Environ Health Perspect
· 2026 May · PMID 42148044
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: Exposure to metals and metalloids (hereafter referred to as 'metals') during gestation and early childhood may affect children's neurodevelopment. However, few studies have simultaneously evaluated the impact of exposu...: Exposure to metals and metalloids (hereafter referred to as 'metals') during gestation and early childhood may affect children's neurodevelopment. However, few studies have simultaneously evaluated the impact of exposure to both essential and nonessential metals across specific windows of exposure on children's neurodevelopmental outcomes. : To investigate whether levels of metals during gestation and the early postnatal period, individually and as a mixture, are related to child cognition at 5 years of age among participants in the New Hampshire Birth Cohort Study (NHBCS). : We followed 278 NHBCS pregnancy-offspring dyads for up to approximately 5 years of age. Total arsenic (As), copper (Cu), manganese (Mn), lead (Pb), selenium (Se), and zinc (Zn) were measured in toenail samples collected from pregnant persons at ∼24 to 28 weeks of gestation (representing periconception and early pregnancy) and at ∼6 weeks postpartum (representing midpregnancy), and their infants at ∼6 weeks of age (representing early infancy). Cognitive development at 5 years was assessed using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV), which includes measures of the full-scale intelligence quotient (FSIQ) and five composite indices. Associations between ln-metal toenail concentrations across multiple exposure windows and the six WPPSI-IV scores were estimated through mean field variational Bayes for lagged kernel machine regression (MFVB-LKMR). Potential effect modification by other elements in the mixture as well as sex was further explored. : Biomarkers of As exposures of periconception and early pregnancy, midpregnancy, and early infancy were associated with lower cognitive scores at 5 years of age (e.g., FSIQ: -0.16 (95% Credible Interval (CrI): -0.24, -0.08) SD change). Periconception and early pregnancy exposures to Mn and Cu were associated with higher child cognitive scores. Sex differences were observed, especially with Mn exposure, with stronger positive associations among males during periconception and early pregnancy and among females during midpregnancy. For Pb and Zn exposures, associations with cognitive scores differed across exposure windows, exhibiting both positive and negative associations. By evaluating multiple essential and nonessential elements across the three previously mentioned exposure windows, we found evidence of sensitive periods of susceptibility to child cognitive measures. While results for As indicated detrimental effects, those for Cu and Mn suggested beneficial trends across all exposure windows.
Huang CY, Nuwagira E, Tisza M
… +11 more, Kim M, Tayebwa M, Vieira J, Lam N, Wallach E, Wiens M, Tsai AC, Valeri L, Vallarino J, Allen JG, Lai PS
Environ Health Perspect
· 2026 May · PMID 42148043
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Emerging observational studies suggest that air pollution can influence the gut microbiome. However, this association is often highly confounded by factors, such as diet and poverty. The gut virome may influence respirat...Emerging observational studies suggest that air pollution can influence the gut microbiome. However, this association is often highly confounded by factors, such as diet and poverty. The gut virome may influence respiratory health independent of the gut microbiome. We recently demonstrated in a randomized waitlist-controlled trial (ClinicalTrials.gov NCT03351504) that a clean lighting intervention reduced the level of personal exposure to air pollution among adult women in rural Uganda. To determine the effect of a solar lighting intervention on changes to the gut microbiome and virome and secondarily to determine the association between these changes on lung health. Between 2018 and 2019, we collected stool samples and assessed respiratory symptoms and spirometry from 80 adult women living in rural Uganda at baseline and 12 and 18 months postrandomization. The intervention group received a solar lighting system after randomization, while the waitlist-controlled group received one at 12 months. Deep metagenomics sequencing of stool was performed and profiled for nonviral and viral taxonomic composition. The primary analysis focused on pre- vs postintervention changes due to power considerations, adjusting for potential confounding by age, diet, antibiotic use, and season. A sensitivity analysis was conducted using intention-to-treat principles. When comparing pre- vs postintervention periods, we used sparse partial least-squares models to identify nonviral and viral signatures of reduced air pollution exposure. Mixed effects models were used to evaluate changes in health outcomes as well as associations between microbial signatures of reduced air pollution exposure and health. The average age was 39.2 years. The solar lighting intervention led to larger changes in viral compared to nonviral microbial community structure and differential abundance of bacteria, eukaryotes, and viruses. Provision of solar lighting systems was associated with a reduction in the presence of respiratory symptoms from 57.1% to 36.1% ( = 0.002), while there was no impact on lung function. Microbiome and virome signatures had AUCs of 0.74 and 0.76, respectively, in predicting pre- vs postintervention stool samples. Microbiome signatures were associated with a lower risk of respiratory symptoms (OR = 0.68 (0.49 - 0.94), = 0.020). Among adult women living in rural Uganda, both nonviral and viral components of the gut microbial community changed after a clean lighting intervention. Microbiome signatures reflective of lower air pollution exposures were associated with improved respiratory symptoms. These observations suggest that air pollution may influence lung health through the gut-lung axis, warranting further exploration in future intervention studies.
Alwadi Y, Alahmad B, Weisskopf MG
… +1 more, Koutrakis P
Environ Health Perspect
· 2026 May · PMID 42148042
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Traditional temperature-health studies have predominantly relied on temperature measurements from stations or modeled spatial averages from gridded temperature data sets. It has been suggested that population-weighted sp...Traditional temperature-health studies have predominantly relied on temperature measurements from stations or modeled spatial averages from gridded temperature data sets. It has been suggested that population-weighted spatial averages would perform better in remote regions with large temperature and population variability. This would be particularly true in regions other than North America and Europe where outcome data are often only available on a crude spatial scale, but no studies have examined this in such regions, where temperatures can be particularly hot. Using the Middle East as a climate hotspot, our objective was to illustrate the utility of population weighting temperature exposures in understudied regions with large health data aggregation areas. We used a daily 1 km × 1 km temperature data set for 152 administrative regions in 12 Middle Eastern countries. From 2003 to 2020, for each administrative region, we computed daily minimum and maximum population-weighted and unweighted spatial average temperatures. To illustrate, we examined temperature-mortality associations in two countries: Kuwait and Jordan. We used distributed lag nonlinear models to estimate the daily time series temperature-mortality associations in using three temperature exposure measurement approaches: station temperatures, unweighted spatial averages, and population-weighted temperatures. For each scenario, we fitted country-specific optimized parameters and compared them using three metrics: 1) exposure-response relationships, 2) minimum mortality temperatures, and 3) attributable mortality estimates. The study region had geographically sporadic yet densely populated areas within each country. In both Kuwait and Jordan, population-weighted and unweighted spatial average temperatures resulted in fairly similar exposure-response curves, whereas both were notably different from station temperatures. Minimum mortality temperatures were 30.2, 28.6, and 28.3 °C in Kuwait for station, unweighted spatial average, and population-weighted temperatures, respectively. In Jordan, the corresponding temperatures were 20.6, 20.9, and 20 °C. Heat attributable mortality calculated using population-weighted temperatures increased by 15% compared to the traditionally used station temperatures in Kuwait and Jordan, respectively, and -0.4% and 5% compared to unweighted spatial average temperatures. Spatial averaging, whether weighted or unweighted, is a valuable tool for estimating heat-attributable mortality. This is especially true in regions like the Middle East, where granular temperature data are often unavailable and health studies are urgently needed. Population-weighted temperatures may better capture localized exposures in areas with significant population clustering, though their exact added effect on top of unweighted spatial averages remains a tentative conclusion.
Joubert BR, Palmer G, Dunson D
… +2 more, Kioumourtzoglou MA, Coull BA
Environ Health Perspect
· 2026 May · PMID 42148041
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: Human exposure to complex, changing, and variably correlated mixtures of environmental chemicals has presented analytical challenges to epidemiologists and human health researchers. There has been a wide variety of rec...: Human exposure to complex, changing, and variably correlated mixtures of environmental chemicals has presented analytical challenges to epidemiologists and human health researchers. There has been a wide variety of recent advances in statistical methods for analyzing mixtures data, with most methods having open-source software for implementation. However, there is no one-size-fits-all method for analyzing mixture data given the considerable heterogeneity in scientific focus and study design. For example, some methods focus on predicting the overall health effect of a mixture and others seek to disentangle main effects and pairwise interactions. Some methods are only appropriate for cross-sectional designs, while other methods can accommodate longitudinally measured exposures or outcomes. : This article focuses on simplifying the task of identifying which methods are most appropriate to a particular study design, data type, and scientific focus. : We present an organized workflow for statistical analysis considerations in environmental mixtures data and two example applications implementing the workflow. This systematic strategy builds on epidemiological and statistical principles, considering specific nuances for the mixtures' context. We also present an accompanying methods repository to increase awareness of and inform application of existing methods and new methods as they are developed. : We note several methods may be equally appropriate for a specific context. This article does not present a comparison or contrast of methods or recommend one method over another. Rather, the presented workflow can be used to identify a set of methods that are appropriate for a given application. Accordingly, this effort will inform application, educate researchers (e.g., new researchers or trainees), and identify research gaps in statistical methods for environmental mixtures that warrant further development.
Zhang G, Zhao L, Wang J
… +9 more, Wang K, Ji X, Hu R, Hou T, Zhang L, Li R, Sun Q, Zhang K, Liu C
Environ Health Perspect
· 2026 May · PMID 42148040
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Liver injury is a frequent complication of heatstroke and constitutes a direct cause of death. However, only a few studies examined the mechanism underlying heatstroke-induced liver injury. We aimed to evaluate the role...Liver injury is a frequent complication of heatstroke and constitutes a direct cause of death. However, only a few studies examined the mechanism underlying heatstroke-induced liver injury. We aimed to evaluate the role of peroxisome proliferator-activated receptor α (PPARα) in heatstroke-induced liver injury and to explore the potential mechanisms. Male C57BL/6N mice were subjected to a control (22 ± 1 °C) or extreme heat temperature (39.5 ± 0.5 °C) to induce a heatstroke-associated liver injury animal model. PPARα agonist, ferroptosis inhibitor, and AAV8-mediated PPARα overexpression were administered to the mice to investigate the role of PPARα and ferroptosis in the heatstroke-induced liver injury. Serum was collected for liver function evaluation. Liver tissues were applied for morphological observation, staining detection, ferroptosis examination, and mechanistic exploration. Compared with the control group, extreme heat exposure-induced temperature dysregulation, impaired liver function, and morphological damage in mice. Proteomics screened PPARα as a protein of interest, with its level being significantly decreased in response to extreme heat exposure. Both PPARα activation and overexpression attenuated extreme heat-induced heatstroke and liver injury. Hmox1 was next screened and higher Hmox1 expression was identified, accompanied by elevated markers of ferroptosis including prostaglandin-endoperoxide synthase 2 (Ptgs2), malondialdehyde (MDA), lipid peroxidation (LPO) and Fe levels. Ferroptosis inhibition mitigated heatstroke and liver injury induced by heat exposure. In the setting of extreme heat exposure, PPARα activation suppressed Hmox1 expression and the levels of ferroptosis markers. It not only induced differences in the expression of members of iron generation, efflux and uptake process and reduced hepatic intracellular Fe accumulation, but also stimulated expression of molecules for countering lipid peroxidation including Nrf2-SLC7A11-GPX4 axis and FSP1 signaling. PPARα played an essential role in extreme heat exposure-induced heatstroke and liver injury, and PPARα intervention conferred protection against it via inhibition of ferroptosis.
Tang C, Zhang Y, Zhang F
… +11 more, Sun Y, Zhu Y, Xue F, Wang Z, Wu Y, Ruan J, Yue Y, Yang C, Ge W, He C, Zuo Z
Environ Health Perspect
· 2026 May · PMID 42148039
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: Ovarian folliculogenesis is crucial for female reproduction. This can be disrupted by various factors, including pollutants with aryl hydrocarbon receptor (AHR) agonistic activity, but the underlying mechanisms remain...: Ovarian folliculogenesis is crucial for female reproduction. This can be disrupted by various factors, including pollutants with aryl hydrocarbon receptor (AHR) agonistic activity, but the underlying mechanisms remain unclear. : Using the herbicide neburon, a moderate AHR agonist among current pesticides, we investigated its effects on ovarian folliculogenesis in zebrafish through life-cycle exposure at environmentally relevant concentrations to elucidate the associated mechanisms. : Wild-type (WT) and three different genotypes of female zebrafish ( ; , ; , ; ) were exposed to neburon for 150 days. Neburon and its metabolites in fish were quantified using LC-MS/MS. Ovarian pathology was assessed by H&E and TUNEL staining. The differentially expressed pathways were identified by transcriptome analysis, followed by validation using RT-qPCR, WB, IHC, and ELISA. Finally, AHR antagonist, ChIP-RT-qPCR, and other methods were used to further elucidate the mechanism in mouse granulosa cell line (KK1). : After neburon exposure, only four metabolites of neburon were detected but not the metabolite itself, and all these metabolites had AHR agonistic activity, indicating the persistent toxicity of neburon. Neburon exposure altered the follicle-stage distribution and poorer oocyte quality in WT zebrafish. Further experiments found that neburon exposure induced greater secretion of anti-Mullerian hormone (Amh), greater expression of genes in the Amh/Bmpr2a pathway, accelerated follicular development, and lower expression of insulin-like growth factors, which was associated with oocyte atresia. Notably, ; zebrafish showed a rescued phenotype with regard to these neburon-associated outcomes. Moreover, AHR exhibited specific binding to the promoter in KK1 cells, and neburon treatment enhanced their interaction. : In zebrafish, AMH was identified as a critical target for reproductive disorders following neburon exposure. Despite the short half-lives of the currently used pesticides, their metabolites might still have significant toxicological risks. This study provides novel insight into how one AHR agonistic pollutant affects female zebrafish reproduction.
Nishie T, Taya T, Omori S
… +23 more, Ueno K, Okamoto Y, Higaki S, Oka M, Mitsuishi Y, Tanaka T, Nakamoto M, Kawahara H, Teraguchi N, Kotaka T, Sawabe M, Takahashi M, Kitaike S, Wada M, Iida K, Yamashita A, Jinno H, Ichimura A, Tooyama I, Sakai N, Hibi M, Hirasawa A, Takada T
Environ Health Perspect
· 2025 Jun · PMID 40554690
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Xiang Y, Tang G, Hu X
… +13 more, Yu X, Feng Y, Huang Z, Luo Y, Jiang Z, Lv Y, Sun X, Zhang Y, Cheng L, Xin Y, Qian Y, Li B, Wang B
Environ Health Perspect
· 2025 Jun · PMID 40512651
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BACKGROUND: Fat-soluble toxicants such as chlorpyrifos (CPF) can accumulate in adipose tissue and the liver. During weight loss, these compounds may be released into circulation, but the metabolic consequences of this mo...BACKGROUND: Fat-soluble toxicants such as chlorpyrifos (CPF) can accumulate in adipose tissue and the liver. During weight loss, these compounds may be released into circulation, but the metabolic consequences of this mobilization remain poorly understood. OBJECTIVES: This study aimed to investigate the mobilization of CPF during weight loss and its effects on liver health and adipose tissue metabolism in mice. METHODS: C57BL/6J mice were fed high-fat or low-fat diets and exposed to 2 mg/kg BW/day CPF by oral gavage. Weight loss was induced by β3-adrenergic stimulation (CL316243) or treadmill exercise for 4 or 10 weeks. CPF was quantified in serum and tissues using HPLC. Tissue histology, expression of genes related to CPF metabolism, liver injury markers, and metabolic protein levels were assessed. RESULTS: CPF-exposed LFD mice showed more severe liver fibrosis and adipose inflammation than HFD counterparts. While obese mice had lower adipose CPF concentrations, they showed higher hepatic accumulation. CPF-exposed weight loss mice had higher levels of CPF in adipose tissue, liver, and brain and higher expression of CPF metabolism-related genes, including Paraoxinase-1 and cytochrome P450 genes, and greater glucose intolerance, compared to their counterparts without CPF administration. Molecular analyses revealed suppressed AMPK signaling and P62 accumulation indicating mitophagy disruption in CPF-exposed mice after weight loss. These effects occurred even at human-relevant low doses (0.45 mg/kg BW/day) and persisted across sexes. DISCUSSION: Weight loss mobilizes CPF and its metabolites from fat stores, leading to tissue accumulation and damage. Even low-dose exposure contributes to hepatic and metabolic disruption in mice, highlighting a potential risk of toxicant mobilization during fat reduction.. https://doi.org/10.1289/EHP16079.
Qi W, Kong M, Meng X
… +13 more, Sun Z, Mei Z, Pu Y, Zhou X, Wang Q, Qiu JG, Jiang BH, Shen J, Yuan C, Ji JS, Wang X, Kan H, Zheng Y
Environ Health Perspect
· 2025 Jun · PMID 40512497
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BACKGROUND: Growing evidence links air pollution to cognitive dysfunction in older adults. The gut microbiome and circulating metabolites present an important yet unexplored pathway, given their crucial role in the gut-b...BACKGROUND: Growing evidence links air pollution to cognitive dysfunction in older adults. The gut microbiome and circulating metabolites present an important yet unexplored pathway, given their crucial role in the gut-brain axis. OBJECTIVES: We aimed to explore the potential roles of gut bacteria, fungi, microbial functional potentials, and circuiting metabolites in the association of residential PM and O exposures with cognitive dysfunction. METHODS: We analyzed gut microbiome data from 1,027 older adults using metagenome and internal transcribed spacer sequencing to profile bacterial and fungal taxa, functional pathways, and enzyme abundances. Targeted metabolomics quantified 195 circulating metabolites, such as amino acids and organic acids. Annual average ambient PM and O exposures were estimated using satellite-based models. Cognitive outcomes, including mild cognitive impairment and cognitive decline, were assessed using the Mini-mental State Examination and Hasegawa dementia scale. Statistical analyses included Microbiome Multivariable Association with Linear Models (with a false discovery rate threshold of 0.25) for microbial associations and multivariate regression for metabolites and cognitive outcomes. RESULTS: Higher PM and O exposures were associated with disturbances in microbial composition, altered taxonomic profiles (e.g., decreased abundances of and ), and disrupted functional pathways, particularly those regulating 2-oxoglutarate. These findings were partially replicated in an independent population. Higher air pollution levels were associated with increased circulating levels of 2-oxoglutarate and L-glutamine (key metabolites in neurodegenerative progression), which were further linked to higher odds of concurrent mild cognitive impairment (OR: 1.39-1.56) and an increased 2-year risk of cognitive decline (OR: 1.26-1.37). These associations were partially mediated by air pollution-related changes in microbial anaerobic energy metabolism pathways, especially involving 2-oxoglutarate metabolism and the enzyme aspartate transaminase. CONCLUSIONS: Our findings highlight the role of the gut microbiome and microbial metabolites in mediating the detrimental impact of air pollution on cognitive health in older adults, providing new insights into the underlying etiology for future hypothesis generation. https://doi.org/10.1289/EHP16515.
Shirke AV, Radke EG, Jones R
… +13 more, Allen BD, Lin CJ, Ross A, Vetter N, Lemeris C, Hartman P, Eftim S, Varghese A, Blain R, Hubbard H, Williams AJ, Thayer KA, Carlson LM
Environ Health Perspect
· 2025 Jun · PMID 40505091
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BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a research priority for the U.S. Environmental Protection Agency (EPA). Because PFAS include thousands of structurally diverse chemicals, there is a pressing nee...BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a research priority for the U.S. Environmental Protection Agency (EPA). Because PFAS include thousands of structurally diverse chemicals, there is a pressing need for identifying what data are available to assess the human health hazard of these compounds. OBJECTIVES: We used systematic evidence map (SEM) methods to summarize the available epidemiological and mammalian bioassay evidence for ∿14,735 chemicals identified as PFAS by EPA's Center for Computational Toxicology and Exposure (CCTE). This work is a continuation of our previous 2022 and 2024 SEMs that inventoried evidence on a separate set of ∿500 PFAS. The Comprehensive PFAS Dashboard includes evidence identified from our past SEMs and completed EPA assessments. METHODS: We conducted literature searches from peer-reviewed and gray literature sources to identify, screen, and inventory mammalian bioassay and epidemiological literature. A combination of manual review and machine learning software were utilized. A diverse array of potentially relevant supplemental content was also tracked, including mechanistic data, exposure-only studies, and studies informing chemical toxicokinetics and clearance. For each study meeting predefined population, exposure, comparator, and outcome (PECO) criteria, experimental design details and health endpoints evaluated were summarized in interactive web-based literature inventory visuals. Epidemiology studies and animal bioassay studies with ≥21-day exposure duration or reproductive/developmental study design proceeded to undergo a study evaluation for risk of bias and sensitivity, as well as detailed extraction of health endpoint data. Underlying data are publicly available and can be downloaded. RESULTS: Scientific database searches retrieved 152,205 references. After full-text screening, there were 347 mammalian bioassay and 44 epidemiological studies that met PECO criteria. The mammalian bioassay and epidemiological evidence assessed 99 and 30 individual PFAS, respectively (n = 18 PFAS with both). The epidemiological evidence assessed 15 health systems and the mammalian bioassay evidence assessed 16 health systems. DISCUSSION: Results from our 2022 and 2024 SEMs and completed EPA assessments are compiled into Comprehensive PFAS Dashboard. This dashboard is a resource for better understanding the currently available PFAS human health hazard data. It can be used as a tool for researchers and regulators interested in PFAS data gaps and research needs. Across all the data sources compiled into the Comprehensive PFAS Dashboard, only 1.4% (214/14,735) of PFAS had any mammalian bioassay or epidemiological data available. The vast majority of PFAS lack publicly available information about the potential human health effects of exposure to these chemicals.. https://doi.org/10.1289/EHP16952.
Goel V, Ziade M, Chan B
… +12 more, Yunus M, Ali MT, Khan MAF, Alam MN, Faruque A, Babu S, Kabir MM, Delamater PL, Serre ML, Sobsey MD, Islam MS, Emch M
Environ Health Perspect
· 2025 Jun · PMID 40504602
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BACKGROUND: Diarrheal diseases remain a leading cause of mortality and morbidity among under-five children in South Asia. In rural Bangladesh, deep tubewells that tap into low-arsenic deep aquifers have been installed to...BACKGROUND: Diarrheal diseases remain a leading cause of mortality and morbidity among under-five children in South Asia. In rural Bangladesh, deep tubewells that tap into low-arsenic deep aquifers have been installed to provide microbially safe and arsenic-free drinking-water at source. However, unlike more widely used shallow tubewells, deep tubwells are sparsely distributed, and households often travel farther for drinking-water consumption from such wells. Hence, benefits from deep tubewells may be abated by higher levels of microbial contamination during water handling and storage that could increase the risk of diarrheal diseases. OBJECTIVES: We examined the association between deep tubewell use and diarrheal disease risk in under-five children and investigated the role of social and environmental factors on modifying the association. METHODS: We implemented community diarrheal disease surveillance across households with under-five children using deep and shallow tubewells in Matlab, Bangladesh from March 2018 to October 2019. We used Generalized Estimating Equations (GEE) to measure the association between deep tubewell use compared to shallow tubewell use on diarrheal disease prevalence. RESULTS: Children in households using deep tubewells had diarrheal disease prevalence 0.83 times that of children in households using shallow tubewells (95% Confidence interval (CI): 0.71-0.96). Protective effects of deep tubewell use on diarrhea risk were observed among children in households that drank from wells within their household compound (Risk ratio (RR) =0.70, 95% CI: 0.54-0.91), were in flood-prone areas (RR=0.83, 95% CI: 0.75-0.92), and used unimproved latrines (RR=0.62, 95% CI: 0.43-0.89). Deep tubewell use was more protective against diarrhea than shallow tubewell use during the dry season (RR = 0.71, 95% CI: 0.52-0.97). CONCLUSIONS: Despite concerns, using deep tubewells may not translate to higher diarrhea risk among under-five children, and may reduce diarrhea further especially in social and environmental contexts associated with higher groundwater microbial contamination. https://doi.org/10.1289/EHP15725.
Motsinger-Reif AA, Balshaw DM, Birnbaum LS
… +9 more, Cui Y, DellaValle CT, Dixon CA, Iturriaga E, Jett DA, Miller AK, Shanmugam VK, Temkin SM, Kwok RK
Environ Health Perspect
· 2025 Jun · PMID 40503926
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BACKGROUND: Exposomics is a conceptual framework positioned at the intersection of environmental health sciences and precision medicine. It seeks to comprehensively understand how environmental exposures and the body's r...BACKGROUND: Exposomics is a conceptual framework positioned at the intersection of environmental health sciences and precision medicine. It seeks to comprehensively understand how environmental exposures and the body's response to these exposures impact human health across the life course. Introduced in 2005, the exposome concept represents a paradigm shift from single-pollutant studies to an integrated approach considering a broad range of exposures. OBJECTIVES: This commentary explores the ongoing efforts to operationalize the exposome, with a focus on NIH initiatives aimed at building capacity in exposomics research and integrating lifecourse exposure data into health research. METHODS: This commentary draws on a structured review of current NIH funding opportunities, initiatives, and strategic documents related to exposomics. Key NIH-supported projects and collaborations were identified through analysis of publicly available agency reports, grant announcements, and program descriptions. Additional insights were gathered from relevant literature and international research activities to contextualize the NIH's role in promoting exposomics and integrating life-course exposure data into health research. DISCUSSION: Operationalizing the exposome is essential for advancing the field of environmental health and precision medicine. NIH-supported initiatives, alongside international collaborations, aim to standardize methodologies, develop tools, and promote interdisciplinary research. Addressing the complexities of exposomics requires integrating diverse datasets and fostering global coordination, paving the way for innovative strategies to improve human health outcomes. https://doi.org/10.1289/EHP15561.
Quinlivan V, Park DE, Aziz M
… +15 more, Casey JA, Davis M, Hu Q, Innes G, Nachman K, Nyaboe A, Pomichowski M, Rabanes HG, Roberts A, Roloff E, Takhar HS, Tartof SY, Liu C, Price L, KP & GWU ARES team
Environ Health Perspect
· 2025 Jun · PMID 40499131
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BACKGROUND: Antimicrobial use in food-animal production selects for antimicrobial-resistant that can be transmitted to humans via contaminated meat products. California Senate Bill 27 (SB27), which took effect on Januar...BACKGROUND: Antimicrobial use in food-animal production selects for antimicrobial-resistant that can be transmitted to humans via contaminated meat products. California Senate Bill 27 (SB27), which took effect on January 1, 2018, restricts the use of medically important antimicrobials in California food-animal production. Over time, SB27 could reduce the prevalence of antimicrobial-resistant on meat produced in California. OBJECTIVES: We aimed to assess whether the implementation of SB27 was associated with significant decreases in resistance to medically important antimicrobials among strains contaminating raw chicken produced in California. METHODS: We purchased raw chicken products in Southern California, including those produced in and outside of California, from 2017 to 2021 and cultured them for . Susceptibility to 19 antimicrobials was determined using the disk diffusion method. Changes in antimicrobial susceptibility over the course of the study were evaluated using the Mann-Kendall test. RESULTS: We observed significant decreases in resistance to multiple classes of antimicrobials in isolated from retail chicken meat from 2017 to 2021. Resistance to penicillins had a relative decrease of 14-18% annually in E. coli from chicken raised in California but not from chicken raised outside California, potentially indicating that SB27 was effective. Resistance to multiple other classes of antimicrobials saw an absolute decrease of up to 8% in chicken produced both inside and outside California. DISCUSSION: Our findings suggest that the downward trends in antimicrobial resistance among E. coli populations from California-produced chicken products reflect national trends. It is possible that the California SB27 legislation helped motivate industry-wide decreases in antimicrobial use among broiler chicken producers. Alternatively, the changes observed in California may have been driven by industry-wide trends independent of SB27. The lack of publicly available data regarding actual antimicrobial use in California and non-California broiler chicken production limits our ability to make stronger conclusions about our observations. https://doi.org/10.1289/EHP16115.
Environ Health Perspect
· 2025 Jun · PMID 40499048
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BACKGROUND: Organophosphate ester flame retardants and plasticizers (OPEs) have myriad uses in industry and consumer products. Increasing human exposure to OPEs has raised concerns about their potential effects on child...BACKGROUND: Organophosphate ester flame retardants and plasticizers (OPEs) have myriad uses in industry and consumer products. Increasing human exposure to OPEs has raised concerns about their potential effects on child neurodevelopment during pregnancy. OBJECTIVE: We investigated whether OPE urinary concentrations during pregnancy were associated with child autism-related outcomes. METHODS: We included 4159 mother-child pairs from 15 cohorts in the NIH Environmental influences on Child Health Outcomes (ECHO) Consortium, with children born from 2006-2020 (median age [interquartile range]: 6 [4,10] years). Nine OPE biomarkers were measured in urine samples collected mid- to late pregnancy. Dilution-adjusted biomarkers were modeled continuously, categorically (high [> median], moderate [≤ median], non-detect), or as detect/non-detect depending on their detection frequency. We assessed child autism-related traits via a) parent report on the Social Responsiveness Scale (SRS) and b) clinical autism diagnosis. We examined associations of OPEs with child outcomes, including modification by child sex, using generalized estimating equations to account for clustering by ECHO cohort. RESULTS: Compared with non-detectable concentrations, high exposure to bis(butoxyethyl) phosphate (BBOEP) was associated with higher autistic trait scores (adj-β 0.97, 95% confidence interval [CI]: 0.42, 1.52) and greater odds of autism diagnosis (adjusted odds ratio [adj-OR]: 1.27, 95% CI: 1.07, 1.50). Bis(1-chloro-2-propyl) phosphate (BCPP) showed associations with autistic trait scores (BCPP adj-β for high exposure vs. non-detect: 0.34, 95% CI: -0.46, 1.13; BCPP adj-β for moderate exposure vs. non-detect: 0.72, 95% CI: 0.24, 1.20). High exposure to bis(2-chloroethyl) phosphate (BCETP) was associated with lower odds of autism diagnosis (adj-OR: 0.76, 95% CI: 0.60, 0.95). Other OPEs showed no associations in adjusted models. Associations between BBOEP and higher autistic trait scores were stronger in males than females. DISCUSSION: Prenatal exposure to OPEs, specifically BCPP and BBOEP, may be associated with higher risk of autism diagnosis and related traits in childhood. https://doi.org/10.1289/EHP16177.
Environ Health Perspect
· 2025 Jun · PMID 40498683
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BACKGROUND: Environmental epidemiology studies increasingly integrate "big" geospatial and health datasets to examine associations between environmental factors and health outcomes. Using such datasets - and linking betw...BACKGROUND: Environmental epidemiology studies increasingly integrate "big" geospatial and health datasets to examine associations between environmental factors and health outcomes. Using such datasets - and linking between them - presents a number of complexities with regard to study design and analytic approaches. These complexities are often magnified with the integration of additional contextual data representing other neighborhood characteristics, including socioeconomic factors. Guidance regarding the design of environmental health studies that leverage "big" geospatial and health outcome data is limited and fragmented. OBJECTIVE: Drawing on methodological literature and case studies, this commentary outlines common challenges related to geospatial and health data linkages, posing a series of guiding questions and considerations for investigators conducting environmental health studies, particularly analyses with an etiological focus. DISCUSSION: Recommendations include: 1) using a target trial approach to guide causal analysis, 2) aligning measures with hypothesized causal mechanisms, 3) exploring opportunities to "groundtruth" and validate data, and 4) prioritizing interdisciplinary science. The goal of the commentary is to consolidate insights from multiple disciplines - including exposure science, epidemiology, and sociology - to provide a foundation for etiologic research focused on advancing environmental health for all populations. https://doi.org/10.1289/EHP15756.