Environmental Health最新文献

Background: The impact of heat exposure on patients with end-stage kidney disease (ESKD) is of growing concern in the context of climate change. In this study, we investigated the association of heat exposure with hospitalization and mortality, and how the risk of these adverse health outcomes varied by climate region in the US.

Methods: We obtained hospitalization and mortality data for patients with ESKD receiving in-center hemodialysis treatment between 2012 and 2018 at Fresenius Kidney Care facilities located within the contiguous US. We used the treatment facility location to assign heat exposure using maximum universal thermal climate index temperature data. We conducted a space-time-stratified case-crossover study using conditional Poisson regression with distributed lag nonlinear models to examine the effects of heat exposure at the 95th percentile of the region-specific temperature distribution for lags of three days. Stratified analyses were run to assess differences in associations across nine climate regions and three latitude bands.

Results: The cumulative lag 0-3 risk of hospitalization associated with heat exposure was highest in the West (rate ratio [RR]: 1.099; 95% confidence interval [CI]: 1.041, 1.160), whereas the highest risk of mortality was observed in the Northwest region (RR: 1.097; 95% CI: 1.007, 1.195). We observed significant increases in the risk of hospitalization at the low- and mid-latitude bands and a significant increase in the risk of mortality in the mid-latitude band.

Conclusion: We observed spatial heterogeneity across US climate regions. The strongest effects of heat exposure were observed in the Ohio Valley, South, and West regions for hospitalization and the Upper Midwest, Southeast, and Northwest regions for mortality. Findings may be used to inform targeted interventions to patients with ESKD residing in areas with higher risks of adverse health outcomes following heat exposure.

Exposure to endocrine disruptors (EDs) is associated with increased susceptibility to obesity and metabolic dysfunction in epidemiological and preclinical studies. Accumulating evidence supports that various EDs promote energy intake and fat storage, but little is known about how they affect energy expenditure (EE). This systematic review examined the effect of EDs on EE in murine models and on mitochondrial bioenergetics in cell-based studies. We included 12 in vivo studies, which assessed the effect of phytoestrogens, DDT, tolylfluanid, benzene, bisphenol A, bisphenol S, butyl-phthalate, deltamethrin, and the mixtures of 23 chemicals and of organophosphate flame retardants. DDT, tolylfluanid, benzene, and the mixtures of 23 chemicals and of flame retardants decreased; bisphenol A, bisphenol S, and butyl-phthalate had a neutral effect; and phytoestrogens and deltamethrin increased EE. The effects of some EDs were sexually dimorphic, dose-dependent, and interacted with diet. Nine cell-based studies were included and indicated that mitochondrial bioenergetics was impaired by tolylfluanid, bisphenol A, and DDT in muscle cells; by bisphenol AF, BDE-99, DDT, DDE, and the mixture of DDE, trans-nonachlor, and oxychlordane in adipocytes; by bisphenol A in hepatocytes; and by tributyltin in pluripotent cells. Our findings indicate that EDs affect EE in mice in a sexually dimorphic pattern and impair mitochondrial bioenergetics in cellular models which are representative of key tissues involved in energy balance. While further studies are needed to fully elucidate the impact of EDs on energy balance and mitochondrial function, this review underscores the plausibility of mitochondrial dysfunction and altered EE as key pathways linking ED exposure to metabolic diseases.

Background: Chronic fluorosis, characterized by excessive exposure to fluoride, is associated with a greater risk of frailty in endemic populations. While fluoride correlates with inflammation and frailty, the mediating role of interleukins (ILs) remains unclear. This study investigated the potential multiple mediation pathways of ILs on the relationship between fluoride exposure and frailty in skeletal fluorosis patients.

Methods: A multicenter cross-sectional cohort (N= 678; age: ≥40 years) from high-fluoride areas in China (2023-2024) was enrolled. Urine fluoride (uF) was used to assess exposure. Frailty was measured via the FRAIL scale, and serum ILs (IL-6, IL-8, IL-1β, and IFN-α) were measured via ELISA. Associations and potential mediating pathways were evaluated via chain mediation models (PROCESS macro, SPSS),which test IL-mediated pathways between uF and frailty and adjust for age/sex. Bootstrapping (5,000 resamples) was used to estimate 95% CIs.

Results: Frailty prevalence (5.9%) surpassed that of the general population (2.3%). A high uF value was directly associated with frailty risk (β = 0.2856, P < 0.001). Two potential pathways were identified: the inflammatory cascade: uF→IL-6↑ (β= 0.2947) → IL-1β↑ (β= 0.3936) →frailty (β= 0.0893), and the indirect association accounted for 3.6% of the total effect. Muscle-nutrition depletion: IL-1β↑ → sarcopenia↑ (β= 0.1137)→ increased undernutrition risk↑ (β=-0.2148)→ frailty (β=-0.1990); the indirect association accounted for 4.2% of the total effect. IFN-α attenuated the association of fluoride with IL-1β (P = 0.0113) and was linked to lower frailty risk (β = -0.086, P < 0.01).  CONCLUSIONS : The"IL-6→IL-1β" pathway is a potential mechanism for inflammation-related frailty, and nutritional interventions could disrupt the "IL-1β→sarcopenia→malnutrition" cycle. IFN-α has a protective effect on fluoride-induced inflammation.

Background: Lead is a well-known neurotoxicant with no identified safe level. Prior studies found that childhood lead exposure is associated with decreased intelligence quotient (IQ) scores. However, most studies rely on a limited number of blood lead measurements. In this prospective pregnancy and birth cohort, we estimated cumulative childhood lead exposure using repeated blood lead concentrations and regression calibration, allowing for more accurate assessment of lead burden over time and its association with IQ.

Methods: This prospective study included 262 mother-child dyads from Greater Cincinnati enrolled in the Health Outcomes and Measures of the Environment (HOME) Study from 2003 to 2006. We obtained serial blood lead measurements and estimated cumulative childhood lead exposure using a regression calibration method. Outcome was assessed via Wechsler-based IQ testing at ages 5-12 years. We examined the association between estimated cumulative childhood lead exposure and child IQ using linear regression models.

Results: Our cohort had low levels of estimated lifetime average lead exposure (geometric mean: 1.21 μg/dL). Overall, estimated lead exposure decreased from age 12 months to time of IQ test. Cumulative childhood lead exposure estimate was associated with decreased IQ at ages 5-12 years in unadjusted analyses, but not after adjusting for maternal IQ, household income, reported prenatal vitamin use, Home Observation for Measurement of the Environment score, and maternal serum cotinine. Sensitivity analyses additionally adjusting for prenatal total folate did not markedly change our results. We assessed early-life, school-age, or concurrent blood lead exposure estimate in place of cumulative childhood lead exposure estimate and observed a similar pattern of results.

Conclusions: We used a regression calibration method to leverage robust, repeated lead exposure data in our prospective pregnancy and birth cohort. In this cohort with low levels of lead exposure, cumulative childhood lead exposure estimate was negatively associated with school-age IQ in unadjusted analyses but not adjusted analyses. We considered sociodemographic and maternal factors previously associated with cognitive development. Our results suggest these factors may confound the association between low-level child lead exposure and child IQ.

Background: The prevalence of autism spectrum disorder has risen in recent decades. Given the growing evidence that prenatal fluoride exposure may be neurotoxic, we examined associations between prenatal fluoride exposure and parent-reported autistic behaviors in preschool-aged children.

Methods: We studied 453 mother-child pairs using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) study, a prospective Canadian birth cohort. Autistic behaviors were assessed in children at 3 to 4 years using the Social Responsiveness Scale-Second Edition (SRS-2) Preschool Form, where a higher score indicates more autistic behaviors. We estimated prenatal fluoride exposure using three methods: (i) maternal urinary fluoride adjusted for specific gravity (MUF_SG), from spot urine samples collected at each trimester and the mean calculated across samples, (ii) daily maternal fluoride intake, based on self-reported consumption of tap water, coffee, and tea during the first and third trimesters, and (iii) water fluoride concentration in tap water. We used multivariable linear regression models to estimate associations between the SRS-2 scale T-scores and each fluoride exposure separately. We used multivariable logistic regression to estimate the association between each prenatal fluoride exposure and an elevated SRS-2 total T-score (i.e., 90th percentile or higher). Potential effect modification of MUF_SG was examined by child sex, daily folic acid supplementation, and plasma total folate in pregnancy.

Results: The mean SRS-2 total T-score for children aged 3 to 4 years was 45.3 (SD = 6.1, range = 34 to 85). The median MUF_SG concentration was 0.43 mg/L (interquartile range = 0.33 mg/L). MUF_SG was not significantly associated with the SRS-2 total T-score in multivariable linear regression (β = -0.16; 95% CI, -1.70, 1.39) or logistic regression (OR = 0.76; 95% CI, 0.29, 1.96). Similarly, estimated daily fluoride intake and water fluoride concentration were not associated with the SRS-2 total T-score. No effect modification was observed.

Conclusions: There was no evidence of an association between prenatal fluoride exposure and autistic behaviors in preschool-aged children, in contrast to previous MIREC research findings on lead and phthalates. Given that this cohort has relatively few children with high SRS-2 scores, further research is needed in other groups of children to more fully explore this association.

Background: The widespread use of pesticides, including glyphosate-based herbicides (e.g., Roundup®, R) and chlorpyrifos-based insecticides (e.g., Clorpi48®, C), has raised concerns about their environmental and human health impacts. Growing evidence links pesticide exposure to cancer development. Given the critical role of immune surveillance in tumor growth control, environmental pollutants such as pesticides should also be evaluated for immunotoxicity. Moreover, while individual pesticides have been extensively studied, the effects of pesticide mixtures on human immune cells remain poorly explored. Here, we assessed the impact of environmentally relevant doses of R, C, or their combination (R+C) on immune cell functions.

Methods: Peripheral blood mononuclear cells (PBMCs), NK cells, and T cells from healthy donors were exposed to environmentally relevant doses of R, C, or R+C. NK cell cytotoxicity, T-bet expression and IFN-g production were analyzed by flow cytometry, and immune synapse formation (LFA-1 localization) and perforin polarization were analyzed by confocal microscopy. T-cell proliferation, Th1 differentiation, and IL-2 signaling were also evaluated by flow cytometry. Oxidative stress was quantified using a fluorometric assay by measuring H₂O₂ production in PBMCs exposed to R, C, or R+C. Also, the role of oxidative stress in T-cell dysfunction was assessed.

Results: The combination of R+C, but not the individual compounds, significantly impaired NK cell cytotoxicity, IFN-g production, and immune synapse formation, as evidenced by disrupted LFA-1 localization and defective perforin polarization. In T cells, R+C exposure inhibited proliferation, Th1 differentiation, IL-2 signaling, and IFN-g secretion by CD8⁺ T cells, all key functions for effective antitumor responses. Mechanistically, oxidative stress contributed to the antiproliferative effect, as scavenging of H₂O₂ by catalase addition restored T cell proliferation.

Conclusions: Environmentally relevant doses of glyphosate and chlorpyrifos-based pesticide mixtures disrupt innate and adaptive immune effector functions that are critical for the control of neoplastic cells and nascent tumor foci, suggesting that current risk assessments underestimate the immunotoxicity of combined formulations.