Exposure Settings Research Articles

Surveillance of Waterborne Disease Outbreaks Associated with Drinking Water - United States, 2015-2020.

Public health agencies in U.S. states, territories, and freely associated states investigate and voluntarily report waterborne disease outbreaks to CDC through the National Outbreak Reporting System (NORS). This report summarizes NORS drinking water outbreak epidemiologic, laboratory, and environmental data, including data for both public and private drinking water systems. The report presents outbreak-contributing factors (i.e., practices and factors that lead to outbreaks) and, for the first time, categorizes outbreaks as biofilm pathogen or enteric illness associated. 2015-2020. CDC launched NORS in 2009 as a web-based platform into which public health departments voluntarily enter outbreak information. Through NORS, CDC collects reports of enteric disease outbreaks caused by bacterial, viral, parasitic, chemical, toxin, and unknown agents as well as foodborne and waterborne outbreaks of nonenteric disease. Data provided by NORS users, when known, for drinking water outbreaks include 1) the number of cases, hospitalizations, and deaths; 2) the etiologic agent (confirmed or suspected); 3) the implicated type of water system (e.g., community or individual or private); 4) the setting of exposure (e.g., hospital or health care facility; hotel, motel, lodge, or inn; or private residence); and 5) relevant epidemiologic and environmental data needed to describe the outbreak and characterize contributing factors. During 2015-2020, public health officials from 28 states voluntarily reported 214 outbreaks associated with drinking water and 454 contributing factor types. The reported etiologies included 187 (87%) biofilm associated, 24 (11%) enteric illness associated, two (1%) unknown, and one (<1%) chemical or toxin. A total of 172 (80%) outbreaks were linked to water from public water systems, 22 (10%) to unknown water systems, 17 (8%) to individual or private systems, and two (0.9%) to other systems; one (0.5%) system type was not reported. Drinking water-associated outbreaks resulted in at least 2,140 cases of illness, 563 hospitalizations (26% of cases), and 88 deaths (4% of cases). Individual or private water systems were implicated in 944 (43%) cases, 52 (9%) hospitalizations, and 14 (16%) deaths.Enteric illness-associated pathogens were implicated in 1,299 (61%) of all illnesses, and 10 (2%) hospitalizations. No deaths were reported. Among these illnesses, three pathogens (norovirus, Shigella, and Campylobacter) or multiple etiologies including these pathogens resulted in 1,225 (94%) cases. The drinking water source was identified most often (n = 34; 7%) as the contributing factor in enteric disease outbreaks. When water source (e.g., groundwater) was known (n = 14), wells were identified in 13 (93%) of enteric disease outbreaks.Most biofilm-related outbreak reports implicated Legionella (n = 184; 98%); two nontuberculous mycobacteria (NTM) (1%) and one Pseudomonas (0.5%) outbreaks comprised the remaining. Legionella-associated outbreaks generally increased over the study period (14 in 2015, 31 in 2016, 30 in 2017, 34 in 2018, 33 in 2019, and 18 in 2020). The Legionella-associated outbreaks resulted in 786 (37%) of all illnesses, 544 (97%) hospitalizations, and 86 (98%) of all deaths. Legionella also was the outbreak etiology in 160 (92%) public water system outbreaks. Outbreak reports cited the premise or point of use location most frequently as the contributing factor for Legionella and other biofilm-associated pathogen outbreaks (n = 287; 63%). Legionella was reported to NORS in 2015 and 2019 as the cause of three outbreaks in private residences (2). The observed range of biofilm and enteric drinking water pathogen contributing factors illustrate the complexity of drinking water-related disease prevention and the need for water source-to-tap prevention strategies. Legionella-associated outbreaks have increased in number over time and were the leading cause of reported drinking water outbreaks, including hospitalizations and deaths. Enteric illness outbreaks primarily linked to wells represented approximately half the cases during this reporting period. This report enhances CDC efforts to estimate the U.S. illness and health care cost impacts of waterborne disease, which revealed that biofilm-related pathogens, NTM, and Legionella have emerged as the predominant causes of hospitalizations and deaths from waterborne- and drinking water-associated disease. Public health departments, regulators, and drinking water partners can use these findings to identify emerging waterborne disease threats, guide outbreak response and prevention programs, and support drinking water regulatory efforts.

Validation of Salamander Dermal Mucus Swabs as a Novel, Nonlethal Approach for Amphibian Metabolomics and Glutathione Analysis Following Pesticide Exposure.

Evaluating biomarkers of stress in amphibians is critical to conservation, yet current techniques are often destructive and/or time-consuming, which limits ease of use. In the present study, we validate the use of dermal swabs in spotted salamanders (Ambystoma maculatum) for biochemical profiling, as well as glutathione (GSH) stress response following pesticide exposure. Thirty-three purchased spotted salamanders were acclimated to laboratory conditions at Washington College (Chestertown, MD, USA) for 4 weeks. Following acclimation, salamanders were randomly sorted into three groups for an 8-h pesticide exposure on soil: control with no pesticide, 2,4-dichlorophenoxyacetic acid (2,4-D), or chlorpyrifos. Before and after exposure, mucus samples were obtained by gently rubbing a polyester-tipped swab 50 times across the ventral and dorsal surfaces. Salamanders were humanely euthanized and dissected to remove the brain for acetylcholinesterase and liver for GSH and hepatic metabolome analyses, and a whole-body tissue homogenate was used for pesticide quantification. Levels of GSH were present in lower quantities on dermal swabs relative to liver tissues for chlorpyrifos, 2,4-D, and control treatments. However, 2,4-D exposures demonstrated a large effect size increase for GSH levels in livers (Cohen's d = 0.925, p = 0.036). Other GSH increases were statistically insignificant, and effect sizes were characterized as small for 2,4-D mucosal swabs (d = 0.36), medium for chlorpyrifos mucosal swabs (d = 0.713), and negligible for chlorpyrifos liver levels (d = 0.012). The metabolomics analyses indicated that the urea cycle, alanine, and glutamate metabolism biological pathways were perturbed by both sets of pesticide exposures. Obtaining mucus samples through dermal swabbing in amphibians is a viable technique for evaluating health in these imperiled taxa. Environ Toxicol Chem 2024;43:1126-1137. © 2024 SETAC.

Early Pulmonary Fibrosis-like Changes in the Setting of Heat Exposure: DNA Damage and Cell Senescence.

It is well known that extreme heat events happen frequently due to climate change. However, studies examining the direct health impacts of increased temperature and heat waves are lacking. Previous reports revealed that heatstroke induced acute lung injury and pulmonary dysfunction. This study aimed to investigate whether heat exposure induced lung fibrosis and to explore the underlying mechanisms. Male C57BL/6 mice were exposed to an ambient temperature of 39.5 ± 0.5 °C until their core temperature reached the maximum or heat exhaustion state. Lung fibrosis was observed in the lungs of heat-exposed mice, with extensive collagen deposition and the elevated expression of fibrosis molecules, including transforming growth factor-β1 (TGF-β1) and Fibronectin (Fn1) (p < 0.05). Moreover, epithelial-mesenchymal transition (EMT) occurred in response to heat exposure, evidenced by E-cadherin, an epithelial marker, which was downregulated, whereas markers of EMT, such as connective tissue growth factor (CTGF) and the zinc finger transcriptional repressor protein Slug, were upregulated in the heat-exposed lung tissues of mice (p < 0.05). Subsequently, cell senescence examination revealed that the levels of both senescence-associated β-galactosidase (SA-β-gal) staining and the cell cycle protein kinase inhibitor p21 were significantly elevated (p < 0.05). Mechanistically, the cGAS-STING signaling pathway evoked by DNA damage was activated in response to heat exposure (p < 0.05). In summary, we reported a new finding that heat exposure contributed to the development of early pulmonary fibrosis-like changes through the DNA damage-activated cGAS-STING pathway followed by cellular senescence.

The DECam Ecliptic Exploration Project (DEEP). VI. First Multiyear Observations of Trans-Neptunian Objects

We present the first set of trans-Neptunian objects (TNOs) observed on multiple nights in data taken from the DECam Ecliptic Exploration Project. Of these 110 TNOs, 105 do not coincide with previously known TNOs and appear to be new discoveries. Each individual detection for our objects resulted from a digital tracking search at TNO rates of motion, using two-to-four-hour exposure sets, and the detections were subsequently linked across multiple observing seasons. This procedure allows us to find objects with magnitudes m VR ≈ 26. The object discovery processing also included a comprehensive population of objects injected into the images, with a recovery and linking rate of at least 94%. The final orbits were obtained using a specialized orbit-fitting procedure that accounts for the positional errors derived from the digital tracking procedure. Our results include robust orbits and magnitudes for classical TNOs with absolute magnitudes H ∼ 10, as well as a dynamically detached object found at 76 au (semimajor axis a ≈ 77 au). We find a disagreement between our population of classical TNOs and the CFEPS-L7 three-component model for the Kuiper Belt.

Machine learning-driven identification of air toxic combinations associated with asthma symptoms among elementary school children in Spokane, Washington, USA

Air toxics are atmospheric pollutants with hazardous effects on health and the environment. Although methodological constraints have limited the number of air toxics assessed for associations with health and disease, advances in machine learning (ML) enable the assessment of a much larger set of environmental exposures. We used ML methods to conduct a retrospective study to identify combinations of 109 air toxics associated with asthma symptoms among 269 elementary school students in Spokane, Washington. Data on the frequency of asthma symptoms for these children were obtained from Spokane Public Schools. Their exposure to air toxics was estimated by using the Environmental Protection Agency's Air Toxics Screening Assessment and National Air Toxics Assessment. We defined three exposure periods: the most recent year (2019), the last three years (2017–2019), and the last five years (2014–2019). We analyzed the data using the ML-based Data-driven ExposurE Profile (DEEP) extraction method. DEEP identified 25 air toxic combinations associated with asthma symptoms in at least one exposure period. Three combinations (1,1,1-trichloroethane, 2-nitropropane, and 2,4,6-trichlorophenol) were significantly associated with asthma symptoms in all three exposure periods. Four air toxics (1,1,1-trichloroethane, 1,1,2,2-tetrachloroethane, BIS (2-ethylhexyl) phthalate (DEHP), and 2,4-dinitrophenol) were associated only in combination with other toxics, and would not have been identified by traditional statistical methods. The application of DEEP also identified a vulnerable subpopulation of children who were exposed to 13 of the 25 significant combinations in at least one exposure period. On average, these children experienced the largest number of asthma symptoms in our sample. By providing evidence on air toxic combinations associated with childhood asthma, our findings may contribute to the regulation of these toxics to improve children's respiratory health.

Effects of low-dose ionizing radiation on the molecular pathways linking neurogenesis and autism spectrum disorders in zebrafish embryos

Prenatal exposure to environmental factors may play an important role in the aetiopathogenesis of autism spectrum disorder (ASD). We aim to investigate the potential effects of low-dose x-rays from dental diagnostic x-rays on neurodevelopment and molecular mechanisms associated with ASD in developing zebrafish embryos. Zebrafish embryos were divided into four groups and exposed using a dental x-ray unit: control, 0.08, 0.15 and 0.30 seconds, which are exemplary exposure settings for periapical imaging. These exposure times were measured as 7.17, 23.17 and 63.83 mSv using optical stimulated luminescence dosimeters. At the end of 72 hours post-fertilization, locomotor activity, oxidant-antioxidant status, and acetylcholine esterase (AChE) activity were analyzed. Expression of genes related to apoptosis (bax, bcl2a, p53), neurogenesis (α1-tubulin, syn2a, neurog1, elavl3) and ASD (eif4eb, adsl2a, shank3) was determined by RT-PCR. Even at reduced doses, developmental toxicity was observed in three groups as evidenced by pericardial edema, yolk sac edema and scoliosis. Deleterious effects of dental x-rays on neurogenesis through impaired locomotor activity, oxidative stress, apoptosis and alterations in genes associated with neurogenesis and ASD progression were more pronounced in the 0.30s exposure group. Based on these results we suggest that the associations between ASD and low-dose ionizing radiation need a closer look.

A meta-analysis highlighting the increasing relevance of the hair matrix in exposure assessment to organic pollutants

Owing to a wide range of advantages, such as stability, non-invasiveness, and ease of sampling, hair has been used progressively for comprehensive biomonitoring of organic pollutants for the last three decades. This has led to the development of new analytical and multi-class analysis methods for the assessment of a broad range of organic pollutants in various population groups, ranging from small-scale studies to advanced studies with a large number of participants based on different exposure settings. This meta-analysis summarizes the existing literature on the assessment of organic pollutants in hair in terms of residue levels, the correlation of hair residue levels with those of other biological matrices and socio-demographic factors, the reliability of hair versus other biomatrices for exposure assessment, the use of segmental hair analysis for chronic exposure evaluation and the effect of external contamination on hair residue levels. Significantly high concentrations of organic pollutants such as pesticides, flame retardants, polychlorinated biphenyls and polycyclic aromatic hydrocarbon were reported in human hair samples from different regions and under different exposure settings. Similarly, high concentrations of pesticides (from agricultural activities), flame retardants (E-waste dismantling activities), dioxins and furans were observed in various occupational settings. Moreover, significant correlations (p < 0.05) for hair and blood concentrations were observed in majority of studies featuring pesticides and flame retardants. While among sociodemographic factors, gender and age significantly affected the hair concentrations in females and children in general exposure settings, whereas adult workers in occupational settings. Furthermore, the assessment of the hair burden of persistent organic pollutants in domestic and wild animals showed high concentrations for pesticides such as HCHs and DDTs whereas the laboratory-based studies using animals demonstrated strong correlations between exposure dose, exposure duration, and measured organic pollutant levels, mainly for chlorpyrifos, diazinon, terbuthylazine, aldrin, dieldrin and pyrethroid metabolites. Considering the critical analysis of the results obtained from literature review, hair is regarded as a reliable matrix for organic pollutant assessment; however, some limitations, as discussed in this review, need to be overcome to reinforce the status of hair as a suitable matrix for exposure assessment.

Intraoperative navigation increases the projected lifetime cancer risk in patients undergoing surgery for adolescent idiopathic scoliosis

BACKGROUND CONTEXTAdolescent idiopathic scoliosis (AIS) is a common condition, often requiring surgical correction. Computed tomography (CT) based navigation technologies, which rely on ionizing radiation, are increasingly being utilized for surgical treatment. Although this population is highly vulnerable to radiation, given their age and female predominance, there is little available information elucidating modeled iatrogenic cancer risk. PURPOSETo model lifetime cancer risk associated with the use of intraoperative CT-based navigation for surgical treatment of AIS. STUDY DESIGN/SETTINGThis retrospective cross-sectional study took place in a quaternary care academic pediatric hospital in the United States. PATIENT SAMPLEAdolescents aged 10–18 who underwent posterior spinal fusion for a diagnosis of AIS between July 2014 and December 2019. OUTCOMES MEASURESEffective radiation dose and projected lifetime cancer risk associated with intraoperative doses of ionizing radiation. METHODSClinical and radiographic parameters were abstracted, including total radiation dose during surgery from flat plate radiographs, fluoroscopy, and intraoperative CT scans. Multivariable regression analysis was used to assess differences in radiation exposure between patients treated with conventional radiography versus intraoperative navigation. Radiation exposure was translated into lifetime cancer risk using well-established algorithms. RESULTSIn total, 245 patients were included, 119 of whom were treated with navigation. The cohort was 82.9% female and 14.4 years of age. The median radiation exposure (in millisieverts, mSv) for fluoroscopy, radiography, and navigation was 0.05, 4.14, and 8.19 mSv, respectively. When accounting for clinical and radiographic differences, patients treated with intraoperative navigation received 8.18 mSv more radiation (95%CI: 7.22–9.15, p<.001). This increase in radiation projects to 0.90 iatrogenic malignancies per 1,000 patients (95%CI 0.79–1.01). CONCLUSIONSOurs is the first work to define cancer risk in the setting of radiation exposure for navigated AIS surgery. We project that intraoperative navigation will generate approximately one iatrogenic malignancy for every 1,000 patients treated. Given that spine surgery for AIS is common and occurs in the context of a multitude of other radiation sources, these data highlight the need for radiation budgeting protocols and continued development of lower radiation dose technologies. LEVEL OF EVIDENCETherapeutic, III.

Exposure and protection protocols of dentomaxillofacial imaging applied by paediatric dentists in Europe.

Evaluate exposure and protection practices regarding dentomaxillofacial imaging among pediatric dentists in Europe and determine the effect of different clinician specific characteristics on their implementation. A cross-sectional study involving an electronic questionnaire addressed to paediatric dentists, participating in a seminar on dental radiology organized by the European Academy of Paediatric Dentistry. Participants were asked to respond to questions regarding dentomaxillofacial imaging in terms of applied radiation dose, adoption of radiation protection techniques, and different patterns of radiographic studying and exchange between patients and colleagues. Data analysis was performed and distribution of responses was tested using chi-square and Fisher's exact tests. A total of 151 paediatric dentists, 119 females and 32 males, with a mean chronological age of 42.8years (s.e. 11.3years), successfully completed the questionnaire (response rate = 82%). Regardless of the type of radiograph, majority of respondents (68%), reported that they perform the radiographs themselves, while 21% reported that they refer the patients. Half of the respondents (51%), indicated requesting a small (localized) field of view (FOV) when referring for a cone beam computed tomography (CBCT) with only a small proportion (11%) reporting a large (maxillofacial) FOV. Thyroid collars and optimizing exposure settings were the most commonly reported patient protection measures used. Lastly, paediatric dentists have adopted the latest technological capacities for the study of dental images. Dentomaxillofacial imaging protection and exposure protocols used are common among paediatric dentists with none of their specific characteristics having a significant effect.

CTLA-4 Checkpoint Inhibition Improves Sepsis Survival in Alcohol-Exposed Mice.

Chronic alcohol use increases morbidity and mortality in the setting of sepsis. Both chronic alcohol use and sepsis are characterized by immune dysregulation, including overexpression of T cell coinhibitory molecules. We sought to characterize the role of CTLA-4 during sepsis in the setting of chronic alcohol exposure using a murine model of chronic alcohol ingestion followed by cecal ligation and puncture. Results indicated that CTLA-4 expression is increased on CD4+ T cells isolated from alcohol-drinking septic mice as compared with either alcohol-drinking sham controls or water-drinking septic mice. Moreover, checkpoint inhibition of CTLA-4 improved sepsis survival in alcohol-drinking septic mice, but not water-drinking septic mice. Interrogation of the T cell compartments in these animals following pharmacologic CTLA-4 blockade, as well as following conditional Ctla4 deletion in CD4+ T cells, revealed that CTLA-4 deficiency promoted the activation and proliferation of effector regulatory T cells and the generation of conventional effector memory CD4+ T cells. These data highlight an important role for CTLA-4 in mediating mortality during sepsis in the setting of chronic alcohol exposure and may inform future approaches to develop targeted therapies for this patient population.

INTIMATE RELATIONSHIPS, SOCIAL ISOLATION, AND COGNITION

Abstract This symposium considers the cognitive impacts of a spectrum of social relationships, including both intimate partnerships and, in contrast, social isolation. Drawing on rich data from the Wisconsin Longitudinal Study (WLS), the Health and Retirement Study (HRS), the National Social Life, Health, and Aging Project (NSHAP), and the Mexican Health and Aging Study (MHAS), the papers showcase empirical linkages between older adults’ cognitive health with a set of exposures including marital status and relationship characteristics, social activities, and a lack of social connections. We begin with papers that examine the impact of particular marital relationship attributes and social behaviors on cognition and health. One paper employs the WLS to explore the impact of concordance and discordance in marital couples’ reports of similarity with and closeness to their spouse on cognition, while the second draws on NSHAP to consider the cognitive consequences of various domains of couples’ sexuality. The third paper uses the HRS to examine couples’ co-trajectories of physical, mental, and cognitive health, focusing particularly on how a spouse’s cognitive decline influences the other partner’s subsequent health trajectory. The fourth paper shifts our attention to variation by marital status in the cognitive impacts of leisure activities via data from MHAS, while the fifth focuses specifically socially-isolated older adults in the HRS and highlights variation in the relationship between social isolation and dementia by race and ethnicity. The symposium will conclude with a discussion of future directions for research on the cognitive consequences of relationships, social connections, and social isolation.

Linking Prenatal Environmental Exposures to Lifetime Health with Epigenome-Wide Association Studies: State-of-the-Science Review and Future Recommendations.

The prenatal environment influences lifetime health; epigenetic mechanisms likely predominate. In 2016, the first international consortium paper on cigarette smoking during pregnancy and offspring DNA methylation identified extensive, reproducible exposure signals. This finding raised expectations for epigenome-wide association studies (EWAS) of other exposures. We review the current state-of-the-science for DNA methylation associations across prenatal exposures in humans and provide future recommendations. We reviewed 134 prenatal environmental EWAS of DNA methylation in newborns, focusing on 51 epidemiological studies with meta-analysis or replication testing. Exposures spanned cigarette smoking, alcohol consumption, air pollution, dietary factors, psychosocial stress, metals, other chemicals, and other exogenous factors. Of the reproducible DNA methylation signatures, we examined implementation as exposure biomarkers. Only 19 (14%) of these prenatal EWAS were conducted in cohorts of 1,000 or more individuals, reflecting the still early stage of the field. To date, the largest perinatal EWAS sample size was 6,685 participants. For comparison, the most recent genome-wide association study for birth weight included more than 300,000 individuals. Replication, at some level, was successful with exposures to cigarette smoking, folate, dietary glycemic index, particulate matter with aerodynamic diameter and , nitrogen dioxide, mercury, cadmium, arsenic, electronic waste, PFAS, and DDT. Reproducible effects of a more limited set of prenatal exposures (smoking, folate) enabled robust methylation biomarker creation. Current evidence demonstrates the scientific premise for reproducible DNA methylation exposure signatures. Better powered EWAS could identify signatures across many exposures and enable comprehensive biomarker development. Whether methylation biomarkers of exposures themselves cause health effects remains unclear. We expect that larger EWAS with enhanced coverage of epigenome and exposome, along with improved single-cell technologies and evolving methods for integrative multi-omics analyses and causal inference, will expand mechanistic understanding of causal links between environmental exposures, the epigenome, and health outcomes throughout the life course. https://doi.org/10.1289/EHP12956.

Re-analysis and meta-analysis of summary statistics from gene-environment interaction studies.

statistics from genome-wide association studies enable many valuable downstream analyses that are more efficient than individual-level data analysis while also reducing privacy concerns. As growing sample sizes enable better-powered analysis of gene-environment interactions, there is a need for gene-environment interaction-specific methods that manipulate and use summary statistics. We introduce two tools to facilitate such analysis, with a focus on statistical models containing multiple gene-exposure and/or gene-covariate interaction terms. REGEM (RE-analysis of GEM summary statistics) uses summary statistics from a single, multi-exposure genome-wide interaction study to derive analogous sets of summary statistics with arbitrary sets of exposures and interaction covariate adjustments. METAGEM (META-analysis of GEM summary statistics) extends current fixed-effects meta-analysis models to incorporate multiple exposures from multiple studies. We demonstrate the value and efficiency of these tools by exploring alternative methods of accounting for ancestry-related population stratification in genome-wide interaction study in the UK Biobank as well as by conducting a multi-exposure genome-wide interaction study meta-analysis in cohorts from the diabetes-focused ProDiGY consortium. These programs help to maximize the value of summary statistics from diverse and complex gene-environment interaction studies. REGEM and METAGEM are open-source projects freely available at https://github.com/large-scale-gxe-methods/REGEM and https://github.com/large-scale-gxe-methods/METAGEM.

Modular chimeric cytokine receptors with leucine zippers enhance the antitumour activity of CAR T cells via JAK/STAT signalling.

The limited availability of cytokines in solid tumours hinders maintenance of the antitumour activity of chimeric antigen receptor (CAR) T cells. Cytokine receptor signalling pathways in CAR T cells can be activated by transgenic expression or injection of cytokines in the tumour, or by engineering the activation of cognate cytokine receptors. However, these strategies are constrained by toxicity arising from the activation of bystander cells, by the suboptimal biodistribution of the cytokines and by downregulation of the cognate receptor. Here we show that replacement of the extracellular domains of heterodimeric cytokine receptors in T cells with two leucine zipper motifs provides optimal Janus kinase/signal transducer and activator of transcription signalling. Such chimeric cytokine receptors, which can be generated for common γ-chain receptors, interleukin-10 and -12 receptors, enabled T cells to survive cytokine starvation without induction of autonomous cell growth, and augmented the effector function of CAR T cells in vitro in the setting of chronic antigen exposure and in human tumour xenografts in mice. As a modular design, leucine zippers can be used to generate constitutively active cytokine receptors in effector immune cells.

Reducing Transdermal Uptake of Semivolatile Plasticizers from Indoor Environments: A Clothing Intervention.

Models and laboratory studies suggest that everyday clothing influences the transdermal uptake of semivolatile organic compounds, including phthalate plasticizers, from indoor environments. However, this effect has not been documented in environmental exposure settings. In this pilot study, we quantified daily excretion of 17 urinary metabolites (μg/day) for phthalates and phthalate alternatives in nine participants during 5 days. On Day 0, baseline daily excretion was determined in participants' urine. Starting on Day 1, participants refrained from eating phthalate-heavy foods and using personal care products. On Days 3 and 4, participants wore precleaned clothing as an exposure intervention. We observed a reduction in the daily excretion of phthalates during the intervention; mono-n-butyl phthalate, monoisobutyl phthalate (MiBP), and monobenzyl phthalate were significantly reduced by 35, 38, and 56%, respectively. Summed metabolites of di(2-ethylhexyl)phthalate (DEHP) were also reduced (27%; not statistically significant). A similar reduction among phthalate alternatives was not observed. The daily excretion of MiBP during the nonintervention period strongly correlated with indoor air concentrations of diisobutyl phthalate (DiBP), suggesting that inhalation and transdermal uptake of DiBP from the air in homes are dominant exposure pathways. The results indicate that precleaned clothing can significantly reduce environmental exposure to phthalates and phthalate alternatives.

Injury incidence among adolescent and senior basketball players: a prospective study in 19 teams across an entire season

ABSTRACT Objective To quantify and compare injury incidence between national-level, adolescent and regional-level, senior, male basketball players competing in Serbia overall and according to injury mechanism (contact, non-contact, or overuse), exposure setting (training or games), and history (new or recurrent). Methods A total of 218 male basketball players from 19 teams (106 senior and 112 adolescent players) volunteered to participate in the study. Descriptive data regarding game and training injury incidence were gathered across all players and reported per 10,000 athlete-exposures (AE) with 95% confidence intervals. Results Overall, 26 injuries were reported across 52,509 AE. Ankle (n = 10, incidence rate [IR] = 1.90 [0.97, 3.40]) and knee injuries (n = 8, IR = 1.52 [0.71, 2.89]) accounted for 69% of all reported injuries, with only 1–2 injuries documented for other body regions. Ankle injuries were attributed to contact (60%, IR = 1.14 [0.46, 2.38]) or non-contact mechanisms (40%, IR = 0.76 [0.24, 1.84]). Most knee injuries occurred due to overuse (50%, IR = 0.76 [0.24, 1.84]) or non-contact mechanisms (38%, IR = 0.57 [0.15, 1.56]). Comparisons according to exposure setting revealed significantly higher knee (incidence rate ratio [IRR] = 9.95 [1.85, 53.41], p = 0.004) and ankle (IRR = 39.79 [7.94, 384.67], p < 0.001) injuries per 10,000 AE during games compared to training. Recurrent injuries were most prominent in the ankle (30% of all ankle injuries, p = 0.11). Total contact (p = 0.04), non-contact (p = 0.04), and recurrent IR (p = 0.005) were significantly higher in senior than adolescent players. Conclusion The players examined were most susceptible to ankle and knee injuries, particularly during games compared to training. Ankle injuries were mostly attributed to player contact, while knee injuries were mostly attributed to overuse and non-contact mechanisms. Senior players were at a greater risk of sustaining contact, non-contact and recurrent injuries than adolescent players.

Cell toxicity assessment in co-treatment to metalworking fluids and vibration: an in vitro study of occupational exposure setting

ABSTRACT This study was designed to study dual risk of MWFs and vibration according to exposure simulation of selected industry. Air samples of two types MWFs were evaluated according to NIOSH 5026. Vibration acceleration exposure was assessed based on the ISO 8041:2005 standard. Cell treatment of both MWF air samples and vibration as the same as dual exposure to MWF airborne and vibration was assessed. There is a potency of nitrosamine formation in airborne samples of ethylamine containing MWF, while heterocyclic including bore is found in airborne bore containing MWF. DNA breaks caused by boron-containing MWF were higher than nitrosamine air samples. Oxidative stress production and chronic inflammation were highlighted in the response to cell treatments. The risk of cell toxicity in machining workers was evaluated at a level lower than the occupational exposure limit for MWFs and vibration.

NCMP-26. PANCEREBELLITIS ASSOCIATED WITH CISPLATIN THERAPY IN A PATIENT WITH OROPHARYNGEAL/ NASOPHARYNGEAL SQUAMOUS CELL CARCINOMA

Abstract Cisplatin, a platinum-based drug, is one of the oldest and most widely used chemotherapeutic agents. It exerts its anti-tumor effect by forming DNA inter-strand and intra-strand cross-links, resulting in lesions that eventually activate apoptotic pathways. Cisplatin remains widely used for the treatment of several solid tumors, though this is often limited by its toxicity which can affect many organ systems, including nephrotoxicity, hepatotoxicity, ototoxicity, and neurotoxicity. A dose-dependent peripheral sensory neuropathy is the most reported cisplatin-induced neurotoxicity. Central nervous system (CNS) toxicity is less common, likely due to the large molecular size of cisplatin preventing its passage through the blood-brain barrier (BBB). There have been reports of cognitive impairment, posterior reversible encephalopathy syndrome, and optic neuritis associated with cisplatin. We present a case of a 38-year-old patient who was treated with concurrent cisplatin and radiation therapy for oropharyngeal/nasopharyngeal squamous cell carcinoma, and around a month after the end of therapy, was found to have imaging findings concerning for pancerebellitis. Extensive workup into infectious causes of cerebellitis was negative. Although there are no reports in the literature of cerebellitis due to cisplatin, it could be the culprit in this case. Animal studies have shown cerebellar dysfunction occurring in the setting of cisplatin exposure. Moreover, it is thought that the drug can reach the CNS if there is a disruption of the BBB, this is supported by the fact that CNS toxicity is more seen in patients who have primary CNS neoplasia, CNS metastatic disease, radiation exposure to the head, among other mechanisms that could potentially disrupt the BBB. Thus, it is important to consider CNS adverse effects, including cerebellitis, in patients receiving cisplatin, especially among those with a potentially compromised BBB.

Outdoor artificial light at night and cardiovascular disease in adults: a Chinese nationwide cohort study

Abstract Background Although the electric light is a significant promotion in the human progress and civilization, its adverse effects of outdoor artificial light at night (ALAN) are being extensively studied. However, the association of outdoor ALAN and cardiovascular disease (CVD) has never been confirmed in large nationwide studies, especially in urban areas with high exposure levels and in rural areas with low exposure levels, respectively. Purpose To explore the association between outdoor ALAN and CVD. Methods This national study enrolled 12,686 adults ≥ 40 years across China. The outdoor ALAN exposure (nW/cm2/sr) with the resolution of the 500 meters around each participant's location was obtained from satellite image data via Visible Infrared Imaging Radiometer Suite day-night band on board the Joint Polarorbiting Satellite System. CVD was defined by a doctor's record of diagnoses, including heart disease and stroke. Poisson regression model and restricted cubic spline models were used to estimate the relationship between outdoor ALAN and CVD in urban and rural areas, respectively. Subgroup analysis was also conducted using Poisson models for each subgroup. Results At a median follow-up of 7 years, 1,732 cases of CVD were identified. The mean age of the participants was 58 years and 49% were males. In urban areas, outdoor ALAN exposure at the highest quartile (Q4) increased the incidence of CVD among participants by 34% compared to those exposure at the lowest quartile (Q1) (incident rate ratio, IRR: 1.34,95% CI: 1.07—1.69, p = 0.01), adjusting for age, sex, BMI, education, smoke ever, alcohol consumption, physical activity and household consumption. In rural areas, compared with those at the Q1 of outdoor ALAN exposure, exposure at the Q4 reduced the incidence of CVD by 17% (IRR: 0.83, 95% CI: 0.70—0.98, p = 0.028) after full adjustment. Dose-response relationship indicated that outdoor ALAN levels were linearly associated with decreased CVD in rural area (p for non-linearity = 0.370), while the association between outdoor ALAN levels and CVD was shown as an inverse "U" shape in urban area (p for non-linearity ≤ 0.001). Subgroup analysis shown that the CVD risk of middle-aged people, people with history of alcohol consumption, or people with low levels of physical activity were susceptible to outdoor ALAN exposure. Conclusions Outdoor ALAN exposure was associated with the risk of CVD, which was heterogeneous with different levels of exposure range. In rural areas with low outdoor ALAN exposure settings, outdoor ALAN exposure was negatively correlated with the risk of developed CVD, while the association was reverse in urban areas with high outdoor ALAN exposure settings. We call for a reduction in the use of high-intensity ALAN and to pay attention to the effects of emotional, psychological, and biological changes associated with outdoor ALAN exposure on cardiovascular health.Figure 1

Suspected intermediate syndrome in a dog after organophosphate poisoning.

To discuss the clinical presentation and successful treatment of a suspected case of intermediate syndrome due to organophosphate (OP) poisoning in a dog. Two dogs presented with acute cholinergic signs after ingesting an OP insecticide containing 50% acephate. Clinical signs consistent with acute cholinergic crisis resolved in both dogs within 24hours postingestion. One dog developed an onset of neurological signs consistent with intermediate syndrome approximately 24hours postingestion. This patient's clinical signs resolved with the use of pralidoxime chloride. OP poisoning most commonly presents as an acute cholinergic crisis, with rare instances of animals developing intermediate syndrome. Few reports of successful treatment and recovery from intermediate syndrome exist in the veterinary literature, particularly with instances in which 2 dogs within the same exposure setting were treated for acute cholinergic signs and only 1 progressed to an intermediate syndrome. This report also highlights the importance of early intervention with pralidoxime chloride prior to the onset of aging.