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When Dr. Benjamin Pauli moved to Flint, Michigan, in June 2015, the town was already one year into a water crisis without knowing it. He was to begin his role [...]

Introduction Ambient particulate matter (PM) air pollution is considered to be one of the greatest environmental threats to human health due to its near ubiquity and widespread effects. (1) In [...], BACKGROUND: Emerging literature suggests that fine particulate matter [with aerodynamic diameter [less than or equal to]2.5 [micro]m ([PM.sub.2.5])] air pollution and its components are linked to various neurodevelopmental outcomes. However, few studies have evaluated how [PM.sub.2.5] component mixtures from distinct sources relate to cognitive outcomes in children. OBJECTIVES: This cross-sectional study investigated how ambient concentrations of [PM.sub.2.5] component mixtures relate to neurocognitive performance in 9- to 10-year-old children, as well as explored potential source-specific effects of these associations, across the US. METHODS: Using spatiotemporal hybrid models, annual concentrations of 15 chemical components of [PM.sub.2.5] were estimated based on the residential address of child participants from the Adolescent Brain Cognitive Development (ABCD) Study. General cognitive ability, executive function, and learning/memory scores were derived from the NIH Toolbox. We applied positive matrix factorization to identify six major [PM.sub.2.5] sources based on the 15 components, which included crustal, ammonium sulfate, biomass burning, traffic, ammonium nitrate, and industrial/residual fuel burning. We then utilized weighted quantile sum (WQS) and linear regression models to investigate associations between [PM.sub.2.5] components' mixture, their potential sources, and children's cognitive scores. RESULTS: Mixture modeling revealed associations between cumulative exposure and worse cognitive performance across all three outcome domains, including shared overlap in detrimental effects driven by ammonium nitrates, silicon, and calcium. Using the identified six sources of exposure, source-specific negative associations were identified between ammonium nitrates and learning & memory, traffic and executive function, and crustal and industrial mixtures and general cognitive ability. Unexpected positive associations were also seen between traffic and general ability as well as biomass burning and executive function. DISCUSSION: This work suggests nuanced associations between outdoor [PM.sub.2.5] exposure and childhood cognitive performance, including important differences in cognition related both to individual chemicals as well as to specific sources of these exposures. https://doi.org/10.1289/EHP14418

Introduction Association between Hydraulic Fracturing and Perinatal Outcomes Hydraulic fracturing (HF), more commonly known as fracking, is the injection of water, sand, and chemicals into the ground at high pressures [...], BACKGROUND: Risk of preterm birth (PTB) and low birth weight (LBW) due to hydraulic fracturing (HF) exposure is a growing concern. Regional studies have demonstrated links, but results are often contradictory among studies. OBJECTIVES: This is the first US national study to our knowledge linking fracturing fluid ingredients to the human hormone pathways targeted--estrogen, testosterone, or other hormones (e.g., thyroid hormone)--to assess the effect of HF ingredients on rates of PTB and LBW. METHODS: We constructed generalized linear regression models of the impact of HF well density and hormone targeting chemicals in HF fluids (2001-2018) on the county-level average period prevalence rates of PTB and LBW (2015-2018) with each outcome measured in separate models. Our data sources consisted of publicly available datasets, including the WellExplorer database, which uses data from FracFocus, the March of Dimes Peristats, the US Census Bureau, the US Department of Agriculture, and the Centers for Disease Control and Prevention. We conducted additional stratified analyses to address issues of confounding. We used stratification to address issues regarding outcomes in rural vs. urban communities by assessing whether our models achieved similar results in nonmetro counties, as well as farming and mining counties. We also stratified by the year of the HF data to include HF data that was closer to the time of the birth outcomes. We also added covariate adjustment to address other important factors linked to adverse birth outcomes, including the proportion of the population belonging to various racial and ethnic minority populations (each modeled as a separate variable); education (bachelor's degree and high school); use of fertilizers, herbicides, and insecticides, acres of agricultural land per square mile; poverty; insurance status; marital status; population per square mile; maternal care deserts; and drug deaths per 100,000 people. RESULTS: We found that the density of HF wells in a county was significantly associated with both PTB and LBW rates (percentage of live births) in our fully adjusted models. We report the results from our more restrictive stratified analysis with a subset including only the 2014-2018 data, because this resulted in the most meaningful time frame for comparison. Across all models, the magnitude of effect was highest for wells with ingredients that include estrogen targeting chemicals (ETCs), testosterone targeting chemicals (TTCs) and other hormone targeting chemicals (OHTCs), and, finally, all wells grouped regardless of chemical type. For every unit increase in well density per square mile of wells that use chemicals that include an ETC, we observed a 3.789-higher PTB rate (95% CI: 1.83,5.74) compared with counties with no ETC wells from 2014 to 2018 and likewise, we observed a 1.964-higher LBW rate (95% CI: 0.41,3.52). Similarly, for every unit increase in well density per square mile of wells that use TTC, we observed a 3.192-higher PTB rate (95% CI: 1.62,4.77) compared with counties with no TTC wells. Likewise, for LBW, we found a 1.619-higher LBW rate (95% CI: 0.37,2.87). We also found that an increase in well density per square mile among wells that use chemicals that include an OHTC resulting in a 2.276-higher PTB rate (95% CI: 1.25, 3.30) compared with counties with no OHTC wells, and for LBW, we found a 1.244-higher LBW rate (95% CI: 0.43,2.06). We also explored the role of HF well exposure in general (regardless of the chemicals used) and found that an increase in total well density (grouped regardless of hormonal targeting status of the chemicals used) resulted in a 1.228-higherPTB rate (95% CI: 0.66, 1.80) compared with counties with no wells, and for LBW, we found a 0.602-higher LBW rate (95% CI: 0.15,1.05) compared with counties with no wells. We found similar results in our primary analysis that used all data without any exclusions and the statistical significance did not change. DISCUSSION: Our findings reinforce previously identified regional associations between HF and PTB and LBW, but on a national scale. Our findings point to dysregulation of hormonal pathways underpinning HF exposure risk on birth outcomes, which warrants further exploration. Future research must consider the specific ingredients used in HF fluids to properly understand the differential effects of exposure. https://doi.org/10.1289/EHP12628

Introduction Inorganic arsenic in drinking water (wAs) remains an environmental exposure of concern, potentially linked to several prevalent chronic diseases in the US. (1,2) According to the American Heart Association [...], BACKGROUND: Inorganic arsenic in drinking water (wAs) is linked to atherosclerosis and cardiovascular disease. However, risk is uncertain at lower levels present in US community water supplies (CWS), currently regulated at the federal maximum contaminant level of 10 [micro]g/L. OBJECTIVES: We evaluated the relationship between long-term wAs exposure from CWS and cardiovascular disease in the California Teachers Study cohort. METHODS: Using statewide health care administrative records from enrollment through follow-up (1995-2018), we identified fatal and nonfatal cases of ischemic heart disease (IHD) and cardiovascular disease (CVD). Participants' residential addresses were linked to a network of CWS boundaries and annual wAs concentrations (1990-2020). Most participants resided in areas served by a CWS (92%). Exposure was calculated as a time-varying, 10-year moving average up to a participant's event, death, or end of follow-up. Using Cox models, we estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the risk of IHD or CVD. We evaluated wAs exposure categorized by concentration thresholds relevant to regulation standards ( RESULTS: Our analysis included 98,250 participants, 6,119 IHD cases, and 9,936 CVD cases. The HRs for IHD at concentration thresholds (reference, 55 years of age at enrollment ([p.sub.interaction] = 0:006 and 0.012 for IHD and CVD, respectively). DISCUSSION: Long-term wAs exposure from CWS, at and below the regulatory limit, may increase cardiovascular disease risk, particularly IHD. https://doi.org/10.1289/EHP14410

Introduction Thyroid hormones (THs) are essential for human growth, development, metabolism, cardiovascular homeostasis, and the immune system. (1) Their circulating levels are strictly regulated via a negative feedback loop along [...], BACKGROUND: Some pesticides have been shown to interfere with thyroid functions through changes in thyroid hormone (TH) levels. However, few human studies have explored associations between TH levels and environmental exposure to currently used pesticides, including neonicotinoids, phenylpyrazoles, phenoxy acids, and azoles. Moreover, such studies often measure biomarkers of exposure in urine or blood, and thus reveal only recent exposure. In contrast, hair has been demonstrated to be a suitable matrix for assessing chronic exposure to both persistent and nonpersistent organic pollutants. OBJECTIVES: We investigated 54 biomarkers of pollutant exposure in relation to tetraiodothyronine (T4), 3,3',5-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), and 3,3'-diiodothyronine (T2). METHODS: In a cross-sectional study of 196 healthy Chinese women of reproductive age (25-45 years of age), concentrations of both pollutants and THs were analyzed in the first 12 cm (starting from the scalp) of the hair matrix, collected in 2016. Associations between pollutants and TH levels were explored using stability-enhanced least absolute shrinkage and selection operator (lasso) by regressing all exposures against each outcome of interest, adjusted for age, body mass index, and city. RESULTS: Each TH was associated with the mixture of at least eight of the examined pesticides. We found associations of [beta]-HCH, PCP, DMP, DETP, 3Me4NP, carbofuran, [ClCF.sub.3]CA, imidacloprid, 2,4-D, metolachlor, difenoconazole, and tebuconazole with THs. For example, a 2-standard deviation (SD) increase in [log.sub.10]-transformed hair DMP concentration was associated with lower hair T4 concentration [-15:0% (95% CI: -26:1, -2:21%)] and higher hair T3 concentration [8.16% (95% CI: 1.73, 15.0%)] in the adjusted unpenalized regression models. We also found associations of some pesticides with T3/T4, rT3/T4, and rT3/T3 molar ratios, including PCP, DMP, 2,4-D, metolachlor, difenoconazole, and tebuconazole. DISCUSSION: Our results suggest that exposure to the low levels of pesticides examined here may disrupt thyroid homeostasis in humans. Further studies are needed to confirm our results and to evaluate the long-term consequences of these subtle interferences. https://doi.org/10.1289/EHP14378

Introduction Lead exposure has a detrimental effect on child neurodevelopment. (1-3) Although exposure is decreasing, no safe level or threshold has been identified. (3) Moreover, lead exposure is higher among [...], BACKGROUND: Folic acid (FA) supplementation may attenuate the associations between gestational exposure to certain chemicals and autism or autistic-like behaviors, but to our knowledge, this has not been assessed for lead. OBJECTIVES: We examined whether the relationship between gestational blood-lead levels (BLLs) and autistic-like behaviors was modified by gestational plasma total folate concentrations, FA supplementation, and maternal methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype. METHODS: We used data from the Maternal--Infant Research on Environmental Chemicals study (2008-2011), a Canadian pregnancy and birth cohort study. Childhood autistic-like behaviors were documented in 601 children 3-4 y of age with the Social Responsiveness Scale-2 (SRS-2), where higher scores denote more autistic-like behaviors. We measured BLLs and plasma total folate concentrations during the first and third trimesters of pregnancy. We also estimated gestational FA supplementation via surveys and genotyped the maternal MTHFR 677C>T single nucleotide polymorphism (SNP). We estimated the confounder-adjusted associations between [log.sub.2]-transformed BLLs and SRS-2 scores by two indicators of folate exposure and maternal MTHFR 677C>T genotype using linear regression. RESULTS: Third-trimester BLLs were associated with increased SRS-2 scores [[[beta].sub.adj] = 3:3; 95% confidence interval (CI): 1.1, 5.5] among participants with low (T SNP ([[beta].sub.adj] = 0:9; 95% CI: -1:2, 3.1) than those without the T allele ([[beta].sub.adj] = -0:3; 95% CI: -1:3, 0.7), but the difference was not statistically significant (p-interaction = 0:28). DISCUSSION: Folate may modify the associations between gestational lead exposure and childhood autistic-like behaviors, suggesting that it mitigates the neurotoxic effects of prenatal lead exposure. https://doi.org/10.1289/EHP14479

Introduction Myocardial infarction (MI), a potentially fatal cardiovascular condition, develops when the blood flow through the coronary arteries is diminished due to various factors, leading to inadequate oxygen supply to [...], BACKGROUND: Unraveling gene--environment interaction can provide a novel insight into early disease prevention. Nevertheless, current understanding of the interplay between genetic predisposition and air pollution in relation to myocardial infarction (MI) risk remains limited. Furthermore, the potential long-term influence of air pollutants on MI incidence risk warrants more conclusive evidence in a community population. OBJECTIVE: We investigated interactions between genetic predisposition and exposure to air pollutants on MI incidence. METHODS: This study incorporated a sample of 456,354 UK Biobank participants and annual mean air pollution ([PM.sub.2.5], [PM.sub.10], [NO.sub.2], and [NO.sub.x]) from the UK Department for Environment, Food and Rural Affairs (2006-2021). The Cox proportional hazards model was employed to explore MI incidence after chronic air pollutants exposure. By quantifying genetic risk through the calculation of polygenic risk score (PRS), this study further examined the interactions between genetic risk and exposure to air pollutants in the development of MI on both additive and multiplicative scales. RESULTS: Among 456,354 participants, 9,114 incident MI events were observed during a median follow-up of 12.08 y. Chronic exposure to air pollutants was linked with an increased risk of MI occurrence. Specifically, the hazard ratios (per interquartile range) were 1.12 (95% CI: 1.10, 1.13) for [PM.sub.2.5], 1.20 (95% CI: 1.19, 1.22) for [PM.sub.10], 1.13 (95% CI: 1.12, 1.15) for [NO.sub.2], and 1.12 (95% CI: 1.11, 1.13) for [NO.sub.x]. In terms of the joint effects, participants with high PRS and high level of air pollution exposure exhibited the greatest risk of MI among all study participants ( ~ 255% to 324%). Remarkably, both multiplicative and additive interactions were detected in the ambient air pollutants exposure and genetic risk on the incidence of MI. DISCUSSION: There were interactions between exposure to ambient air pollutants and genetic susceptibility on the risk of MI onset. Moreover, the joint effects of these two exposures were greater than the effect of each factor alone. https://doi.org/10.1289/EHP14291

Introduction Human exposure to the >42,000 chemicals in active commerce in the United States, many of which are known or suspected to be toxic, is a source of increasing concern. [...], BACKGROUND: The prevalence of toxic chemicals in US commerce has prompted some states to adopt laws to reduce exposure. One with broad reach is California's Proposition 65 (Prop 65), which established a list of chemicals that cause cancer, developmental harm, or reproductive toxicity. The law is intended to discourage businesses from using these chemicals and to minimize consumer exposure. However, a key question remains unanswered: Has Prop 65 reduced population-level exposure to the listed chemicals? OBJECTIVE: We used national biomonitoring data from the Centers for Disease Control and Prevention (CDC) to evaluate the impact of Prop 65 on population-level exposures. METHODS: We evaluated changes in blood and urine concentrations of 37 chemicals (including phthalates, phenols, VOCs, metals, PAHs, and PFAS), among US National Health and Nutrition Examination Survey (NHANES) participants in relation to the time of chemicals' Prop 65 listing. Of these, 11 were listed prior to, 11 during, and 4 after the biomonitoring period. The remaining 11 were not listed but were closely related to a Prop 65-listed chemical. Where biomonitoring data were available from before and after the date of Prop 65 listing, we estimated the change in concentrations over time for Californians compared with non-Californians, using a difference-in-differences model. We used quantile regression to estimate changes in exposure over time, as well as differences between Californians and non-Californians at the 25th, 75th, and 95th percentiles. RESULTS: We found that concentrations of biomonitored chemicals generally declined nationwide over time irrespective of their inclusion on the Prop 65 list. Median bisphenol A (BPA) concentrations decreased 15% after BPA's listing on Prop 65, whereas concentrations of the nonlisted but closely related bisphenol S (BPS) increased 20% over this same period, suggesting chemical substitution. Californians generally had lower levels of biomonitored chemicals than the rest of the US population. DISCUSSION: Our findings suggest that increased scientific and regulatory attention, as well as public awareness of the harms of Prop 65-listed chemicals, prompted changes in product formulations that reduced exposure to those chemicals nationwide. Trends in bisphenols and several phthalates suggest that manufacturers replaced some listed chemicals with closely related but unlisted chemicals, increasing exposure to the substitutes. Our findings have implications for the design of policies to reduce toxic exposures, biomonitoring programs to inform policy interventions, and future research into the regulatory and market forces that affect chemical exposure. https://doi.org/10.1289/EHP13956

Background Drinking water at US Marine Corps (USMC) Base Camp Lejeune, North Carolina, is sourced from groundwater supply wells. Eight treatment plants supplied drinking water to different areas of the [...], BACKGROUND: Drinking water at US Marine Corps Base Camp Lejeune, North Carolina, was contaminated with trichloroethylene and other industrial solvents from 1953 to 1985. METHODS: A cohort cancer incidence study was conducted of Marines/Navy personnel who began service and were stationed at Camp Lejeune (N = 154,821) or Camp Pendleton, California (N = 163,484) between 1975 and 1985 and civilian workers employed at Camp Lejeune (N = 6,494) or Camp Pendleton (N = 5,797) between October 1972 and December 1985. Camp Pendleton's drinking water was not contaminated with industrial solvents. Individual-level information on primary invasive cancers and in situ bladder cancer diagnosed between 1996 and 2017 was obtained from 54 US cancer registries. Proportional hazards regression was used to calculate adjusted hazard ratios (aHRs) comparing cancer incidence between the Camp Lejeune and Camp Pendleton cohorts, adjusted for sex, race, education, and rank (or blue-collar work), with age as the time variable. Precision of aHRs was evaluated using the 95% confidence interval (CI) ratio (CIR). RESULTS: Cancers among Camp Lejeune Marines/Navy personnel and civilian workers totaled 12,083 and 1,563, respectively. Cancers among Camp Pendleton Marines/Navy personnel and civilian workers totaled 12,144 and 1,416, respectively. Compared with Camp Pendleton, Camp Lejeune Marines/Navy personnel had aHRs [greater than or equal to]1:20 with CIRs [less than or equal to]3 for all myeloid cancers (HR = 1:24; 95% CI: 1.03, 1.49), acute myeloid leukemia (HR = 1:38; 95% CI: 1.03, 1.85), myelodysplastic and myeloproliferative syndromes (HR = 1:68; 95% CI: 1.07, 2.62), polycythemia vera (HR = 1:41; 95% CI: 0.94, 2.11), and cancers of the esophagus (HR = 1:27; 95% CI: 1.03, 1.56), larynx (HR = 1:21; 95% CI: 0.98, 1.50), soft tissue (HR = 1:21; 95% CI: 0.92, 1.59), and thyroid (HR = 1:22; 95% CI: 1.03, 1.45). Lymphoma subtypes mantle cell and marginal zone B-cell and lung cancer subtypes adenocarcinoma and non-small cell lung cancer also had aHRs [greater than or equal to]1:20 with CIRs [less than or equal to]3. Compared with Camp Pendleton, Camp Lejeune civilian workers had aHRs [greater than or equal to]1:20 with CIRs [less than or equal to]3 for all myeloid cancers (HR = 1:40; 95% CI: 0.83, 2.36), squamous cell lung cancer (HR = 1:63; 95% CI: 1.10, 2.41), and female breast (HR = 1:21; 95% CI: 0.97, 1.52) and ductal cancer (HR = 1:32; 95% CI: 1.02, 1.71). CONCLUSION: Increased risks of several cancers were observed among Marines/Navy personnel and civilian workers exposed to contaminated drinking water at Camp Lejeune compared with Camp Pendleton. https://doi.org/10.1289/EHP14966

Introduction Despite being an occupational hazard, environmental exposure to lead (Pb) has been and will continue to be a major public health concern, because this metal is widely present in [...], BACKGROUND: The role of environmental factors in Alzheimer's disease (AD) pathogenesis remains elusive. Mounting evidence suggests that acute and past exposure to the environmental toxicant lead (Pb) is associated with longitudinal decline in cognitive function, brain atrophy, and greater brain [beta]-amyloid (A[beta]) deposition. However, the nature of Pb-induced amyloid deposition and how it contributes to AD development remain unclear. OBJECTIVES: This study investigates the role of Pb in the pathogenesis of cerebral amyloid angiopathy (CAA) and whether plasminogen activator inhibitor-1 (PAI-1) contributes to this process in the APP/PS1 mouse model. METHODS: Female APP/PS1 mice at 8 wk of age were administered either 50 mg/kg Pb-acetate (PbAc) (i.e., 27 mg Pb/kg) or an equivalent molar concentration of sodium acetate (NaAc) via oral gavage once daily for 8 wk. Amyloid deposition and vascular amyloid were determined by immuno-staining. In addition, A[beta] perivascular drainage, vascular binding assay, and microglial endocytosis were examined to determine underlying mechanisms. Furthermore, magnetic resonance imaging demyelination imaging was performed in vivo measure the level of demyelination. Finally, Y-maze and Morris water maze tests were assessed to evaluate the cognitive function of mice. RESULTS: APP/PS1 mice (an AD mice model) exposed to PbAc demonstrated more vascular amyloid deposition less neocortical myelination, and lower cognitive function, as well as greater vascular binding to A[beta]40, higher A[beta]40/A[beta]42 ratios, strikingly lower A[beta]40 levels in the perivascular drainage, and microglial endocytosis. Importantly, exposure to a specific PAI-1 inhibitor, tiplaxtinin, which previously was reported to lower CAA pathology in mice, resulted in less CAA-related outcomes following PbAc exposure. DISCUSSION: Our findings suggest that PbAc induced CAA/AD pathogenesis via the PAI-1 signaling in the APP/PS1 mouse model, and the inhibition of PAI-1 could be a potential therapeutic target for PbAc-mediated CAA/AD disorders. https://doi.org/10.1289/EHP14384

INTRODUCTION The World Food Program (WFP) specified that food insecurity in Ethiopia is aggravated by limited market access, health and nutrition services interruption, household displacement and instability due to conflict, [...], The severity of food insecurity in Ethiopia is among the worst globally, with record-breaking food assistance needs by various factors. This study tries to uncover various aspects of food security related to food availability, food access, food utilization and food stability dimensions of food security. The study was executed in the west Hararghe zone of the Oromia region of Ethiopia. Its main objective was to determine the food security status of households, with specific objectives aiming at computing individual daily kilo calorie intake, determining the average food requirement, comparing the relative risk between food secure and insecure households and identifying factors that affect household food security status. A multistage sampling procedure, involving the purposive selection of; the Zone and Woreda, and a simple random selection of households, to draw the required number of representative sample respondents, was adopted. Hence, from 4163 total households, 134 were selected for collecting primary data. Data were analyzed using descriptive statistics, relative risk analysis using Cohorts and independent tests using ANOVA. Food security status was measured using the Household Food Balance Model (HFBM). Using this model, the study obtained 1973 kilo calories per individual per day intake and 2108 kilo calorie as their requirement, which indicated households were energy deficient by 135 kilo calorie with [.sup.2-sided]-value < 0.1 critical level (t= -1.747, df =133 & [sig.sub.2-sided]. 0.083). Independent test results showed that farm income (at p-value < 0.1), gross product (at p-value < 0.05), age of household head (at p-value < 0.1), years of owning land (at p < 0.1) and family size (at p-value < 0.1) contributed significantly to food security status. Cross-tabulation showed a linear relationship between food security and higher education level (at p-value < 0.05), which urges a concern in improving farming societies&apos; literacy to the desired level. In the study areas, about 91.8% of the population produces crops depending on the seasonal rainfall and their daily kilo calorie consumed depends on it; this is statistically correlated with the food insecurity problem at p-value < 0.1 critical level (lambada = 1.75 & sig. = 0.08). Therefore, to tackle the food insecurity problem, alternative method of crop production should be devised such as the establishment of irrigation schemes, water harvesting structures, and water conservation practices, among others. Key words: food security, calorie requirement, food availability, relative risk

Oncocytic follicular cell-derived thyroid neoplasms, formerly known as Hurthle cell tumors, are characterized by expansile nodular growths of thyroid follicular epithelium displaying abundant granular eosinophilic cytoplasm. The topic of oncocytic [...], * Context.--Oncocytic thyroid tumors displaying a papillary growth pattern are rare and may cause diagnostic problems. Objective.--To examine the clinicopathologic features of a series of 32 follicular cell-derived tumors composed of cells with oncocytic cytoplasm and displaying papillary architecture. Design.--Thirty-two cases were collected and studied to assess clinicopathologic features, including immunohistochemical and molecular testing for BRAF V600E. Results.--The patients were 26 women and 6 men, aged 17 to 77 years. The nodules ranged from 0.3 to 6.0 cm. Eighteen cases showed features of oncocytic hyperplastic nodules and were identified against a background of thyroid follicular nodular disease; 4 cases showed features of oncocytic follicular adenoma; and 10 cases corresponded to carcinomas with oncocytic and papillary features. Nuclear features of papillary thyroid carcinoma were absent or exceedingly rare. All cases were negative for HBME-1 and cytokeratin 19 (CK19) and wild type for BRAF V600E. Follow-up in 25 patients showed that all patients with hyperplastic nodules and oncocytic follicular adenomas were alive and well and free of disease from 7 to 20 years. One patient with oncocytic follicular carcinoma showed metastases and died of tumor at 16 months; 2 patients with carcinoma had metastases and recurrence at 6 and 7 years; and 5 patients with invasive tumors were free of disease from 5 to 10 years. Conclusions.--Oncocytic thyroid tumors with papillary features can span a spectrum from benign hyperplastic, to encapsulated neoplastic, to invasive malignant lesions. Owing to their papillary features, it is important not to confuse them for other types of thyroid tumors, such as oncocytic papillary thyroid carcinoma. (Arch Pathol Lab Med. 2024;148:997-1006; doi: 10.5858/arpa.2023-0309-OA)

Pancreatic neuroendocrine neoplasms (PanNENs) represent a heterogeneous group of epithelial tumors of the pancreas showing a neuroendocrine differentiation. (1-4) Among all pancreatic malignancies, the prevalence of PanNENs is around 2% [...], * Context.--Pancreatic neuroendocrine neoplasms (PanNENs) represent a heterogeneous group of epithelial tumors of the pancreas showing neuroendocrine differentiation. These neoplasms are classified into well-differentiated pancreatic neuroendocrine tumors (PanNETs), which include G1, G2, and G3 tumors, and poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs), which are G3 by definition. This classification mirrors clinical, histologic, and behavioral differences and is also supported by robust molecular evidence. Objective.--To summarize and discuss the state of the art regarding neoplastic progression of PanNENs. A better comprehension of the mechanisms underpinning neoplastic evolution and progression of these neoplasms may open new horizons for expanding biologic knowledge and ultimately for addressing new therapeutic strategies for patients with PanNENs. Data Sources.--Literature review of published studies and the authors&apos; own work. Conclusions.--PanNETs can be seen as a unique category, where G1-G2 tumors may progress to G3 tumors mainly driven by DAXX/ATRX mutations and alternative lengthening of telomeres. Conversely, PanNECs display totally different histomolecular features more closely related to pancreatic ductal adenocarcinoma, including TP53 and Rb alterations. They seem to derive from a nonneuroendocrine cell of origin. Even the study of PanNEN precursor lesions corroborates the rationale of considering PanNETs and PanNECs as separate and distinct entities. Improving the knowledge regarding this dichotomous distinction, which guides tumor evolution and progression, will represent a critical basis for PanNEN precision oncology. (Arch Pathol Lab Med. 2024;148:975-979; doi: 10.5858/arpa.2022-0417-RA)

Intraductal papillary neoplasm of the bile duct (IPNB) is a precursor lesion of cholangiocarcinoma. (1-3) Since the concept of this neoplasm was proposed almost 20 years ago, (4) it has [...], * Context.--Intraductal papillary neoplasm of the bile duct (IPNB) is classified into types 1 and 2 based on criteria proposed in 2019. Recent studies investigated the clinicopathologic and molecular features of IPNB, which contributed to a more detailed understanding of this undercharacterized neoplasm. Objective.--To summarize driver gene mutations, radiologic tumor evolution, and a potentially unique pattern of tumor progression in IPNB. Data Sources.--Data were derived from a literature review and personal clinical and research experiences. Conclusions.--In contrast to de novo cholangiocarcinoma, type 1 IPNB often has mutations in APC, CTNNB1, STK11, and GNAS. These molecular features are shared with intraductal papillary mucinous neoplasm of the pancreas; however, the frequencies of individual gene abnormalities differ between these 2 neoplasms. A radiologic review of sequential images suggested that type 1 IPNB is a slow-growing neoplasm, with an ~1-cm increase in size every 2 to 3 years, and remains in a noninvasive state for many years. A similar papillary neoplasm may develop in the biliary tree years after the complete surgical resection of IPNB. The second neoplasm has the same genetic abnormalities as the first neoplasm, indicating intrabiliary implantation rather than multifocal lesions. In contrast to type 1 IPNB, most cases of type 2 IPNB have invasive malignancy at the initial presentation. Type 2 IPNB shares many clinicopathologic and molecular features with de novo cholangiocarcinoma, questioning the distinctness of this tumor entity. The molecular mechanisms underlying malignant transformation in IPNB warrant further study. (Arch Pathol Lab Med. 2024;148:989-996; doi: 10.5858/arpa.2022-0407-RA)

Despite recent progress toward elimination, persisting malaria transmission in the Americas continues to pose a risk for infection to 120 million persons (1). The Amazon Basin, spanning 9 countries of [...]

Background: The aim of our work was to examine differences between trauma patients in rural and urban areas who presented to a tertiary trauma centre in the province of Saskatchewan, Canada. Methods: We identified a historical cohort of all level 1 trauma activations presenting to Royal University Hospital (RUH) from April 1, 2020, to March 31, 2022. We divided the cohort into 2 groups (urban and rural), according to the trauma location. The primary outcome of interest was 30-day mortality. Secondary outcomes of interest were hospital length of stay, readmission to hospital within 30 days of discharge, and complication rate. Results: Trauma patients in rural areas were younger (34.1 v. 37 yr; p = 0.002) and more likely to be male (80.3% v. 74.4%; p = 0.040), with higher Injury Severity Scores (12.3 v. 8.3; p < 0.0001). Trauma patients in urban areas were more likely to sustain penetrating trauma (42.5% v. 28.5%; p < 0.0001). We saw no differences in morbidity and mortality between the 2 groups, but the rural trauma group had longer median lengths of stay (5 v. 3 d; p < 0.0007). Conclusion: Although we identified key differences in patient demographics, injury type, and injury severity, outcomes were largely similar between the urban and rural trauma groups. This finding contradicts comparable studies within Canada and the United States, a difference that may be attributable to the lack of inclusion of prehospital mortality in the rural trauma group. The longer length of stay in trauma patients from rural areas may be attributed to disposition challenges for patients who live remotely. Contexte: Notre travail avait pour but d'analyser les diff rences entre les patient les de traumatologie provenant de milieux ruraux et urbains ayant consult dans un centre de traumatologie tertiaire de la province de la Saskatchewan, au Canada. M thodes: Nous avons constitu une cohorte historique de tous les cas d'activation de niveau 1 en traumatologie ayant consult l'H pital universitaire royal entre le 1er avril 2020 et le 31 mars 2022. Nous avons scind la cohorte en 2 groupes (milieux urbains et ruraux), selon le lieu de survenue du traumatisme. Le param tre principal tait la mortalit 30 jours. Les param tres secondaires taient la dur e du s jour hospitalier, la r hospitalisation dans les 30 jours suivant le cong , et le taux de complications. R sultats: La patient le de traumatologie provenant de r gions rurales tait plus jeune (34,1 c. 37 ans; p = 0,002) et plus susceptible d' tre de sexe masculin (80,3% c. 74,4%; p = 0,040) et de pr senter des indices de gravit des blessures plus lev s (12,3 c. 8,3; p < 0,0001). La patient le de traumatologie provenant de milieux urbains tait plus susceptible d'avoir subi un traumatisme p n trant (42,5% c. 28,5%; p < 0,0001). Nous n'avons observ aucune diff rence aux plans de la morbidit et de la mortalit entre les 2 groupes, mais la dur e m diane du s jour hospitalier du groupe provenant de milieux ruraux a t plus longue (5 c. 3 j; p < 0,0007). Conclusion: M me si nous avons observ des diff rences cl s aux plans des donn es d mographiques ainsi que du type et de la gravit des blessures, les param tres se sont r v l s assez semblables entre les patient les de traumatologie des milieux urbains et ruraux. Cette observation se d marque de celles d' tudes canadiennes et am ricaines comparables, ce qui pourrait s'expliquer par l'exclusion de la mortalit pr hospitali re dans le groupe de milieux ruraux. La dur e plus longue du s jour chez la patient le de traumatologie de milieux ruraux pourrait tre attribuable des enjeux relatifs l' tat de ces malades au moment de leur cong ., The province of Saskatchewan, Canada, has a geographically dispersed population, with about 60% living more than an hour away from a tertiary care centre and 48% living more than an [...]

BACKGROUND: Following the removal of lead from gasoline, paint and pipes were thought to be the main sources of lead exposure in the United States. However, consumer products, such as certain spices, ceramic and metal cookware, traditional health remedies, and cultural powders, are increasingly recognized as important sources of lead exposure across the United States. OBJECTIVE: This paper reviews data from four US jurisdictions that conduct in-home investigations for children with elevated blood lead levels (BLLs) to examine the prevalence of lead exposures associated with consumer products, in comparison with housing-related sources. METHODS: Authors reviewed investigation data (2010-2021) provided by California, Oregon, New York City, and King County, Washington, and compared the extent of lead exposures associated with housing-related vs. consumer products--related sources. DISCUSSION:The proportion of investigations identifying consumer products--related sources of lead exposure varied by jurisdiction (range: 15%-38%). A review of US CDC and US FDA alerts and New York City data indicates that these types of lead-containing products are often sourced internationally, with many hand carried into the United States during travel. Based on surveillance data, we believe that US immigrant and refugee communities are at an increased risk for lead exposures associated with these products. To engage health authorities, there is a need for evidentiary data. We recommend implementing a national product surveillance database systematically tracking data on consumer products tested by childhood lead poisoning prevention programs. The data repository should be centralized and accessible to all global stakeholders, including researchers and governmental and nongovernmental agencies, who can use these data to inform investigations. Effectively identifying and addressing the availability of lead-containing consumer products at their source can focus resources on primary prevention, reducing lead exposures for users abroad and in the United States. https://doi.org/10.1289/EHP14336, Introduction Blood lead levels (BLLs) of children in the United States have declined significantly since the 1970s. Based on the National Health and Nutrition Examination Survey (NHANES), there was a [...]

BACKGROUND: Evidence suggested that abiotic airborne exposures may be associated with changes in body composition. However, more evidence is needed to identify key pollutants linked to adverse health effects and their underlying biomolecular mechanisms, particularly in sensitive older adults. OBJECTIVES: Our research aimed to systematically assess the relationship between abiotic airborne exposures and changes in body composition among healthy older adults, as well as the potential mediating mechanisms through the serum lipidome. METHODS: From September 2018 to January 2019, we conducted a monthly survey among 76 healthy adults (60-69 years old) in the China Biomarkers of Air Pollutant Exposure (BAPE) study, measuring their personal exposures to 632 abiotic airborne pollutions using MicroPEM and the Fresh Air wristband, 18 body composition indicators from the InBody 770 device, and lipidomics from venous blood samples. We used an exposome-wide association study (ExWAS) and deletion/substitution/addition (DSA) model to unravel complex associations between exposure to contaminant mixtures and body composition, a Bayesian kernel machine regression (BKMR) model to assess the overall effect of key exposures on body composition, and mediation analysis to identify lipid intermediators. RESULTS: The ExWAS and DSA model identified that 2,4,5-T methyl ester (2,4,5-TME), 9,10-Anthracenedione (ATQ), 4b,8-dimethyl-2-isopropyl-phenanthrene, and 4b,5,6,7,8,8a,9,10-octahydro-(DMIP) were associated with increased body fat mass (BFM), fat mass indicators (FMI), percent body fat (PBF), and visceral fat area (VFA) in healthy older adults [Bonferroni-Hochberg false discovery rate ([FDR.sub.BH]) < 0.05]. The BKMR model demonstrated a positive correlation between contaminants (anthracene, ATQ, copaene, di-epi-a-cedrene, and DMIP) with VFA. Mediation analysis revealed that phosphatidylcholine [PC, PC(16:1e/18:1), PC(16:2e/18:0)] and sphingolipid [SM, SM(d18:2/24.1)] mediated a significant portion, ranging from 12.27% to 26.03% (p-value DISCUSSION: Based on the evidence from multiple model results, ATQ and DMIP were statistically significantly associated with the increased VFA levels of healthy older adults, potentially regulated through lipid intermediators. These findings may have important implications for identifying potentially harmful environmental chemicals and developing targeted strategies for the control and prevention of chronic diseases in the future, particularly as the global population is rapidly aging. https://doi.org/10.1289/EHP13865, Introduction The global population is currently undergoing a notable aging trend, primarily driven by declining fertility rates and increased life expectancy. (1) This demographic shift is evident as the number [...]

Introduction Research has shown that exposure to traffic-related air pollution (TRAP) can damage the respiratory mucosa by decreasing epithelial barrier function, exaggerating inflammatory responses at the mucosal surface, and impairing [...]

BACKGROUND: Increased exposure to ambient air pollution, especially fine particulate matter [less than or equal to]2.5 [micro]m ([PM.sub.2.5]) is associated with poorer brain health and increased risk for Alzheimer's disease (AD) and related dementias. The locus coeruleus (LC), located in the brainstem, is one of the earliest regions affected by tau pathology seen in AD. Its diffuse projections throughout the brain include afferents to olfactory areas that are hypothesized conduits of cerebral particle deposition. Additionally, extensive contact of the LC with the cerebrovascular system may present an additional route of exposure to environmental toxicants. OBJECTIVE: Our aim was to investigate if exposure to [PM.sub.2.5] was associated with LC integrity in a nationwide sample of men in early old age, potentially representing one pathway through which air pollution can contribute to increased risk for AD dementia. METHODS: We examined the relationship between [PM.sub.2.5] and in vivo magnetic resonance imaging (MRI) estimates of LC structural integrity indexed by contrast to noise ratio ([LC.sub.CNR]) in 381 men [mean age = 67.3; standard deviation (SD) = 2.6] from the Vietnam Era Twin Study of Aging (VETSA). Exposure to [PM.sub.2.5] was taken as a 3-year average over the most recent period for which data were available (average of 5.6 years prior to the MRI scan). We focused on [LC.sub.CNR] in the rostral-middle portion of LC due to its stronger associations with aging and AD than the caudal LC. Associations between [PM.sub.2.5] exposures and LC integrity were tested using linear mixed effects models adjusted for age, scanner, education, household income, and interval between exposure and MRI. A co-twin control analysis was also performed to investigate whether associations remained after controlling for genetic confounding and rearing environment. RESULTS: Multiple linear regressions revealed a significant association between [PM.sub.2.5] and rostral-middle [LC.sub.CNR] (b = -0.16; p = 0.02), whereby higher exposure to [PM.sub.2.5] was associated with lower [LC.sub.CNR]. A co-twin control analysis found that, within monozygotic pairs, individuals with higher [PM.sub.2.5] exposure showed lower [LC.sub.CNR] (b = - 0.11; p = 0.02), indicating associations were not driven by genetic or shared environmental confounds. There were no associations between [PM.sub.2.5] and caudal [LC.sub.CNR] or hippocampal volume, suggesting a degree of specificity to the rostral-middle portion of the LC. DISCUSSION: Given previous findings that loss of LC integrity is associated with increased accumulation of AD-related amyloid and tau pathology, impacts on LC integrity may represent a potential pathway through which exposure to air pollution increases AD risk. https://doi.org/10.1289/EHP14344, Introduction Neuropathological studies indicate that abnormal tau may first appear in the locus coeruleus (LC) starting early in life, (1,2) with substantial accumulation occurring during the course of Alzheimer's disease [...]

BACKGROUND: Microplastics are a pervasive contaminant cycling through food webs--leading to concerns regarding exposure and risk to humans. OBJECTIVES: We aimed to quantify and characterize anthropogenic particle contamination (including microplastics) in fish caught for human consumption from the Humber Bay region of Lake Ontario. We related quantities of anthropogenic particles to other factors (e.g., fish size) that may help in understanding accumulation of microplastics in fish. METHODS: A total of 45 samples of six fish species collected from Humber Bay in Lake Ontario near Toronto, Ontario, Canada, were examined for anthropogenic particles in their gastrointestinal (GI) tracts and fillets. Using microscopy and spectroscopy, suspected anthropogenic particles were identified and characterized. RESULTS: We observed anthropogenic particles in the GI tracts and fillets of all species. Individual fish had a mean[+ or -] standard deviation of 138 [+ or -] 231 anthropogenic particles, with a single fish containing up to 1,508 particles. GI tracts had 93 [+ or -] 226 particles/fish (9.8 [+ or -] 32.6 particles/gram), and fillets had 56 [+ or -] 61 particles/fish (0.5 [+ or -] 0.8 particles/gram). Based on a consumption rate of 2 servings/week, the average yearly human exposure through the consumption of these fish fillets would be 12,800 [+ or -] 18,300 particles. DISCUSSION: Our findings suggest that consumption of recreationally caught freshwater fish can be a pathway for human exposure to microplastics. The elevated number of particles observed in fish from Humber Bay highlights the need for large-scale geographic monitoring, especially near sources of microplastics. Currently, it is unclear what the effects of ingesting microplastics are for humans, but given that recreationally caught freshwater fish are one pathway for human exposure, these data can be incorporated into future human health risk assessment frameworks for microplastics. https://doi.org/10.1289/EHP13540, Introduction It has been well documented that microplastics, pieces of plastic 1 [micro]m-5 mm in size, are a pervasive contaminant in the environment globally. (1) More recently, scientists have demonstrated [...]

BACKGROUND: The National Institute of Environmental Health Sciences (NIEHS) continues to prioritize research to better understand the health effects resulting from exposure to mixtures of chemical and nonchemical stressors. Mixtures research activities over the last decade were informed by expert input during the development and deliberations of the 2011 NIEHS Workshop "Advancing Research on Mixtures: New Perspectives and Approaches for Predicting Adverse Human Health Effects." NIEHS mixtures research efforts since then have focused on key themes including a) prioritizing mixtures for study, b) translating mixtures data from in vitro and in vivo studies, c) developing cross-disciplinary collaborations, d) informing component-based and whole-mixture assessment approaches, e) developing sufficient similarity methods to compare across complex mixtures, f) using systems-based approaches to evaluate mixtures, and g) focusing on management and integration of mixtures-related data. OBJECTIVES: We aimed to describe NIEHS driven research on mixtures and combined exposures over the last decade and present areas for future attention. RESULTS: Intramural and extramural mixtures research projects have incorporated a diverse array of chemicals (e.g., polycyclic aromatic hydrocarbons, botanicals, personal care products, wildfire emissions) and nonchemical stressors (e.g., socioeconomic factors, social adversity) and have focused on many diseases (e.g., breast cancer, atherosclerosis, immune disruption). We have made significant progress in certain areas, such as developing statistical methods for evaluating multiple chemical associations in epidemiology and building translational mixtures projects that include both in vitro and in vivo models. DISCUSSION: Moving forward, additional work is needed to improve mixtures data integration, elucidate interactions between chemical and nonchemical stressors, and resolve the geospatial and temporal nature of mixture exposures. Continued mixtures research will be critical to informing cumulative impact assessments and addressing complex challenges, such as environmental justice and climate change. https://doi.org/10.1289/EHP14340, Introduction Biomonitoring programs (1-3) indicate that people experience diverse chemical exposures from their use of personal care and household products, diet, lifestyle choices, occupational exposures, and incidental contact with environmental [...]

BACKGROUND: Organophosphate esters (OPEs), used ubiquitously as flame retardants and plasticizers in consumer products, are suspected of having developmental toxicity. OBJECTIVES: Our study aimed to estimate associations between prenatal exposure to OPEs and fetal growth, including both ultrasound (head circumference, abdominal circumference, femur length, and estimated fetal weight) and delivery [birth weight z-score, small-for-gestational age (SGA), and large-for-gestational age (LGA)] measures of growth. METHODS: In the LIFECODES Fetal Growth Study (2008-2018), an enriched case--cohort of 900 babies born at the small and large ends of the growth spectrum, we quantified OPE biomarkers in three urine samples per pregnant participant and abstracted ultrasound and delivery measures of fetal growth from medical records. We estimated associations between pregnancy-averaged log-transformed OPE biomarkers and repeated ultrasound measures of fetal growth using linear mixed-effects models, and delivery measures of fetal growth using linear (birth weight) and logistic (SGA and LGA) regression models. RESULTS: Most OPE biomarkers were positively associated with at least one ultrasound measure of fetal growth, but associations with delivery measures were largely null. For example, an interquartile range (IQR; 1.31 ng=mL) increase in bis(2-chloroethyl) phosphate concentration was associated with larger z-scores in head circumference [mean difference (difference): 0.09; 95% confidence interval (CI): 0.01, 0.17], abdominal circumference (difference: 0.10; 95% CI: 0.02, 0.18), femur length (difference: 0.11; 95% CI: 0.03, 0.19), and estimated fetal weight (difference: 0.13; 95% CI: 0.04, 0.22) but not birth weight (difference: 0.04; 95% CI: -0.08, 0.17). At delivery, an IQR (1.00 ng=mL) increase in diphenyl phosphate (DPHP) concentration was associated with an SGA birth (odds ratio: 1.46; 95% CI: 1.10, 1.94). CONCLUSIONS: In a large prospective cohort, gestational OPE exposures were associated with larger fetal size during pregnancy, but associations at delivery were null. DPHP concentrations were associated with heightened risk of an SGA birth. These findings suggest that OPE exposure may affect fetal development. https://doi.org/10.1289/EHP14647, Introduction Organophosphate esters (OPEs) are high-production chemicals in widespread global use. (1) They are organic esters of phosphoric acid--containing alkyl chains or aryl groups, which may be halo-genated or nonhalogenated. [...]

BACKGROUND: Environmental contamination by fluorinated chemicals, in particular chemicals from the per- and polyfluoroalkyl substances (PFAS) class, has raised concerns around the globe because of documented adverse impacts on human health, wildlife, and ecosystem quality. Recent studies have indicated that pesticide products may contain a variety of chemicals that meet the PFAS definition, including the active pesticide ingredients themselves. Given that pesticides are some of the most widely distributed pollutants across the world, the legacy impacts of PFAS addition into pesticide products could be widespread and have wide-ranging implications on agriculture and food and water contamination, as well as the presence of PFAS in rural environments. OBJECTIVES: The purpose of this commentary is to explore different ways that PFAS can be introduced into pesticide products, the extent of PFAS contamination of pesticide products, and the implications this could have for human and environmental health. METHODS: We submitted multiple public records requests to state and federal agencies in the United States and Canada and extracted relevant data from those records. We also compiled data from publicly accessible databases for our analyses. DISCUSSION: We found that the biggest contributor to PFAS in pesticide products was active ingredients and their degradates. Nearly a quarter of all US conventional pesticide active ingredients were organofluorines and 14% were PFAS, and for active ingredients approved in the last 10 y, this had increased to 61% organofluorines and 30% PFAS. Another major contributing source was through PFAS leaching from fluorinated containers into pesticide products. Fluorination of adjuvant products and "inert" ingredients appeared to be limited, although this represents a major knowledge gap. We explored aspects of immunotoxicity, persistence, water contamination, and total fluorine load in the environment and conclude that the recent trend of using fluorinated active ingredients in pesticides may be having effects on chemical toxicity and persistence that are not given adequate oversight in the United States. We recommend a more stringent risk assessment approach for fluorinated pesticides, transparent disclosure of "inert" ingredients on pesticide labels, a complete phase-out of post-mold fluorination of plastic containers, and greater monitoring in the United States. https://doi.org/10.1289/EHP13954, Introduction Pesticides are commonly used in the United States and around the world to kill or suppress certain organisms on farmland and in areas where people live and work. Although [...]

BACKGROUND: Parametric g-computation is an attractive analytic framework to study the health effects of air pollution. Yet, the ability to explore biologically relevant exposure windows within this framework is underdeveloped. OBJECTIVES: We outline a novel framework for how to incorporate complex lag-responses using distributed lag models (DLMs) into parametric g-computation analyses for survival data. We call this approach "g-survival-DLM" and illustrate its use examining the association between [PM.sub.2.5] during pregnancy and the risk of preterm birth (PTB). METHODS: We applied the g-survival-DLM approach to estimate the hypothetical static intervention of reducing average [PM.sub.2.5] in each gestational week by 20% on the risk of PTB among 9,403 deliveries from Beth Israel Deaconess Medical Center, Boston, Massachusetts, 2011-2016. Daily [PM.sub.2.5] was taken from a 1-km grid model and assigned to address at birth. Models were adjusted for sociodemographics, time trends, nitrogen dioxide, and temperature. To facilitate implementation, we provide a detailed description of the procedure and accompanying R syntax. RESULTS: There were 762 (8.1%) PTBs in this cohort. The gestational week-specific median [PM.sub.2.5] concentration was relatively stable across pregnancy at ~7[micro]g/[m.sup.3]. We found that our hypothetical intervention strategy changed the cumulative risk of PTB at week 36 (i.e., the end of the preterm period) by -0.009 (95% confidence interval: -0.034, 0.007) in comparison with the scenario had we not intervened, which translates to about 86 fewer PTBs in this cohort. We also observed that the critical exposure window appeared to be weeks 5-20. DISCUSSION: We demonstrate that our g-survival-DLM approach produces easier-to-interpret, policy-relevant estimates (due to the g-computation); prevents immortal time bias (due to treating PTB as a time-to-event outcome); and allows for the exploration of critical exposure windows (due to the DLMs). In our illustrative example, we found that reducing fine particulate matter [particulate matter (PM) with aerodynamic diameter, Introduction Pregnant individuals and their fetuses are particularly susceptible to environmental pollutants. (1) Yet, identifying whether environmental exposures cause preterm birth (PTB)--for which the long-term sequelae have been well established [...]

Rocky Mountain spotted fever (RMSF), a tickbome disease caused by Rickettsia rickettsii, is the leading cause of death from rickettsial infections in the Western Hemisphere (1). The disease can progress [...]

Syphilis transmission remains a public health challenge; [approximately equal to]7.1 million new cases were reported in 2020 (2). Despite its relatively low incidence, if left untreated, syphilis results in substantial [...]

Spotted fever rickettsiosis in solid organ transplant recipients is rarely described, and all reports document disease acquired months to years after the transplant, after recognized tick bites or exposures to [...]

Orthohantavirus is a genus of globally distributed RNA viruses in the family Hantaviridae. In the Americas, the viruses are hosted by native rodent species within the Cricetidae family (2). Although [...]

Scrub typhus is a leading cause of nonmalarial febrile illness in Southeast Asia (1). Scrub typhus is caused by miteborne Orentia tsutsugamushi infections, which until recently were thought to be [...]

In 2020, Canada's largest cluster of Bartonella quintana endocarditis, an infection caused by a louseborne bacterium, was detected among persons experiencing homelessness in Winnipeg, Manitoba, Canada (1). Over a 6-month [...]

Biting midge-borne bluetongue virus (BTV), an Orbivirus of the Sedoreoviridae family, can cause epizootic disease in domestic and wild ruminants (2). Bluetongue (BT) is a World Organisation for Animal Health-listed [...]

Since the arrival of clade 2.3.4.4b avian influenza A(H5N1) in North America in late 2021, frequent mammal spillover events have occurred in a diverse range of species, including 1 human [...]

The novel tickborne virus Alongshan virus (ALSV) belongs to the Jingmenvirus group of the Flaviviridae family and is associated with human febrile illness (2). Initially identified in tick-bitten patients and [...]

BA.2 is a subvariant of the SARS-CoV-2 Omicron variant. XBB.1.5 and XBB.1.16, recombinants of the BA.2.10.1 and BA.2.75 sublineages, were circulating SARS-CoV-2 variants of interest in July 2023 (1,2), but [...]

Three classes of direct-acting antivirals targeting the influenza virus matrix protein 2 (M2) ion channel, neuraminidase (NA), or polymerase cap-dependent endonuclease (CEN) are approved to treat influenza in many countries [...]

Mpox is caused by infection with monkeypox vi rus (MPXV). Phylogenomically and clinically, clades I and II can be distinguished; clade II has 2 subcodes, Ha and IIb (1). In [...]

Tuberculosis (TB) remains a major public health challenge and the most frequent cause of illness and death among persons living with HIV (PLHIV) (1). Globally, TB occurs in congregate settings [...]

COVID-19 has caused a significant global disease burden since it was first identified in December 2019; as of May 2024, [greater than or equal to]750 million cases had been confirmed, [...]

Highly pathogenic avian influenza (HPAI) viruses pose a threat to wild birds and poultry globally, and HPAI H5N1 viruses are of even greater concern because of their frequent spillover into [...]

The recent discovery that dairy cattle can be infected by highly pathogenic avian influenza (HPAI) virus of the H5N1 subtype (2,2), in combination with the virus's propensity to replicate in [...]

The COVID-19 pandemic demonstrated the influence community attitudes have on the health behaviors of its residents (e.g., wearing facemasks, accepting vaccines). Evidence on COVID-19 spread indicates that within-community contexts affect [...]

" ... could not avoid a spasm of horror at the sight of men with ruptures sitting in their doorways on hot afternoons, fanning their enormous testicle as if it [...]

Lyme disease, caused by infection with the bacterium Borrelia burgdorferi, is the most common vectorborne illness in the United States and is steadily affecting an expanding area of the country [...]

Globally, the COVID-19 pandemic resulted in >650 million infections and 6.5 million deaths during March 2020-December 2022 (2,2). Uganda recorded its first case of SARS-CoV-2 infection on March 21, 2020; [...]

Rickettsioses are undifferentiated febrile illnesses, often accompanied by myalgia and rash, that are caused by intracellular gram-negative bacteria of the genus Rickettsia. Spotted fever group (SFG) Rickettsia are transmitted through [...]

Crimean-Congo hemorrhagic fever (CCHF) is caused by a tickborne virus belonging to the genus Nairovirus within the family Bunyaviridae. The disease was first observed among military personnel from the former [...]