Cutting Edge: T Cell Responses to B.1.1.529 (Omicron) SARS-CoV-2 Variant Induced by COVID-19 Infection and/or mRNA Vaccination Are Largely Preserved.

Several studies have demonstrated that the SARS-CoV-2 variant-of-concern B.1.1.529 (Omicron) exhibits a high degree of escape from Ab neutralization. Therefore, it is critical to determine how well the second line of adaptive immunity, T cell memory, performs against Omicron. To this purpose, we analyzed a human cohort (n = 327 subjects) of two- or three-dose mRNA vaccine recipients and COVID-19 postinfection subjects. We report that T cell responses against Omicron were largely preserved. IFN-γ-producing T cell responses remained equivalent to the response against the ancestral strain (WA1/2020), with some (∼20%) loss in IL-2 single or IL-2+IFN-γ+ polyfunctional responses. Three-dose vaccinated participants had similar responses to Omicron relative to post-COVID-19 participants and exhibited responses significantly higher than those receiving two mRNA vaccine doses. These results provide further evidence that a three-dose vaccine regimen benefits the induction of optimal functional T cell immune memory.

Serum per- and polyfluoroalkyl substance concentrations in four municipal US fire departments.

BACKGROUND: Firefighters have occupational and environmental exposures to per- and polyfluoroalkyl substances (PFAS). The goal of this study was to compare serum PFAS concentrations across multiple United States fire departments to National Health and Nutrition Examination Survey (NHANES) participants. METHODS: Nine serum PFAS were compared in 290 firefighters from four municipal fire departments (coded A-D) and three NHANES participants matched to each firefighter on sex, ethnicity, age, and PFAS collection year. Only Departments A and C had sufficient women study participants (25 and six, respectively) to compare with NHANES. RESULTS: In male firefighters compared with NHANES, geometric mean perfluorohexane sulfonate (PFHxS) was elevated in Departments A-C, sum of branched perfluoromethylheptane sulfonate isomers (Sm-PFOS) was elevated in all four departments, linear perfluorooctane sulfonate (n-PFOS) was elevated in Departments B and C, linear perfluorooctanoate (n-PFOA) was elevated in Departments B-D, and perfluorononanoate (PFNA) was elevated in Departments B-D, but lower in A. In male firefighters compared with NHANES, perfluoroundecanoate (PFUnDA) was more frequently detected in Departments B and D, and 2-(N-methyl-perfluorooctane sulfonamido) acetate (MeFOSAA) was less frequently detected in Departments B-D. In female firefighters compared with NHANES, PFHxS and Sm-PFOS concentrations were elevated in Departments A and C. Other PFAS concentrations were elevated and/or reduced in only one department or not significantly different from NHANES in any department. CONCLUSIONS: Serum PFHxS, Sm-PFOS, n-PFOS, n-PFOA, and PFNA concentrations were increased in at least two of four fire departments in comparison to NHANES.

Neutralizing Antibody Response to Pseudotype Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Differs Between mRNA-1273 and BNT162b2 Coronavirus Disease 2019 (COVID-19) Vaccines and by History of SARS-CoV-2 Infection.

BACKGROUND: Data on the development of neutralizing antibodies (nAbs) against SARS-CoV-2 after SARS-CoV-2 infection and after vaccination with mRNA COVID-19 vaccines are limited. METHODS: From a prospective cohort of 3975 adult essential and frontline workers tested weekly from August 2020 to March 2021 for SARS-CoV-2 infection by reverse transcription-polymerase chain reaction assay irrespective of symptoms, 497 participants had sera drawn after infection (170), vaccination (327), and after both infection and vaccination (50 from the infection population). Serum was collected after infection and each vaccine dose. Serum-neutralizing antibody titers against USA-WA1/2020-spike pseudotype virus were determined by the 50% inhibitory dilution. Geometric mean titers (GMTs) and corresponding fold increases were calculated using t tests and linear mixed-effects models. RESULTS: Among 170 unvaccinated participants with SARS-CoV-2 infection, 158 (93%) developed nAbs with a GMT of 1003 (95% confidence interval, 766-1315). Among 139 previously uninfected participants, 138 (99%) developed nAbs after mRNA vaccine dose 2 with a GMT of 3257 (2596-4052). GMT was higher among those receiving mRNA-1273 vaccine (GMT, 4698; 3186-6926) compared with BNT162b2 vaccine (GMT, 2309; 1825-2919). Among 32 participants with prior SARS-CoV-2 infection, GMT was 21 655 (14 766-31 756) after mRNA vaccine dose 1, without further increase after dose 2. CONCLUSIONS: A single dose of mRNA vaccine after SARS-CoV-2 infection resulted in the highest observed nAb response. Two doses of mRNA vaccine in previously uninfected participants resulted in higher nAbs to SARS-CoV-2 than after 1 dose of vaccine or SARS-CoV-2 infection alone. nAb response also differed by mRNA vaccine product.

Linking Oxidative Stress and Magnitude of Compensatory Responses with Life-Stage Specific Differences in Sensitivity of White Sturgeon (Acipenser transmontanus) to Copper or Cadmium.

Sensitivity of white sturgeon (Acipenser transmontanus) to copper (Cu) or cadmium (Cd) has been shown to significantly differ as a function of life-stage. This study investigated oxidative stress, metal homeostasis, and associated compensatory responses as potential mechanisms of this sensitivity pattern in three early life-stages. Sturgeon were most sensitive to Cu at 15 days post hatch (dph), which was accompanied by a significant increase in lipid peroxidation (LPO). Genes involved with amelioration of oxidative stress were significantly less inducible at this stage than in older, less sensitive fry. At 48 dph, acute lethality of sturgeon exposed to Cd was greatest and body LPO was significantly induced by 3.5-fold at 5 µg Cd/L. Moreover, there was a small but significant increase in antioxidative responses. At 139 dph, sturgeon were most tolerant to Cu and Cd and accumulation of these metals was least. Also, expression of metallothionein (MT) and apoptotic genes were greatest while expression of metal transporters was reduced and concentration of LPO was not different from controls. Our results suggest that life-stage specific sensitivity of white sturgeon to metals is complex, encompassing differences in the ability to mount compensatory responses important for metal homeostasis and combating oxidative stress and concomitant damages.

Differences in activation of aryl hydrocarbon receptors of white sturgeon relative to lake sturgeon are predicted by identities of key amino acids in the ligand binding domain.

Dioxin-like compounds (DLCs) are pollutants of global environmental concern. DLCs elicit their adverse outcomes through activation of the aryl hydrocarbon receptor (AhR). However, there is limited understanding of the mechanisms that result in differences in sensitivity to DLCs among different species of fishes. Understanding these mechanisms is critical for protection of the diversity of fishes exposed to DLCs, including endangered species. This study investigated specific mechanisms that drive responses of two endangered fishes, white sturgeon (Acipenser transmontanus) and lake sturgeon (Acipenser fulvescens) to DLCs. It determined whether differences in sensitivity to activation of AhRs (AhR1 and AhR2) can be predicted based on identities of key amino acids in the ligand binding domain (LBD). White sturgeon were 3- to 30-fold more sensitive than lake sturgeon to exposure to 5 different DLCs based on activation of AhR2. There were no differences in sensitivity between white sturgeon and lake sturgeon based on activation of AhR1. Adverse outcomes as a result of exposure to DLCs have been shown to be mediated through activation of AhR2, but not AhR1, in all fishes studied to date. This indicates that white sturgeon are likely to have greater sensitivity in vivo relative to lake sturgeon. Homology modeling and in silico mutagenesis suggests that differences in sensitivity to activation of AhR2 result from differences in key amino acids at position 388 in the LBD of AhR2 of white sturgeon (Ala-388) and lake sturgeon (Thr-388). This indicates that identities of key amino acids in the LBD of AhR2 could be predictive of both in vitro activation by DLCs and in vivo sensitivity to DLCs in these, and potentially other, fishes.

Impact of Predator Cues on Responses to Silver Nanoparticles in Daphnia carinata.

The past decades have witnessed a boom in nanotechnology that has led to increasing production and application of silver nanoparticles (AgNPs) in the textile industry due to their antimicrobial properties. Increase in the manufacture and use of NPs inevitably has resulted in their increased release into aquatic environments resulting in the exposure of organisms living in these environments. Recently, the risk of exposure to NPs and the potential interaction with biological systems has received increasing attention. The present study investigated the potential effects of predator cues on the toxicity of environmentally relevant concentrations of AgNPs in Daphnia carinata at organismal and biochemical levels. The results of this study show that exposure to environmentally relevant concentrations of AgNPs can result in adverse effects on daphnids with 24- and 48-h LC50 values of 3.56 and 1.75 µg/L, respectively. Furthermore, significant inhibition of reproduction was observed at concentrations as low as 0.5 µg/L. Exposure to predator cues alone resulted in an increase in reproduction and inhibition of superoxide dismutase activity in daphnids. However, coexposure to predator cues interacted in an antagonistic manner with AgNPs with a 24-h LC50 value of 10.81 µg/L compared with 3.56 µg/L for AgNPs alone. In summary, AgNPs could pose risks to aquatic invertebrates at environmentally relevant concentrations. Interestingly, the presence of other factors, such as predator cues, moderated the effects of exposure to AgNPs. Therefore, there is a need to further investigate the potential interactions between NPs and biological factors that can modulate toxicity of NPs for application to the risk assessment of aquatic invertebrates.

Comparison of Serum Per- and Polyfluoroalkyl Substances Concentrations in Incumbent and Recruit Firefighters and Longitudinal Assessment in Recruits.

OBJECTIVE: Firefighters are occupationally exposed to per- and polyfluoroalkyl substances (PFAS). This study objective was to compare serum PFAS concentrations in incumbent and recruit firefighters and evaluate temporal trends among recruits. METHODS: Serum PFAS concentrations were measured in 99 incumbent and 55 recruit firefighters at enrollment in 2015-2016, with follow-up 20 to 37 months later for recruits. Linear and logistic regression and linear mixed-effects models were used for analyses. Fireground exposure impact on PFAS concentrations was investigated using adjusted linear and logistic regression models. RESULTS: Incumbents had lower n-PFOA and PFNA than recruits and most PFAS significantly decreased over time among male recruits. No significant links were found between cumulative fireground exposures and PFAS concentrations. CONCLUSIONS: Serum PFAS concentrations were not increased in incumbent firefighters compared with recruits and were not associated with cumulative fireground exposures.

Firefighting, per- and polyfluoroalkyl substances, and DNA methylation of genes associated with prostate cancer risk.

Prostate cancer is the leading incident cancer among men in the United States. Firefighters are diagnosed with this disease at a rate 1.21 times higher than the average population. This increased risk may result from occupational exposures to many toxicants, including per- and polyfluoroalkyl substances (PFAS). This study assessed the association between firefighting as an occupation in general or PFAS serum levels, with DNA methylation. Only genomic regions previously linked to prostate cancer risk were selected for analysis: GSTP1, Alu repetitive elements, and the 8q24 chromosomal region. There were 444 male firefighters included in this study, with some analyses being conducted on fewer participants due to missingness. Statistical models were used to test associations between exposures and DNA methylation at CpG sites in the selected genomic regions. Exposure variables included proxies of cumulative firefighting exposures (incumbent versus academy status and years of firefighting experience) and biomarkers of PFAS exposures (serum concentrations of 9 PFAS). Proxies of cumulative exposures were associated with DNA methylation at 15 CpG sites and one region located within FAM83A (q-value <0.1). SbPFOA was associated with 19 CpG sites (q < 0.1), but due to low detection rates, this PFAS was modeled as detected versus not detected in serum. Overall, there is evidence that firefighting experience is associated with differential DNA methylation in prostate cancer risk loci, but this study did not find evidence that these differences are due to PFAS exposures specifically.

Excretion of polybrominated diphenyl ethers and AhR activation in breastmilk among firefighters.

Excretion of toxicants accumulated from firefighter exposures through breastmilk represents a potential hazard. We investigated if firefighting exposures could increase the concentration of polybrominated diphenyl ethers (PBDEs) and aryl hydrocarbon receptor (AhR) activation in excreted breastmilk. Firefighters and non-firefighters collected breastmilk samples prior to any firefighting responses (baseline) and at 2, 8, 24, 48, and 72 hours after a structural fire (firefighters only). Five PBDE analytes (BDEs 15, 28, 47, 99, and 153) detected in at least 90% of samples were summed for analyses. The AhR in vitro DR CALUX® bioassay assessed the mixture of dioxin-like compounds and toxicity from breastmilk extracts. Baseline PBDEs and AhR response were compared between firefighters and non-firefighters. Separate linear mixed models assessed changes in sum of PBDEs and AhR response among firefighters over time and effect modification by interior or exterior response was assessed. Baseline PBDE concentrations and AhR responses did not differ between the 21 firefighters and 10 non-firefighters. There were no significant changes in sum of PBDEs or AhR response among firefighters over time post-fire, and no variation by interior or exterior response. Plots of sum of PBDEs and AhR response over time demonstrated individual variation but no consistent pattern. Currently, our novel study results do not support forgoing breastfeeding after a fire exposure. However, given study limitations and the potential hazard of accumulated toxicants from firefighter exposures excreted via breastfeeding, future studies should consider additional contaminants and measures of toxicity by which firefighting may impact maternal and child health.

Occupational Years of Service and Leukocyte Epigenetic Aging: Relationships in United States Firefighters.

OBJECTIVE: The aim of the study is to examine associations between years of firefighting service and eight chronological age-adjusted measures of blood leukocyte epigenetic age acceleration: Horvath, Hannum, SkinBloodClock, Intrinsic, Extrinsic, PhenoAge, GrimAge, and DNAm telomere length. METHODS: The study used a repeated measures analysis of data from 379 incumbent firefighters from eight career departments and 100 recruit firefighters from two of the departments, across the United States. RESULTS: Incumbent firefighters had on average greater epigenetic age acceleration compared with recruit firefighters, potentially due to the cumulative effect of occupational exposures. However, among incumbent firefighters, additional years of service were associated with epigenetic age deceleration, particularly for GrimAge, a strong predictor of mortality. CONCLUSIONS: Long-term studies with more specific occupational exposure classification are needed to better understand the relationship between years of service and aging biomarkers.

Associations Between Epigenetic Age Acceleration and microRNA Expression Among U.S. Firefighters.

Epigenetic changes may be biomarkers of health. Epigenetic age acceleration (EAA), the discrepancy between epigenetic age measured via epigenetic clocks and chronological age, is associated with morbidity and mortality. However, the intersection of epigenetic clocks with microRNAs (miRNAs) and corresponding miRNA-based health implications have not been evaluated. We analyzed DNA methylation and miRNA profiles from blood sampled among 332 individuals enrolled across 2 U.S.-based firefighter occupational studies (2015-2018 and 2018-2020). We considered 7 measures of EAA in leukocytes (PhenoAge, GrimAge, Horvath, skin-blood, and Hannum epigenetic clocks, and extrinsic and intrinsic epigenetic age acceleration). We identified miRNAs associated with EAA using individual linear regression models, adjusted for sex, race/ethnicity, chronological age, and cell type estimates, and investigated downstream effects of associated miRNAs with miRNA enrichment analyses and genomic annotations. On average, participants were 38 years old, 88% male, and 75% non-Hispanic white. We identified 183 of 798 miRNAs associated with EAA (FDR q < 0.05); 126 with PhenoAge, 59 with GrimAge, 1 with Horvath, and 1 with the skin-blood clock. Among miRNAs associated with Horvath and GrimAge, there were 61 significantly enriched disease annotations including age-related metabolic and cardiovascular conditions and several cancers. Enriched pathways included those related to proteins and protein modification. We identified miRNAs associated with EAA of multiple epigenetic clocks. PhenoAge had more associations with individual miRNAs, but GrimAge and Horvath had greater implications for miRNA-associated pathways. Understanding the relationship between these epigenetic markers could contribute to our understanding of the molecular underpinnings of aging and aging-related diseases.

Humoral Immune Response to Messenger RNA Coronavirus Disease 2019 Vaccination Among Children Aged 5-11 Years in a Multisite Prospective Cohort Study, September 2021-September 2022.

Background: The PROTECT study is a longitudinal cohort study initiated in July 2021 with weekly testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 4 states: Arizona, Florida, exas, and Utah. This study aims to examine vaccine-elicited antibody response against postvaccination SARS-CoV-2 infections. Methods: Children aged 5-11 years had serum collected 14-59 days after their second dose of monovalent Pfizer-BioNTech coronavirus disease 2019 messenger RNA vaccine. Vaccine-elicited antibodies were measured using the area under the curve (AUC) and end-point titer using enzyme-linked immunosorbent assay (receptor-binding domain [RBD] and S2) and surrogate neutralization assays against ancestral (WA1) and Omicron (BA.2). Results: 79 vaccinated participants (33 [41.7%] female; median age, 8.8 years [standard deviation, 1.9 years]), 48 (60.8%) were from Tucson, Arizona; 64 (81.0%) were non-Hispanic white; 63 (80.8%) attended school in person; 68 (86.1%) did not have any chronic conditions; and 47 (59.5%) were infected after vaccination. Uninfected children had higher AUCs against WA1 (P = .009) and Omicron (P = .02). The geometric mean and surrogate neutralization titer above the limit of detection was 346.0 for WA1 and 39.7 for Omicron, an 8.7-fold decrease (P < .001). After adjustment of covariates in the WA1-specific model, we observed a 47% reduction in the odds of postvaccination infection for every standard deviation increase in RBD AUC (aOR, 0.53 [95% confidence interval, .29-.97) and a 69% reduction in the odds of infection for every 3-fold increase in RBD end titer (0.31 [.06-1.57]). Conclusions: Children with higher antibody levels experienced a lower incidence of postvaccination SARS-CoV-2 infection.

Formation of nitrogenous disinfection byproducts in MP UV-based water treatments of natural organic matters: The role of nitrate.

UV-based water treatment processes have been reported to induce genotoxicity during the treatments of surface water, drinking water and artificial water with natural organic matters (NOMs), causing genotoxicity concerns for the drinking water safety. Nitrogenous disinfection byproducts (N-DBPs) were generally reported to be much more genotoxic than their non-nitrogenous analogues, and might be responsible for the genotoxicity in UV processes. Although nitrate-rich water was getting attention for the possibility of genotoxicity and N-DBPs during UV treatments, the impact mechanism of nitrate on the degradation of NOMs, the formation of N-DBPs and genotoxicity has not been explicated. Here simulation experiments of NOM degradation under medium-pressure (MP) UV and MP UV/H2O2 treatments were conducted to explore the effect of nitrate on the molecular characteristics of NOM, the nitrate-derived N-DBPs and the potential genotoxicity through non-targeted analysis and CALUX® reporter gene assays. The results showed that nitrate can accelerate the degradation of NOMs in the MP UV process but inhibit the degradation of NOMs in the MP UV/H2O2 process. During the degradation of NOMs, the molecular compositions varied by the effect of nitrate on oxygen atoms, molecule analogs, and saturation. A total of 105 and 374 nitrate-derived N-DBPs were identified in the MP UV and MP UV/H2O2 treatment, respectively. Most of these N-DBPs contain one nitrogen atom, and the representative features are nitro-, methoxy- (or hydroxyl-) and ester- groups on benzene. No genotoxicity was observed without nitrate spiking, whereas genotoxicity was induced after both MP UV and MP UV/H2O2 treatments when nitrate was spiked, which is worthy of attention for the drinking water safety management.

Exploring the genotoxicity triggers in the MP UV/H2O2-chloramination treatment of bisphenol A through bioassay coupled with non-targeted analysis.

Bisphenol A (BPA) is a well-known xenoestrogen, and UV/H2O2 advanced oxidation process (AOP) is one of the most effective technologies to remove BPA from water. Using BPA spiked tap water, a batch-scale photochemical experiment was conducted to investigate whether BPA can pose a genotoxicity concern during the medium pressure (MP) UV/H2O2 treatment and the post-chloramination. Samples at different UV exposure and post-chloramination durations were collected and analyzed by CALUX® gene reporter assays regarding estrogen receptor α (ERα) and p53 transcriptional activity. MP UV/H2O2 process did not cause extra estrogenic effects from the degradation of BPA, whereas genotoxicity occurred when the treated water was exposed with monochloramine. Seven frequently reported nitrogenous disinfection byproducts (N-DBPs) were detected, but none of them were responsible for the observed genotoxicity. Employed with gas chromatography-quadrupole time-of-flight mass spectrometry (GC-QTOF-MS), four compounds possibly contributed to the genotoxicity were tentatively identified and two of them with aminooxy- or cyano- group were considered as "new" N-DBPs. This study demonstrated that by-products differ from their parent compounds in toxicity can be formed in the UV oxidation with post-disinfection process, which should become a cause for concern.

Longitudinal evaluation of whole blood miRNA expression in firefighters.

BACKGROUND: Dysregulated microRNA (miRNA) expression could provide a mechanism linking firefighter exposure to increased cancer risk. OBJECTIVE: To determine if changes in longitudinal miRNA expression in firefighters are associated with occupational exposures. METHODS: Whole blood MiRNA was evaluated in 52 new recruits prior to live-fire training and 20-37 months later. Linear mixed effects models adjusted for age, ethnicity, BMI, and batch effects were used to determine associations separately for all fires and structure fires only between employment duration, cumulative fire-hours and fire-runs, and time since most recent fire with (1) nine a priori and (2) the full array of 799 miRNAs. RESULTS: For multivariable models including all fires, two a priori miRNAs were associated with employment duration and four with time since most recent fire. For multivariable models restricted to structure fires, three a priori miRNAs were associated with employment duration and one with fire-runs. Additional miRNAs from the full array were associated with employment duration for all fires and/or structure fires. In general, tumor suppressive miRNAs decreased and oncogenic miRNAs increased with exposure. SIGNIFICANCE: Changes in miRNAs may serve as biomarkers of exposure effects and a mechanism for increased cancer risk in firefighters.

Incidence of SARS-CoV-2 Infection Among Health Care Personnel, First Responders, and Other Essential Workers During a Prevaccination COVID-19 Surge in Arizona.

Importance: Understanding the relative risk of SARS-CoV-2 infection across occupations can inform guidance to protect workers and communities. Less is known about infection risk for first responders and other essential workers than for health care personnel. Objective: To compare the prevaccination incidence of SARS-CoV-2 infection among first responders and other essential workers with incidence among health care personnel. Design Setting and Participants: This was a prospective cohort study of health care personnel, first responders, and other essential workers in Arizona from July 20, 2020, to March 14, 2021. Participants were seronegative at enrollment, had frequent direct contact with others at work, worked at least 20 hours per week, and submitted weekly nasal swab specimens for real-time reverse transcriptase polymerase chain reaction analysis. Data analyses were performed from April 19, 2021, to June 4, 2021. Exposures: Occupation was the primary exposure of interest. Confounders assessed were sociodemographic characteristics, health status, community exposure, and work exposure. Main Outcomes and Measures: Crude incidence of SARS-CoV-2 infection was defined as the sum of first positive SARS-CoV-2 infections in participants divided by person-weeks at risk. Negative binomial regression was used to model SARS-CoV-2 infection by occupation to estimate unadjusted and adjusted incidence rate ratios (IRRs). The least absolute shrinkage and selection operator (LASSO) method was used to generate a parsimonious multivariable model. Results: The study cohort comprised 1766 Arizona workers (mean age [SD], 43.8 [11.1] years; 1093 [61.9%] female; 401 [22.7%] were Hispanic and 1530 [86.6%] were White individuals) of whom 44.2% were health care personnel, 22.4% first responders, and 33.4% other essential workers. The cohort was followed up for 23 393 person-weeks. Crude incidence of SARS-CoV-2 infection was 6.7, 13.2, and 7.4 per 1000 person-weeks at risk for health care personnel, first responders, and other essential workers, respectively. In unadjusted models, first responders had twice the incidence of infection as health care personnel (IRRs, 2.01; 95% CI, 1.44-2.79). While attenuated, this risk remained elevated in adjusted LASSO-optimized models (IRR, 1.60; 95% CI, 1.07-2.38). Risk of infection among other essential workers was no different than for health care personnel in unadjusted or adjusted models. Conclusions and Relevance: This prospective cohort study found that first responders had a higher incidence of SARS-CoV-2 infection than health care personnel, even after adjusting for potential confounding factors. Given their frequent contact with each other and with the public and their high rates of SARS-CoV-2 infection, the safety challenges for first responders warrant greater public health attention and research.

Evaluation of fireground exposures using urinary PAH metabolites.

BACKGROUND: Firefighters have increased cancer incidence and mortality rates compared to the general population, and are exposed to multiple products of combustion including known and suspected carcinogens. OBJECTIVE: The study objective was to quantify fire response exposures by role and self-reported exposure risks. METHODS: Urinary hydroxylated metabolites of polycyclic aromatic hydrocarbons (PAH-OHs) were measured at baseline and 2-4 h after structural fires and post-fire surveys were collected. RESULTS: Baseline urine samples were collected from 242 firefighters. Of these, 141 responded to at least one of 15 structural fires and provided a post-fire urine. Compared with baseline measurements, the mean fold change of post-fire urinary PAH-OHs increased similarly across roles, including captains (2.05 (95% CI 1.59-2.65)), engineers (2.10 (95% CI 1.47-3.05)), firefighters (2.83 (95% CI 2.14-3.71)), and paramedics (1.84 (95% CI 1.33-2.60)). Interior responses, smoke odor on skin, and lack of recent laundering or changing of hoods were significantly associated with increased post-fire urinary PAH-OHs. SIGNIFICANCE: Ambient smoke from the fire represents an exposure hazard for all individuals on the fireground; engineers and paramedics in particular may not be aware of the extent of their exposure. Post-fire surveys identified specific risks associated with increased exposure.

Aryl hydrocarbon receptor nuclear translocators (ARNT1, ARNT2, and ARNT3) of white sturgeon (Acipenser transmontanus): Sequences, tissue-specific expressions, and response to ß-naphthoflavone.

Sturgeons (Acipenseridae) are ancient fishes that have tissue-specific profiles of transcriptional responses to dioxin-like compounds (DLCs) that are unique from those generally measured in teleost fishes. Because DLCs exert their critical toxicities through activation of the aryl hydrocarbon receptor (AHR), this transcription factor has been the subject of intensive study. However, less attention has focused on the aryl hydrocarbon receptor nuclear translocator (ARNT), which is the dimerization partner of the AHR and required for AHR-mediated transcription. The present study sequenced ARNT1, ARNT2, and ARNT3 in a representative species of sturgeon, the white sturgeon (Acipenser transmontanus), and quantified tissue-specific basal transcript abundance for each ARNT and the response following exposure to the model agonist of the AHR, ß-naphthoflavone. In common with other proteins in sturgeons, the amino acid sequences of ARNTs are more similar to those of tetrapods than are ARNTs of other fishes. Transcripts of ARNT1, ARNT2, and ARNT3 were detected in all tissues investigated. Expression of ARNTs are tightly regulated in vertebrates, but ß-naphthoflavone caused down-regulation in liver and up-regulation in gill, while an upward trend was measured in intestine. ARNTs are dimeric partners for multiple proteins, including the hypoxia inducible factor 1α (HIF1α), which mediates response to hypoxia. A downward trend in abundance of HIF1α transcript was measured in liver of white sturgeon exposed to ß-naphthoflavone. Altered expression of ARNTs and HIF1α caused by activation of the AHR might affect the ability of certain tissues in sturgeons to respond to hypoxia when co-exposed to DLCs or other agonists.

Assessment of the toxicity of firefighter exposures using the PAH CALUX bioassay.

Firefighters can be exposed to a complex set of contaminants while at a fire scene. Identifying new ways to monitor and assess exposure, particularly relating to toxicity is essential to determine the effectiveness of intervention techniques to reduce exposure. This study investigated the use of the polycyclic aromatic hydrocarbon (PAH) CALUX® bioassay for the assessment of exposure and associated toxicity firefighters might encounter. This was done through analysis of extracts of dermal wipes and urine samples collected from firefighters before and after a controlled fire. An increased bioassay response was observed from post-fire neck and calf samples, indicating a greater concentration of PAH-like compounds on the skin. The use of a baby wipe to clean the face and neck during rehab resulted in the attenuation of the observed bioassay response from the neck post-fire. Though a correlation was observed between the bioassay response and hydroxylated PAH concentrations found in the urine, the increased bioassay response from the post-fire urine samples was likely due to unknown compounds other than the hydroxylated PAHs tested. Our results suggest that this bioassay provides a useful measure of firefighter exposure, particularly relating to the potential toxicity of contaminants.

Evaluation of Interventions to Reduce Firefighter Exposures.

OBJECTIVE: Evaluate the effectiveness of firefighter exposure reduction interventions. METHODS: Fireground interventions included use of self-contained breathing apparatus by engineers, entry team wash down, contaminated equipment isolation, and personnel showering and washing of gear upon return to station. Urinary polycyclic aromatic hydrocarbon metabolites (PAH-OHs) were measured after structural fire responses before and after intervention implementation. Separately, infrared sauna use following live-fire training was compared to standard postfire care in a randomized trial. RESULTS: The fireground interventions significantly reduced mean total urinary postfire PAH-OHs in engineers (-40.4%, 95%CI -63.9%, -2.3%) and firefighters (-36.2%, 95%CI -56.7%, -6.0%) but not captains (-11.3% 95%CI -39.4%, 29.9%). Sauna treatment non-significantly reduced total mean PAH-OHs by -43.5% (95%CI -68.8%, 2.2%). CONCLUSIONS: The selected fireground interventions reduced urinary PAH-OHs in engineers and firefighters. Further evaluation of infrared sauna treatment is needed.