Low Exposure Group Research Articles

Metal Exposure, Smoking, and the Risk of COPD: A Nested Case-Control Study in a Chinese Occupational Population.

Chronic obstructive pulmonary disease (COPD) was the third leading cause of death worldwide in 2019, with a significant disease burden. We conducted a nested case–control study using data from the China Metal-Exposed Workers Cohort Study (Jinchang Cohort) and assessed the associations of exposure to metals and tobacco smoking with the risk of COPD. We used the logistic regression model and the interaction multiplication model to assess the independent and combined effects of heavy metal and smoke exposure on COPD. The cumulative incidence of COPD was 1.04% in 21,560 participants during a median of two years of follow-up. The risk of COPD was significantly elevated with an increase in the amount of tobacco smoked daily (p < 0.05), the number of years of smoking (ptrend < 0.05), and the number of packs of cigarettes smoked per year (ptrend < 0.01). Compared with the low metal exposure group, the adjusted OR was 1.22 (95% CI: 0.85–1.76) in the medium exposure group (mining/production workers) and 1.50 (95% CI: 1.03–2.18) in the high exposure group; smoking and metal exposure had a combined effect on the incidence of COPD (pinteraction < 0.01), with an OR of 4.60 for those with >40 pack-years of smoking who also had the highest metal exposures. Both exposures to metals and smoking were associated with the risk of COPD, and there was an interaction between the two exposures for the risk of COPD.

Interaction of fluoride exposure and CREB1 gene polymorphisms on thyroid function in school-age children

To evaluate the effects of CREB1 gene polymorphisms and long-term exposure to fluoride on thyroid function of children. A total of 424 children (including 226 boys and 198 girls) aged 7-12 years old were enrolled in Kaifeng, China by cross-sectional study in 2017. The concentrations of urinary fluoride (UF) and creatinine (UCr) were measured using fluoride ion-selective electrode assay and creatinine assay kit (picric acid method), respectively. The concentration of UCr-adjusted UF (CUF) was calculated. Children were divided into high fluoride exposure group (HFG, CUF >1.41mg/L) and low fluoride exposure group (LFG, CUF ≤1.41mg/L) according to the median concentration of CUF (1.41mg/L). The serum thyroid-stimulating hormone (TSH), total triiodothyronine (TT3) and total thyronine (TT4) levels were detected by the radiation immunoassay. The B-mode ultrasound was performed to test the thyroid volume (Tvol). Genotyping of CREB1 gene was conducted by a custom-by-design 48-plex SNPscan™ Kit. Associations between CUF concentration, CREB1 single nucleotide polymorphisms (SNPs) and thyroid function were assessed by multiple linear regression models. Negative and positive associations between serum TT4 level (β=-0.721, 95%CI: -1.209, -0.234) and Tvol (β=0.031, 95%CI: 0.011, 0.050) and CUF concentration were observed respectively. Children carrying CREB1 rs11904814 TG and rs2254137 AC genotypes had lower TT3 levels (P<0.05). Children in HFG carrying rs11904814 TT, rs2253206 GG genotypes and rs6740584 C allele easily manifested lower serum TT4 levels (P<0.05). Moreover, interactions between excessive fluoride exposure and CREB1 SNPs on Tvol were observed, and the interaction among different loci of CREB1 gene could modify serum TT3 level (P<0.05, respectively). Fluoride could alter children's serum TT4 levels and Tvol. Interactions between fluoride exposure and CREB1 polymorphisms may modify thyroid volume of children.

Changes of GSH-PX activity and γ-GCS mRNA expression in serum of workers exposed to manganese

Objective: To explore the changes of γ-GCS mRNA expression and GSH-PX in serum of workers exposed to manganese in order to provide scientific basis for early diagnosis of manganese poisoning. Methods: In June 2017, a total of 180 workers from a motorcycle manufacturer were selected by stratified random sampling, including 115 welders as the exposure group and 65 administrative office workers as the Control Group, the exposure group was divided into high exposure group (43 persons) and low exposure group (72 persons) according to whether the exposure group exceeded the standard limit. The levels of γ-gcs Mrna expression and GSH-Px activity in serum were determined by Occupational Health Survey, and the differences of γ-gcs Mrna expression and GSH-Px activity among different groups were analyzed. Results: Compared with the control group, the serum GSH-Px activity was lower and the serum γ-GCS mRNA expression level was higher in the exposed group (F=370.52, 275.95, P<0.01) . Compared with the control group, there was significant difference in γ-GCS mRNA expression level and GSH-Px activity (F=0.475、1.06, P<0.01; F=48.53、111.70, P<0.01) . The concentrations of manganese in air, welding dust and urine were positively correlated with the level of γ-GCS mRNA (r=0.71, 0.50, 0.31, P<0.01) The serum GSH-Px activity was negatively correlated with the concentrations of manganese in air, welding dust and urine (r=-0.80, -0.52, -0.30, P< 0.01) , There was no correlation between Serum γ-GSH-Px activity and age and years of exposure (P>0.05) . Conclusion: Serum γ-GCS mRNA expression level and GSH-Px activity level can be used as early biomarkers of manganese poisoning. The concentrations of manganese in workplace air, welding dust and urine manganese in workers are the influencing factors.

Comprehensive suspect screening for the identification of contaminants of emerging concern in urine of Flemish adolescents by liquid chromatography high-resolution mass spectrometry

The increasing human exposure to contaminants of emerging concern (CECs) cannot be fully assessed by targeted biomonitoring methods alone as these are limited to a subset of known analytes. On the contrary, suspect screening approaches based on liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) allow the simultaneous detection of a high number of CECs and/or their (predicted) metabolites leading to a more comprehensive assessment of possible human exposure to these compounds. Within this study, 83 urine samples of Flemish adolescents (47 males, 36 females) collected in the frame of the 4th cycle of the Flemish Environment and Health Study (FLEHS IV) were selected with the aim of including a high and a low exposure group based on the overall exposure of 45 known contaminants. Samples were analyzed using a previously developed method involving a suspect screening approach to annotate CECs and their metabolites. The applied suspect list contained a total of >12,500 CECs and their known and predicted metabolites resulting from metabolization reactions, such as hydroxylation, glucuronidation and methylation. In total, 63 compounds were annotated at a confidence level of 3 or better, with most of the detected compounds not included in current biomonitoring programs. 5 out of the 63 compounds could be assigned with confidence level 2. Five compounds could unequivocally be identified (confidence level 1) through the comparison with reference standards. Personal care products were the main detected compound class (42% of detected compounds). Additionally, a detailed literature search indicated potential toxic effects for several of the detected CECs. Lastly, in the urine samples, a significantly higher number (p < 0.05) of compounds was detected in the high exposure group as opposed to the low exposure group. This difference could only be observed between high and low exposure load samples of female participants (p < 0.01).

Elevated exposures to persistent endocrine disrupting compounds impact the sperm methylome in regions associated with autism spectrum disorder.

Environmental exposures to endocrine disrupting compounds (EDCs) such as the organochlorines have been linked with various diseases including neurodevelopmental disorders. Autism spectrum disorder (ASD) is a highly complex neurodevelopmental disorder that is considered strongly genetic in origin due to its high heritability. However, the rapidly rising prevalence of ASD suggests that environmental factors may also influence risk for ASD. In the present study, whole genome bisulfite sequencing was used to identify genome-wide differentially methylated regions (DMRs) in a total of 52 sperm samples from a cohort of men from the Faroe Islands (Denmark) who were equally divided into high and low exposure groups based on their serum levels of the long-lived organochlorine 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), a primary breakdown product of the now banned insecticide dichlorodiphenyltrichloroethane (DDT). Aside from being considered a genetic isolate, inhabitants of the Faroe Islands have a native diet that potentially exposes them to a wide range of seafood neurotoxicants in the form of persistent organic pollutants (POPs). The DMRs were mapped to the human genome using Bismark, a 3-letter aligner used for methyl-seq analyses. Gene ontology, functional, and pathway analyses of the DMR-associated genes showed significant enrichment for genes involved in neurological functions and neurodevelopmental processes frequently impacted by ASD. Notably, these genes also significantly overlap with autism risk genes as well as those previously identified in sperm from fathers of children with ASD in comparison to that of fathers of neurotypical children. These results collectively suggest a possible mechanism involving altered methylation of a significant number of neurologically relevant ASD risk genes for introducing epigenetic changes associated with environmental exposures into the sperm methylome. Such changes may provide the potential for transgenerational inheritance of ASD as well as other disorders.

Association between secondhand smoke and cancers in adults in the US population.

Tobacco use is the leading preventable cause of cancer and premature death, smoking has a clear causal relationship with a variety of cancers. However, the relationship between exposure to secondhand smoke (SHS) and other cancers besides lung cancer is not clear. In this study, we intend to investigate the cancers mortality risks especially other cancers besides lung cancer associated with exposure to SHS. The National Health and Nutrition Examination Survey is a longitudinal population-based, nationally representative health survey and mortality rates linked to the National Death Index (NDI) database. In this study, the participants completed a questionnaire assessing sociodemographic data, anthropometry, and lifestyle information, including smoking and alcohol consumption, meanwhile, all the participants were screened for serum cotinine. First, Spearman correlation analysis was performed to confirm the correlation between serum cotinine level and exposure status. And then, exposure to SHS was divided into two groups: low exposure group (serum cotinine level between 0.015 and 10) and high exposure group (serum cotinine level ≥ 10), Cox proportional hazards regression modeling was used to evaluate the association between exposure to SHS and eight different types of smoke-related cancer. In this study, we evaluated a cohort of 25,794 US residents older than 19years from 2005 to 2016 and were followed for mortality through the February 2019. We conducted Spearman correlation analysis to confirm the correlation between serum cotinine level and exposure status (including smoking and exposure to SHS), it demonstrated the correlation coefficient between serum cotinine level and exposure to smoke was 0.976, p < 0.00001. By Cox proportional hazards regression modeling, high exposure group were found to be positively associated with all neoplasms with a total Hazard Ratio (HR) of 1.748 (95% Confidence Interval (CI), 1.415-2.159), had higher all-cause mortality risks than non-exposure to tobacco smoke. Regarding the specific types, we found the following associations: cancer of the lung (HR, 1.484; 95% CI, 1.191-1.849), stomach (HR, 1.491; 95% CI, 1.199-1.854), bladder (HR, 1.487; 95% CI, 1.198,1.846), esophageal (HR, 1.487; 95% CI 1.194-1.852), kidney (HR, 1.497; 95% CI, 1.201-1.865), pancreatic (HR, 1.479; 95% CI 1.189-1.841), leukemia (HR, 1.479; 95% CI 1.190-1.839), cervical (HR, 1.490; 95% CI 1.198-1.853). However, low exposure group were non-existent statistically significant with a Hazard Ratio (HR) of 1.062 (95% Confidence Interval (CI), 0.953-1.183). The research demonstrated that serum cotinine has a significant correlation with smoke exposure status, which confirmed serum cotinine can be used as an indicator to reflect human smoke exposure. What's more, our results confirmed high exposure of SHS (serum cotinine level ≥ 10) has a significant effect on lung, stomach, bladder, esophagus, kidney, pancreatic, leukemia, cervical cancer.

Long-term personal PM2.5 exposure and lung function alternation: A longitudinal study in Wuhan urban adults

BackgroundThe effect of long-term PM2.5 exposure on lung function has not been well established. ObjectivesTo investigate the effects of long-term personal PM2.5 exposure on lung function decline, obstructive, and restrictive ventilatory disorders. MethodPersonal PM2.5 concentrations were evaluated using an estimation model. Lung function parameters including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and peak expiratory flow (PEF) were measured in 3053 Wuhan participants from the Wuhan-Zhuhai cohort and were repeated every 3 years. Participants were classified into persistently high exposure group, persistently low exposure group and inconsistent exposure group according to the median of PM2.5 concentration of each visit. Mixed linear models with subject-specific random intercept were used to assess the association of 3-year change of lung function with personal PM2.5 exposure, and generalized linear models were used to assess the association of 6-year change of lung function with personal PM2.5 exposure. Cox regression models were applied to assess the associations of PM2.5 with obstructive and restrictive ventilatory disorders. ResultsThe medians of personal PM2.5 concentrations at baseline and two follow-ups were 153.18, 209.57 and 83.78 μg/m3, respectively. Compared with participants in the persistently low exposure group, participants in the persistently high exposure group showed a 2.99 % (95 % CI: 0.91, 5.08), a 380.15 mL/s (95 % CI: 32.82, 727.48) and a 5.98 % (95 % CI: 0.84, 11.11) additional decline in FEV1/FVC, PEF and PEFpred after 6 years, respectively. Stratified analyses showed that age, gender, body mass index, smoking status and drinking status had no significant modification effect on the associations. The associations of PM2.5 exposure with obstructive and restrictive ventilatory disorders were not significant, except for a positive association between persistently high PM2.5 exposure and restrictive ventilatory disorder among ever drinkers. ConclusionLong-term high PM2.5 exposure was associated with FEV1/FVC, PEF and PEFpred declines.

Concentrations of blood and urinary arsenic species and their characteristics in general Korean population

Arsenic (As) exposure has been extensively studied by investigating As species (e.g., inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)) in urine, yet recent research suggests that blood could be a possible biomarker of As exposure. These investigations, however, were conducted on iAs-contaminated areas, and evidence on populations exposed to low levels of iAs is limited. This study aimed to describe the levels and distributions of As species in urine and blood, as well as to estimate methylation efficiency and related factors in the Korean population. Biological samples were obtained by the Korean Ministry of Food and Drug Safety. A total of 2025 urine samples and 598 blood samples were utilized in this study. Six As species were measured using ultra-high-performance liquid chromatography with inductively coupled plasma mass spectrometry (UPLC-ICP-MS): As(V), As(III), MMA, DMA, arsenobetaine (AsB), and arsenocholine (AsC). Multiple linear regression models were used to examine the relationship between As species (concentrations and proportions) and covariates. AsB was the most prevalent species in urine and blood. The relative composition of iAs, MMA, DMA, and AsC in urine and blood differed significantly. Consumption of blue-backed fish was linked to higher levels of AsB in urine and blood. Type of drinking water and multigrain rice consumption were associated with increased iAs concentration in urine. Except for iAs, every species had correlations in urine and blood in both univariate and multivariate analyses. Adolescents and smokers presented a lower methylation efficiency (higher %MMA and lower %DMA in urine) and females presented a higher methylation efficiency (lower %iAs, %MMA, and higher %DMA in urine). In conclusion, blood iAs concentration cannot represent urinary iAs; nonetheless, different compositions of urine and blood might reflect distinct information about iAs exposure. Further investigations on exposure factors and health are needed using low-exposure groups.

Assessment of Lung Function of People, Chronically Exposed to Air Pollution in Delhi/NCR, India

Background: Air pollution in India is a serious issue with the major sources being motor vehicle emissions, thermal power stations, cooling towers, biomass burning, fuel adulteration, factory smoke, and stubble burning. Chronic exposure to ambient air pollution has obtunded effects on the development of lung function in children and detrimental effects on lung function of adults. The adverse effects of pollution on lung function increase the development of lung diseases in the future. Aims and Objective: The aim of the study was a comparison of lung function between two groups of population with different occupations, one group with outdoor occupation (high exposure) and second group with indoor occupation (low exposure). Settings and Design: It was a cross-sectional study and the sampling approach was Quota sampling. Quota sampling is a type of non-probabilistic sampling. There are certain groups of people who are particularly vulnerable to ambient air pollution because of their sustained high exposure like traffic police personnel deputed at traffic junctions, auto rickshaw driver/Taxi driver, E-Rickshaw driver plying in this area, and road side vendors this group. Low exposure group chosen were employee of offices and showrooms who are working indoor. Methods and Materials: This study was a two groups of 245 participants in each. First group with outdoor occupation and second group with indoor occupation having different level of exposure to air pollution due to their nature of occupation. Lung function parameters FEV1, FVC, FEV1/FVC, PEFR, and FEF were compared between two groups. Statistical Analysis: SPSS 26 software was used. Independent “T” test for continuous data type for different population, paired “T” test within the group, and Chi-square test for categorical data were applied. Results: Among high exposure group, 62.7% and 9.4% were found to have restrictive and normal lung function pattern, respectively. In comparison, among low exposure group, 31% and 59.5% were found to have restrictive and normal lung function pattern, respectively. Among outdoor group, there was a significant decline of lung function parameters such as FEV1, FVC, FEV1/FVC, PEFR, and FEF in comparison to indoor group. Conclusion: In this study, the lung function parameters were decreased in population working outdoor and chronically exposed to air pollution, in comparison to indoor subjects.

Effects of partial replacement of dietary flour meal with seaweed polysaccharides on the resistance to ammonia stress in the intestine of hybrid snakehead (Channa maculatus ♀ × Channa argus ♂)

The purpose of this study was to evaluate the effects of partial replacement of dietary flour meal with seaweed polysaccharides on survival rate, histology, intestinal oxidative stress levels, and expression of immune-related genes in hybrid snakeheads under acute ammonia stress. Four experimental diets were set: (C) basal diet with 0% of seaweed polysaccharides as the control group, (MR) basal diet with 10% of seaweed polysaccharides, (HR) basal diet with 15% of seaweed polysaccharides, (HF) basal diet with 10% of fish oil. After 60 days of feeding, fish fed with the diet of C group were sampled as the control group, and other fish were exposed to ammonia nitrogen for 48 h. Two concentrations of total ammonia nitrogen (TAN) were used in this study: 120 mg/L TAN (low concentration exposure group), and 1200 mg/L TAN (high concentration exposure group). After exposure to ammonia nitrogen for 48 h, fish were sampled. The results indicated that adding seaweed polysaccharides to the diet could improve the survival rate of hybrid snakeheads under high concentration of ammonia stress. Histopathological analysis demonstrated multiple abnormalities in gills and intestines after exposure to two concentrations of TAN. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and lactate dehydrogenase (LDH) were all increased in the MR group under two concentrations of TAN stress. The mRNA abundance of immune-related genes in fish intestinal tissues was significantly induced or inhibited. These results suggested that partial replacement of dietary flour meal with seaweed polysaccharides improved the ability of hybrid snakeheads to resist ammonia stress.

Association of serum bisphenol AF concentration with depressive symptoms in adolescents: A nested case–control study in China

BackgroundAs an important alternative to bisphenol A (BPA), bisphenol AF (BPAF) is widely used and can be detected in multiple human biological samples. However, there are few studies on neurotoxicity of BPAF at present. In particular, no epidemiological studies have investigated BPAF in relation to depressive symptoms in adolescents. Here, our study aimed to evaluate the associations between serum BPAF concentrations and depressive symptoms in adolescents. MethodsA nested case-control study within an ongoing longitudinal prospective adolescent cohort that was established in Huaibei, China was conducted. A total of 175 participants who had new-onset depressive symptoms (cases) and 175 participants without depressive symptoms (controls) were included. Serum BPAF concentrations was measured using ultra–high–performance liquid chromatography–tandem mass spectrometry. The associations between BPAF exposure and the risk of depressive symptoms in adolescents were assessed using conditional logistic regression. The dose-response relationship between BPAF level and depressive symptoms was estimated using restricted cubic spline analyses. ResultsIn this study, the detection rate of serum BPAF was 100%, and the median (interquartile range, IQR) serum BPAF concentration was 5.24 (4.41–6.11) pg/mL in the case group and 4.86 (4.02–5.77) pg/mL in the control group (P = 0.009). Serum BPAF exposure was a risk factor for depressive symptoms (odds ratio (OR)= 1.132, 95% confidence interval (CI):1.013–1.264). After adjustment for all for confounders, compared with the low–exposure group, the high–exposure group had a 2.806-fold increased risk of depressive symptoms (OR=2.806, 95% CI: 1.188–6.626). Stratified analysis by sex revealed that males were more vulnerable to BPAF exposure than females. After adjustment for all confounders, compared with the low-exposure group, the relative risk of depressive symptoms in the high-exposure group was 3.858 (95% CI: 1.118–12.535) for males, however, no significant association between BPAF exposure and depressive symptoms was found in females. In addition, there was a marked linear association between BPAF exposure and the risk of depressive symptoms in the total population and in males. ConclusionsThe adolescents in this study were widely exposed to low levels of BPAF. A significant positive association was found between serum BPAF levels and the risk of depressive symptoms. The association was significantly modified by sex, and males were more vulnerable to BPAF exposure than females.

Exposure to Per- and Polyfluoroalkyl Substances and Mortality in U.S. Adults: A Population-Based Cohort Study.

Background:Per- and polyfluoroalkyl substances (PFAS) are widespread environmental contaminants associated with diseases such as cancer and dyslipidemia. However, few studies have investigated the association between PFAS mixture exposure and mortality in general populations.Objectives:This study aimed to explore the association between PFAS mixture, perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS) and mortality in U.S. adults by a nationally representative cohort.Methods:Adults of age who were enrolled in the National Health and Nutrition Examination Survey (NHANES) (1999–2014) were included in our study. Baseline serum concentrations of seven PFAS were measured and individuals were followed up to 31 December 2015. Hazard ratios (HRs) and confidence intervals (CIs) were estimated using Cox proportional hazards models. Association between PFAS mixture exposure and mortality was analyzed using the k-means method by clustering PFAS mixtures into subgroups. Association between PFOA/PFOS exposure and mortality was subsequently analyzed in both continuous and categorical models.Results:During the follow-up period, 1,251 participants died. In the mixture analysis, the k-means algorithm clustered participants into low-, medium-, and high-exposure groups. Compared with the low-exposure group, participants in the high-exposure group showed significantly higher risks for all-cause mortality (; 95% CI: 1.07, 1.80), heart disease mortality (; 95% CI: 1.05, 2.51), and cancer mortality (; 95% CI: 1.08, 2.84). In single PFAS analysis, PFOS was found to be positively associated with all-cause mortality (third vs. first tertile ; 95% CI: 1.22, 2.07), heart disease mortality (third vs. first tertile ; 95% CI: 1.09, 2.57), and cancer mortality (third vs. first tertile ; 95% CI: 1.10, 2.83), whereas PFOA exposure had no significant association with mortality. Assuming the observed association is causal, the number of deaths associated with PFOS exposure ( vs. ) was (95% CI: 176,000, 588,000) annually between 1999 and 2015, and it decreased to 69,000 (95% CI: 28,000, 119,000) annually between 2015 and 2018. The association between PFOS and mortality was stronger among women and people without diabetes.Discussion:We observed a positive association between PFAS mixture exposure and mortality among U.S. adults. Limitations of this study include the potential for unmeasured confounding, selection bias, a relatively small number of deaths, and only measuring PFAS at one point in time. Further studies with serial measures of PFAS concentrations and longer follow-ups are necessary to elucidate the association between PFAS and mortality from specific causes. https://doi.org/10.1289/EHP10393

TWO-YEAR RESPONSES OF HEART RATE AND HEART RATE VARIABILITY TO FIRST OCCUPATIONAL LEAD EXPOSURE

Objective: Because of the falling lead exposure, the literature relating autonomous nervous function to blood lead has limited relevance. Design and method: In the longitudinal Study for Promotion of Health in Recycling Lead (URL: https://www.clinicaltrials.gov; Unique identifier: NCT02243904), we recorded the 2-year responses of heart rate, heart rate variability (Cardiax, International Medical Equipment Developing, Budapest, Hungary), and median nerve conduction velocity (Brevio, NeuMed, West Trenton, NJ), a routine test in occupational medicine, to first lead exposure in 195 newly hired workers (91.3% men; mean age, 27.8 years). High- and low-frequency heart rate variability power and orthostatic heart rate variability responses were derived from 5-minute eletrocardiograms in the supine and standing positions by Fourier transform and autoregression. Blood lead was determined by inductively coupled plasma mass spectrometry. Results: From baseline to follow-up, blood lead increased from 4.22 to 14.1 ug/dL and supine/standing HR from 63.6/75.5 to 67.1/78.8 beats per minute. In analyses stratified by fourths of blood lead changes, trends in heart rate and Fourier/autoregressive heart rate variability did not reveal a dose-response curve (0.074&lt; = P&lt; = 0.98). In multivariable-adjusted mixed models, heart rate, Fourier/autoregressive heart rate variability, and nerve conduction velocity changes were unrelated to blood lead except for a weak inverse association between supine heart rate and blood lead changes (-0.55%; P = 0.029). The expected associations between heart rate variability and heart rate changes were preserved with no differences at baseline/follow-up. Analyses ichotomised by baseline median blood lead or cumulative blood lead index (4.30 ug/dL or 32.1 ug/dL × year) suggested an heart rate variability increase versus decrease in the low versus high baseline exposure group. Conclusions: Thus, a &gt; 3-fold blood lead increment did not affect autonomous neural function as captured by heart rate variability.

Realistic biomarkers from plasma extracellular vesicles for detection of beryllium exposure

PurposeExposures related to beryllium (Be) are an enduring concern among workers in the nuclear weapons and other high-tech industries, calling for regular and rigorous biological monitoring. Conventional biomonitoring of Be in urine is not informative of cumulative exposure nor health outcomes. Biomarkers of exposure to Be based on non-invasive biomonitoring could help refine disease risk assessment. In a cohort of workers with Be exposure, we employed blood plasma extracellular vesicles (EVs) to discover novel biomarkers of exposure to Be.MethodsEVs were isolated from plasma using size-exclusion chromatography and subjected to mass spectrometry-based proteomics. A protein-based classifier was developed using LASSO regression and validated by ELISA.ResultsWe discovered a dual biomarker signature comprising zymogen granule protein 16B and putative protein FAM10A4 that differentiated between Be-exposed and -unexposed subjects. ELISA-based quantification of the biomarkers in an independent cohort of samples confirmed higher expression of the signature in the Be-exposed group, displaying high predictive accuracy (AUROC = 0.919). Furthermore, the biomarkers efficiently discriminated high- and low-exposure groups (AUROC = 0.749).ConclusionsThis is the first report of EV biomarkers associated with Be exposure and exposure levels. The biomarkers could be implemented in resource-limited settings for Be exposure assessment.

Association between cadmium and lead co-exposure, blood pressure, and hypertension: a cross-sectional study from northwest China

Cadmium (Cd) and lead (Pb) co-exposure have been inconsistently associated with blood pressure (BP) and hypertension (HTN). This cross-sectional study included 309 participants who completed a health examination and had blood Cd (Cd-B) and Pb (Pb-B) levels measured. The association between Cd, Pb, and their combined exposure levels, with systolic (SBP) and diastolic blood pressure (DBP) and HTN was evaluated using models which were stratified according to sex, age, BMI, and smoking habit categories. The results found both increasing Cd-B and Pb-B were associated with elevated SBP and DBP in the overall population. In addition, increases in Cd-B and Pb-B were also associated with increased risk of HTN in overall and stratified models. Moreover, compared with the low exposure group, co-exposure to high levels of Cd and Pb was associated with increased SBP (β = 10.95, 95% CI: 5.69, 16.21), increased DBP (β = 5.09, 95% CI: 1.53, 8.66), and increased HTN risk (OR = 2.45, 95% CI: 1.15, 5.21) in the overall model, and above results were different in the stratified model. This study provides evidence of an association between Cd and/or Pb exposure levels, BP, and HTN. However, the significance of this association differed according to sex, age, BMI, and smoking habit. Highlights Cadmium/lead exposure is associated with elevated blood pressure and hypertension. Cadmium and lead co-exposure increased blood pressure in a dose-dependent manner. Results revealed differences according to sex, age, BMI, and smoking habit category. Health oversight should be implemented for residents with high heavy metal exposure.

Evaluating the Dissemination and Implementation of a Community Health Worker-Based Community Wide Campaign to Improve Fruit and Vegetable Intake and Physical Activity among Latinos along the U.S.-Mexico Border.

This study evaluated the dissemination and implementation of a culturally tailored community-wide campaign (CWC), Tu Salud ¡Si Cuenta! (TSSC), to augment fruit and vegetable (FV) consumption and physical activity (PA) engagement among low-income Latinos of Mexican descent living along the U.S.-Mexico Border in Texas. TSSC used longitudinal community health worker (CHW) home visits as a core vehicle to enact positive change across all socioecological levels to induce behavioral change. TSSC’s reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) was examined. A dietary questionnaire and the Godin-Shepherd Exercise Questionnaire measured program effectiveness on mean daily FV consumption and weekly PA engagement, respectively. Participants were classified based on CHW home visits into “low exposure” (2–3 visits) and “high exposure” (4–5 visits) groups. The TSSC program reached low-income Latinos (n = 5686) across twelve locations. TSSC demonstrated effectiveness as, compared to the low exposure group, the high exposure group had a greater FV intake (mean difference = +0.65 FV servings daily, 95% CI: 0.53–0.77) and an increased PA (mean difference = +185.6 MET-minutes weekly, 95% CI: 105.9–265.4) from baseline to the last follow-up on a multivariable linear regression analysis. Multivariable logistic regression revealed that the high exposure group had higher odds of meeting both FV guidelines (adjusted odds ratio (AOR) = 2.03, 95% CI: 1.65–2.47) and PA guidelines (AOR = 1.36, 95% CI: 1.10–1.68) at the last follow-up. The program had a 92.3% adoption rate, with 58.3% of adopting communities meeting implementation fidelity, and 91.7% of communities maintaining TSSC. TSSC improved FV consumption and PA engagement behaviors among low-income Latinos region wide. CHW delivery and implementation funding positively influenced reach, effectiveness, adoption, and maintenance, while lack of qualified CHWs negatively impacted fidelity.

Integrative Analysis of Pharmacokinetic and Metabolomic Profiles for Predicting Metabolic Phenotype and Drug Exposure Caused by Sotorasib in Rats.

Sotorasib is a novel targeted inhibitor of Kirsten rat sarcoma (KRAS) (G12C) that has shown exciting tumor-suppressing effects not only for single targeted agents but also for combination with immune checkpoint inhibitors. However, no integrative analysis of the pharmacokinetics (PK) and pharmacometabolomics (PM) of sotorasib has been reported to date. In the present study, a sensitive and robust high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) method was firstly developed and fully validated for the quantitation of sotorasib in rat plasma. After one-step protein precipitation, sotorasib and an internal standard (carbamazepine) were separated on a Waters XBrige C18 column (50 mm × 2.1 mm, 3.5 μm) and analyzed in electrospray ionization positive ion (ESI+) mode. The optimized method was fully validated according to guidance and was successfully applied for the PK study of sotorasib at a dose of 10 mg/kg. In addition, a longitudinal and transversal PM was employed and correlated with PK using partial least squares model and Pearson’s analysis. With multivariate statistical analysis, the selected six (AUC model) and nine (C max model) metabolites completely distinguished the high- and low-exposure groups after sotorasib treatment, which indicates that these potential biomarkers can predict drug exposure or toxicity. The results of this study will not only shed light on how sotorasib disturbs the metabolic profiles and the relationship between PK and PM but also offer meaningful references for precision therapy in patients with the KRAS (G12C) mutation.

Impact of hydroxyurea dose and adherence on hematologic outcomes for children with sickle cell anemia.

Hydroxyurea is the primary treatment for sickle cell anemia (SCA), yet real-world implementation in high-income settings is suboptimal. Variation in prescribed hydroxyurea dose and patient adherence in these settings can both affect actual exposure to hydroxyurea. Quantifying the contributions of hydroxyurea dose and medication adherence to the relationship between hydroxyurea exposure and hematologic parameters could inform strategies to optimize exposure and improve outcomes. We evaluated the relationship between hydroxyurea exposure, defined by average prescribed dose and adherence, and hematologic parameters using data from children with SCA who were enrolled in two prospective hydroxyurea adherence studies. Hydroxyurea adherence was assessed by video directly observed therapy or electronic pill bottle and medication administration record. Average prescribed dose was abstracted from prescriptions in patients' electronic medical record. Participants with a hydroxyurea exposure >20mg/kg/day and ≤20mg/kg/day were included in the higher and lower exposure groups, respectively. Forty-five participants were included in the analysis (56% male; median age 12years [range 2-19]; 98% Black). Higher exposed participants (n=23) were prescribed a higher dose (27.2 vs. 24.4mg/kg/day, p=.002) and had better adherence (0.92 vs. 0.71, p≤.001) compared to lower exposed participants (n=22). Higher exposure was associated with higher fetal hemoglobin (p=.04) and mean corpuscular volume (p=.02). Higher hydroxyurea exposure is associated with improved hematologic parameters in the high-income setting and is affected by both prescribed dose and adherence. Future studies are needed to optimize both adherence and hydroxyurea prescribing and confirm that increasing exposure improves clinical outcomes in this setting.

Moderate Sun Exposure Is the Complementor in Insufficient Vitamin D Consumers.

Background and AimsVitamin (Vit) D plays a vital role in human health, and the prevalence of Vit D deficiency worldwide has been a rising concern. This study investigates the serum 25-hydroxy-Vit D [25(OH)D] status in healthy US civilians and identifies how the two main sources, sun exposure and dietary Vit D intake, determine the final 25(OH)D levels in individuals.MethodsA total of 2,360 of participants from The National Health and Nutrition Examination Survey (NHANES) 2009–2014 were analyzed. We divided the levels of sun exposure and dietary Vit D intake of all subjects into 10 strata and gave a score ranging from 1 to 10 points, respectively. Scores 1–5 in sun exposure and dietary intake were considered as relatively low exposure groups, whereas scores 6–10 were considered as relatively high exposure groups. Serum Vit D inadequacy was defined as <50 nmol/L. Linear and logistic regression analyses were used to examine the associations between sources of Vit D and serum 25(OH)D levels.ResultsIn relatively low Vit D intake groups (Vit D intake score 1–5), relatively high sun exposure (sun exposure score >5) resulted in higher serum 25(OH)D levels (average 57 nmol/L) compared with relatively low sun exposure (sun exposure score <5) (average 50 nmol/L), whereas this difference became negligible in high intake groups (Vit D intake score 6–10). Moreover, the greatest slope occurred in the low Vit D intake curve (decile 3 of Vit D intake), which shows increased sun exposure time causing the greatest degree of change in serum 25(OH)D level in this group.ConclusionSun exposure can significantly make up for deficiencies in subjects who consume insufficient dietary Vit D. Compared with the extra cost and time for building habits of Vit D supplementation, moderate sun exposure appears to be a simple and costless means for the public to start in daily practice.

The association between environmental cadmium exposure, blood pressure, and hypertension: a systematic review and meta-analysis.

We performed a systematic and meta-analysis study to find the association between cadmium (Cd) exposure and blood pressure (BP)/hypertension (HTN) in exposed general populations. We searched main databases for literature published between year 2000 and April 15, 2021. Qualityassessmentwasperformedwiththe Joanna Briggs Institute (JBI) critical appraisal tools.Heterogeneity between studies was determined by I-squared (I2) statistic. The random effects model was used todeterminethe association between blood and urine Cd levels with hypertension.The overall standard differences in mean for Cd level in hypertensive and control groups were 3.34, 1.79, and 8.09 based on samples from blood, urine, and hair, respectively. The overall standard differences in mean for Cd level in the low and high exposure groups were - 0.795 and - 1.036 based on blood and urinary samples, respectively. Our findings indicate a positive relationship between blood and hair Cd levels and hypertension. We also found that hair is the optimal biological sample to find the relationship between Cd exposure and hypertension for both genders. However, more studies are needed to confirm these findings.