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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' 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: 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 [...]

BACKGROUND: Accumulating evidence suggests that domestic water hardness is linked to health outcomes, but its association to all-cause and cause-specific cancers warrants investigation. OBJECTIVE: The aim of this study was to investigate the association of domestic hard water with all-cause and cause-specific cancers. METHODS: In the prospective cohort study, a total of 447,996 participants from UK Biobank who were free of cancer at baseline were included and followed up for 16 y. All-cause and 22 common cause-specific cancer diagnoses were ascertained using hospital inpatient records and self-reported data until 30 November 2022. Domestic water hardness, measured by CaC[O.sub.3] concentrations, was obtained from the local water supply companies across England, Scotland, and Wales in 2005. Data were analyzed using Cox proportional hazard models, with adjustments for known measured confounders, including demographic, socioeconomic, clinical, biochemical, lifestyle, and environmental factors. RESULTS: Over a median follow-up of 13.6 y (range: 12.7-14.4 y), 58,028 all-cause cancer events were documented. A U-shaped relationship between domestic water hardness and all-cause cancers was observed (p for nonlinearity 60-120 mg/L), 0.88 (95% CI: 0.84, 0.91) for those exposed to hard water (>120-180 mg/L) and 1.06 (95% CI: 1.04, 1.08) for those exposed to very hard water (>180 mg/L). Additionally, domestic water hardness was associated with 11 of 22 cause-specific cancers, including cancers of the esophagus, stomach, colorectal tract, lung, breast, prostate, and bladder, as well as non-Hodgkin lymphoma, multiple myeloma, malignant melanoma, and hematological malignancies. Moreover, we observed a positive linear relationship between water hardness and bladder cancer. DISCUSSION: Our findings suggest that domestic water hardness was associated with all-cause and multiple cause-specific cancers. Findings from the UK Biobank support a potentially beneficial association between hard water and the incidence of all-cause cancer. However, very hard water may increase the risk of all-cause cancer. https://doi.org/10.1289/EHP13606, Introduction Cancer is a leading cause of mortality worldwide in 2020, nearly 10 million deaths were due to cancer, accounting for approximately one-sixth of all deaths. (1-3) It is projected [...]

BACKGROUND: Overweight and obesity impose a considerable individual and social burden, and the urban environments might encompass factors that contribute to obesity. Nevertheless, there is a scarcity of research that takes into account the simultaneous interaction of multiple environmental factors. OBJECTIVES: Our objective was to perform an exposome-wide association study of body mass index (BMI) in a multicohort setting of 15 studies. METHODS: Studies were affiliated with the Dutch Geoscience and Health Cohort Consortium (GECCO), had different population sizes (688-141,825), and covered the entire Netherlands. Ten studies contained general population samples, others focused on specific populations including people with diabetes or impaired hearing. BMI was calculated from self-reported or measured height and weight. Associations with 69 residential neighborhood environmental factors (air pollution, noise, temperature, neighborhood socioeconomic and demographic factors, food environment, drivability, and walkability) were explored. Random forest (RF) regression addressed potential nonlinear and nonadditive associations. In the absence of formal methods for multimodel inference for RF, a rank aggregation-based meta-analytic strategy was used to summarize the results across the studies. RESULTS: Six exposures were associated with BMI: five indicating neighborhood economic or social environments (average home values, percentage of high-income residents, average income, livability score, share of single residents) and one indicating the physical activity environment (walkability in 5-km buffer area). Living in high-income neighborhoods and neighborhoods with higher livability scores was associated with lower BMI. Nonlinear associations were observed with neighborhood home values in all studies. Lower neighborhood home values were associated with higher BMI scores but only for values up to [euro]300,000. The directions of associations were less consistent for walkability and share of single residents. DISCUSSION: Rank aggregation made it possible to flexibly combine the results from various studies, although between-study heterogeneity could not be estimated quantitatively based on RF models. Neighborhood social, economic, and physical environments had the strongest associations with BMI. https://doi.org/10.1289/EHP13393, Introduction Overweight and obesity impose a considerable individual and social burden, with global rates that have nearly tripled since 1975. (1) This striking rise could be attributed to changes in [...]

BACKGROUND: Maternal cigarette smoking during pregnancy (MSDP) is associated with numerous adverse health outcomes in infants and children with potential lifelong consequences. Negative effects of MSDP on placental DNA methylation (DNAm), placental structure, and function are well established. OBJECTIVE: Our aim was to develop biomarkers of MSDP using DNAm measured in placentas (N =96), collected as part of the Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function double-blind, placebo-controlled randomized clinical trial conducted between 2012 and 2016. We also aimed to develop a digital polymerase chain reaction (PCR) assay for the top ranking cytosine--guanine dinucleotide (CpG) so that large numbers of samples can be screened for exposure at low cost. METHODS: We compared the ability of four machine learning methods [logistic least absolute shrinkage and selection operator (LASSO) regression, logistic elastic net regression, random forest, and gradient boosting machine] to classify MSDP based on placental DNAm signatures. We developed separate models using the complete EPIC array dataset and on the subset of probes also found on the 450K array so that models exist for both platforms. For comparison, we developed a model using CpGs previously associated with MSDP in placenta. For each final model, we used model coefficients and normalized beta values to calculate placental smoking index (PSI) scores for each sample. Final models were validated in two external datasets: the Extremely Low Gestational Age Newborn observational study, N = 426; and the Rhode Island Children's Health Study, N = 237. RESULTS: Logistic LASSO regression demonstrated the highest performance in cross-validation testing with the lowest number of input CpGs. Accuracy was greatest in external datasets when using models developed for the same platform. PSI scores in smokers only (n = 72) were moderately correlated with maternal plasma cotinine levels. One CpG (cg27402634), with the largest coefficient in two models, was measured accurately by digital PCR compared with measurement by EPIC array ([R.sup.2] = 0.98). DISCUSSION: To our knowledge, we have developed the first placental DNAm-based biomarkers of MSDP with broad utility to studies of prenatal disease origins. https://doi.org/10.1289/EHP13838, Introduction Maternal cigarette smoking during pregnancy (MSDP) is associated with increased risk of low birth weight, prematurity, and perinatal mortality. (1-4) MSDP is also associated with greater risk of cardiovascular, [...]

BACKGROUND: Evidence linking gaseous air pollution to late-life brain health is mixed. OBJECTIVE: We explored associations between exposure to gaseous pollutants and brain magnetic resonance imaging (MRI) markers among Atherosclerosis Risk in Communities (ARIC) Study participants, with attention to the influence of exposure estimation method and confounding by site. METHODS: We considered data from 1,665 eligible ARIC participants recruited from four US sites in the period 1987-1989 with valid brain MRI data from Visit 5 (2011-2013). We estimated 10-y (2001-2010) mean carbon monoxide (CO), nitrogen dioxide (N[O.sub.2]), nitrogen oxides (N[O.sub.x]), and 8-and 24-h ozone ([O.sub.3]) concentrations at participant addresses, using multiple exposure estimation methods. We estimated site-specific associations between pollutant exposures and brain MRI outcomes (total and regional volumes; presence of microhemorrhages, infarcts, lacunes, and severe white matter hyperintensities), using adjusted linear and logistic regression models. We compared meta-analytically combined site-specific associations to analyses that did not account for site. RESULTS: Within-site exposure distributions varied across exposure estimation methods. Meta-analytic associations were generally not statistically significant regardless of exposure, outcome, or exposure estimation method; point estimates often suggested associations between higher N[O.sub.2] and N[O.sub.x] and smaller temporal lobe, deep gray, hippocampal, frontal lobe, and Alzheimer disease signature region of interest volumes and between higher CO and smaller temporal and frontal lobe volumes. Analyses that did not account for study site more often yielded significant associations and sometimes different direction of associations. DISCUSSION: Patterns of local variation in estimated air pollution concentrations differ by estimation method. Although we did not find strong evidence supporting impact of gaseous pollutants on brain changes detectable by MRI, point estimates suggested associations between higher exposure to CO, N[O.sub.x], and N[O.sub.2] and smaller regional brain volumes. Analyses of air pollution and dementia-related outcomes that do not adjust for location likely underestimate uncertainty and may be susceptible to confounding bias. https://doi.org/10.1289/EHP13906, Introduction Growing evidence links air pollution to late-life cognitive health. Currently, the strongest evidence supports an effect of particulate matter (PM) air pollution. (1) In comparison with PM, fewer studies [...]

BACKGROUND: Cadmium (Cd) is a highly toxic and widespread environmental oxidative stressor that causes a myriad of health problems, including osteoporosis and bone damage. Although nuclear factor erythroid 2-related factor 2 (NRF2) and its Cap 'n' Collar and basic region Leucine Zipper (CNC-bZIP) family member nuclear factor erythroid 2-related factor 1 (NRF1) coordinate various stress responses by regulating the transcription of a variety of antioxidant and cytoprotective genes, they play distinct roles in bone metabolism and remodeling. However, the precise roles of both transcription factors in bone loss induced by prolonged Cd exposure remain unclear. OBJECTIVES: We aimed to understand the molecular mechanisms underlying Cd-induced bone loss, focusing mainly on the roles of NRF2 and NRF1 in osteoclastogenesis provoked by Cd. METHODS: Male wild-type (WT), global Nrf2-knockout (Nrf[2.sup.-/-]) and myeloid-specific Nrf2 knockout [Nrf2(M)-KO] mice were administered Cd (50 or 100 ppm) via drinking water for 8 or 16 wk, followed by micro-computed tomography, histological analyses, and plasma biochemical testing. Osteoclastogenesis was evaluated using bone marrow-derived osteoclast progenitor cells (BM-OPCs) and RAW 264.7 cells in the presence of Cd (10 or 20 nM) with a combination of genetic and chemical modulations targeting NRF2 and NRF1. RESULTS: Compared with relevant control mice, global Nrf[2.sup.-/-] or Nrf2(M)-KO mice showed exacerbated bone loss and augmented osteoclast activity following exposure to 100ppm Cd in drinking water for up to 16 wk. In vitro osteoclastogenic analyses suggested that Nrf2-deficient BM-OPCs and RAW 264.7 cells responded more robustly to low levels of Cd (up to 20 nM) with regard to osteoclast differentiation compared with WT cells. Further mechanistic studies supported a compensatory up-regulation of long isoform of NRF1 (L-NRF1) and subsequent induction of nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 1 (NFATc1) as the key molecular events in the Nrf2 deficiency-worsened and Cd-provoked osteoclastogenesis. L-Nrf1 silenced (via lentiviral means) Nrf2-knockdown (KD) RAW cells exposed to Cd showed dramatically different NFATc1 and subsequent osteoclastogenesis outcomes compared with the cells of Nrf2-KD alone exposed to Cd, suggesting a mitigating effect of the Nrf1 silencing. In addition, suppression of reactive oxygen species by exogenous antioxidants N-acetyl-L-cysteine (2mM) and mitoquinone mesylate (MitoQ; 0.2 [micro]M) mitigated the L-NRF1-associated effects on NFATc1-driven osteoclastogenesis outcomes in Cd-exposed Nrf2-KD cells. CONCLUSIONS: This in vivo and in vitro study supported the authors' hypothesis that Cd exposure caused bone loss, in which NRF2 and L-NRF1 responded to Cd and osteoclastogenic stimuli in a cooperative, but contradictive, manner to coordinate Nfatc1 expression, osteoclastogenesis and thus bone homeostasis. Our study suggests a novel strategy targeting NRF2 and L-NRF1 to prevent and treat the bone toxicity of Cd. https://doi.org/10.1289/EHP13849, Introduction Cadmium (Cd), a nonessential heavy metal, is considered as one of the most toxic environmental and occupational hazards. (1) Human long-term exposure to Cd, which occurs mainly from consumption [...]

BACKGROUND: The potential health benefits of exposure to vegetation, or greenness, are well documented, but there are few nationwide studies in Brazil, a country facing challenges related to land-use planning, deforestation, and environmental health risks. OBJECTIVES: In this study, we investigated the association between greenness and hospitalizations for cardiorespiratory diseases in Brazil. METHODS: We accessed hospital admissions data from 967,771 postal codes (a total of 26,724,624 admissions) covering Brazil for the period between 2008 and 2018. We used Normalized Difference Vegetation Index (NDVI) data from the Moderate Resolution Imaging Spectroradiometer (MODIS) to measure greenness at the postal-code level. First, we applied a quasi-Poisson regression model to estimate the association between greenness and hospitalizations for circulatory and respiratory diseases, adjusted for air pollution, weather variables, and area-level socioeconomic status. We stratified the analyzes by sex, age group, health outcome, and Brazilian regions. In the second stage, we performed a meta-analysis to estimate pooled effects across the Brazilian regions. RESULTS: The national meta-analysis for the whole population, incorporating both urban and nonurban areas, showed that higher levels of greenness were associated with a lower risk of hospitalizations for circulatory diseases. An interquartile range (IQR = 0:18) increase in average NDVI was associated with a 17% (95% confidence interval: 8%, 27%) lower risk of cardiovascular admissions. In contrast, there was no association found between greenness and respiratory admissions. When specifically examining urban areas, the results remained consistent with the overall findings. However, the analyses of nonurban areas revealed divergent results, suggesting that higher levels of greenness in rural regions are associated with a lower risk of hospital admissions for both circulatory and respiratory diseases. DISCUSSION: The findings emphasize the importance of prioritizing the preservation and creation of green spaces in urban areas as a means of promoting cardiovascular health in Brazil. https://doi.org/10.1289/EHP13442, Introduction Cardiovascular and respiratory diseases are the leading causes of morbidity and mortality worldwide. (1) In Brazil, these diseases are responsible for a significant number of hospital admissions and deaths. [...]

SARS-CoV-2 is characterized by diverse variants (1) with differing transmissibility and disease severity (2). The rapid evolution and spread of new variants has required a nimble public health response to [...]

Extreme heat contributes to 8000-12 000 excess U.S. deaths per year. Partly due to increasing summer temperatures and a renewed focus on environmental justice, local governments started new initiatives to manage and adapt to extreme heat. For example, Miami-Dade County, Florida, United States, appointed Jane Gilbert as the world's first Chief Heat Officer. This manuscript summarizes Miami-Dade County's preliminary efforts to build local evidence, engage the community, and rapidly respond to extreme heat. The manuscript's goal is to expedite the translation of existing tools into mainstream extreme heat, health, and equity planning. The study generated local evidence to identify the places and periods of time with elevated heat-related illness using a statistical vulnerability and time series analysis, respectively. The places with the highest severe heat-related illness rates had hotter land surface temperatures and/or higher proportions of people who were outdoor workers, Indigenous, living in poverty or mobile homes, and households with children. "Everyday" summer conditions instead of rare heatwaves increase the risk of a heat-related death. The Chief Heat Officer convened workshops that engaged 298 unique community members on six cross-sectoral heat topics. Key recommendations included increasing multisectoral heat monitoring and risk communication, building more affordable housing, preserving and expanding greenspace, and creating heat resilience hubs. The activities culminated in a Heat Action Plan, which was completed in less than two years from the receipt of project funding. SIGNIFICANCE STATEMENT: Extreme heat is a contributing factor to more U.S. deaths per year than any other weather hazard. This manuscript summarizes the world's first Chief Heat Officer's efforts to build local heat and health evidence. The places with the highest heat-related illness rates had hotter surface temperatures and/or higher proportions of people who were outdoor workers, Indigenous, and living in poverty or mobile homes. On hot and humid days, 7.8% (603 deaths) of the summer deaths per year were associated with the concurrent and preceding day's heat exposures. In response, Miami-Dade County is targeting heat interventions, lowering heat advisory thresholds, and considering new heat safety laws. KEYWORDS: Adaptation; Health; Heat islands; Societal impacts; Vulnerability, 1. Introduction Over 2002-20, an increasing proportion of jurisdictions considered extreme heat in their planning activities (Bernard and McGeehin 2004; Meerow and Keith 2021). In Miami-Dade County, Florida, United States [...]

BACKGROUND: In response to the COVID-19 pandemic, new evidence-based strategies have emerged for reducing transmission of respiratory infections through management of indoor air. OBJECTIVES: This paper reviews critical advances that could reduce the burden of disease from inhaled pathogens and describes challenges in their implementation. DISCUSSION: Proven strategies include assuring sufficient ventilation, air cleaning by filtration, and air disinfection by germicidal ultraviolet (UV) light. Layered intervention strategies are needed to maximize risk reduction. Case studies demonstrate how to implement these tools while also revealing barriers to implementation. Future needs include standards designed with infection resilience and equity in mind, buildings optimized for infection resilience among other drivers, new approaches and technologies to improve ventilation, scientific consensus on the amount of ventilation needed to achieve a desired level of risk, methods for evaluating new air-cleaning technologies, studies of their long-term health effects, workforce training on ventilation systems, easier access to federal funds, demonstration projects in schools, and communication with the public about the importance of indoor air quality and actions people can take to improve it. https://doi.org/10.1289/EHP13878, Introduction The status of the Coronavirus disease (COVID-19) pandemic as a public health emergency ended in May 2023, more than 3 y after the first cases were reported in Wuhan, [...]

BACKGROUND: More frequent and intense exposure to extreme heat conditions poses a serious threat to public health. However, evidence on the association between heat and specific diagnoses of morbidity is still limited. We aimed to comprehensively assess the short-term association between cause-specific hospital admissions and high temperature, including the added effect of temperature variability and heat waves and the effect modification by humidity and air pollution. METHODS: We used data on cause-specific hospital admissions, weather (i.e., temperature and relative humidity), and air pollution [i.e., fine particulate matter with aerodynamic diameter [less than or equal to]2.5 [micro]m ([PM.sub.2.5]), fine particulate matter with aerodynamic diameter [less than or equal to]10 [micro]m ([PM.sub.10]), N[O.sub.2], and ozone ([O.sub.3])] for 48 provinces in mainland Spain and the Balearic Islands between 1 January 2006 and 31 December 2019. The statistical analysis was performed for the summer season (June-September) and consisted of two steps. We first applied quasi-Poisson generalized linear regression models in combination with distributed lag nonlinear models (DLNM) to estimate province-specific temperature--morbidity associations, which were then pooled through multilevel univariate/multivariate random-effect meta-analysis. RESULTS: High temperature had a generalized impact on cause-specific hospitalizations, while the added effect of temperature variability [i.e., diurnal temperature range (DTR)] and heat waves was limited to a reduced number of diagnoses. The strongest impact of heat was observed for metabolic disorders and obesity [relative risk (RR) = 1.978; 95% empirical confidence interval (eCI): 1.772, 2.208], followed by renal failure (1.777; 95% eCI: 1.629, 1.939), urinary tract infection (1.746; 95% eCI: 1.578, 1.933), sepsis (1.543; 95% eCI: 1.387, 1.718), urolithiasis (1.490; 95% eCI: 1.338, 1.658), and poisoning by drugs and nonmedicinal substances (1.470; 95% eCI: 1.298, 1.665). We also found differences by sex (depending on the diagnosis of hospitalization) and age (very young children and the elderly were more at risk). Humidity played a role in the association of heat with hospitalizations from acute bronchitis and bronchiolitis and diseases of the muscular system and connective tissue, which were higher in dry days. Moreover, heat-related effects were exacerbated on high pollution days for metabolic disorders and obesity ([PM.sub.2.5]) and diabetes ([PM.sub.10], [O.sub.3]). DISCUSSION: Short-term exposure to heat was found to be associated with new diagnoses (e.g., metabolic diseases and obesity, blood diseases, acute bronchitis and bronchiolitis, muscular and connective tissue diseases, poisoning by drugs and nonmedicinal substances, complications of surgical and medical care, and symptoms, signs, and ill-defined conditions) and previously identified diagnoses of hospital admissions. The characterization of the vulnerability to heat can help improve clinical and public health practices to reduce the health risks posed by a warming planet. https://doi.org/10.1289/EHP13254, Introduction Climate change is increasing the frequency and intensity of exposure to extreme heat conditions, which poses a serious threat to public health globally. (1) In some high-income regions such [...]