Environmental Research

Fetal development is highly sensitive to environmental influences, including maternal smoking during pregnancy (MSDP) and air pollution. The placenta may play a central role in mediating these effects through epigenetic mechanisms, including small non-coding RNAs (sncRNAs). While most studies have focused on microRNAs (miRNAs), other sncRNA classes remain poorly characterized. Here, we characterized the placental sncRNA landscape and investigated its associations with prenatal exposure to MSDP and air pollution. The sncRNA expression profile of 390 chorionic villi samples from the Barcelona Life Study Cohort (BiSC) was measured using small RNA sequencing and the seqBuster/seqCluster pipeline. MSDP was assessed via questionnaire, and prenatal exposure to black carbon (BC), particulate matter [≤]2.5 m (PM2.5), and nitrogen dioxide (NO2) was estimated using hybrid dispersion-land-use regression (LUR) spatiotemporal models. Associations were evaluated using linear regressions adjusted for relevant covariates. We identified 979 placental sncRNA clusters, assigned primarily to miRNAs (33.2%), piRNAs (26.4%), snoRNAs (12.2%), tRFs (7.8%), and others (20.4%). MSDP was associated with the downregulation of miR-421 and the upregulation of multiple snoRNAs from the imprinted DLK1-DIO3 locus (SNORD113-4, SNORD114-2, SNORD114-3, and SNORD114-17), as well as the piR-26394. No sncRNAs remained significantly associated with air pollution after multiple-testing correction, although several miRNAs showed suggestive associations. Overall, this study provides a comprehensive characterization of placental sncRNAs and identifies previously unreported smoking-associated sncRNAs within the imprinted DLK1-DIO3 locus, expanding our understanding of placental epigenetic responses to prenatal environmental exposures.

Background: Observational studies have linked air pollution to otitis media, but confounding and reverse causation preclude causal inference. We used two-sample Mendelian randomization (MR) to assess genetic causal effects of six air pollutants on non-suppurative otitis media, represented by otitis media with effusion (OME). Methods: Exposure GWAS for PM2.5, PM2.5 absorbance, PM2.5-10, PM10, NO2 and NOx were obtained from UK Biobank (MRC-IEU), and the outcome was FinnGen R13 H8_NONSUPPNAS (12,397 cases, 464,237 controls). Inverse-variance weighting was primary, with MR-Egger, weighted median and mode, MR-PRESSO, leave-one-out and Steiger analyses, reverse MR and exploratory multivariable MR (MVMR). Asthma, allergic rhinitis and chronic rhinosinusitis served as positive controls, and three suppurative otitis media phenotypes served as negative controls. Results: After false-discovery-rate correction, none of the six pollutants was significantly associated with OME; the sole nominal signal was PM10 (OR=1.555, 95% CI 0.947-2.553, P=0.081), which reversed with the 88-SNP pooled set (OR=0.64, 0.24-1.69, P=0.365). At 80% power, minimum detectable ORs ranged widely from 1.69 to 32.09; only PM2.5-10 and PM10 had values near 2, so moderate effects (OR 1.2-1.5) cannot be excluded. Confirmatory positive controls using phenotype-specific instruments were strongly positive, whereas negative-control outcomes showed no associations (all FDR>0.85). Every nominal reverse-MR signal had a significant MR-Egger intercept (the PM2.5 absorbance signal also showed significant heterogeneity and MR-PRESSO tests), indicating horizontal pleiotropy rather than reverse causation. MVMR was exploratory only, as conditional F statistics were below 10. Conclusions: We found no evidence for large-effect genetic causal associations between the six air pollutants and OME. These null findings argue against large, lifetime-average causal effects, and the associations reported in observational studies may instead reflect residual confounding, shared comorbidity or differences in exposure windows.

Background: Non-optimal air temperature increases the risk of preterm birth, but how temperature-related risks may translate into future population burden remains uncertain. We aimed to estimate the association between temperature and preterm birth in Sweden and assess how preterm birth burden may change under plausible future temperature conditions. Methods: We conducted a nationwide population-based cohort study of singleton births in Sweden from 1973 to 2018. Weekly mean temperature was assigned at the parish level according to maternal residence. Cox proportional hazards models with a distributed lag nonlinear model were used to estimate nonlinear and delayed associations between temperature and preterm birth. The estimated exposure response relationship and baseline hazards were then incorporated into an individual-based microsimulation of gestational progression under projected temperatures for 2025 to 2055. Future projections were examined across multiple climate models under SSP1-2.6 and SSP3-7.0 scenarios. Outcomes included the annual number and cumulative incidence of preterm births and the temperature-attributable fraction. Results: Among 4,338,825 singleton births, 211,397 (4.9%) were preterm. Temperature preterm birth associations were modest overall. The clearest increase in hazard was observed following exposure to very low temperatures, particularly -10C at short lags. Higher temperatures showed no clear increase in risk. From 2025 to 2055, the annual cumulative incidence of preterm birth and the temperature-attributable fraction was expected to remain broadly stable, with limited differences between emissions scenarios. In contrast, the absolute number of preterm births was expected to over the projection period, primarily reflecting increases in the projected number of pregnancies rather than substantial changes in temperature-associated risk. Conclusions: Very low temperatures were associated with a modest short-term increase in preterm birth risk in Sweden, hot temperatures showed little evidence of increased risk. Applying these associations to future climate conditions suggested limited changes in preterm birth incidence or the proportion attributable to temperature through 2055. However, the absolute burden of preterm birth may increase as the population at risk grows. This highlights the importance of considering demographic change alongside climate projections when assessing future maternal and neonatal health burden.

Total serum perfluorooctane sulfonate (PFOS) concentration and its isomer composition describe different aspects of internal exposure, but their respective associations with depressive symptoms remain uncertain. We examined adults aged 18-25 years in NHANES August 2021-August 2023 using survey-weighted models of the Patient Health Questionnaire-9 (PHQ-9). Total measured PFOS was the sum of linear PFOS and pooled monomethyl-branched PFOS; composition was their log-ratio. The analytic cohort included 169 participants, with 147 complete cases for core adjustment. Median total PFOS was 1.70 ng/mL, the median linear fraction was 72.2%, and the weighted prevalence of PHQ-9 [≥]10 was 22.6%. In the joint adjusted model, a doubling of total PFOS at fixed composition corresponded to -0.49 PHQ-9 points (95% CI, -1.65 to 0.68); a doubling of the linear-to-branched ratio at fixed total corresponded to 0.21 points (-1.94 to 2.36). Algebraic rescaling across the reported interquartile ranges yielded differences of -0.58 points (-1.95 to 0.81) for total PFOS and 0.13 points (-1.16 to 1.41) for composition. The inverse continuous-score association weakened with adjustment, whereas the screening odds ratio primarily lost precision. Excluding three observations with an isomer below detection shifted both joint coefficients. The data therefore do not establish an independent composition association or equivalent isomer effects. Experimental evidence supports candidate oxidative, inflammatory, and synaptic pathways, but differential protein binding and elimination prevent a serum composition ratio from being interpreted directly as brain dose or toxicity. Larger longitudinal analyses with isomer-resolved exposure and toxicokinetic measurements are needed to test these pathways.

Objective: Environmental pollutants are increasingly recognized as potential risk factors for metabolic dysfunction-associated steatotic liver disease (MASLD), yet the effects of mixed exposures and underlying mechanisms remain unclear. We evaluated associations between environmental chemical mixtures and MASLD and the mediating role of inflammation-related biomarkers. Methods: We analyzed 60 environmental chemicals across six categories among 39,061 U.S. adults from the National Health and Nutrition Examination Survey (NHANES) 1999-2020. Principal Component Pursuit with Principal Component Analysis (PCP-PCA) identified latent exposure patterns. MASLD was identified using multisociety Delphi consensus criteria and the Hepatic Steatosis Index (HSI [&ge;] 36). Logistic regression, restricted cubic spline models, and mediation analysis were applied. Results: PCP-PCA generated 5-17 dimensions per chemical category, with first-dimension variance contributions ranging from 30.70% to 98.88%. Six dimensions from four categories were retained, with phthalate esters (PAEs) and organophosphate flame retardants (OPFRs) showing the most consistent associations with MASLD. PAEs Dim.1, explaining 90.71% of variance, showed a significant non-linear dose-response association (P-nonlinear = 0.0001). Significant associations were identified for mono-isobutyl phthalate (MiBP; OR 1.12, 95% CI 1.07-1.19), mono(carboxyoctyl) phthalate (MCOP; OR 1.08, 95% CI 1.02-1.14), mono(carboxynonyl) phthalate (MCNP; OR 1.12, 95% CI 1.03-1.21), and bis(1,3-dichloro-2-propyl) phosphate (BDCP; OR 1.15, 95% CI 1.08-1.23). C-reactive protein (CRP) and red cell distribution width (RDW) were the primary mediators, accounting for 32.42% and 19.62% of the MiBP-MASLD association, respectively (both p < 0.0001). Conclusion: Environmental co-exposure, particularly to PAEs and OPFRs, was associated with higher MASLD risk, with systemic inflammation potentially contributing to these associations.

Background: Lead is a cumulative environmental toxicant for which no safe level of exposure has been identified, and pregnant women and their fetuses are particularly vulnerable because lead readily crosses the placenta and can be mobilised from maternal bone stores. Bangladesh conducted its first nationally representative blood lead testing among pregnant women through the 2025 Multiple Indicator Cluster Survey (MICS), but a detailed, multi-domain analysis of the determinants of elevated blood lead level (BLL) among this population has not yet been reported. Methods: We conducted a secondary cross-sectional analysis of 1,928 pregnant women aged 15-49 years with complete data from the women's dataset of Bangladesh MICS 2025. Elevated BLL was defined as [&ge;]5 g/dL. Survey-weighted logistic regression was used to estimate unadjusted and adjusted odds ratios (aOR) for co-exposure to arsenic, cadmium and mercury and sociodemographic and socioeconomic covariates. Slope Index of Inequality (SII) as well as Relative Index of Inequality (RII) were used to quantify wealth-related inequality. Population attributable fractions (PAF) were estimated for three counterfactual scenarios, and adaptive least absolute shrinkage and selection operator (LASSO) regression was used as a sensitivity analysis. Results: Elevated BLL was present among 6.2% of participants. In the adjusted model, a 2-fold rise in blood cadmium was associated with higher odds of elevated BLL (aOR: 1.54; 95% CI: 1.21-1.96), whereas a 2-fold rise in blood mercury (aOR: 0.63; 95% CI: 0.48-0.83), rural residence (aOR: 0.55; 95% CI: 0.32-0.94), secondary education (aOR: 0.49; 95% CI: 0.28-0.85) and post-secondary education (aOR: 0.22; 95% CI: 0.11-0.46) were associated with lower odds. Belonging to progressively wealthier quintiles was associated with markedly higher odds, BLL rising to an aOR of 10.32 (95% CI: 4.41-24.15) for the richest versus poorest quintile. The RII was 8.59 (95% CI: 4.24-17.40) and the SII was 0.159 (95% CI: 0.101-0.218), indicating a substantial pro-rich gradient in elevated BLL. Counterfactual scenarios suggested that shifting the population to secondary-level education could reduce the prevalence of elevated BLL by 52.9% (95% CI: 20.6-72.0) and shifting to rural residence by 24.3% (95% CI: 1.4-41.9). Adaptive LASSO variable selection produced estimates consistent in direction and magnitude with the fully adjusted model. Conclusion: In this national sample, approximately one out of every 16 pregnant women had blood lead levels that met or exceeded the action threshold set by the World Health Organization, with this issue being particularly prevalent among wealthier, urban, and less-educated women, and was compounded by co-exposure to cadmium. In Bangladesh, the typical pattern observed for maternal and child health indicators does not align with the inverse relationship found between household wealth and lead exposure. This suggests that the sources of exposure are not merely indicators of material poverty. Antenatal blood lead screening, source investigation, and equity-informed lead-reduction strategies that specifically reach wealthier and urban households are warranted.

Abstract Background Air pollution contributes substantially to morbidity and mortality in low-income countries, where reliance on solid fuels leads to high levels of household exposure. Colonisation of the upper respiratory tract by Streptococcus pneumoniae is a prerequisite for pneumococcal disease, and inhaled air pollutants may influence colonisation through impaired mucociliary clearance. Therefore, we investigated the association between S. pneumoniae colonisation and personal exposure to particulate matter (PM2.5) and carbon monoxide (CO) as well as temperature and relative humidity in older children in The Gambia. Methods We conducted a prospective study of 134 children aged 5-14 years across eight visits in rural Gambia. Personal 24-hour PM2.5, CO, temperature and relative humidity exposures were measured using personal monitors. Concurrently, combined nasopharyngeal/oropharyngeal swabs were collected at each visit, and S. pneumoniae colonisation was determined by microbiological culture. Mixed-effects logistic regression models were used to examine associations between environmental exposures and colonisation. Exposures were additionally decomposed into between-child and within-child components. Models were adjusted for age, season, and household income tertile. Results A total of 554 child visits with paired exposure and microbiological data were analysed. Overall, 24-hour geometric mean PM2.5 and CO were 12.6 {micro}g/m3 (95% CI 12.2-13.1) and 0.16 ppm (95% CI 0.14-0.19) respectively and overall S. pneumoniae colonisation prevalence was 39.7%. In conventional models, PM2.5, CO, temperature, and relative humidity were not significantly associated with S. pneumoniae colonisation after adjustment for confounders. In the within-between decomposition analysis, higher between-child temperature exposure was consistently associated with lower odds of colonisation (mutually adjusted model: OR 0.74, 95% CI 0.56-0.98; p = 0.034). Relative humidity showed an inverse within-child association in crude analysis (OR 0.70, 95% CI 0.52-0.93; p = 0.013), which attenuated after adjustment for season and other confounders. No associations were observed for PM2.5 or CO exposures. Conclusion At the exposure levels observed in this cohort of older children, PM2.5 and CO exposures were not independently associated with S. pneumoniae colonisation. The pattern observed for temperature suggests that longer-term temperature conditions may be more relevant to pneumococcal colonisation than short-term exposure variation in this setting.

Background Short-term weather conditions can trigger paediatric hospital admissions, but evidence remains limited on the health relevance of intraday temperature variability, humidity, and precipitation, and generally on which subgroups are most susceptible. Methods We conducted a nationwide case time-series study of Swedish children and adolescents aged 6-18 years using linked register data. Associations between daily mean temperature, intraday temperature variability, relative humidity, and precipitation and inpatient hospitalisations were estimated with Poisson regression (individual fixed effects) combined with distributed lag non-linear models over lags 0-21 days. Outcomes included all-cause hospitalisation and cause-specific admissions. Effect modification was examined by sex, age group, socioeconomic indicators, region, and calendar periods. Findings Among 4,638,247 children and adolescents in the cohort, 1,070,702 (23.1%) experienced at least one inpatient hospitalisation, contributing 1,736,169 hospitalisation events. All-cause hospitalisation increased with higher mean temperature, with risk highest at hot extremes. Intraday temperature variability showed a U-shaped association, with higher rates at both lowest and highest exposure levels. Relative humidity showed no association with hospitalisation risk. Higher precipitation was associated with increased hospitalisation risk, but estimates at high rainfall levels were imprecise. Stratified analyses indicated modest differences by sex and socioeconomic indicators, but clearer heterogeneity by age and region, with the highest risks among younger children and in East Sweden; associations varied across calendar periods and were imprecise for most cause-specific outcomes. Sensitivity analyses mostly showed that the main curve shapes were robust. Interpretation Short-term exposure to hot temperatures, both low and high intraday temperature variability, and higher levels of precipitation were associated with an increased risk of all-cause hospitalisation among children in Sweden, with clearer variation by age group and region than by sex or socioeconomic position. These findings support targeting paediatric climate-health preparedness and early-warning systems toward younger children and higher-risk regions such as eastern Sweden and extending such systems beyond mean temperature to include intraday temperature variability, a distinct, currently overlooked driver of risk that heat-focused systems are not designed to capture. Fundings This research was funded by Formas the Swedish Research Council for Sustainable Development (grant no. 2023-01774 and 2022-01845) and the Swedish Research Council (2025-02804 and 2022-06599).

Background: Chronic arsenic exposure in drinking water causes skin lesions and cancers and raises infant, cardiovascular and all-cause mortality in Bangladesh. National surveys tested source water in 2012-13, 2019 and 2025 with different kits, so the trend is uncertain. Objectives: We estimated how arsenic in source water changed after laboratory adjustment of 2012-13 readings, and how many people remained exposed. We also assessed whether districts high in earlier surveys held most people exposed in 2025. Methods: We analysed 11,624 households in three Multiple Indicator Cluster Surveys. We counted arsenic strictly above 10 and 50 parts per billion (ppb). Results: Estimates reproduced published 2019 and 2025 tables. After laboratory adjustment of 2012-13, the share above 10 ppb fell from 24.0% to 14.4% (adjusted ratio 0.61, sampling 95% CI 0.55 to 0.67; 0.69 with interview month). Above 50 ppb it fell from 10.9% to 8.6% (0.80, 0.69 to 0.93; 0.93 with month). Most of the fall at 10 ppb occurred within source types. Without false positives, it would vanish only if later kits detected 61% of sources above 10 ppb. About 26 million people used such water in 2025 (kit scenarios 23 to 32 million). The 25 districts high in 2012-13 and 2019 held 39% of the population but 72% of those exposed (bootstrap 95% interval 60 to 76). Clustering was evident, but no district was a significant hotspot. Conclusions: Arsenic above 10 ppb was lower in 2025 than in 2012-13, but the size of the fall depends on unverified later kits. Change at 50 ppb and since 2019 was unclear after month adjustment. One household in seven exceeded the WHO guideline in 2025. Districts found high earlier held most exposed people, supporting prioritised well testing there alongside broader surveillance. Future surveys need one kit with a laboratory cross-check.

Background: In coastal Bangladesh, saline drinking water has been linked to raised blood pressure. The 2025 Multiple Indicator Cluster Survey (MICS) measured electrical conductivity (EC), a salinity indicator, in source water, but its report gave no population counts or district estimates. Objectives: To estimate how many people live in households whose tested source has high EC, and to describe patterns by place, household characteristics, source type and arsenic. Methods. EC was measured in source water of 6,040 households in 64 districts, February to June. In 14.5% of households the tested source was not the main drinking-water source. Primary outcomes were EC above 1,500 and 3,000 microsiemen/cm, survey risk classes that are not health-based standards. Estimates were survey weighted; comparisons were observational. Results: EC exceeded 1,500 microsiemen/cm in 5.3% of households (95% CI 4.7 to 5.9), about 9.0 million people, including 1.8 million above 3,000 microsiemen/cm. Coastal-zone districts held 26% of households but 70% of those above 1,500 microsiemen/cm. Shares varied little by wealth or in households with young children or pregnant women. Nationally, deep tube wells more often had high EC because most are coastal. In the coastal zone, deep and shallow wells had similar shares (16.1% and 17.9%). After district adjustment, EC was about 18% lower in deep wells (geometric mean ratio 0.82, 0.73 to 0.92). Within upazilas (restricted sample) it was 0.93 (0.80 to 1.07). Arsenic above 10 ppb was more common where EC was high, but this link weakened after district adjustment. Conclusions: Millions of people live in households whose tested source has high EC, mostly in coastal and south-central districts. Deep wells had modestly lower EC after geographic adjustment, but the difference shrank within upazilas and depended on the handling of implausibly low readings. The findings support measuring EC alongside arsenic, with documented meter calibration.

This study assesses the spatial dynamics of heavy metals and associated trace elements in the water and sediment of the Slana River approximately one and half year after an environmental accident and river contamination caused by mining effluent. Using PCA and standardized environmental indices (CF, PLI), we modelled the distribution of contaminants across the macro-gradient of the river and within the micro-gradient surrounding the source of pollution. We found that although the situation in the water column has improved and stabilized, the sediment remains the primary reservoir of trace elements, including toxic arsenic, with the highest concentrations recorded near the source and in its immediate vicinity. Although the concentration of primary mining indicators decreases relatively rapidly along the stream, this is systematically offset by the accumulation of other elements, including sulphur and aluminium. As a result of these geochemical processes, the total pollution load index (PLI) remains statistically unchanged along the entire stream, but indicates a chronic, spatially uniform (PLI = 1.06-1.16) toxicological burden on the ecosystem.

Introduction: Pesticide exposure has been associated with poorer mental health, yet little is known about whether seasonal fluctuations in agricultural pesticide use are associated with cyclical changes in mood among people living in agricultural communities. We evaluated associations between 10 peak and off-peak pesticide spray seasons and ecological momentary assessment (EMA)-derived mood in a floricultural region in Ecuador. Methods: 496 participants completed repeated EMA surveys across 10 assessment administrations over 2.5 years (2022-2024), including one single-assessment administration and nine 10-day bursts (Nobservations=14,332). Mood outcomes included negative affect (sadness, anxiety, stress, anger, tiredness, difficulty concentrating; overall mean=2.79, Standard Deviation [SD]=1.32), positive affect (happiness, motivation; overall mean=4.21, SD=1.60), and behavioral dysregulation (aggression and impulsivity, overall mean=1.86, SD=1.29). Generalized linear mixed models estimated pooled, between-person and within-person associations between peak pesticide spray seasons and mood, adjusting for demographic and longitudinal factors Effect modification by sex, floricultural occupation, and cohabitation with a floricultural worker was assessed. Results: Peak spray seasons were associated with higher negative affect ({beta}=0.11 [0.06, 0.16]) and behavioral dysregulation ({beta}=0.10 [0.05, 0.15]) but not positive affect ({beta}=0.01 [-0.05, 0.07]). Associations were driven by within-person changes. Sex modified associations with negative affect, which were stronger in males than females. Floricultural occupation modified associations, with poorer mood, greater behavioral dysregulation and lower positive affect among floricultural workers than non-workers. Discussion: Peak pesticide spray seasons were associated with worsening of negative affect and behavioral dysregulation. EMA may provide a sensitive approach for detecting short-term neurobehavioral changes associated with seasonal pesticide exposure.

Long-term PM2.5 exposure is associated with increased mortality and is usually represented by annual mean concentration, which does not capture how concentrations are distributed across days. We tested whether the prespecified PM2.5 magnitude-rank index (PMRI), a summary of within-year daily concentration structure, improves mortality prediction beyond the annual mean. Daily modeled PM2.5 estimates were linked to age-adjusted mortality rates for 27,289 county-years from 3,064 U.S. counties during 2003-2011. PMRI is the largest k for which at least k days reached k micrograms per cubic meter. County-grouped 10-fold cross-validation compared models with annual mean alone versus annual mean plus PMRI, with additional geographic, temporal, cause-specific, and specification analyses. Annual mean PM2.5 had the highest standalone predictive performance. Adding PMRI increased county-held-out R-squared from 0.0802 to 0.1391 (increase in R-squared = 0.0589; 95% CI, 0.0499-0.0677) and reduced RMSE and MAE. Improvement persisted across geographic and temporal validations and all six cause-specific mortality outcomes. Within-year PM2.5 exposure structure therefore contains reproducible mortality-predictive information not captured by annual mean concentration.

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants with the potential to disrupt metabolic processes and contribute to carcinogenesis; however, molecular evidence linking alternative and emerging PFAS to ovarian cancer (OC) remains limited. We conducted a biomarker-based case-control study integrating exposureomics with multi-omics profiling. Plasma samples from 128 patients with OC and 128 controls were analyzed for 26 PFAS, untargeted metabolomics, lipidomics, and clinical phenotypes, while urine samples from an additional 100 patients and 100 controls underwent untargeted metabolomic and clinical profiling. Single-compound, burden-based, and mixture models were integrated with PFAS-omics association scans, cross-matrix metabolite prioritization, observational exposure-omics-clinical association-chain analyses, and repeated internal cross-validation. Higher PFAS burdens were consistently associated with OC case status, and DONA, GenX, PFNA, PFPeS, PFUdA, and PFTrDA constituted an OC-prioritized six-PFAS mixture. DONA and GenX exhibited the broadest lipid-related bridging signals, particularly across phospholipids, lysophospholipids, sphingolipids, neutral lipids, and acylcarnitines. Integrated plasma and urine analyses further identified five shared metabolites-elaidic acid, hippuric acid, betaine, corticosterone, and taurocholic acid-that provided incremental and complementary discrimination beyond reference models based on clinical variables and tumor markers in internal cross-validation. Collectively, these findings demonstrate that both alternative and emerging PFAS are associated with a distinct OC-related molecular phenotype involving coordinated lipidomic, metabolomic, and hematologic alterations, while highlighting DONA and GenX as the most prominent exposure-related signals.

Antimicrobial resistance (AMR) is a major threat to modern medicine and an emerging environmental pollutant. Wastewater-based monitoring offers a scalable alternative to traditional surveillance by enabling population-level monitoring across One Health compartments. However, it remains unclear how well bacterial variants detected in wastewater reflect those causing clinical infections. Here, we assessed the prevalence of carbapenem-resistant Escherichia coli (CREC) in wastewater from Uppsala, Sweden, and compared wastewater isolates with clinical isolates from the same region and period. We observed partial overlap between wastewater and clinical CREC populations, but several common clinical variants were not detected in wastewater and vice versa. CREC prevalence was an order of magnitude higher in wastewater receiving hospital effluent, yet this did not improve concordance with clinical isolates, suggesting that hospital wastewater may artificially inflate CREC prevalence estimates. These findings indicate that wastewater CREC prevalence does not necessarily reflect the regional clinical burden. Furthermore, metagenomic sequencing of wastewater-derived E. coli populations rarely detected CREC resistance genes, suggesting that CREC abundance is below the detection limit of this approach and that targeted enrichment is required for reliable monitoring. Together, our results show that while wastewater-based monitoring can complement AMR surveillance, it should be interpreted cautiously when used as an indicator of clinical risk.

Objective Reducing household air pollution exposure during gestation and infancy may have longer-term benefits for child linear growth. We examined whether a liquefied petroleum gas (LPG) cookstove and fuel intervention delivered during gestation and infancy could improve height-for-age Z scores (HAZ) and reduce the risk of stunting at ages 2-5 years in India, Rwanda, and Guatemala. Materials and method The Household Air Pollution Intervention Network (HAPIN) was a randomized controlled trial that enrolled ~3200 pregnant women across Guatemala, India, Peru, and Rwanda. Women in the intervention group received an LPG cookstove and free fuel during pregnancy and until the infant reached 12 months of age. Following the HAPIN trial, we continued following children in Guatemala, India, and Rwanda (N=2169) and measured child height at ages 2, 3, 4, and 5 years (HAPIN 2.0). As prespecified in the study protocol, we used mixed-effects models, as well as linear and log-binomial regression, within the intention to treat (ITT) framework, to evaluate the interventions effect on HAZ and stunting. Subgroup analyses were performed to assess effect modification by child sex, maternal height, and intervention country. Results The intervention reduced gestational exposures to particulate matter (PM2.5: 80.7 vs 117.5 {micro}g/m3), carbon monoxide (CO: 1.3 vs 2.0 ppm), and black carbon (BC: 8.6 vs 12.1 {micro}g/m3) and infancy exposures (PM2.5: 36.9 vs 113.2 {micro}g/m3; CO: 0.60 vs 2.2 ppm). Post-trial PM2.5 exposure were similar between arms: 99.9 vs 98.7 {micro}g/m3. We found no statistically significant effect of the intervention on repeated measures of HAZ ({beta} = -0.06, 95% CI: -0.16, 0.03 p=0.204), annual HAZ, stunting, nor severe stunting at any age during the follow-up. There was no statistically significant effect modification by subgroups. Conclusion Despite substantial reductions in air pollution exposures during the trial, the LPG intervention did not improve growth or reduce stunting risk from ages 2 through 5 years in this multi-country cohort. These findings, consistent with prior results of the lack of effects on growth through 12 months, provide additional evidence that a clean cooking intervention alone may not be sufficient to address childhood stunting in low-resource settings. Future exposure-response analyses will supplement these ITT analyses.

Background: Childhood lead exposure is a major global health concern. The 2025 Bangladesh Multiple Indicator Cluster Survey (MICS7) measured blood lead in a nationally representative sample of children aged 12-59 months for the first time. Preliminary reports suggested elevated blood lead was more common in wealthier urban households, contrary to the usual assumption. Methods: We analysed 10,622 children with a valid blood lead result (10,458 with complete covariate data for regression models). Elevated blood lead was defined as >=5 ug/dL. Prevalences are survey-weighted with design-based confidence intervals. Associations were estimated with survey-weighted logistic regression using stratified-cluster (Taylor-linearised) variance, and checked with a stratified bootstrap of primary sampling units and Benjamini-Hochberg false-discovery-rate control. Sensitivity analyses varied the outcome definition, the sample, and the weighting. Results: Survey-weighted prevalence of elevated blood lead was 38.5% (95% confidence interval [CI] 37.2-39.9%). Prevalence rose monotonically from 30.2% in the poorest to 51.9% in the richest wealth quintile. In the fully adjusted model, each wealth quintile was associated with 23% higher odds (adjusted odds ratio [AOR] 1.23, 95% CI 1.16-1.30), each level of maternal education with 20% lower odds (AOR 0.80, 95% CI 0.76-0.84), and urban residence with 37% higher odds (AOR 1.37, 95% CI 1.18-1.59). Household crowding was associated with higher odds (AOR 1.17 per person per room, 95% CI 1.10-1.24). The wealth-education interaction had AOR 0.95 (95% CI 0.92-0.98). In an exploratory contrast, weighted prevalence was 76.2% among children in the richest quintile with mothers having at most primary education versus 19.5% among those in the poorest quintile with mothers having higher secondary or tertiary education (prevalence ratio 3.9, 95% CI 2.6-6.0). Adjusted odds relative to Barishal ranged from 0.39 in Rajshahi to 3.29 in Dhaka. Conclusions: In this cross-sectional survey, elevated blood lead was more prevalent among wealthier and urban households and among children of less educated mothers, with large geographic variation. Lead prevention and source-identification efforts should therefore not be restricted to poor communities; prevalence remained high even in the poorest quintile. Interpretation is limited by substantial missing blood lead results and coding uncertainty.

Background: Millions of textile and agricultural workers inhale organic dust containing endotoxin, an exposure associated with impaired respiratory function. However, the underlying biological pathways remain unclear. We conducted a two-cohort epigenome-wide association study (EWAS) to identify airborne endotoxin-associated DNA methylation (DNAm) alterations and pathways. Methods: In the discovery phase, we compared blood DNAm in 281 endotoxin-exposed cotton workers and 253 unexposed silk-workers from the Shanghai Textile Worker Study (STWS) measured using Illumina MethylationEPICv2 arrays. STWS endotoxin assessment combined detailed work histories and onsite measurements. For targeted parallel validation, we tested STWS signals in 686 incident lung cancer cases and 683 matched controls from the Shanghai Women's Health Study (SWHS), using occupation-derived low, medium, or high exposure-intensity ranks based on published evidence. To gain biological insight, we analyzed pathway enrichment, immune-cell composition, DNAm inflammation risk scores (IRSs), and respiratory phenotype associations in STWS. Results: In STWS, we identified 36 epigenome-wide significant DNAm sites (P<5e-8), of which, 35 were hypomethylated. Among 30 sites testable in SWHS, 18 had concordant effect directions, and four were nominally significant: cg11869499 (POLG; P=0.041), cg16290931 (TSKS; P=0.044), cg05019530 (EPIC1; P=0.042), and cg26033526 (PSMB9/TAP1; P=0.013). Enrichment implicated immune and signal-transduction pathways, including IgSF cell-adhesion-molecule signaling (FDR=8.2e-6;). Neutrophil were higher in cotton workers than in silk workers (63.5% vs 58.9%, p=7.52e-10). Cumulative endotoxin was associated with higher CRP-based IRSs, which showed the most consistent associations with lower lung function and airflow obstruction. Conclusions: Our EWAS findings suggest that occupational endotoxin may operate partly through immune-cell composition and inflammatory pathways.

Per- and polyfluoroalkyl substances (PFAS) are present throughout the environment due to decades of use in many commercial products and industrial processes. These molecules contain a hydrophobic fluorocarbon tail and a functional headgroup (typically a carboxylic or sulfonic acid) that allows hydrophilic interactions with the surrounding environment. These properties make them inherently resistant to degradation, difficult to track through the environment, readily bioaccumulative, and likely to impact human health. Through collaboration with town officials, multiple meetings with local sustainability committee members and school officials, and direct contact with individual homeowners, we conducted community-driven sampling of PFAS in well water from 105 houses in Tremont, ME, a rural coastal town that relies on private wells for drinking water. The rate of PFAS detection for one or more analytes across all wells (N=105) was 69%. Of all wells tested, 16 (15%) exceeded the current public drinking water standard in Maine (20 ng/L for 6 PFAS), and an additional 17 (totaling 31% of all wells tested) exceeded Maine's newly adopted public drinking water standards for the state (based on EPA 2024 standards). Because private wells are unregulated, homeowners may use these results as a guide for taking action to maintain safe drinking water. Both hierarchical cluster analyses and pairwise Spearman's rank correlation of PFAS test results revealed similar profiles in households near and far from one another. Along with the absence of obvious, large-scale potential point sources of PFAS contamination, these findings support septic systems as the primary source of PFAS contamination in drinking water across this town. The community-driven approach to the sampling effort has enabled information sharing on the importance of water filtration options, discussion of long-term pollution abatement strategies for individual households and the town, and focused efforts for future well water testing and PFAS mitigation.

Background Italy experiences a substantial heat-related mortality burden, but evidence on cause-specific mortality across its heterogeneous climatic settings remains limited. We aimed to quantify cause-specific mortality attributable to summer heat in Italy at national and ecological region levels and to map its distribution across municipalities. Methods We analysed daily deaths classified by underlying cause in eight ICD-10 groups among individuals aged 18-64 years and 65 years or older across 7,864 municipalities during June-August, 2004-2023. Mortality data were linked to area-weighted ERA5-Land daily maximum temperature. Nonlinear temperature-mortality associations were estimated with Bayesian hierarchical Poisson models, fitted separately for each cause, age group, and ecological region, with municipality-level attributable fractions. Findings High temperatures were associated with mortality from a broad range of causes, particularly among individuals aged 65 years or older. Among the study population, heat-attributable fractions were highest for nervous system diseases (14.93%, 95% credible interval 14.22-15.69) and mental and behavioural disorders (14.47%, 13.55-15.39). Circulatory diseases accounted for the largest absolute burden, with 85,524 heat-attributable deaths (82,762-88,271) across the summers of the 20 years considered. Interpretation The mortality burden associated with summer heat in Italy extended well beyond circulatory and respiratory diseases, highlighting the relevance of a broader range of health outcomes. These findings support heat-health strategies that account for cause-specific and geographical differences in heat-related risk, with greater consideration of neurological and mental health outcomes alongside established cardiorespiratory risks. Funding NextGenerationEU (CUP: B53C23002660006); Imperial College Research Fellowship; NIHR Imperial Biomedical Research Center (BRC: NIHR203323).