Environmental Research

BackgroundAir pollution is a potentially modifiable risk factor for dementia with a population attributable risk fraction of 3%. Little is known about the causal mechanisms behind the association, so we aimed to investigate this. MethodsData from the UK Biobank were used to investigate the association between six measures of air pollution (NO2, NOx, PM2{middle dot}5-10, PM2{middle dot}5, PM2{middle dot}5 absorbance and PM10) and dementia incidence. Indirect pathways through four mediators (cardiovascular conditions, mental health treatment, insufficient exercise and social isolation) were explored. Logistic regression was used to model the associations between air pollution, mediators and dementia. Casual mediation analysis implemented using the g-formula was used to investigate the joint indirect effect through the mediators. FindingsExposure to the highest quintile of PM2{middle dot}5 (Rte:1{middle dot}14, 95% CI:1{middle dot}06-1{middle dot}23), NOx (Rte:1{middle dot}11, 95% CI:1{middle dot}03-1{middle dot}20) or NO2 (Rte:1{middle dot}08, 95% CI:0{middle dot}99-1{middle dot}16), compared to the lowest quintile, was associated with higher dementia risk. Most of the observed association resulted from the direct effect of air pollution, consisting of pathways not captured through considered mediators. Amongst those in the highest PM2{middle dot}5 quintile, jointly intervening on the four mediators would result in a 1% reduction in risk of dementia (Rpnie:1{middle dot}01, 95% CI: 1{middle dot}01-1{middle dot}02). The randomised pure natural indirect effect was similar for NO2 (Rpnie:1{middle dot}01, 95% CI: 1{middle dot}00-1{middle dot}01) and NOx (Rpnie:1{middle dot}01, 95% CI: 1{middle dot}01-1{middle dot}02). InterpretationMost of the association between dementia and PM2{middle dot}5, NO2 and NOx occurs through the direct effect of air pollution, or other unmeasured mediators, and not pathways through these four mediators. FundingMedical Research Council (Grant MR/W006774/1).

ObjectiveTo investigate associations between long-term environmental exposures, both external (ambient air pollution and built environment) and internal (circulating anthropogenic chemicals), and the human plasma metabolome, with the aim of generating biologically plausible hypotheses about affected metabolic pathways. MethodsWe analyzed plasma from 989 Estonian Biobank participants using untargeted LC-HRMS (Metabolon HD4). External exposures (PM2.5, PM10, NO2, ozone and built-environment metrics) were assigned using spatiotemporally resolved models developed in the EXPANSE project. Internal exposures were defined as ubiquitous anthropogenic compounds detected in the same metabolomics dataset. Associations between exposures and individual metabolites were quantified using left-censored regression models and then mapped to metabolite classes (Metabolon) and KEGG pathways. For enrichment analyses, one-sided Kolmogorov-Smirnov tests were applied to external exposures and Fishers exact tests to internal exposures. False discovery rate was controlled at 1% per exposure and database. ResultsExternal air pollutants exhibited distinct metabolic patterns: Higher NO2 exposure was associated with enrichment of metabolites involved in tyrosine metabolism; higher ozone with monohydroxy and dicarboxylate fatty acids (consistent with lipid peroxidation); and higher PM2.5 with acyl-carnitine subclasses and carbohydrate metabolism (glycolysis / gluconeogenesis / pyruvate). Built-environment associations were heterogeneous across metabolites and pathways. Internal anthropogenic chemicals showed broader metabolic associations than external exposures, involving a larger number of metabolites and metabolic classes. PFAS (PFOA, PFOS) were associated with long-chain polyunsaturated fatty acids (n3/n6) and lysophospho-lipids. Associations with 4-hydroxychlorothalonil, a fungicide, pointed to androgenic steroid metabolites and alpha-linolenic acid metabolism. The phenolic 2,4-di-tert-butylphenol, a plastic associated chemical, showed widespread associations with lipid classes, suggesting disruption of membrane remodeling and fatty acid handling. ConclusionLong-term environmental exposures, both external and internal, are measurably reflected in the human plasma metabolome. Across exposure domains, recurrent signals involved lipid metabolism, membrane composition, and oxidative stress-related pathways, highlighting these as common biological targets of environmental exposures. The findings generate testable hypotheses, including nitrosative stress-related alterations for NO2, lipid peroxidation for ozone, energy-metabolism perturbations for PM2.5, potential endocrine activity for chlorothalonil metabolites, and possible obesogenic effects of 2,4-di-tert-butylphenol.

Background/ObjectivesOccupational exposure to neurotoxicants such as pesticides, metals, and solvents has long been implicated in Parkinsons disease (PD) and Parkinsonism, yet the cumulative impact of multiple occupational exposure families over the working life remains insufficiently characterized. This study evaluated whether long-term cumulative occupational exposures, derived from the ALOHA+ Job-Exposure Matrix (ALOHA+-JEM), were associated with PD and Parkinsonism. MethodsA hospital-based matched case-control study was conducted in the province of Brescia, Italy, including 668 participants (334 PD/Parkinsonism cases and 334 matched controls). Cases and controls were 1:1 matched based on sex, age, and lifetime occupational duration. Lifetime occupational histories were coded using ISCO-08 and harmonized to ISCO-88 for linkage with ALOHA+-JEM. Conditional logistic regression estimated associations between cumulative exposures (none/low/high) and disease status, adjusting for smoking, parental history of PD/tremor, and SNCA rs356219 genotype. Multi-agent occupational exposure burden indexes were evaluated using positively constrained repeated-holdout Weighted Quantile Sum (WQS) regression (100 bootstraps, 100 holdouts) ResultsIn conditional logistic regression, parental history of PD or tremor (OR = 4.55, 95% CI: 2.44-8.48; q < 0.001) and the SNCA rs356219 CC genotype (OR = 2.17, 95% CI: 1.33-3.52; q = 0.013) were significantly associated with disease. High cumulative all pesticide exposure showed positive associations with combined PD + Parkinsonism (OR = 2.98, 95% CI: 1.23-7.25) and PD alone (OR = 3.56, 95% CI: 1.25-10.15). In WQS analyses, the composite occupational exposure burden index was positively associated with disease (combined PD + Parkinsonism: OR = 1.15, 95% CI: 1.00-1.30). All pesticides received the highest mean weight in all models (w = 0.434 for combined PD + Parkinsonism), followed by metals (w = 0.210), identifying them as contributing most strongly to the composite exposure index. ConclusionsLong-term cumulative occupational exposures were associated with increased odds of PD and Parkinsonism. All pesticides and metals were most strongly associated with PD and Parkinsonism, consistent with established neurotoxic mechanisms attributable to occupational environments. These findings underscore the importance of occupational exposure prevention and risk-reduction strategies in occupational settings and highlight workplace exposures as preventable contributors to Parkinsonian disorders.

BackgroundEvidence suggests maternal exposure to ambient air pollution increases the risk of stillbirth, but few studies conducted in the United States have evaluated temporally varying exposures or susceptibility across gestational windows. Moreover, the generalizability of existing findings is often limited by restricted geographic coverage or reliance on selected study populations. MethodsUsing Georgia vital records from 2005 to 2014, we conducted a matched case-control study including 8,384 stillbirths and 33,459 live birth controls matched on maternal county of residence and conception month. We used stratified Cox proportional hazards models with time-varying covariates to estimate hazard ratios (HRs) for ten air pollutants across five exposure windows (first month, weekly, and first, second, and third trimester). Our primary analysis included all stillbirths combined, with subgroup analyses separating second and third trimester losses. ResultsStillbirths had a median gestational age of 27 weeks (IQR: 6.67) compared with 38 weeks for live births (IQR: 2.13). Particulate matter showed strong associations in the second trimester exposure window for all stillbirths (PM10: HR = 1.07; 95% CI: 1.04, 1.11; PM2.5: HR = 1.05; 95% CI: 1.01, 1.09). This pattern was consistent for NO2 and NH4, which also exhibited positive associations across early and entire pregnancy exposure windows (first month, first trimester, weekly), with the strongest associations for the second trimester exposures. Associations were larger for second trimester stillbirths, whereas estimates for third trimester stillbirths were largely null or negative. ConclusionsIn this population-based study in Georgia, time-varying ambient air pollution exposures during pregnancy were associated with increased risk of stillbirth, particularly for second trimester exposures and for stillbirths occurring earlier in pregnancy. These findings highlight the importance of considering gestational timing when evaluating environmental risk factors for stillbirth. What this study addsThis study is the first to evaluate maternal ambient air pollution exposure and stillbirth using time-varying exposures on vital records in the state of Georgia. By examining ten air pollutants across multiple gestational windows and subset analyses by timing of stillbirth, we identified second trimester susceptibility to NO2, PM10, PM2.5, and NH4. These findings highlight periods of vulnerability to ambient air pollution during pregnancy.

Antimicrobial resistance (AMR) in ESKAPE pathogens represents a major global health threat. Although these organisms are well established as causes of healthcare-associated infections, aquatic environments may function as reservoirs and transmission pathways for resistance. This systematic review aimed to estimate the prevalence of AMR in ESKAPE pathogens isolated from water and wastewater and to compare resistance patterns with those observed in human clinical isolates. The review followed PRISMA guidelines and was registered in PROSPERO (CRD420251020930). PubMed, Embase, and the Cochrane Library were searched to January 14, 2025. Eligible studies were original research reporting antimicrobial susceptibility data for ESKAPE pathogens isolated from both aquatic environmental matrices and clinical samples. Pooled resistance prevalence was estimated using generalized linear mixed models, with heterogeneity assessed using {tau}{superscript 2} and I{superscript 2} statistics and small-study effects evaluated by funnel plots and Eggers test. Of 304 records identified, 18 studies met the inclusion criteria. The pooled overall resistance prevalence was 0.46 (95% CI: 0.36-0.57), with heterogeneity (I{superscript 2} = 98.8%). Resistance was higher in clinical isolates (0.67; 95% CI: 0.55-0.77) than in environmental isolates (0.24; 95% CI: 0.14-0.39), and environmental resistance was greater in effluent-impacted waters than in non-effluent sources. Interpretation is limited by methodological heterogeneity, selective isolation approaches in environmental studies, and imprecision due to small and unevenly distributed samples. Overall, AMR in ESKAPE pathogens remains more prevalent in clinical settings, but aquatic environments, particularly wastewater, represent resistance reservoirs, underscoring the need for standardized methodologies within a One Health framework. Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251020930, CRD420251020930 HighlightsAntimicrobial resistance was higher in clinical isolates than in aquatic isolates. Resistance patterns showed extreme heterogeneity across studies. Effluent-impacted waters showed higher resistance than non-effluent sources. Higher environmental resistance in some classes reflected methodological artifacts.

Benzalkonium chloride (BAC) is widely used as a disinfectant in cleaning products and is frequently detected in indoor dust. In this study, we assessed dust samples, along with information on cleaning product use, from 24 pregnant participants. Dust samples were analyzed for BAC concentration and microbial tolerance. Different chain lengths of BAC (C12, C14, and C16) were quantified using LC-MS/MS, and bacterial isolates were tested for BAC tolerance using minimum inhibitory concentration (MIC) assays. BAC was ubiquitously detected, with C12 and C14 being dominant. Higher BAC concentrations were associated with reported disinfectant use and increased microbial tolerance. These findings suggest that indoor antimicrobial use may promote microbial resistance, highlighting potential exposure risks in indoor environments and the need for further investigation into health and ecological impacts.

Bullous pemphigoid (BP) is an autoimmune blistering disease with a growing incidence, and environmental factors are receiving increasing attention. Tetrabromobisphenol A (TBBPA), a widely used brominated flame retardant, is a significant environmental pollutant. However, the molecular mechanisms by which TBBPA contributes to BP pathogenesis remain unclear. This study integrated network toxicology, molecular docking, and molecular dynamics (MD) simulations to systematically investigate the molecular mechanisms of TBBPA-induced BP. Using network toxicology, we identified 797 potential targets of TBBPA and 446 BP-related targets. A Venn diagram analysis revealed 48 common targets. Protein-protein interaction (PPI) network and topological analyses further identified five core hub targets: TNF, CXCL8, MMP9, ICAM1, and ITGB1. Gene enrichment analysis indicated that these targets were significantly enriched in immune-inflammatory pathways, such as leukocyte migration, inflammatory responses, and the IL-17 signaling pathway, as well as in various pathogen infection and cancer-related pathways. Molecular docking revealed that TBBPA stably binds to all five core targets with binding energies [&le;] -5 kcal/mol, driven primarily by hydrophobic interactions and {pi}-{pi} stacking. Subsequent MD simulations confirmed that TBBPA complexes with TNF, CXCL8, and MMP9 remained stable throughout the 100 ns simulation. The overall protein structures remained compact, and the ligands were effectively encapsulated within the binding pockets, forming stable networks of hydrogen bonds and hydrophobic interactions. In conclusion, this study, for the first time, proposes a systematic molecular framework using integrated computational biology. Our findings suggest that the environmental pollutant TBBPA may act as a potential risk factor in BP pathogenesis by targeting core proteins (TNF, CXCL8, and MMP9). These interactions potentially disrupt critical signaling pathways related to immune inflammation, cell migration, and tissue remodeling. This study offers a novel mechanistic hypothesis regarding environmental chemical exposure in autoimmune blistering diseases, although further experimental validation is required. HighlightsO_LINetwork toxicology identified 48 common targets linking Tetrabromobisphenol A(TBBPA) exposure to Bullous Pemphigoid (BP). C_LIO_LIFive core targets (TNF, CXCL8, MMP9, ICAM1, ITGB1) were screened as potential mediators. C_LIO_LITBBPA stably binds to TNF, CXCL8, and MMP9 with binding energies [&le;] -5 kcal/mol. C_LIO_LIMolecular dynamics simulations confirm stable binding and structural integrity of complexes. C_LIO_LIThis study provides a mechanistic framework for TBBPA as an environmental risk factor in BP. C_LI

IntroductionParticulate Matter (PM2.5) exposure contributes to the global disease burden, yet its monitoring remains sparse and uneven and is limited in many limited ground monitoring network settings. Road-traffic proxy indicators can provide indirect estimates of PM2.5 where measurements are limited but require context-specific validation. We evaluated three PM2.5 road-traffic related proxies:(I) population-Weighted Road Network Density (WRND), (ii) Euclidean (straight line) distance from highways (EH), and (iii) Euclidean distance from main roads (EM). MethodsWe validated proxies using high-resolution outdoor filtered PM2.5 personal exposure measurements collected over 1 year from 343 postpartum participants in The Gambia, Kenya, and Mozambique. Village-level spatial patterns for the PM2.5-proxy relationship were mapped using 5 km hexagonal aggregated tessellations. Proxy-PM2.5 associations were assessed using Spearman correlation, and predictive utility was tested using country-specific and global Random Forest (RF) models (3-fold cross-validation), reporting R2, RMSE, and feature importance ResultsSpatial mapping showed heterogeneous proxy-PM2.5 relationships across and within sites, with elevated PM2.5 occurring in both low- and high-proxy contests. WRND-PM2.5 correlations were weak overall and statistically significant only in Mozambique (r = 0.351; p = 0.005), with non-significant associations in Kenya (r = -0.041; p = 0.673) and The Gambia (r = -0.020; p = 0.909). EH-PM2.5 correlations were positive in The Gambia (r = 0.335; p = 0.053) and Mozambique (r = 0.292; p = 0.020) but negative and significant in Kenya (r = -0.224; p = 0.018).Single-variable RF models performed poorly across all countries (R2 < 0.45) and the Global model (R2=0.42). Combining proxies improved performance in Kenya (R2=0.52; RMSE=31.7{micro}g/m3) and Mozambique (R2=0.60; RMSE=8.9 {micro}g/m3), Global R2=0.46; RMSE=29.1 {micro}g/m3), although in The Gambia, the combined model (R2=0.53; RMSE=37.6 {micro}g/m3) did not exceed the best single-proxy model. ConclusionRoad-network proxies provide context-dependent signals of personal PM2.5 exposure, and predictive performance is strengthened when proxies are combined in a hybrid model.

Background Prenatal exposure to pesticides and psychosocial factors often co-occurs, particularly in low- and middle-income settings, yet their joint effects on epigenetic age acceleration (EAA) in early life remain unknown. We investigated the joint associations of prenatal pesticides metabolites and psychosocial factors on EAA in the first five years of life in the South African Drakenstein Child Health Study. Methods In 643 mothers, we measured 11 urinary pesticide metabolites and seven psychosocial factors during the second trimester of pregnancy. Child DNA methylation was measured in whole blood at ages 1, 3, and 5 years. EAA was estimated using the Horvath, Skin & Blood Horvath (skinHorvath), and Wu epigenetic clocks. Longitudinal associations were estimated using generalized estimating equations, adjusted for confounders. Joint mixture associations were evaluated using weighted quantile sum regression (WQS) and quantile g-computation (QGCOMP). Results The joint prenatal exposure mixture was positively associated with Wu ({beta} per one quintile increase in the mixture [95% CI]: 0.41 years [0.15, 0.80]), skinHorvath (0.11 years [0.06, 0.16]), and Horvath EAA (0.31 years [0.20, 0.46]) over time using WQS. Psychosocial factors, particularly food insecurity, physical interpersonal violence, and stress biomarkers, contributed most to the total mixture effect for all clocks. Pyrethroid metabolites PBA and TDCCA were top pesticide contributors to Wu EAA. Pathway enrichment analyses of clock-specific CpGs revealed distinct biological architectures, with the Wu clock enriched for neurodevelopmental and immune pathways, and metabolic pathways for the Horvath clock. Discussion Joint prenatal exposure to pesticides and psychosocial factors was associated with increased EAA across early childhood, with psychosocial factors contributing the most to the total effect. These findings highlight the importance of assessing chemical and non-chemical stressors jointly and clock-specific biological interpretation in epigenetic aging research.

Background Ambient air pollution is a leading global health risk and disproportionately affects populations of Low- and Middle-Income Countries (LMICs). In 2021, WHO revised its Air Quality Guidelines (AQG), lowering recommended annual limits for Particulate Matter 2.5 (PM2.5) and Nitrogen Dioxide (NO2). We estimated the potential health and economic impacts of achieving WHO Interim Target 3 (IT3) and AQG concentrations across LMICs. Methods We conducted a health impact assessment across 136 LMICs to quantify one-year changes in all-cause and cause-specific mortality (chronic obstructive pulmonary disease [COPD], ischaemic heart disease [IHD], and stroke) and disease incidence (COPD, dementia, IHD, and stroke) under WHO IT3 and AQG counterfactual scenarios for PM2.5 and NO2. Concentration-response functions were applied at 1km x 1km resolution. Economic welfare impacts of mortality risk reductions were estimated using country-adjusted values of a statistical life (VSL, Int$ PPP-adjusted 2021). Direct medical and productivity-related costs associated with incident cases were estimated using a cost-of-illness (COI) framework. Uncertainty intervals (UI) reflect uncertainty in concentration-response functions. Results Attainment of WHO IT3 and AQG concentrations for PM2.5 was associated with an estimated 16.04% reduction (6.58million, UI: 6.10-7.07million) and 22.97% reduction (9.43million, UI: 8.75-10.11million) in annual deaths, respectively. Corresponding VSL-based estimates of deaths averted were Int$5.5 trillion (7.0% of aggregate LMIC GDP) and Int$8.4 trillion (10.6% of GDP), respectively. For NO2, IT3 and AQG scenarios were associated with estimated reductions of approximately 1.06% (approximately 435,000 deaths, UI: 388,000-483,000) and 2.79% (435,000 deaths; UI: 388,000-483,000), yielding gains of Int$0.6 trillion (0.7% of GDP) and Int$1.5 trillion (1.9% of GDP). Disease-specific mortality reductions were most prominent for IHD and stroke in Asia and Africa. Under the PM2.5 AQG scenario, an estimated 2.82million (1.67-2.97) COPD, 1.10million (0.83-1.37) dementia, 7.3million (6.41-8.19) IHD, and 2.3million (2.19-2.41) stroke cases could be delayed or averted in one year. Associated reductions in direct medical and productivity-related costs were greatest for IHD, COPD, and stroke. NO2-related morbidity reductions were smaller across all outcomes. All estimates represent one-year changes in risk relative to counterfactual exposure and may reflect delayed rather than permanently avoided events. Discussion Achieving both WHO IT3 and AQG values in LMICs could yield substantial reductions in premature mortality and disease incidence, particularly for cardiovascular and respiratory conditions, alongside large, monetised welfare gains from reduced mortality risk. These findings underscore the considerable societal value of air quality improvements and support accelerated action toward meeting WHO guideline levels in regions bearing the highest pollution burden.

Rapid urbanisation has profoundly shaped microbial diversity across different ecosystems. Freshwater microbiomes are particularly affected by urbanisation activities, such as eutrophication, pollution, runoff, and sewage. This is of significant concern as marginalised communities often depend on waterbodies for their livelihood. Freshwater bodies play a crucial role in maintaining both human and ecological health at population level. Currently, we lack a systematic understanding of the global impacts of urbanisation on freshwater microbiomes in relation to human health, ecosystem functioning, and sustainability. We identified 90 eligible papers from the last 25 years after screening based on the inclusion exclusion criteria. We extracted data that examined changes in the functional traits such as antimicrobial resistance (AMR), nutrient cycling of the microbiome in urban waterbodies and several other factors. Data were extracted by a thematic analysis followed by a narrative synthesis on specific functional traits. This systematic review presents a comprehensive analysis on the changes and challenges brought about by urbanisation on freshwater bodies. Our results indicate that urbanisation leads to reduced bacterial diversity of urban waterbodies, with a striking increase in reporting of Proteobacteria, Cyanobacteria and Coliform bacteria. These insights will help inform public health strategies and sustainable urban planning. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/715732v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@18db38dorg.highwire.dtl.DTLVardef@70a79org.highwire.dtl.DTLVardef@40aaaborg.highwire.dtl.DTLVardef@184ecca_HPS_FORMAT_FIGEXP M_FIG C_FIG Waterbodies in urban areas function as convergence platforms for anthropogenic and environmental microbiomes. Runoffs, wastewater and effluents contain antimicrobial resistance genes and other pathogens that survive in water due to inadequate treatment. Disposal, use, and overflow of wastewater cause restructuration of microbial communities, proliferation of opportunistic microorganisms, and spread of antimicrobial resistance in aquatic ecosystems.

Ocean acidification, a consequence of climate change, has become a significant threat to marine organisms. Globally, tremendous efforts have been made to understand its impact on different ecological and biological processes. In India, this research area is still not fully explored, but expanding at an exponential rate. Hence, it is essential to consolidate the fragmented knowledge into a systematic review, which will assist future researchers to develop their work. In this study, we utilized the Scopus, Web of Science and Ocean Acidification - International Coordination Centre bibliography to conduct a systematic review of ocean acidification research in India. We used the Biblioshiny package in R to conduct a bibliometric analysis, identify spatial and temporal research trends, and highlight the growth of literature in ocean acidification research, as well as existing knowledge gaps. We used the following keywords: ocean acidification, lowered pH, acidifying ocean, elevated carbon dioxide, elevated CO2, marine carbonate chemistry, shell decalcification and affiliation as India to obtain relevant publications. We selected 353 publications by applying relevance filtering and adherence to PRISMA guidelines. Almost one-third of the publications were non-primary articles. Among research articles, only 71 publications were found to investigate the response of marine organisms to ocean acidification. Majority of them involved single stressors, for a short term on very limited taxa. Lack of molecular-level investigation, multifactorial experimental design, and long-term observations were major gaps. This review aims to support researchers, policymakers, and other stakeholders involved in the planning, monitoring, and developing adaptation strategies. Finally, it provides recommendations for future research and policy development.

IntroductionAtmospheric conditions under climate change increase pressure on healthcare systems. Especially, the intensive care units (ICU) are vulnerable due to low buffer capacity and high utilization rates. MethodsDaily ICU cases from 2009 to 2023 were derived from the German statutory health insurance data of eleven regional AOK insurances. Cases were stratified by age and sex. Generalized additive models were used to investigate the associations between daily ICU cases and lagged atmospheric variables. Thirteen intensive care relevant diseases were analyzed using disease-specific predictor sets. Analyses were conducted for regions derived from a human-biometeorological characterization of Germany. Model performance was assessed using (weighted) explained deviance. ResultsOver the 15-year study period, 9,970,548 ICU patients were recorded (44% women), 74.3% aged [&ge;]60 years. Trauma was the most common ICU-related disease, followed by non-ST elevation myocardial infarction (NSTEMI), pneumonia and ischemic stroke. ICU demand was most sensitive (p [&le;] 0.05) to pressure-related factors, thermo-physiological parameters and ozone concentration. In terms of sex-age differences, atmospheric factors affected men more frequently, while women were more impacted by cold weather and particulate matter (PM10). Heat was more relevant for patients aged [&ge;]60 years. The NSTEMI model in Central Eastern Germany performed best (weighted explained deviance of 49.3%). In males [&ge;]60 years, heatwaves were associated with a reduced risk of ICU cases (Relative Risk = 0.94, 95%-Confidence Interval 0.89 to 0.99). ConclusionThe study identified key atmospheric factors for ICU, enabling the German healthcare system to prepare better for short-term impacts of meteorological and air quality factors. KEY MESSAGESWhat is already known on this topic: O_LIThe atmospheric changes have a direct impact on public health and the inpatient care, particularly in intensive care units. C_LIO_LIConsequently, there is a necessity to investigate the influence of atmospheric factors on intensive care in order to prepare the healthcare system for the new circumstances. C_LI What this study adds: O_LIThe study provides evidence that atmospheric factors influence the intensive care in Germany and describes age and sex-specific aspects. C_LIO_LIThe results offer valuable insights into how different atmospheric factors affect the demand for intensive care in hospitals. C_LI How this study might affect research, practice or policy: O_LIThe study enables the German healthcare system to better prepare for short-term effects of atmospheric factors, and structural or resource-related adjustments could be made in hospitals to anticipate for short-term fluctuations in intensive care demand. C_LI

Aims Indoor air pollution resulting from combustion of unclean cooking fuels has been linked to adverse health outcomes, but evidence regarding its association with mental health in low- and middle-income countries remains limited. We investigated the association between household use of unclean cooking fuels, as a proxy for indoor air pollution, and depression symptoms among adults aged 45 years and older in India, and assessed effect modification by age, sex, caste, and rural/urban residence. Methods We conducted a cross-sectional analysis of the first wave (2017-2018) of data from the Longitudinal Aging Study in India (LASI), a nationally representative survey of adults aged [&ge;]45 years. Cooking fuel type was classified as clean or unclean, and depression symptoms were assessed using the 10-item Centre for Epidemiologic Studies Depression (CES-D-10) scale. We used logistic regression to estimate odds ratios for depression symptoms, and linear regression to compare mean CES-D-10 scores by cooking fuel type, adjusting for sociodemographic and housing characteristics. Results We included 62,650 respondents. Median age was 57 years (IQR: 50-65), 46.7% were women, 47.6% reported using unclean cooking fuels, and 27.6% screened positive on the CES-D-10. After adjusting for sociodemographic and housing characteristics, use of unclean cooking fuels was associated with higher odds of screening positive on the CES-D-10 (aOR: 1.08; 95% CI: 1.02, 1.15), and higher mean CES-D-10 scores (adjusted mean difference: 0.34; 95% CI: 0.24, 0.44). The association was more pronounced among individuals living in urban areas (aOR: 1.36; 95% CI: 1.21, 1.53). Conclusion Use of unclean cooking fuels was associated with depression symptoms among older adults in India, and especially among those living in urban areas.

BackgroundSea fish traditionally serves as a protein source and plays a crucial and indispensable role in providing nutrition for the people of Bangladesh. However, frequent consumption may potentially indicate health risks through contamination with toxic heavy metals. The main purpose of this study is to evaluate the levels of heavy metal concentrations (Cr, Fe, Ni, Mn, Cu, and Pb) in selected sea fish from Chattogram and Coxs Bazar districts in Bangladesh. MethodsA wet digestion technique was employed to prepare the samples for analyzing heavy metals. Atomic Absorption Spectrophotometry (AAS) in flame and furnace technique was utilized for the estimation of heavy metal content. The health risk of human was evaluated grounded on Estimated Daily Intake (EDI), Target Hazard Quotient (THQ), Total Target Hazard Quotient (TTHQ) or Hazard Index (HI), and Target Cancer Risk (CR). ResultThe descending chronology of average concentrations for the selected heavy metals was as follows: Fe (32.36) > Ni (12.12) > Pb (9.70) > Cu (7.29) > Mn (5.94) > Cr (5.22). The correlations (r0.587) between Cr and Mn were found significantly positive which indicated the parameters were interconnected with each other and likely have a common origin within the study area. EDI values of four samples in the case of Cr and six values for Pb exceeded the reference doses (RfD) which included Bombay Duck, Ilish, Silver Pomfret, Longfin Tuna, Indian Threadfin, and Bigeye Ilisha. In six sea fish samples, the THQ for Cr and Pb crossed the allowable limit of 1. The TTHQ/HI values for seven fish species were higher than 1 ranging from Bigeye Ilisha (3.25) to Indian Mackerel (1.35). The CR values for the majority of the heavy metals fell within an acceptable range. ConclusionsFrom a public health perspective, this study revealed that continuous consumption of heavy metals, resulting in non-oncogenic and oncogenic health implications as well.

Lead exposure is a major environmental health concern, especially in childhood, due to its neurotoxic effects even at low levels. This cross-sectional observational study aims to evaluate the association between lead accumulation in tooth enamel, cognitive performance, and dietary patterns in children aged 7 to 9 years belonging to the Archdiocesan Educational Network of Guayaquil, Ecuador. A total of 384 participants will be selected using stratified sampling according to socioeconomic status. Lead levels will be assessed using a validated dental enamel biopsy technique, while IQ will be measured using the Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V). Dietary intake will be assessed using a Food Frequency Questionnaire (FFQ) validated for the Ecuadorian population. All procedures will ensure the safety, comfort, and confidentiality of participants. Potential risks, such as emotional distress or academic disruption, will be minimized through adapted protocols and ethical safeguards. This study seeks to provide critical local evidence on environmental lead exposure and its association with cognitive outcomes and dietary, to help inform future public health efforts.

Exposures to pervasive chemical toxicants such as endocrine disrupting chemicals (EDCs) are associated with adverse neurological and neurodevelopmental deficits. Although EDCs are widespread as sparse mixtures in the environment, most research has focused on single chemicals at high concentrations. Here, we studied the effects of ldEDC: a low-dose mixture of widely prevalent toxicants at doses representative of normal human exposure levels. Primary cultured mouse neurons treated with ldEDC exhibited altered gene expression compared to vehicle controls in genes critical for neuron activity, indicating low doses EDCs can affect neuronal function directly. We next tested persistent exposure through the maternal diet to define perinatal effects on offspring. Exposed offspring exhibited differences in development, tactile sensitivity, and sex-specific changes in motor behavior. Cortical single-nuclei sequencing identified broad transcriptomic changes, particularly in distinct cortical layer subpopulations, excitatory neurons, and astrocytes. Cell-cell signaling between neurons and non-neuronal populations were altered in exposed mice, specifically in pathways associated with cellular adhesion. Transcriptomic differences were also sex-specific. Together, these in vitro and in vivo findings reveal molecular and phenotypic consequences of EDC exposure at a mixture of doses well below commonly studied levels and highlights common functional pathways of susceptibility.

Soils are vital reservoirs of biodiversity and providers of ecosystem services, yet they are increasingly threatened by agricultural intensification and pesticide use. Residues often persist as complex mixtures, while environmental risk assessment still largely focuses on single substances, potentially underestimating mixture effects. Earthworms play a key role in soil functioning and are particularly vulnerable to pesticide contamination. We investigated the effects of a binary mixture of epoxiconazole and imidacloprid, two persistent and frequently detected pesticides, on life-history traits of Aporrectodea caliginosa. We estimated each compound relative potency using dose-response experiments on juvenile growth and cocoon production. Next, we assessed the potential for synergy or antagonism in a fixed-ratio ray design including five concentration ratios and seven additive isoboles (36 conditions). Both compounds showed significant toxicity. Imidacloprid showed high potency (juvenile growth NOEC = 0.28 mg/kg; reproduction EC50 = 0.55 mg/kg), whereas epoxiconazole had moderate effects (juvenile growth NOEC = 9.3 mg/kg; reproduction EC50 = 126.8 mg/kg). Reproductive endpoints were more sensitive than adult growth, with juvenile growth being the most sensitive overall. Mixture analysis using Jonkers models revealed significant deviation from Independent Action only under the simple interaction model, indicating synergism, consistent with cytochrome P450 interference reported in other taxa. Field-reported imidacloprid concentrations often approach effect thresholds, suggesting potential risks for earthworm populations. Overall, the combined effects of epoxiconazole and imidacloprid may exceed predictions not taking interactions into account. These results highlight the need to incorporate pesticide mixture effects into environmental risk assessment. Environmental ImplicationsPesticide residues persist in agricultural soils as complex mixtures, yet risk assessment still focuses mainly on single substances. This study shows that the combined effects of imidacloprid and epoxiconazole on earthworm reproduction can exceed predictions based on Independent Action, with evidence of synergistic interactions. Effect thresholds for imidacloprid approach reported maximum environmental concentrations, indicating limited safety margins for soil organisms. These findings suggest that mixture exposures may pose greater ecological risks than currently anticipated and highlight the need to integrate pesticide mixture toxicity and potential synergism into environmental risk assessment frameworks. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=116 SRC="FIGDIR/small/707680v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@18c89ceorg.highwire.dtl.DTLVardef@1ab4dd2org.highwire.dtl.DTLVardef@1823edaorg.highwire.dtl.DTLVardef@1ec9782_HPS_FORMAT_FIGEXP M_FIG C_FIG

The global industrialization and rapid urbanization elevated the risk of toxic pollutant exposure, which affects human health specially during pregnancy. Pregnant mothers are daily exposed to bisphenol-A (BPA), which is a common plastic leachate and a prominent toxic pollutant present in our environment. BPA act as an endocrine disrupting chemical (EDCs) by altering feto-placental homeostasis. This persistent and potent exposure of BPA during gestation can trigger placental damage affecting trophoblast cell function and survival. BPA even disrupts specific signalling cascades by altering post translational protein phosphorylation. However, this BPA mediated dysregulation of signalling nodes in early trimester placenta is still unexplored. Therefore, this study investigates the global proteome changes in post-BPA exposed extravillous trophoblast (EVTs) cells, which revealed a BPA mediated dynamic regulation of phosphoproteome-signatures and their associated kinases. Further inspection showed that the altered phosphorylation of c-JUN (S63) and GSK3 (Y279) is associated with BPA toxicity in EVTs and placenta. This altered phosphorylation affects the cellular signalling downstream, imparting damage upon the growing feto-placental unit. This highlights an altered phosphorylation mediated mechanism of BPA toxicity in placenta which can cause an onset of adverse pregnancy outcome. Data are available via ProteomeXchange with the identifiers PXD074780.

BackgroundAcute respiratory infection (ARI) remains a leading cause of morbidity and mortality among children under five in Nigeria. Although polluting cooking fuels are widely considered a key risk factor, their effects may be shaped by broader socioeconomic and geographic conditions. This study examined both individual and structural determinants of ARI and assessed how these factors intersect to pattern risk. MethodsWe analysed data from 28,728 children under five in the 2024 Nigeria Demographic and Health Survey. Three ARI definitions were applied. Survey-weighted quasibinomial logistic regression estimated associations between ARI and cooking fuel type, child age and sex, household wealth quintile, residence type, geopolitical zone, and parental education. To examine intersectional patterning, we conducted a Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA), constructing strata defined by combinations of cooking fuel, wealth, residence, and geopolitical zone. The intraclass correlation coefficient (ICC) quantified between-strata variance. ResultsStrict ARI prevalence was 1.9%, and 8.3% of children had broader respiratory symptoms. In unadjusted analyses, polluting fuel use was associated with higher odds of respiratory symptoms (OR 1.85, 95% CI 1.43-2.39). After adjustment, this association was substantially attenuated, indicating confounding by structural factors. Child age was the most consistent predictor: children aged 24-59 months had about half the odds of strict ARI compared with infants (aOR 0.53, 95% CI 0.41-0.68). Geopolitical zone showed the strongest overall association. MAIHDA revealed that 9% of total ARI variance lay between intersectional strata (ICC = 0.09), and this variance was not explained by child age or sex. The population-attributable fraction for polluting fuel declined from 41.4% to 12.4% after adjustment. ConclusionsARI risk among Nigerian children is shaped more by structural and geographic inequalities than by household fuel use alone. Equity-focused, subnational policies addressing intersecting socioeconomic and regional disadvantage are needed to reduce the ARI burden.