodology to assess greenness. Comparing the highest versus lowest exposure categories of greenness assessed using the NDVI (6 studies) or LU/LC (6 studies), we found no association with dementia. Dose-response meta-analysis of the association between greenness measured by LU/LC and dementia, based on only 3 studies, indicated a U-shaped association, but estimates were imprecise. Our systematic review and meta-analysis provided some evidence of a slight inverse association between greenness and dementia at intermediate exposure levels, but not at high levels. Potential methodological limitations, such as exposure misclassification and unmeasured confounding, may have affected the results

Association between Outdoor Air Pollution and Childhood Leukemia: A Systematic Review and Dose-Response Meta-Analysis.

BackgroundA causal link between outdoor air pollution and childhood leukemia has been proposed, but some older studies suffer from methodological drawbacks. To the best of our knowledge, no systematic reviews have summarized the most recently published evidence and no analyses have examined the dose-response relation.ObjectiveWe investigated the extent to which outdoor air pollution, especially as resulting from traffic-related contaminants, affects the risk of childhood leukemia.MethodsWe searched all case-control and cohort studies that have investigated the risk of childhood leukemia in relation to exposure either to motorized traffic and related contaminants, based on various traffic-related metrics (number of vehicles in the closest roads, road density, and distance from major roads), or to measured or modeled levels of air contaminants such as benzene, nitrogen dioxide, 1,3-butadiene, and particulate matter. We carried out a meta-analysis of all eligible studies, including nine studies published since the last systematic review and, when possible, we fit a dose-response curve using a restricted cubic spline regression model.ResultsWe found 29 studies eligible to be included in our review. In the dose-response analysis, we found little association between disease risk and traffic indicators near the child's residence for most of the exposure range, with an indication of a possible excess risk only at the highest levels. In contrast, benzene exposure was positively and approximately linearly associated with risk of childhood leukemia, particularly for acute myeloid leukemia, among children under 6 y of age, and when exposure assessment at the time of diagnosis was used. Exposure to nitrogen dioxide showed little association with leukemia risk except at the highest levels.DiscussionOverall, the epidemiologic literature appears to support an association between benzene and childhood leukemia risk, with no indication of any threshold effect. A role for other measured and unmeasured pollutants from motorized traffic is also possible. https://doi.org/10.1289/EHP4381

Dietary cadmium intake and fecundability in a North American preconception cohort study

Objective To evaluate the association between dietary cadmium intake (D-Cd) and fecundability. Diet is one of the main sources of cadmium, and D-Cd is often used as indicator of cadmium exposure, particularly in non-smoking populations. In a previous preconception cohort study of 501 couples,1 high female cadmium concentrations measured in whole blood were associated with reduced fecundability. Design Prospective cohort study (2013-2018). Materials and Methods Pregnancy Online Study (PRESTO) is a North American prospective preconception cohort of pregnancy planners. At baseline, female participants aged 21-45 years completed a web-based questionnaire on demographic, lifestyle, medical and reproductive factors. Ten days after enrollment, participants completed the National Cancer Institute Dietary History Questionnaire II, a validated food frequency questionnaire (FFQ) of average intake during the previous year. D-Cd (\u3bcg/day) was estimated by combining FFQ responses with US Food and Drug Administration data on food cadmium content. Participants were then followed for up to 12 months or until reported pregnancy, whichever came first. The analysis included 4,768 women attempting to conceive for 646 cycles at study entry and not using fertility treatment. We used a proportional probabilities regression model to estimate fecundability ratios (FR) and 95% confidence intervals (CI), adjusted for age, body mass index (BMI), smoking history, parity, physical activity, last method of contraception, daily use of multivitamins, race/ethnicity, education, income, geographic region, and the 2010 healthy eating index score. We used the nutrient residual approach to adjust for energy intake. Results Median D-Cd was 8.0 \u3bcg/day (interquartile range: 7.0-9.1 \u3bcg/day). The top 5 contributors to D-Cd were nuts and seeds; fried potatoes; dark green lettuce; cooked greens; and white potatoes. Compared with an average D-Cd of <6.8 \u3bcg/day, FRs for D-Cd quintiles of 6.8-7.6, 7.7-8.4, 8.5-9.5, and 659.6 \u3bcg/day were 1.03 (CI: 0.92-1.14), 1.07 (CI: 0.96-1.18), 1.07 (CI: 0.96-1.19), and 1.08 (0.97-1.20), respectively. Results were not appreciably different among never smokers with no current passive smoke exposure, for whom cadmium exposure from other sources (e.g., cigarettes) would be lower (respective FRs: 1.02, 1.05, 1.06 and 1.02). Results did not differ materially by age (<30 vs. 6530 years), BMI (<30 vs. 6530 kg/m2), total fiber intake (<25 vs. 6525 g/day), geographic region of residence (West, Midwest, Northeast, South, Canada), or attempt time at study entry (<3 vs. 653 cycles). Conclusions Dietary intake of cadmium was not appreciably associated with fecundability, though exposure misclassification and confounding could explain the null results. References 1 Buck Louis GM, Sundaram R, Schisterman EF, Sweeney AM, Lynch CD, Gore-Langton RE, Chen Z, Kim S, Caldwell KL, Barr DB. Heavy metals and couple fecundity, the LIFE Study. Chemosphere. 2012 Jun;87(11):1201-7. https://doi.org/10.1016/j.chemosphere.2012.01.017. Epub 2012 Feb 4. PubMed PMID: 22309709; PubMed Central PMCID: PMC3327819

The structure and evolution of a forming galaxy cluster at z = 1.62

We present a comprehensive picture of the Cl 0218.3−0510 protocluster at z = 1.623 across 10 comoving Mpc. Using filters that tightly bracket the Balmer and 4000 Å breaks of the protocluster galaxies we obtain precise photometric redshifts resulting in a protocluster galaxy sample that is 89 ± 5 per cent complete and has a contamination of only 12 ± 5 per cent. Both star-forming and quiescent protocluster galaxies are located, which allows us to map the structure of the forming cluster for the first time. The protocluster contains six galaxy groups, the largest of which is the nascent cluster. Only a small minority of the protocluster galaxies are in the nascent cluster (11 per cent) or in the other galaxy groups (22 per cent), as most protocluster galaxies reside between the groups. Unobscured star-forming galaxies predominantly reside between the protocluster’s groups, whereas red galaxies make up a large fraction of the groups’ galactic content, so observing the protocluster through only one of these types of galaxies results in a biased view of the protocluster’s structure. The structure of the protocluster reveals how much mass is available for the future growth of the cluster and we use the Millennium Simulation, scaled to a Planck cosmology, to predict that Cl 0218.3−0510 will evolve into a 2.7+3.9 −1.7 × 1014M cluster by the present day

Secondary Sex Ratio among Women Exposed to Diethylstilbestrol in Utero

BACKGROUND. Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women during the mid-1900s, is a potent endocrine disruptor. Previous studies have suggested an association between endocrine-disrupting compounds and secondary sex ratio. METHODS. Data were provided by women participating in the National Cancer Institute (NCI) DES Combined Cohort Study. We used generalized estimating equations to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the relation of in utero DES exposure to sex ratio (proportion of male births). Models were adjusted for maternal age, child's birth year, parity, and cohort, and accounted for clustering among women with multiple pregnancies. RESULTS. The OR for having a male birth comparing DES-exposed to unexposed women was 1.05 (95% CI, 0.95-1.17). For exposed women with complete data on cumulative DES dose and timing (33%), those first exposed to DES earlier in gestation and to higher doses had the highest odds of having a male birth. The ORs were 0.91 (95% C, 0.65-1.27) for first exposure at ≥ 13 weeks gestation to < 5 g DES; 0.95 (95% CI, 0.71-1.27) for first exposure at ≥ 13 weeks to ≥ 5 g; 1.16 (95% CI, 0.96-1.41) for first exposure at < 13 weeks to < 5 g; and 1.24 (95% CI, 1.04-1.48) for first exposure at < 13 weeks to ≥ 5 g compared with no exposure. Results did not vary appreciably by maternal age, parity, cohort, or infertility history. CONCLUSIONS. Overall, no association was observed between in utero DES exposure and secondary sex ratio, but a significant increase in the proportion of male births was found among women first exposed to DES earlier in gestation and to a higher cumulative dose.National Cancer Institute (N01-CP-21168, N01-CP-51017, N01-CP-01289

Gender Identity and Sexual Orientation Identity in Women and Men Prenatally Exposed to Diethylstilbestrol

We assessed the associations of prenatal diethylstilbestrol (DES) exposure, a potent estrogen, with sexual orientation and gender identity in 3306 women and 1848 men who participated in a study of prenatal DES exposure. Odds ratios (OR) and 95% confidence intervals (CI) were derived from logistic regression models adjusted for birth year, study cohort, and education. Among women, the OR for DES in relation to reporting sexual orientation identity as nonheterosexual was 0.61 (95% CI 0.40-0.92) primarily due to a strong inverse association with a lesbian identity (OR 0.44, 95% CI 0.25-0.76). Among men, the OR for DES in relation to reporting a nonheterosexual sexual orientation identity was 1.4 (95% CI 0.82-2.4), and ORs were similar for having a gay identity (1.4, 95% CI 0.72-2.85) and bisexual identity (1.4, 95% CI 0.57-3.5). Only five individuals reported a gender identity not conforming to that assigned at birth, preventing meaningful analysis. Women who were prenatally exposed to DES were less likely to have a lesbian or bisexual orientation, while DES-exposed men were somewhat more likely to report being gay or bisexual, but estimates were imprecise

Cervical Screening and General Physical Examination Behaviors of Women Exposed In Utero to Diethylstilbestrol

Objective. To estimate whether women exposed in utero to diethylstilbestrol (DES) report receiving more cervical and general physical examinations compared to unexposed women. Materials and Methods. 1994 Diethylstilbestrol Adenosis cohort data are used to assess the degree of recommended compliance of cervical screenings found in 3,140 DES-exposed and 826 unexposed women. Participants were enrolled at 4 sites: Houston, Boston, Rochester, and Los Angeles. Logistic regression modeling was used to analyze mailed questionnaire data, which included reported frequency over the preceding 5 years (1990-1994) of Papanicolaou smears and general physical examinations. Results. Diethylstilbestrol-exposed women exceeded the recommended frequency of Papanicolaou smear screenings [adjusted odds ratio (aOR) = 2.15, 95% CI (confidence interval) = 1.60-2.88] compared to the unexposed. This association held among those without a history of cervical intraepithelial neoplasia (aOR = 1.88, 95% CI = 1.35-2.62). Diethylstilbestrol-exposed women exceeded annual recommendations for physical examinations (aOR = 2.27, 95% CI = 1.16-4.43) among women without a history of chronic disease when compared to unexposed women. Conclusions. Most DES-exposed women are receiving cervical cancer screening at least at recommended intervals, but one third of the women are not receiving annual Papanicolaou smear examinations

Urogenital Abnormalities in Men Exposed to Diethylstilbestrol in Utero: A Cohort Study

Background: Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women during the 1940s70s, has been shown to cause reproductive problems in the daughters. Studies of prenatally-exposed males have yielded conflicting results. Methods: In data from a collaborative follow-up of three U.S. cohorts of DES-exposed sons, we examined the relation of prenatal DES exposure to occurrence of male urogenital abnormalities. Exposure status was determined through review of prenatal records. Mailed questionnaires (1994, 1997, 2001) asked about specified abnormalities of the urogenital tract. Risk ratios (RR) were estimated by Cox regression with constant time at risk and control for year of birth. Results: Prenatal DES exposure was not associated with varicocele, structural abnormalities of the penis, urethral stenosis, benign prostatic hypertrophy, or inflammation/infection of the prostate, urethra, or epididymus. However, RRs were 1.9 (95% confidence interval 1.13.4) for cryptorchidism, 2.5 (1.54.3) for epididymal cyst, and 2.4 (1.54.4) for testicular inflammation/ infection. Stronger associations were observed for DES exposure that began before the 11th week of pregnancy: RRs were 2.9 (1.65.2) for cryptorchidism, 3.5 (2.06.0) for epididymal cyst, and 3.0 (1.75.4) for inflammation/infection of testes. Conclusion: These results indicate that prenatal exposure to DES increases risk of male urogenital abnormalities and that the association is strongest for exposure that occurs early in gestation. The findings support the hypothesis that endocrine disrupting chemicals may be a cause of the increased prevalence of cryptorchidism that has been seen in recent years