Multifaceted paternal exposures before conception and their epigenetic impact on offspring.

As scientific research progresses, there is an increasing understanding of the importance of paternal epigenetics in influencing the health and developmental path of offspring. Prior to conception, the environmental exposures and lifestyle choices of fathers can significantly influence the epigenetic state of sperm, including DNA methylation and histone changes, among other factors. These alterations in epigenetic patterns have the potential for transgenerational transmission potential and may exert profound effects on the biological characteristics of descendants. Paternal epigenetic changes not only affect the regulation of gene expression patterns in offspring but also increase the risk to certain diseases. It is crucial to comprehend the conditions that fathers are exposed to before conception and the potential outcomes of these conditions. This understanding is essential for assessing personal reproductive decisions and anticipating health risks for future generations. This review article systematically summarizes and analyzes current research findings regarding how paternal pre-pregnancy exposures influence offspring as well as elucidates underlying mechanisms, aiming to provide a comprehensive perspective for an enhanced understanding of the impact that paternal factors have on offspring health.

Exploring the potential mechanism of atrazine-induced dopaminergic neurotoxicity based on integration strategy.

BACKGROUND: Atrazine (ATR), a commonly used herbicide, is linked to dopaminergic neurotoxicity, which may cause symptoms resembling Parkinson's disease (PD). This study aims to reveal the molecular regulatory networks responsible for ATR exposure and its effects on dopaminergic neurotoxicity based on an integration strategy. METHODS: Our approach involved network toxicology, construction of protein-protein interaction (PPI) networks, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, as well as molecular docking techniques. Subsequently, we validated the predicted results in PC12 cells in vitro. RESULTS: An integrated analysis strategy indicating that 5 hub targets, including mitogen-activated protein kinase 3 (Mapk3), catalase (Cat), heme oxygenase 1 (Hmox1), tumor protein p53 (Tp53), and prostaglandin-endoperoxide synthase 2 (Ptgs2), may play a crucial role in ATR-induced dopaminergic injury. Molecular docking indicated that the 5 hub targets exhibited certain binding activity with ATR. Cell counting kit-8 (CCK8) results illustrated a dose-response relationship in PC12 cells. Real-time quantitative polymerase chain reaction (RT-qPCR) displayed notable changes in the expression of hub targets mRNA levels, with the exception of Mapk3. Western blotting results suggested that ATR treatment in PC12 cells resulted in an upregulation of the Cat, Hmox1, and p-Mapk3 protein expression levels while causing a downregulation in Tp53, Ptgs2, and Mapk3. CONCLUSION: Our findings indicated that 5 hub targets identified could play a vital role in ATR-induced dopaminergic neurotoxicity in PC12 cells. These results provide preliminary support for further investigation into the molecular mechanism of ATR-induced toxicity.

Exploring the Landscape of Social Epidemiological Research: A Scoping Review of AJE Publications.

As social epidemiology is a growing interdisciplinary field with a broad scope, this scoping review investigated its current landscape based on articles published in the American Journal of Epidemiology. Among 1,194 extracted records between 2013 and 2022 submitted under the "social" category, we identified 178 accepted articles that had a social factor as a primary exposure. We categorized social exposures into nine major domains, and health outcomes into eight domains. Study design, population, and authorship were also analyzed. Our findings indicate that social epi studies reflect a range of social exposures, including socioeconomic position (37%), neighborhood and built environment (20%), race, racism, and discrimination (16%), and policy and social welfare (12%). The most frequently studied health outcomes were non-communicable diseases and chronic conditions (42%), mental health (14%), and maternal and child health outcomes (11%). Most studies had quantitative observational designs and focused on high-income countries, particularly the U.S. contexts. Most authors appeared only once, suggesting a range of voices as contributors. Findings suggest that, to enhance knowledge, social epi could benefit from a greater representation of social factors beyond tangible resources, a broader range of health outcomes, study designs and populations, and low- and middle-income countries.

Communications, engagement, and dissemination strategies for the HEALthy Brain and Child Development (HBCD) Study.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. Study success depends on the engagement and inclusion of diverse populations of pregnant participants and their children across the United States, including those at high and low risk for prenatal substance use. The Communications, Engagement, and Dissemination (CED) Committee is responsible for the development and implementation of a strategy to promote awareness about the study, encourage participation, and engage HBCD families, community partners, and collaborators. Initial work involved developing versatile recruitment and awareness materials with a consistent and inclusive message that reduces stigma and negative bias towards marginalized populations, including people with substance use and other mental health conditions. These efforts were shaped by an integrated product development workflow and early engagement with HBCD partners to address challenges. Ongoing work includes the expansion of HBCD outreach through newsletters and social media platforms with an emphasis on protecting participant privacy. Future activities will focus on disseminating scientific information through generation of infographics and webinars that will inform participants, families, and the public of discoveries generated from HBCD Study data.

The relationship between physical and psychosocial workplace exposures and life expectancy free of musculoskeletal and cardiovascular disease in working life - an analysis based on German health insurance data.

BACKGROUND: Against the backdrop of the debate on extending working life, it is important to identify vulnerable occupational groups by analysing inequalities in healthy life years. The aim of the study is to analyse partial life expectancy (age 30-65) [1] free of musculoskeletal diseases (MSD) and [2] free of cardiovascular diseases (CVD) in occupational groups with different levels of physical and psychosocial exposures. METHODS: The study is based on German health insurance claims data from 2015 to 2018. The study population comprises all employed insured persons aged 18 to 65 years (N = 1,528,523). Occupational exposures were assessed using a Job Exposure Matrix. Life years free of MSD / CVD and life years with MSD /CVD during working age were estimated using multistate life tables. RESULTS: We found inequalities in MSD-free and CVD-free life years, with less disease-free years among men and women having jobs with high levels of physical and psychosocial exposures. Men with low physical exposures had 2.4 more MSD-free and 0.7 more CVD-free years than men with high physical exposures. Women with low psychosocial exposures had 1.7 MSD-free and 1.0 CVD-free years more than women with high psychosocial exposures. CONCLUSIONS: Employees in occupations with high physical and psychosocial demands constitute vulnerable groups for reduced life expectancy free of MSD and CVD. Given the inequalities and high numbers of disease-affected life years during working age, the prevention potential of occupational health care and workplace health promotion should be used more extensively.

Online collaborative research on seasonal work. Collective capabilities to resist on precarious work and living conditions.

BACKGROUND: The number of seasonal workers in the agricultural sector in France is increasing and their working conditions are difficult and disgraceful. While they have been shown in various studies to be subject to processes that result in them being unable to act on occupational health, some of them, mobilized online, have formed a collective whose is permitted them to develop collective actions. OBJECTIVES: Our article aims to describe this online collective and how the power to act emerged from the discussions. The purpose it's also to determine how the functioning of these groups fosters the expression of a collective point of view and the achievement of goals that is not attained elsewhere. METHODS: We carried out a collaborative research online with a collective of seasonal workers, which consisted in following and taking part in discussions about conditions at work and outside of work, using an instant messaging tool. The results of this collaborative research, included testimonies registration and co-produced with seasonal workers, has been analyzed mobilizing A. Sen's capabilities approach. RESULTS: During their online discussions, the seasonal workers allow themselves to share the situations of injustice they are subject to with the other members. Here, we present their output and collective actions which were made possible by the mobilization of the resources of some of their members or by collaborating with other actors. CONCLUSIONS: In spite of the remarkable conversion factors made available through this collective action online, certain "failures" show that in order for these workers to have better access to their rights, effective support by public policy is indispensable.

Civilians under missile attack: post-traumatic stress disorder among the Jewish and Bedouin population of Southern Israel.

BACKGROUND: Over the past 20 years, Jewish and Bedouin civilians in southern Israel have faced the ongoing threat of missile attacks from Gaza, with possible mental health consequences. This study aimed to assess the prevalence of post-traumatic stress disorder (PTSD) among Jewish and Bedouin adult civilians in southern Israel in a period with few missile attacks from Gaza, and no military operations. METHODS: The study population included 389 participants (246 Jews, 143 Bedouins) living within 40 km/25 mi from Gaza for at least 2 years and interviewed between January and March 2023 (before the ongoing war that started on October 7th, 2023). The PTSD Checklist (PCL-5) was used, with a score of 33 as a cutoff point for the presence of PTSD. RESULTS: Compared to Jews, a significantly lower proportion of Bedouins reported accessibility to bomb shelters and siren warning systems. Overall, 20.3% of the respondents exhibited PTSD. Multivariate analysis revealed that after adjustment for demographic and household characteristics, Bedouins had a six-fold significantly higher probability of PTSD in comparison to Jews (OR 5.6, 95%CI 2.8-10.8). Compared to participants with high socioeconomic status (SES), participants with low SES had a six-fold significantly higher probability of PTSD (OR 6.0, 95%CI 2.2-16.5). Participants who did not have an alarm system had more than two-fold odds for PTSD (OR 2.3, 95%CI 1.1-5.5). Being single, living in urban areas, or having a disability significantly increased the probability of PTSD. CONCLUSIONS: The findings of this study demonstrate a significantly higher prevalence of PTSD among the Bedouin population of Southern Israel. Several sociodemographic characteristics were associated with the increased prevalence of PTSD, the most prominent of which was low SES. Healthcare professionals and authorities should be proactive in screening for PTSD, and provide tailored treatment and support, taking into account ethnical and cultural background. Authorities should address the disparity in bomb shelter access and siren warning coverage between Bedouin and Jewish communities.

Lead brownfields and birth defects in North Carolina 2003-2015: A cross-sectional case-control study.

BACKGROUND: Brownfields consist of abandoned and disused sites, spanning many former purposes. Brownfields represent a heterogenous yet ubiquitous exposure for many Americans, which may contain hazardous wastes and represent urban blight. Neonates and pregnant individuals are often sensitive to subtle environmental exposures. We evaluate if residential exposure to lead (Pb) brownfields is associated with birth defects. METHODS: Using North Carolina birth records from 2003 to 2015, we sampled 169,499 births within 10 km of a Pb brownfield with 3255 cardiovascular, central nervous, or external defects identified. Exposure was classified by binary specification of residing within 3 km of a Pb brownfield. We utilized multivariable logistic regression models adjusted for demographic covariates available from birth records and 2010 Census to estimate odds ratios (OR) and 95% confidence intervals (CI). Effect measure modification was assessed by inclusion of interaction terms and stratification for the potential modifiers of race/ethnicity and diabetes status. RESULTS: We observed positive associations between cardiovascular birth defects and residential proximity to Pb brownfields, OR (95%CI): 1.15 (1.04, 1.26), with suggestive positive associations for central nervous 1.16 (0.91, 1.47) and external defects 1.19 (0.88, 1.59). We did observe evidence of effect measure modification via likelihood ratio tests (LRT) for race/ethnicity for central nervous and external defect groups (LRT p values 0.08 and 0.02). We did observe modification by diabetes status for the cardiovascular group (LRT p value 0.08). CONCLUSIONS: Our results from this analysis indicate that residential proximity to Pb brownfields is associated with cardiovascular birth defects with suggestive associations for central nervous and external defects. In-depth analyses of individual defects and other contaminants or brownfield site functions may reveal additional novel associations.

Integrating Multi-Omics with environmental data for precision health: A novel analytic framework and case study on prenatal mercury induced childhood fatty liver disease.

BACKGROUND: Precision Health aims to revolutionize disease prevention by leveraging information across multiple omic datasets (multi-omics). However, existing methods generally do not consider personalized environmental risk factors (e.g., environmental pollutants). OBJECTIVE: To develop and apply a precision health framework which combines multiomic integration (including early, intermediate, and late integration, representing sequential stages at which omics layers are combined for modeling) with mediation approaches (including high-dimensional mediation to identify biomarkers, mediation with latent factors to identify pathways, and integrated/quasi-mediation to identify high-risk subpopulations) to identify novel biomarkers of prenatal mercury induced metabolic dysfunction-associated fatty liver disease (MAFLD), elucidate molecular pathways linking prenatal mercury with MAFLD in children, and identify high-risk children based on integrated exposure and multiomics data. METHODS: This prospective cohort study used data from 420 mother-child pairs from the Human Early Life Exposome (HELIX) project. Mercury concentrations were determined in maternal or cord blood from pregnancy. Cytokeratin 18 (CK-18; a MAFLD biomarker) and five omics layers (DNA Methylation, gene transcription, microRNA, proteins, and metabolites) were measured in blood in childhood (age 6-10 years). RESULTS: Each standard deviation increase in prenatal mercury was associated with a 0.11 [95% confidence interval: 0.02-0.21] standard deviation increase in CK-18. High dimensional mediation analysis identified 10 biomarkers linking prenatal mercury and CK-18, including six CpG sites and four transcripts. Mediation with latent factors identified molecular pathways linking mercury and MAFLD, including altered cytokine signaling and hepatic stellate cell activation. Integrated/quasi-mediation identified high risk subgroups of children based on unique combinations of exposure levels, omics profiles (driven by epigenetic markers), and MAFLD. CONCLUSIONS: Prenatal mercury exposure is associated with elevated liver enzymes in childhood, likely through alterations in DNA methylation and gene expression. Our analytic framework can be applied across many different fields and serve as a resource to help guide future precision health investigations.

Multi-pollutant exposure profiles associated with breast cancer risk: A Bayesian profile regression analysis in the French E3N cohort.

BACKGROUND: Human exposure to air pollution involves complex mixtures of multiple correlated air pollutants. To date, very few studies have assessed the combined effects of exposure to multiple air pollutants on breast cancer (BC) risk. OBJECTIVES: We aimed to assess the association between combined exposures to multiple air pollutants and breast cancer risk. METHODS: The study was based on a case-control study nested within the French E3N cohort (5222 incident BC cases/5222 matched controls). For each woman, the average of the mean annual exposure to eight pollutants (benzo(a)oyrene, cadmium, dioxins, polychlorinated biphenyls (PCB153), nitrogen dioxide (NO2), ozone, particulate matter and fine particles (PMs)) was estimated from cohort inclusion in 1990 to the index date. We used the Bayesian Profile Regression (BPR) model, which groups individuals according to their exposure and risk levels, and assigns a risk to each cluster identified. The model was adjusted on a combination of matching variables and confounders to better consider the design of the nested case-control study. Odds ratios (OR) and their 95 % credible intervals (CrI) were estimated. RESULTS: Among the 21 clusters identified, the cluster characterised by low exposures to all pollutants, except ozone, was taken as reference. A consistent increase in BC risk compared to the reference cluster was observed for 3 clusters: cluster 9 (OR=1.61; CrI=1.13,2.26), cluster 16 (OR=1.59; CrI=1.10,2.30) and cluster 15 (OR=1.38; CrI=1.00,1.88) characterised by high levels of NO2, PMs and PCB153. The other clusters showed no consistent association with BC. DISCUSSION: This is the first study assessing the effect of exposure to a mixture of eight air pollutants on BC risk, using the BPR approach. Overall, results showed evidence of a positive joint effect of exposure to high levels to most pollutants, particularly high for NO2, PMs and PCB153, on the risk of BC.

Insights into soil autotrophic ammonium oxidization under microplastics stress: Crossroads of nitrification, comammox, anammox and Feammox.

Microplastics (MPs) are widespread in agroecosystems and profoundly impact soil microbiome and nutrient cycling. However, the effects of MPs on soil autotrophic ammonium oxidization processes, including nitrification, complete ammonium oxidation (comammox), anaerobic ammonium oxidation (anammox), and anaerobic ammonium oxidation coupled to iron reduction (Feammox), remain unclear. These processes are the rate-limiting steps of nitrogen cycling in agroecosystems. Here, our work unveiled that exposures of polyethylene (PE), polypropylene (PP), polylactic acid (PLA), and polybutylene adipate terephthalate (PBAT) MPs significantly modulated ammonium oxidization pathways with distinct type- and dose-dependent effects. Nitrification remained the main contributor (56.4-70.7 %) to soil ammonium removal, followed by comammox (11.7-25.6 %), anammox (5.0-20.2 %) and Feammox (3.3-11.6 %). Compared with conventional nonbiodegradable MPs (i.e., PE and PP), biodegradable MPs (i.e., PLA and PBAT) exhibited more pronounced impacts on soil nutrient conditions and functional microbes, which collectively induced alterations in soil ammonium oxidation. Interestingly, low-dose PLA and PBAT remarkably enhanced the roles of anammox and Feammox in soil ammonium removal, contributing to the mitigation of soil acidification in agroecosystems. This study highlights the diverse responses of ammonium oxidization pathways to MPs, further deepening our understanding of how MPs affect biogeochemical cycling and enriching strategies for agricultural managements amid increasing MPs pollution.

Site-specific cancer mortality after low level exposure to ionizing radiation: Findings from an update of the International Nuclear Workers Study (INWORKS).

A major update to the International Nuclear Workers Study was undertaken that allows us to report updated estimates of associations between radiation and site-specific solid cancer mortality. A cohort of 309,932 nuclear workers employed in France, the United Kingdom, and United States were monitored for external radiation exposure and associations with cancer mortality were quantified as the excess relative rate (ERR) per gray (Gy) using a maximum likelihood and a Markov chain Monte Carlo method (to stabilize estimates via a hierarchical regression). The analysis included 28,089 deaths due to solid cancer, the most common being lung, prostate, and colon cancer. Using maximum likelihood, positive estimates of ERR per Gy were obtained for stomach, colon, rectum, pancreas, peritoneum, larynx, lung, pleura/mesothelioma, bone and connective tissue, skin, prostate, testis, bladder, kidney, thyroid, and residual cancers; negative estimates of ERR per Gy were found cancers of oral cavity and pharynx, esophagus, and ovary. A hierarchical model stabilized site-specific estimates of association, including for lung (ERR per Gy=0.65; 95% credible interval [CrI]: 0.24, 1.07), prostate (ERR per Gy=0.44; 95% CrI: -0.06, 0.91), and colon cancer (ERR per Gy=0.53; 95% CrI: -0.07, 1.11). The results contribute evidence regarding associations between low dose radiation and cancer.

Burden and social distribution of occupational psychosocial exposures in the United States workforce, 2022.

OBJECTIVE: To characterize the burden and social distribution of occupational psychosocial exposures in the United States (US). METHODS: We merged 2022 US employment and demographic data from the Current Population Survey (CPS) with occupational characteristic data from the Occupational Information Network (O*NET), wage data from the Occupational Employment and Wage Statistics Survey, and hours worked from the CPS, to estimate the number and proportion of US workers at risk of exposure to 19 psychosocial hazards. We additionally estimated the number and proportion of US workers over- or underrepresented in exposure burden. RESULTS: Of the exposures examined, US workers were most commonly employed in occupations with high time pressure (67.5 million US workers exposed; 43.2% US workers exposed), high emotional labor (57.1 million; 36.6%), and low wages (47.8 million; 30.6%). The burden of exposures was uneven across sociodemographic strata, attributable to occupational segregation. The full data set is available online at https://deohs.washington.edu/us-exposure-burden. CONCLUSIONS: Work-related psychosocial exposures are ubiquitous and should be considered in occupational and public health research, policy, and interventions to reduce the burden of disease and health inequities in the United States.

Hypersensitivity pneumonitis secondary to foam exposure in mattress and pillows.

Fibrotic hypersensitivity pneumonitis (HP) has a poor prognosis when no antigen is identified, which occurs in many cases. We present a case of HP due to foam exposure in bedding, an unrecognised cause of HP. A woman was referred for dyspnoea and cough. High-resolution chest computed tomography (HRCT) showed a three-density pattern with gas trapping. Pulmonary function tests (PFTs) revealed restriction and reduced diffusing capacity. Bronchoalveolar lavage showed lymphocytosis (43%) and lung cryobiopsy showed fibrosis, lymphocytic infiltration and multinucleated giant cells. She had foam in mattress and pillows but no other exposures. Her symptoms, PFTs, and imaging improved after avoiding foam in her bedding. After re-exposure to a foam pillow, her symptoms, PFTs, and HRCT worsened. Microbiological analysis of the foam pillow reported Penicillium spp, known to cause HP. Foam exposure is a novel cause of HP, and foam avoidance can prevent disease progression and death.

Perinatal Exposure to Phenols and Poly- and Perfluoroalkyl Substances and Gut Microbiota in One-Year-Old Children.

The role of the gut microbiota in human health calls for a better understanding of its determinants. In particular, the possible effects of chemicals with widespread exposure other than pharmaceuticals are little known. Our aim was to characterize the sensitivity of the early-life gut microbiota to specific chemicals with possible antimicrobial action. Within the SEPAGES French couple-child cohort, we assessed 12 phenols in repeated urine samples from 356 pregnant women and their offspring and 19 poly- and perfluoroalkyl substances (PFASs) in serum from the pregnant women. We collected stool samples from the children at one year of age, in which the V3-V4 region of the 16S rRNA gene was sequenced, allowing for gut bacterial profiling. Associations of each chemical with α- and ß-diversity indices of the gut microbiota and with the relative abundance of the most abundant taxa were assessed using single-pollutant and mixture (BKMR) models. Perinatal exposure to certain parabens was associated with gut microbiota α- and ß-diversity and with Firmicutes and Proteobacteria. Suggestive associations of certain phenols with genera of the Lachnospiraceae and Enterobacteriaceae families were observed, but these were not maintained after correction for multiple testing. Parabens, which have known antimicrobial properties, might disrupt the child gut microbiota, but larger studies are required to confirm these findings.

How will Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and lead (Pb) exposure interact in the cardiovascular system?

The combined effects of lead exposure and the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and how they cause cardiovascular dysfunction are examined in this viewpoint manuscript. Lead was picked as a representative environmental contaminant because it has been studied extensively for more than 40 years, while SARS-CoV-2 illustrates the unpredictability of a new infectious agent that can quickly increase the environmental burden on communities. Given that this interaction represents a plausible combined exposure for many people, it is crucial to discuss how it might happen at a mechanistic level. SARS-CoV-2 causes the coronavirus disease 2019 (COVID-19), which can spread by contact and respiratory droplets. One may be exposed to lead and SARS-CoV-2 simultaneously depending on their living situation. Uncertainty exists regarding the consequences of this exposure on cardiovascular disease and its underlying processes. This paper aims to investigate these mechanisms and provide potential causes behind them. The interaction of lead with SARS-CoV-2 and its effects on the cardiovascular system are likely caused by direct damage, the promotion of reactive oxygen species (ROS) production, oxidative stress, and inflammation. In particular, the stimulation of nuclear factor kappa B (NF-B), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF) were all identified as potentially important pathways. Blood clotting, cytokine storm cycle development, and increased hypoxia may also be the results of this. In summary, the effects on the immune system, coagulation, the renin-angiotensin-aldosterone system, and cardiac contractility were the four primary areas identified.

Multivariable Mendelian randomization with incomplete measurements on the exposure variables in the Hispanic Community Health Study/Study of Latinos.

Multivariable Mendelian randomization allows simultaneous estimation of direct causal effects of multiple exposure variables on an outcome. When the exposure variables of interest are quantitative omic features, obtaining complete data can be economically and technically challenging: the measurement cost is high, and the measurement devices may have inherent detection limits. In this paper, we propose a valid and efficient method to handle unmeasured and undetectable values of the exposure variables in a one-sample multivariable Mendelian randomization analysis with individual-level data. We estimate the direct causal effects with maximum likelihood estimation and develop an expectation-maximization algorithm to compute the estimators. We show the advantages of the proposed method through simulation studies and provide an application to the Hispanic Community Health Study/Study of Latinos, which has a large amount of unmeasured exposure data.

PON1 Status in Relation to Gulf War Illness: Evidence of Gene-Exposure Interactions from a Multisite Case-Control Study of 1990-1991 Gulf War Veterans.

BACKGROUND: Deployment-related neurotoxicant exposures are implicated in the etiology of Gulf War illness (GWI), the multisymptom condition associated with military service in the 1990-1991 Gulf War (GW). A Q/R polymorphism at position 192 of the paraoxonase (PON)-1 enzyme produce PON1192 variants with different capacities for neutralizing specific chemicals, including certain acetylcholinesterase inhibitors. METHODS: We evaluated PON1192 status and GW exposures in 295 GWI cases and 103 GW veteran controls. Multivariable logistic regression determined independent associations of GWI with GW exposures overall and in PON1192 subgroups. Exact logistic regression explored effects of exposure combinations in PON1192 subgroups. RESULTS: Hearing chemical alarms (proxy for possible nerve agent exposure) was associated with GWI only among RR status veterans (OR = 8.60, p = 0.014). Deployment-related skin pesticide use was associated with GWI only among QQ (OR = 3.30, p = 0.010) and QR (OR = 4.22, p < 0.001) status veterans. Exploratory assessments indicated that chemical alarms were associated with GWI in the subgroup of RR status veterans who took pyridostigmine bromide (PB) (exact OR = 19.02, p = 0.009) but not RR veterans who did not take PB (exact OR = 0.97, p = 1.00). Similarly, skin pesticide use was associated with GWI among QQ status veterans who took PB (exact OR = 6.34, p = 0.001) but not QQ veterans who did not take PB (exact OR = 0.59, p = 0.782). CONCLUSION: Study results suggest a complex pattern of PON1192 exposures and exposure-exposure interactions in the development of GWI.

Perceptions of Exposure and Mask Use in Wildland Firefighters.

Wildland firefighters are exposed to airborne particulates, polycyclic aromatic hydrocarbons (PAHs), and other hazardous substances. Respiratory protection is indicated, but information is lacking on the tasks and conditions for which mask wearing should be advised. Studies to assess respiratory protection in wildland firefighters were carried out in western Canada in 2021 and 2023. Sampling pumps measured airborne exposures and urinary 1-hydroxypyrene (1-HP) was assayed to indicate PAH absorption. Participants in 2021 reported the time for which they wore the mask during each task. In 2023, the use of masks was reported, and firefighters rated the smoke intensity. In 2021, 72 firefighters were monitored over 164 shifts and, in 2023, 89 firefighters were monitored for 263 shifts. In 2021, mask wearing was highest for those engaged in initial attack and hot spotting. Urinary 1-HP at the end of rotation was highest for those reporting initial attack, working on a prescribed fire and mop-up. In 2023, firefighter ratings of smoke intensity were strongly associated with measured particulate mass and with urinary 1-HP, but masks were not worn more often when there was higher smoke intensity. The data from the literature did not provide a clear indication of high-exposure tasks. Better task/exposure information is needed for firefighters to make informed decisions about mask wearing.

Elevated Exposure to Air Pollutants Accelerates Primary Glomerular Disease Progression.

Introduction: Environmental contributors to kidney disease progression remain elusive. We explored how residential air pollution affects disease progression in patients with primary glomerulopathies. Methods: Nephrotic Syndrome Study Network (NEPTUNE) and CureGlomerulonephropathy (CureGN) participants with residential census tract data and ≥2 years of follow-up were included. Using Cox proportional hazards models, the associations per doubling in annual average baseline concentrations of total particulate matter with diameter ≤2.5 µm (PM2.5) and its components, black carbon (BC), and sulfate, with time to ≥40% decline in estimated glomerular filtration rate (eGFR) or kidney failure were estimated. Serum tumour necrosis factor levels and kidney tissue transcriptomic inflammatory pathway activation scores were used as molecular markers of disease progression. Results: PM2.5, BC, and sulfate exposures were comparable in NEPTUNE (n = 228) and CureGN (n = 697). In both cohorts, participants from areas with higher levels of pollutants had lower eGFR, were older and more likely self-reported racial and ethnic minorities. In a fully adjusted model combining both cohorts, kidney disease progression was associated with PM2.5 (adjusted hazard ratio 1.55 [95% confidence interval: 1.00-2.38], P = 0.0489) and BC (adjusted hazard ratio 1.43 [95% confidence interval: 0.98-2.07], P = 0.0608) exposure. Sulfate and PM2.5 exposure were positively correlated with serum tumour necrosis factor (TNF) (P = 0.003) and interleukin-1ß levels (P = 0.03), respectively. Sulfate exposure was also directly associated with transcriptional activation of the TNF and JAK-STAT signaling pathways in kidneys (r = 0.55-0.67, P-value <0.01). Conclusion: Elevated exposure to select air pollutants is associated with increased risk of disease progression and systemic inflammation in patients with primary.