Exposure Data Research Articles

Deadly Dust: Protecting Engineered Stone Countertop Workers with Improved Training and Exposure Data from an Industrial Hygienist’s Perspective

Deadly Dust: Protecting Engineered Stone Countertop Workers with Improved Training and Exposure Data from an Industrial Hygienist’s Perspective

Causal effect of lifestyle and metabolic indicator with herpes zoster: a two-sample Mendelian randomization study.

Previous observational studies have reported certain causal relationships between factors such as smoking, alcohol consumption, obesity, physical activity, metabolic disorders, and the incidence of herpes zoster (HZ). However, there is controversy regarding the observed results across different studies. Our objective was to investigate the causal effects of these risk factors on the risk of herpes zoster through a Mendelian randomization analysis using two-sample bidirectional approaches. We conducted two-sample bidirectional Mendelian randomization analyses to explore the causal relationships between different lifestyles, obesity assessment indices, metabolic indicators, and the risk of herpes zoster. All exposure and outcome data were sourced from publicly available data from genome-wide association studies. In the inverse-variance weighted (IVW) analysis, body mass index (BMI) (OR: 1.160, 95% CI: 1.030-1.307, p = 0.014), Body fat percentage (BFP) (OR: 1.241, 95% CI: 1.050-1.467, p = 0.011), and whole body fat mass (WBFM) (OR: 1.199, 95% CI: 1.057-1.362, p = 0.005) exhibited positive associations with the risk of HZ. However, usual walking pace (UWP) (OR: 0.498, 95% CI: 0.254-0.976, p = 0.042) demonstrated a significant negative correlation with HZ risk. Other factors including alcohol intake frequency, smoking initiation, smoking status, insomnia, and sleep duration did not show significant causal relationships with HZ. Mendelian randomization studies revealed that BMI, BFP, and WBFM are risk factors for HZ. UWP showed a protective effect against HZ. These findings provide a straightforward method for evaluating future clinical practices aiming to develop personalized management strategies and assess high-risk populations for HZ.

Ocular surface disorders: office procedures for the allergist/clinical immunologist.

Ocular surface disorders (OSDs) are a prevalent and often debilitating condition encountered in clinical practice, particularly by allergists and clinical immunologists. A comprehensive guide to office procedures for evaluating and managing OSDs, with a specific focus on ocular allergies, would assist in the evaluation process that begins with an initial patient assessment utilizing standardized forms to systematically gather detailed medical history, symptomatology, and environmental exposure data. This structured approach ensures a thorough understanding of the patient's condition and facilitates targeted interventions. In addition to allergy testing, the assessment of the tear film is essential for a comprehensive evaluation of OSDs. The Schirmer test is employed to quantify tear production, providing objective data on tear film adequacy and guiding interventions for tear film deficiencies. This multifaceted diagnostic approach ensures that all contributing factors to OSDs are identified and appropriately managed. By integrating these office procedures, allergists and clinical immunologists can enhance their diagnostic accuracy and therapeutic efficacy, ultimately improving patient outcomes. This manuscript provides a practical resource, outlining some of the methodologies and clinical applications of each procedure, and highlighting their role in the holistic management of OSDs in allergic patients.

Human next-generation risk assessment of trichothecene toxicity

Trichothecenes are naturally occurring chemicals, produced by fungi, that can be found in contaminated crops. Trichothecenes have the potential to indirectly damage DNA and exacerbate genotoxic effects of genotoxicants. However, genotoxicity data for most trichothecenes are limited and data gaps remain. Here we use the γH2AX/pH3 assay to evaluate DNA damage in vitro of 13 trichothecenes. Three human cell lines (SH-SY5Y, ACHN, and HepG2) were exposed to each trichothecene (0.001–100 μM) to assess toxicity as models for the brain, kidney, and liver, respectively. Concentration-dependent induction of DNA damage, illustrated by γH2AX induction, was observed for all trichothecenes. In vitro-in vivo extrapolation (IVIVE) modeling was employed to support in vivo equivalent potency ranking and screen for risk potential. Diacetoxyscirpenol, T-2, and HT-2 had the highest genotoxic potency, notably in SH-SY5Y cells. Administered equivalent doses (AEDs) derived from IVIVE were compared against exposure data from French total diet studies to assess risk potential. AEDs derived for T-2 and HT-2 from the SH-SY5Y model were within 100-fold of exposure levels for infants aged one year or less. Overall, the potential for trichothecenes to damage DNA and higher exposures in infants highlights the need to investigate the cumulative effects across the broader trichothecene family.

Assessing the causal relationship between plasma proteins and osteoporosis: novel insights into pathological mechanisms and therapeutic implications.

This study aims to identify potential therapeutic targets for OP using summary data-based Mendelian randomization (SMR) and colocalization analysis methods. Furthermore, we seek to explore the biological significance and pharmacological value of these drug targets. To identify potential therapeutic targets for OP, we conducted SMR and colocalization analysis. Plasma protein (pQTL, exposure) data were sourced from the study by Ferkingstad et al. (n = 35,559). Summary statistics for bone mineral density (BMD, outcome) were obtained from the GWAS Catalog (n = 56,284). Additionally, we utilized enrichment analysis, protein-protein interaction (PPI) network analysis, drug prediction, and molecular docking to further analyze the biological significance and pharmacological value of these drug targets. In the SMR analysis, while 20 proteins showed significance, only 8 potential drug targets (GCKR, ERBB3, CFHR1, GPN1, SDF2, VTN, BET1L, and SERPING1) received support from colocalization (PP.H4 > 0.8). These proteins are closely associated with immune function in terms of biological significance. Molecular docking also demonstrated favorable binding of drugs to proteins, consistent with existing structural data, further substantiating the pharmacological value of these targets. The study identified 8 potential drug targets for OP. These prospective targets are believed to have a higher chance of success in clinical trials, thus aiding in prioritizing OP drug development and reducing development costs.

Rifabutin central nervous system concentrations in a rabbit model of tuberculous meningitis.

Tuberculous meningitis (TBM) has a high mortality, possibly due to suboptimal therapy. Drug exposure data of antituberculosis agents in the central nervous system (CNS) are required to develop more effective regimens. Rifabutin is a rifamycin equivalently potent to rifampin in human pulmonary tuberculosis. Here, we show that human-equivalent doses of rifabutin achieved potentially therapeutic exposure in relevant CNS tissues in a rabbit model of TBM, supporting further evaluation in clinical trials.

Assessing the Impact of Spatial and Temporal Variability in Fine Particulate Matter Pollution on Respiratory Health Outcomes in Asthma and COPD Patients.

Ambient air pollution's health impacts are well documented, yet the domestic environment remains underexplored. We aimed to compare indoor versus outdoor (I/O) air quality and estimate the association between indoor/ambient fine particulate matter (PM2.5) exposure and lung function in asthma and chronic obstructive pulmonary disease (COPD) patients. The study involved 24 h monitoring of PM2.5 levels indoors and outdoors, daily peak expiratory flow (PEF), and biweekly symptoms collection from five patients with asthma and COPD (average age of 50 years, 40% male) over a whole year. Data analysis was performed with linear mixed effect models for PEF and generalized estimating equations (GEE) for exacerbations. More than 5 million PM2.5 exposure and meteorological data were collected, demonstrating significant I/O PM2.5 ratio variability with an average ratio of 2.20 (±2.10). Identified indoor PM2.5 sources included tobacco use, open fireplaces, and cooking, resulting in average indoor PM2.5 concentrations of 63.89 μg/m3 (±68.41), significantly exceeding revised World Health Organization (WHO) guidelines. Analysis indicated a correlation between ambient PM2.5 levels and decreased PEF over 0-to-3-day lag, with autumn indoor exposure significantly impacting PEF and wheezing. The study underscores the need to incorporate domestic air quality into public health research and policy-making. A personalized approach is required depending on the living conditions, taking into account the exposure to particulate pollution.

Using syndromic surveillance to rapidly assess the impact of a June 2023 wildfire smoke event on respiratory-related emergency department visits, Massachusetts, United States

Abstract A statewide air quality advisory was issued in Massachusetts for 6–7 June 2023 due to smoke originating from wildfires in Canada. Of particular concern was fine particulate matter, which has an aerodynamic diameter of ⩽2.5 μm (PM2.5) and has been linked to adverse respiratory outcomes. The objective of this study was to rapidly assess the impact of this wildfire smoke event on respiratory-related emergency department (ED) visits among Massachusetts residents. For exposure, daily air quality index (AQI) data from the US Environmental Protection Agency were used. Massachusetts counties, where for each day from 6 to 8 June 2023, the daily AQI was ⩾101 (i.e. unhealthy air quality), were considered exposed. For each exposed period, two unexposed reference periods where AQI < 101 (i.e. ‘good’ or ‘moderate’ air quality) were identified within the two weeks prior to the exposed period, with the same days of the week and in the same county. Data from the Massachusetts Department of Public Health’s syndromic surveillance system were used to examine daily counts of ED visits for asthma, air-quality-related respiratory illness, and all causes by county of residence, age group, race, and Hispanic/Latino ethnicity. For each outcome, the numbers of ED visits were compared between the exposed and reference periods. Overall, there were no large increases in ED visits for any conditions examined during this wildfire smoke event. However, residents who were aged 18–64 years, Hispanic/Latino or White experienced small but not statistically significant increases in asthma-related ED visits. These potential differences in the effect on asthma-related ED visits by age and race/ethnicity may be relevant for analyses of future events. This study provides an example of how real-time, publicly available exposure data can be used in conjunction with outcome data from syndromic surveillance to rapidly examine the impact of wildfires and other acute environmental events on health.

Large-scale genetic correlation studies explore the causal relationship and potential mechanism between gut microbiota and COVID-19-associated risks

Recent observational studies suggest that gut microorganisms are involved in the onset and development of coronavirus disease 2019 (COVID-19), but the potential causal relationship behind them remains unclear. Exposure data were derived from the MiBioGen consortium, encompassing 211 gut microbiota (n = 18,340). The outcome data were sourced from the COVID-19 host genetics initiative (round 7), including COVID-19 severity (n = 1,086,211), hospitalization (n = 2,095,324), and susceptibility (n = 2,597,856). First, a two-sample Mendelian randomization (TSMR) was performed to investigate the causal effect between gut microbiota and COVID-19 outcomes. Second, a two-step MR was used to explore the potential mediators and underlying mechanisms. Third, several sensitivity analyses were performed to verify the robustness of the results. Five gut microbes were found to have a potential causality with COVID-19 severity, namely Betaproteobacteria (beta = 0.096, p = 0.034), Christensenellaceae (beta = -0.092, p = 0.023), Adlercreutzia (beta = 0.072, p = 0.048), Coprococcus 1 (beta = 0.089, p = 0.032), Eisenbergiella (beta = 0.064, p = 0.024). Seven gut microbes were found to have a potential causality with COVID-19 hospitalization, namely Victivallaceae (beta = 0.037, p = 0.028), Actinomyces (beta = 0.047, p = 0.046), Coprococcus 2 (beta = -0.061, p = 0.031), Dorea (beta = 0.067, p = 0.016), Peptococcus (beta = -0.035, p = 0.049), Rikenellaceae RC9 gut group (beta = 0.034, p = 0.018), and Proteobacteria (beta = -0.069, p = 0.035). Two gut microbes were found to have a potential causality with COVID-19 susceptibility, namely Holdemanella (beta = -0.024, p = 0.023) and Lachnospiraceae FCS020 group (beta = 0.026, p = 0.027). Multi-omics mediation analyses indicate that numerous plasma proteins, metabolites, and immune factors are critical mediators linking gut microbiota with COVID-19 outcomes. Sensitivity analysis suggested no significant heterogeneity or pleiotropy. These findings revealed the causal correlation and potential mechanism between gut microbiota and COVID-19 outcomes, which may improve our understanding of the gut-lung axis in the etiology and pathology of COVID-19 in the future.

Estimated Exposure to 6 Potentially Hepatotoxic Botanicals in US Adults

Use of herbal and dietary supplements (HDSs) accounts for an increasing proportion of drug hepatotoxicity cases. Turmeric or curcumin, green tea extract, Garcinia cambogia, black cohosh, red yeast rice, and ashwagandha are the most frequently reported hepatoxic botanicals, but their prevalence and reasons for use in the general population are unknown. To assess the prevalence and clinical characteristics of adult consumers of 6 potentially hepatoxic botanicals. This survey study analyzed nationally representative data from the National Health and Nutrition Examination Survey (NHANES), a nationally representative, cross-sectional survey of the general US population. Prescription drug and HDS exposure data in the past 30 days were analyzed, and 2020 US Census data were used for population estimates. Data were analyzed July 1, 2023, to February 1, 2024. Adult NHANES participants enrolled between January 2017 and March 2020. Baseline weighted characteristics of HDS users and users of 6 potentially hepatotoxic botanical products were compared with non-HDS users. Multivariable analysis was undertaken to identify factors associated with HDS use or at-risk botanical use. Among 9685 adults enrolled in this NHANES cohort, the mean (SE) age was 47.5 (0.5) years, and 51.8% (95% CI, 50.2%-53.4%) were female. The overall prevalence of HDS product use was 57.6% (95% CI, 55.9%-59.4%), while the prevalence of using the 6 botanicals of interest was 4.7% (95% CI, 3.9%-5.7%). Turmeric-containing botanicals were most commonly used (n = 236), followed by products containing green tea (n = 92), ashwagandha (n = 28), Garcinia cambogia (n = 20), red yeast rice (n = 20), and black cohosh (n = 19). Consumers of these 6 botanicals were significantly older (adjusted odds ratio [AOR], 2.36 [95% CI, 1.06-5.25]; P = .04 for 40-59 years of age and AOR, 3.96 [95% CI, 1.93-8.11]; P = .001 for ≥60 years of age), had a higher educational level (AOR, 4.78 [95% CI, 2.62-8.75]; P < .001), and were more likely to have arthritis (AOR, 2.27 [95% CI, 1.62-3.29]; P < .001) compared with non-HDS users. An estimated 15 584 599 (95% CI, 13 047 571-18 648 801) US adults used at least 1 of the 6 botanical products within the past 30 days, which was similar to the estimated number of patients prescribed potentially hepatotoxic drugs, including simvastatin (14 036 024 [95% CI, 11 202 460-17 594 452]) and nonsteroidal anti-inflammatory drugs (14 793 837 [95% CI, 13 014 623-16 671 897]). The most common reason for consuming turmeric and green tea was to improve or maintain health. In this survey study, an estimated 15.6 million US adults consumed at least 1 botanical product with liver liability within the past 30 days, comparable with the number of people who consumed nonsteroidal anti-inflammatory drugs and a commonly prescribed hypolipidemic drug. Given a lack of regulatory oversight on the manufacturing and testing of botanical products, clinicians should be aware of possible adverse events from consumption of these largely unregulated products.

On-field Head Acceleration Exposure Measurements Using Instrumented Mouthguards: Multi-stage Screening to Optimize Data Quality.

Instrumented mouthguards (iMGs) are widely applied to measure head acceleration event (HAE) exposure in sports. Despite laboratory validation, on-field factors including potential sensor skull-decoupling and spurious recordings limit data accuracy. Video analysis can provide complementary information to verify sensor data but lacks quantitative kinematics reference information and suffers from subjectivity. The purpose of this study was to develop a rigorous multi-stage screening procedure, combining iMG and video as independent measurements, aimed at improving the quality of on-field HAE exposure measurements. We deployed iMGs and gathered video recordings in a complete university men's ice hockey varsity season. We developed a four-stage process that involves independent video and sensor data collection (Stage I), general screening (Stage II), cross verification (Stage III), and coupling verification (Stage IV). Stage I yielded 24,596 iMG acceleration events (AEs) and 17,098 potential video HAEs from all games. Approximately 2.5% of iMG AEs were categorized as cross-verified and coupled iMG HAEs after Stage IV, and less than 1/5 of confirmed or probable video HAEs were cross-verified with iMG data during stage III. From Stage I to IV, we observed lower peak kinematics (median peak linear acceleration from 36.0 to 10.9g; median peak angular acceleration from 3922 to 942rad/s2) and reduced high-frequency signals, indicative of potential reduction in kinematic noise. Our study proposes a rigorous process for on-field data screening and provides quantitative evidence of data quality improvements using this process. Ensuring data quality is critical in further investigation of potential brain injury risk using HAE exposure data.

Improving spatial exposure data for everyone - lifecourse social context and ascertaining residential history.

Measuring age-specific, contextual exposures is crucial for lifecourse epidemiology research. Longitudinal residential data offers a "golden ticket" to cumulative exposure metrics and can enhance our understanding of health disparities. Residential history can be linked to myriad spatiotemporal databases to characterize environmental, socioeconomic, and policy contexts that a person experienced throughout life. However, obtaining accurate residential history is challenging in the United States due to the limitations of administrative registries and self-reports. Xu et al. (Am J Epidemiol. 2024; 193(2):348-359) detail an approach to linking residential history sourced from LexisNexis ® Accurint ® to a Wisconsin-based research cohort, offering insights into challenges with residential history collection. Researchers must analyze the magnitude of selection and misclassification biases inherent to ascertaining residential history from cohort data. A lifecourse framework can provide insights into why the frequency and distance of moves is patterned by age, birth cohort, racial/ethnic identity, socioeconomic status, and urbanicity. Historic and contemporary migration patterns of marginalized people seeking economic and political opportunities must guide interpretations of residential history data. We outline methodologic priorities for use of residential history in health disparities research, including contextualizing residential history data with determinants of residential moves, triangulating spatial exposure assessment methods, and transparently quantifying measurement error.

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

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

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

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

NTP monograph on the state of the science concerning fluoride exposure and neurodevelopment and cognition: a systematic review.

Fluoride is a common exposure in our environment that comes from a variety of sources and is widely promoted for its dental and overall oral health benefits. Contributions to an individual's total exposure come primarily from fluoride in drinking water, food, beverages and dental products. A 2006 evaluation by the National Research Council (NRC) found support for an association between consumption of high levels of naturally occurring fluoride in drinking water and adverse neurological effects in humans and recommended further investigation. The evidence reviewed at that time was from dental and skeletal fluorosis-endemic regions of China. Since the NRC evaluation, the number and location of studies examining cognitive and neurobehavioral effects of fluoride in humans have grown considerably, including several recent North American prospective cohort studies evaluating prenatal fluoride exposure. In 2016, the National Toxicology Program (NTP) published a systematic review of the evidence from experimental animal studies on the effects of fluoride on learning and memory. That systematic review found a low-to-moderate level of evidence that deficits in learning and memory occur in non-human mammals exposed to fluoride. To conduct a systematic review of the human, experimental animal, and mechanistic literature to evaluate the extent and quality of the evidence linking fluoride exposure to neurodevelopmental and cognitive effects in humans. A systematic review protocol was developed and utilized following the standardized OHAT systematic review approach for conducting literature-based health assessments. This monograph presents the current state of evidence associating fluoride exposure with cognitive or neurodevelopmental health effects and incorporated predefined assessments of study quality and confidence levels. Benefits of fluoride with respect to oral health are not addressed in this monograph. The bodies of experimental animal studies and human mechanistic evidence do not provide clarity on the association between fluoride exposure and cognitive or neurodevelopmental human health effects. Human mechanistic studies were too heterogenous and limited in number to make any determination on biological plausibility. This systematic review identified studies that assessed the association between estimated fluoride exposure and cognitive or neurodevelopmental effects in both adults and children, which were evaluated separately. The most common exposure assessment measures were drinking water concentrations and estimates of total fluoride exposure, as reflected in biomarkers such as urinary fluoride. In adults, only two high-quality cross-sectional studies examining cognitive effects were available. The literature in children was more extensive and was separated into studies assessing intelligence quotient (IQ) and studies assessing other cognitive or neurodevelopmental outcomes. Eight of nine high-quality studies examining other cognitive or neurodevelopmental outcomes reported associations with estimated fluoride exposure. Seventy-two studies assessed the association between fluoride exposure and IQ in children. Nineteen of those studies were considered to be high quality; of these, 18 reported an inverse association between estimated fluoride exposure and IQ in children. The 18 studies, which include 3 prospective cohort studies and 15 cross-sectional studies, were conducted in 5 different countries. Forty-six of the 53 low-quality studies in children also found evidence of an inverse association between estimated fluoride exposure and IQ in children. Existing animal studies provide little insight into the question of whether fluoride exposure affects IQ. In addition, studies that evaluated fluoride exposure and mechanistic data in humans were too heterogenous and limited in number to make any determination on biological plausibility. The body of evidence from studies in adults is also limited and provides low confidence that fluoride exposure is associated with adverse effects on adult cognition. There is, however, a large body of evidence on associations between fluoride exposure and IQ in children. There is also some evidence that fluoride exposure is associated with other neurodevelopmental and cognitive effects in children; although, because of the heterogeneity of the outcomes, there is low confidence in the literature for these other effects. This review finds, with moderate confidence, that higher estimated fluoride exposures (e.g., as in approximations of exposure such as drinking water fluoride concentrations that exceed the World Health Organization Guidelines for Drinking-water Quality of 1.5 mg/L of fluoride) are consistently associated with lower IQ in children. More studies are needed to fully understand the potential for lower fluoride exposure to affect children's IQ.

Higher Levels of Morning and Daytime Light Exposure Associated with Positive Sleep Indices in Professional Team Sport Athletes.

Light exposure techniques have been recommended to combat sleep issues caused by disruption to circadian regularity in the athletic population, although studies are lacking. A total of 17 professional male Australian Football athletes (age ± SD: 22 ± 3 years) wore a wrist actigraph to measure sleep parameters, and a wearable light sensor to measure melanopic equivalent daylight illuminance (mEDI, in lux) for 14 days. Participants completed three sleep questionnaires at the end of the data collection period and completed well-being surveys 6 times. The Sleep Regularity Index (SRI) for each player was also calculated from actigraphy data. Light exposure data were organised into three different timeframes: morning (wake time + 2 hours), daytime (end of morning to 6 pm), and evening (2 hours leading up to bedtime) for analysis. Repeated measures correlation was conducted for objective sleep measures and mEDI values per timeframe. Pearson's correlation was conducted on subjective sleep measures and well-being measures against mEDI values per timeframe. Higher morning light was associated with significantly (p < 0.001) greater total sleep time (r = 0.31). Higher daytime light exposure was associated with higher subjective sleep quality (r = 0.48, p < 0.05). Higher evening light exposure was associated with higher Athlete Sleep Screening Questionnaire (ASSQ) global scores (r = 0.52, p < 0.05). There were no other significant correlations between light exposure and sleep or well-being measures (p > 0.05). Higher morning and daylight exposure levels were associated with various positive objective and subjective sleep measures in professional team sport athletes, supporting the need for education on optimising light exposure to improve circadian function, sleep, and health.

Population pharmacokinetic and exposure-toxicity analyses of nab-paclitaxel after pegylated recombinant human granulocyte colony-stimulating factor administration in patients with metastatic breast cancer.

This study aimed to establish a population pharmacokinetic (PK) model to evaluate the dynamic relationship between the concentrations of total and unbound paclitaxel, and the exposure-response analysis of albumin-bound paclitaxel (nab-paclitaxel) after pegylated recombinant human granulocyte colony-stimulating factor (PEG-G-CSF) administration in patients with metastatic breast cancer. A total of 653 concentrations corresponding to total paclitaxel and 334 concentrations corresponding to unbound paclitaxel were analyzed in 24 subjects who randomized received a single 260 mg/m2 dose of two nab-paclitaxel formulations with a 21-35-day washout period. PEG-G-CSF was administered to all the patients in each cycle to prevent neutropenia. The exposure-response relationships were evaluated using the exposure to total, albumin-coated, and unbound paclitaxel, as well as the reduction in neutrophil count. The exposure data were analyzed using nonlinear mixed-effect modeling. A linear regression model was used to test the statistical significance of the correlation between percentage of reduction in neutrophil count and exposure. The PK characteristics of total paclitaxel were described using a three-compartment model with first-order elimination, and a mechanism-based model incorporating linear release of nab-paclitaxel and the saturated binding of unbound paclitaxel to plasma components was established. The release ratio of paclitaxel from nab-paclitaxel was estimated to be 4.60% and the maximum unbound fraction (2.76%) was reached at the end of the infusion. The study found that a longer duration of total paclitaxel concentration > 0.19 µmol/L was significantly correlated with a reduction in neutrophil count (r2 = 0.23, P = 0.00062). Specifically, a duration of > 8.6h was a predictor of a decreased neutrophil count. The decrease in neutrophils induced by nab-paclitaxel was significantly correlated with the duration above a total paclitaxel concentration of 0.19 µmol/L despite the use of PEG-G-CSF.

Causal role of immune cells in uveitis: a Mendelian randomization study.

Uveitis refers to a group inflammation affecting the uvea, retina, retinal blood vessels as well as vitreous body, which is one of the common causes of blindness. There is growing evidence linking different types of immune cells to uveitis, although it remains uncertain if these associations imply causal relationships. Recent advancements in high-density genetic markers like SNPs or CNVs for genotyping, along with the progress in genome-wide association studies (GWAS) technologies, have improved our understanding of the immunological mechanisms involved in ocular diseases. Therefore, our objective was to investigate the potential causal link between immune cells and uveitis using a Mendelian randomization study. The exposure and outcome GWAS data for this study were sourced from an open-access database (https://gwas.mrcieu.ac.uk/). Two-sample MR analysis was utilized to evaluate the causal relationship between 731 immune cell features and uveitis. Various MR methods were employed to reduce bias and obtain dependable estimates of the causal link between the immune cell variables and the outcomes. Instrumental variable selection criteria were carefully chosen to enhance the accuracy and efficacy of the causal relationship between different immune cell types and the risk of uveitis. Using two-sample MR, IVW modeling showed that GAD had significant effect on immunophenotypes. CD3 levels on CD45RA- CD4+ T cells (OR = 1.087, 95%CI = 1.029 ~ 1.147, p = 0.003) and CD3 levels on CM CD4+ T cells (OR = 1.086, 95%CI = 1.033 ~ 1.141, p = 0.001) were found to be elevated in cases of uveitis. HLA DR levels in CD14- CD16+ monocyte cells (OR = 0.735, 95% CI = 0.635 ~ 0.850, p < 0.001) and HLA DR levels in NK cells (OR = 0.910, 95% CI = 0.851 ~ 0.972, p = 0.005) were observed to be reduced in individuals with uveitis. Furthermore, Two cells were identified to be significantly associated with uveitis risk: HLA DR on in NK cells (OR = 0.938, 95%CI = 0.899 ~ 0.979, p = 0.003), HLA DR on CD14- CD16+ monocytes (OR = 0.924, 95%CI = 0.878 ~ 0.972, p = 0.002). This study highlights the intricate relationship between immune cells and generalized anxiety disorder using genetic methods, offering valuable insights for future clinical investigations.

Application of the occupational health risk assessment model in predicting the risk of noise-induced hearing loss in noise-polluted manufacturers in southern China

Objective. This study aimed to evaluate the correlation between occupational noise-induced hearing loss (ONIHL) and noise exposure in different positions within manufacturing facilities that primarily produce electronic devices, wooden furniture and hardware machinery in southern China and to investigate the practical application of the risk assessment model. Methods. Noise exposure data were collected from 115 workers in 10 manufacturing industries in southern China through on-site investigation. Subsequently, sample testing was conducted in accordance with Chinese standards. The 31 job positions investigated were classified into two similar exposure groups (SEGs). The occupational health risk assessment (OHRA) model was used to evaluate the risks of ONIHL in various job positions. Results. More than half of the positions in both groups had noise levels exceeding 85 dB. In both SEGs, male workers exhibited similar risk patterns of acquiring hearing impairment, with a more pronounced and earlier risk of hearing loss compared to female workers. Age was also found to be a risk factor for hearing impairments. Conclusion. The ORHA model demonstrated a positive correlation between noise exposure levels and NIHL. This model can help employers assess job management with noise exposure and take measures to implement an effective risk management system.

Social cohesion as a modifier of joint air pollution exposure and incident dementia

Social cohesion can reduce stress, increase social interaction, and improve cognitive reserve. These social mechanisms may modify the effects of air pollution on dementia risk. This cohort study examines the potential moderating effect of social cohesion on associations between joint air pollution exposure and incident dementia leveraging data from 5112 community-dwelling adults ≥65 years of age enrolled in the National Health and Aging Trends Study (NHATS). Study participants were enrolled in 2011 and followed through 2018. We assigned 2010 residential census tract-level exposures to five air pollutants, particulate matter (PM) ≤ 10 μm in diameter, PM ≤ 2.5 μm in diameter, carbon monoxide, nitric oxide, and nitrogen dioxide, using the US Environmental Protection Agency's Community Multiscale Air Quality Modeling System. Dementia status was determined based on self- or proxy-reported dementia diagnosis or “probable dementia” according to NHATS cognitive screening tools. Participants' self-rated neighborhood social cohesion was evaluated based on three questions: neighbors knowing each other, being helpful, and being trustworthy. Social cohesion was dichotomized at the median into high vs low social cohesion. Associations between air pollutants and incident dementia were assessed using quantile g-computation Cox proportional hazard models and stratified by high vs low social cohesion, adjusting for age, sex, education, partner status, urbanicity, annual income, race and ethnicity, years lived at current residence, neighborhood disadvantage index, and tract segregation. High social cohesion (HR = 1.20, 95 % CI = 0.98, 1.47) and air pollution (HR = 1.08, 95 % CI = 0.92, 1.28) were not associated with incident dementia alone. However, when stratified, greater joint air pollution exposure increased dementia risk among participants at low (HR = 1.34, 95 % CI = 1.04, 1.72), but not high (HR = 1.00, 95 % CI = 0.93, 1.06) social cohesion. Air pollution was a risk factor for dementia only when reported social cohesion was low, suggesting that social interaction may play a protective role, mitigating dementia risk via air pollution exposure.