Weighted Quantile Sum Regression Research Articles

Using Four Machine Learning Methods to Analyze the Association Between Polycyclic Aromatic Hydrocarbons and Visual Impairment in American Adults: Evidence from NHANES

The causes of visual impairment are complex and may be influenced by exposure to environmental pollutants. Using data from the 2003–2004 National Health and Nutrition Examination Survey (NHANES), we examined the association between exposure to ten polycyclic aromatic hydrocarbons (PAHs) and vision problems in 1149 U.S. adults. We employed various supervised learning methods, including variable selection techniques such as Lasso and elastic net, weighted quantile sum regression (WQS), and Bayesian kernel machine regression (BKMR), to assess the association between PAHs and the occurrence of visual impairments. The mediation effects between urinary 2-fluorene and inflammation were evaluated using mediation analysis. Both the lasso and elastic net models consistently identified two specific PAH congeners, 2-fluorene and 1-phenanthrene, as significant predictors. The WQS regression revealed a positive relationship between the PAH mixture and visual impairment, with notable contributions from urinary 2-fluorene (weight = 0.39) and 9-fluorene (weight = 0.21). BKMR analysis indicated that the likelihood of visual impairment increases with higher PAH exposure, showing a general upward trend. This trend also revealed a positive association between visual impairment and exposure to four specific PAH metabolites, including 2-fluorene. A significant mediation effect was observed for alkaline phosphatase (p = 0.03), with a proportion mediated of 10.48%. Our findings suggest a significant association between PAHs and visual impairment, with multiple statistical models consistently emphasizing the crucial role of 2-fluorene exposure. This study highlights the importance of considering environmental pollutants as significant contributors to visual health outcomes, providing insights for preventing visual impairment.

Heart failure risk assessment using biomarkers in patients with atrial fibrillation: analysis of 32,041 patients from the COMBINE-AF study

Abstract Introduction Heart failure (HF) is one of the most common comorbidities in patients with AF, resulting in a clinical need for robust risk assessment. Purpose To investigate the incremental value of adding NTproBNP, high-sensitivity cardiac troponin T (hs-cTnT), and growth-differentiation factor-15 (GDF-15) to clinical predictors for HF risk stratification in patients with AF, and the individual contribution of each biomarker accounting for inter-biomarker correlation. Methods We used pooled individual patient data from 3 large RCTs investigating DOACs versus VKAs (ARISTOTLE, ENGAGE AF-TIMI 48, RE-LY) from the COMBINE-AF cohort and included all patients with available biomarkers at baseline. The composite primary endpoint was hospitalization for HF (HHF) or CV death (CVD), with HHF as secondary endpoint. We employed analyses of absolute risk and Cox-regression adjusting for clinical factors to assess the association of the individual biomarkers with both endpoints, testing incremental discrimination with the likelihood ratio test from nested models. To address the inter-biomarker correlation, weighted quantile sum (WQS) regression analysis summarizing the adjusted risk of all biomarkers (per quartile) in one index was applied, thereby exploring the individual and additive contribution of each biomarker to risk assessment. Results Data were available in 32,041 patients (median age 71 [IQR 64-77] years, 36.7% female, 23.0% with paroxysmal AF, 41.6% with established HF). Higher biomarker values were associated with a graded increase in absolute risk for HHF/CVD and HHF (Figure 1). In a model adjusting for clinical variables and all biomarkers, hs-cTnT (HR per 1-SD 1.39 [95% CI 1.33-1.44]), NT-proBNP (HR 1.67 [95% CI 1.58-1.76]), and GDF-15 (HR 1.20 [95% CI 1.15-1.25]) were associated with HHF/CVD. The c-index increased with addition of biomarkers (0.70 [0.69, 0.70] to 0.77 [0.76, 0.78]; Likelihood ratio test p<0.001). Results were similar for HHF alone. NTproBNP was significantly correlated with hs-cTnT (r=0.40, p<0.0001) and GDF-15 (r=0.36, p<0.001). To address this correlation, WQS regression analysis was conducted (Figure 2). NTproBNP and hs-cTnT contributed nearly equally to the risk assessment for HHF/CVD and HHF, with GDF-15 providing statistically significant but less contribution to risk assessment (Figure 2). Conclusion Hs-cTnT, NT-proBNP and GDF-15 contribute individually and additively to the risk assessment for HHF/CVD and HHF in patients with AF. Our analysis suggests that hs-cTnT is as important as NTproBNP for HF risk assessment, with significant but less contribution of GDF-15. Our findings support the possible future routine use of biomarkers to distinguish patients with AF at low or high risk for HF and could guide the introduction of therapies to mitigate the risk of HF events in this growing population.Event incidence by biomarker quartilesWeighted quantil sum regression analysis

A cross-sectional study of the association between blood metal mixtures exposure and hyperuricemia.

To determine the association between blood metal mixture and HUA risk. A cross-sectional study was performed based on the populations from Kailuan cohort trial in China. Inductively coupled plasma mass spectrometry was utilized to detect the blood concentrations of iron (Fe), lead (Pb), calcium (Ca), copper (Cu), magnesium (Mg), zinc (Zn), selenium (Se), and manganese (Mn). Multivariate logistic regression (MLR) models and weighted quantile sum (WQS) regression models were employed to assess the relationships. There were 3706 participants included in this study, and 464 (12.52%) were with HUA. The mean level of uric acid was 485.60μmol/L in the subjects with HUA, which was remarkably increased compared to those without HUA (293.10μmol/L). The multivariate-adjusted odds ratios (95% confidence intervals) of HUA were 2.15 (1.40, 3.29) for Pb, 3.42 (2.24, 5.23) for Fe, 1.61 (1.15, 2.25) for Ca, 3.06 (2.04, 4.59) for Mg, and 1.69 (1.26, 2.28) for Zn by comparing the highest and lowest metal quartiles using the single-metal logistic regression model. Meanwhile, the WQS regression models demonstrated a positive association between metal mixtures and HUA risk, to which, Fe, Mg, Pb, and Zn were the major contributors. Pb, Fe, and Zn were still robust in multiple-metal models. Age, gender, weight, smoking, and drinking status could modify these relationships with significant interactions. Co-exposure to Fe, Pb, Ca, Cu, Zn, Mg, Se, and Mn were related to increased HUA risk in Chinese adults, of with, Pb, Fe, and Zn appeared to have greater impacts. These relationships were more obvious in adults aged < 60years, or women, or overweight, or non-smoking, or drinking with significant interactions. Key Points • Increased Fe, Pb, Mg, Ca, and Zn were related to increased HUA risk in dose-response fashion among Chinese adults. • The metal mixture dominated by Fe, Mg, Pb, and Zn was positively associated with HUA risk. Fe, Pb, and Zn were still robust in MM model. • Such association was stronger showed in adults aged < 60years, or women, or overweight, or non-smoking, or drinking with significant interactions.

Correlation of dietary flavonoid intake with chronic bronchitis, emphysema, and asthma in U.S. adults: A large, national, cross-sectional study.

To explore the relationship between dietary flavonoids and bronchitis, emphysema and asthma. A total of 11743 United States adults were extracted from the National Health and Nutrition Examination Survey (NHANES) in 2007-2008, 2009-2010 and 2017-2018. Of these, 47.7% were male and 52.3% female. Dietary flavonoid intake assessed using FDNNS and 24-hour dietary recall data. Inclusion of demographics (gender, age, education, family income), behavioral factors (BMI, smoking, drinking status, diet), chronic disease information (diabetes, hypertension) as covariates to eliminate confounding. Stepwise logistic regression was used to analyze the association between total dietary flavonoid intake and the risk of chronic respiratory disease. Weighted quantile sum regression (WQS) was used to analyze the association between 29 dietary flavonoids and the risk of chronic respiratory disease. Restricted cubic spline was used to analyze the dose-response relationship between dietary flavonoid intake and risk of chronic respiratory disease. Stepwise logistic regression results showed that higher flavonoid intake in men was associated with a lower risk of CB and asthma (OR of CB: 0.55(0.31-0.97); OR of asthma: 0.72(0.52-0.99)), and WQS results showed a mixed health effect for total flavonoids and chronic respiratory tract in response to the 29 flavonoid fractions (OR of asthma: 0.97(0.94-0.99); OR of emphysema: 0.95(0.90-0.99)). Glycitein had the highest health contribution of 26.2% for emphysema; Eriodictyol had the highest health contribution of 32.13% for asthma, respectively. The RCS showed a dose-response relationship between flavonoids and respiratory tract health. The maximum dose for ingesting flavonoids to gain respiratory health benefits is 1500 mg/d. Higher dietary flavonoid intake was associated with lower chronic respiratory risk in adult U.S. men. Also 29 dietary flavonoid components have an overall health effect on respiratory health. Glycitein and Eriodictyol may have potential health effects on the respiratory system. 1500 mg/day may be the Tolerable Upper Intake Level of dietary flavonoids for respiratory health in U.S. adults.

Thyrotoxic Effects of Mixed Exposure to Perfluorinated Compounds: Integrating Population-Based, Toxicogenomic, Animal, and Cellular Evidence to Elucidate Molecular Mechanisms and Identify Potential Effector Targets.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are emerging environmental endocrine disruptors that may adversely affect the human endocrine system, particularly the thyroid gland, the largest endocrine gland in the human body. An epidemiologic survey was conducted involving 318 community residents in Shanghai, China, to assess PFAS exposure levels. The relationship between PFAS exposure and five thyroid function indicators was analyzed using Bayesian Kernel Regression (BKMR) and Weighted Quantile Sum Regression (WQS). Ten effector genes related to PFAS and thyroid diseases were identified through the Comparative Toxicogenomics Database (CTD) for bioinformatics analysis and pathways involved were explored through mediation analysis. In vivo validation of these effector genes was conducted using PCR, complemented by in vitro cellular experiments involving transcriptome sequencing and the construction of animal models to simulate mixed PFAS exposure in the general population. Mixed PFAS exposure was found to impact thyroid health primarily through pathways related to lipid metabolism in toxicogenomic studies and resulted in the upregulation of key genes associated with lipid metabolism in animal models. Our results demonstrate that PFAS exposure could affect the expression of lipid metabolism pathways through the modulation of transcription factors, contributing to the development of thyroid disease.

Identifying effects of volatile organic compounds exposure on kidney stone prevalence in U.S. adults: a cross-sectional analysis of NHANES 2007-2020.

Our aim was to comprehensively investigate the relationship between blood volatile organic compounds (VOCs) and kidney stone prevalence for U.S. adults. In this cross-sectional study, 10,052 participants from the 2007-2020 National Health and Nutrition Examination Survey (NHANES) were included. Multivariate logistic regression model was employed to investigate the association between 9 blood VOCs and kidney stones. We explored the dose-response relationship between blood VOCs and kidney stones using restricted cubic spline (RCS) analysis. Additionally, weighted quantile sum (WQS) regression model was performed to assess the overall association of 9 blood VOCs with kidney stones. Finally, subgroup analyses were conducted to identify the findings in different populations at high prevalence. Logistic regression analysis and dose-response risk curves revealed that blood benzene (aOR = 1.308, 95% CI: 1.118-1.530, P = 0.001), blood ethylbenzene (aOR = 1.280, 95% CI: 1.054-1.554, P = 0.013), blood m-/p-xylene (aOR = 1.187, 95% CI: 1.008-1.398, P = 0.040), blood 2,5-dimethylfuran (aOR = 1.319, 95% CI: 1.135-1.533, P < 0.001) and blood furan (aOR = 1.698, 95% CI: 1.305-2.209, P < 0.001) were positively associated with the prevalence of kidney stones. WQS regression analysis revealed that exposure to mixed blood VOCs was positively correlated with kidney stone prevalence (OR = 1.34, 95% CI: 1.14-1.57), with furans carrying the greatest weight. Subgroup analyses suggested that kidney stones were more susceptible to the effects of blood VOCs in young and middle-aged, female, overweight and obese, non-hypertensive, and non-diabetic populations. In this study, the results indicated that high VOC exposure was positively and independently associated with kidney stones in U.S. adults. This finding highlighted the need for public health strategies to reduce VOC exposure and its role in kidney stone prevention and treatment.

Exposure to PM2.5 and its constituents in relation to thyroid function of pregnant women: Separate and mixture analyses

The relationships between exposure to PM2.5 and its constituents and thyroid hormone (TH) levels in pregnant women are still uncertain, particularly regarding the impact of mixed exposure to PM2.5 constituents on thyroid function during pregnancy. This study aimed to investigate the individual and mixed effect of PM2.5 and its constituents on TH levels during pregnancy. Fluorescence and chemiluminescence immunoassays were utilized to measure serum concentrations of free thyroxine (FT4) and thyroid-stimulating hormone (TSH) in pregnant women participating in the Fujian Birth Cohort Study (FJBCS). PM2.5 and its constituents were obtained from the ChinaHighAirPollutants dataset. Generalized linear regression model and mixture analysis were applied to explore the individual and mixed effect of PM2.5 and its constituents on TH levels. 13711 participants from the FJBCS were taken into the final analysis. In the context of separate exposure, an increase of one interquartile range (IQR) in PM2.5 exposure during the 1st trimester, 2nd trimester, and entire pregnancy was associated with a decrease of −0.042 (−0.050, −0.034), −0.017 (−0.026, −0.009), and −0.011 (−0.017, −0.004) in FT4 level, respectively. As well, significant negative associations were observed between FT4 level and PM2.5 constituents. Additionally, PM2.5 and its constituents were in relation to an increased risk of hypothyroxinemia in pregnant women. It is noteworthy that, in the context of mixed exposure, the weighted quantile sum regression (WQS) indices were significantly associated with both FT4 level (1st trimester: −0.031 (−0.036, −0.026); 2nd trimester: −0.026 (−0.030, −0.023); whole pregnancy: −0.024 (−0.028, −0.020)) and hypothyroxinemia risk (1st trimester: 1.552 (1.312, 1.821); 2nd trimester: 1.453 (1.194, 1.691); whole pregnancy: 1.402 (1.152, 1.713)). PM2.5 and its chemical constituents may affect thyroid function in pregnant women individually and in combination, with the effect observed during early gestational exposure being most pronounced.

Association between dietary intake of carotenoids and metabolic dysfunction-associated fatty liver disease in US adults: National Health and Nutrition Examination Survey 2017-March 2020.

To assess the relationship between dietary intake of α-carotene, β-carotene, β-cryptoxanthin, lycopene and lutein+zeaxanthin (LZ) and occurrence of metabolic dysfunction-associated fatty liver disease (MAFLD). Cross-sectional study design. The MAFLD diagnosis was based on hepatic steatosis and metabolic dysregulation. Carotenoid intake was adjusted for using an energy-adjusted model. Logistic regression and restricted cubic spline (RCS) analyses were used to assess the relationships, with sensitivity analysis to validate the findings. Weighted quantile sum regression (WQS) was used to explore the combined effect of these carotenoids on MAFLD. Subgroup analyses were conducted to identify population-specific associations. National Health and Nutrition Examination Survey (NHANES) 2017-March 2020. This study included 5098 individuals aged 18 years and older. After adjusting for potential confounders, a weak inverse association was observed between α-carotene and β-carotene intakes and MAFLD occurrence (all P value <0·05). The highest quartile of β-carotene intake showed a significantly lower occurrence of MAFLD compared with the lowest quartile (OR = 0·65; 95 % CI: 0·44, 0·97). RCS analysis showed that a significantly lower occurrence of MAFLD was associated with a higher intake of the four carotenoids, excluding lycopene. Furthermore, the WQS analysis revealed a negative relationship between combined carotenoid intake and MAFLD occurrence (OR = 0·95, 95 % CI: 0·90, 1·00, P = 0·037). Subgroup analyses showed dietary carotenoid intake was associated with reduced MAFLD occurrence in populations aged 50-69 years, females, physically active individuals and non-drinkers. Higher dietary intake of carotenoids is associated with lower MAFLD occurrence. However, this relationship varies among individuals of different ages, sexes and lifestyles.

Uncovering the relationship between trace element exposure, cognitive function, and dietary inflammation index in elderly americans from the National Health and Nutrition Examination Survey 2011–2014

BackgroundThe consequences of trace element exposure on cognitive function in elderly adults have been recognized as primarily attributed to the inflammatory response. It is noteworthy that diet can either exacerbate or reduce the inflammatory response. Despite this, there have been limited studies about the effects of diet on the relationship between trace element exposure and cognitive function.MethodsA cross-sectional study utilized data from the 2011–2014 NHANES survey to explore the association between trace element exposure and cognitive function in elderly adults. The study enrolled 1726 participants, and generalized linear regression model (GLM), Bayesian kernel machine regression model (BKMR), weighted quantile sum regression (WQS), and quantile g-computation regression analysis (Qg-comp) were conducted to assess the impact of five trace elements (lead, cadmium, mercury, manganese, and selenium) in blood on cognitive function under the anti-inflammatory and pro-inflammatory diet.ResultsThe GLM analysis showed a positive correlation between selenium (Se) and both the instant recall test (IRT) and digit symbol substitution test (DSST) (β = 2.06, 95% CI: 0.70 ~ 3.41; and β = 6.41, 95% CI: 2.35 ~ 10.46, respectively). In contrast, cadmium (Cd) was negatively associated with DSST (β = -1.17, 95% CI: -2.13~ -0.22), and lead (Pb) was negatively associated with IRT (β = -0.47, 95% CI: -0.82~ -0.11). For the animal fluency test (AFT), the highest quartile of manganese (Mn) was negatively associated with the lowest quartile (β = -0.72, 95% CI: -1.34~-0.10), while mercury (Hg) showed no significant associations with cognitive function tests. Subgroup analysis revealed the effects of Cd on IRT and DSST and Se on DSST under the pro-inflammatory diet. Furthermore, The BKMR analysis showed an inverted U-shaped curve with the negative impact of trace element mixtures and DSST and a linearly negative trend with IRT in the pro-inflammatory diet. Among them, Cd was emphasized as the most potent risk factor, and Se was the most vital protective factor for IRT and DSST in WQS and Qg-comp analysis.ConclusionsThe study suggests that a high-quality diet might alleviate the adverse effects of Cd on IRT and DSST. High Se levels were also associated with better IRT and DSST scores in the pro-inflammatory diet. These findings provide valuable insights into the connection between diet, trace element exposure, and cognitive function in elderly adults.

The correlation between single and mixed trace elements exposure in systemic lupus erythematosus: A case-control study

BackgroundRecent studies have shown an association between trace elements and systemic lupus erythematosus (SLE), but the relationship between trace elements and SLE is still unclear. This study aims to determine the distribution of plasma trace elements in newly diagnosed SLE patients and the association between these essential and toxic element mixtures and SLE. MethodsIn total, 110 SLE patients and 110 healthy controls were included. Blood samples were collected. 15 plasma trace elements were quantified using an inductively coupled plasma mass spectrometer (ICP-MS). Multivariate logistic regression, restricted cubic spline (RCS), weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) are used to analyze the association between single and mixed exposure of elements and SLE. ResultsThe logistic regression model shows that, plasma lithium (Li) [OR (95 % CI): 1.963 (1.49–2.586)], vanadium (V) [OR (95 % CI): 2.617(1.645–4.166)] and lead (Pb) [OR (95 % CI): 1.603(1.197–2.145)] were positively correlated with SLE, while selenium (Se) [OR (95 % CI): 0.055(0.019–0.157)] and barium (Ba) [OR (95 % CI): 0.792(0.656–0.957)] had been identified as protective factors for SLE. RCS results showed a non-linear correlation between the elements Li, V, Ni, copper, Se, rubidium and SLE. In addition, WQS regression, qgcomp, and BKMR models consistently revealed significant positive effects of plasma Li and Pb on SLE, as well as significant negative effects of plasma Se. ConclusionsExposure to heavy metals such as Li and Pb is significantly positively correlated with SLE, but Se may be protective factors for SLE. In addition, there is a nonlinear correlation between the elements Li and Se and SLE, and there are complex interactions between the elements. In the future, larger populations and prospective studies are needed to confirm these associations.

Associations between Urinary Phthalate Metabolites with BDNF and Behavioral Function among European Children from Five HBM4EU Aligned Studies.

Based on toxicological evidence, children's exposure to phthalates may contribute to altered neurodevelopment and abnormal regulation of brain-derived neurotrophic factor (BDNF). We analyzed data from five aligned studies of the Human Biomonitoring for Europe (HBM4EU) project. Ten phthalate metabolites and protein BDNF levels were measured in the urine samples of 1148 children aged 6-12 years from Italy (NACII-IT cohort), Slovakia (PCB-SK cohort), Hungary (InAirQ-HU cohort) and Norway (NEBII-NO). Serum BDNF was also available in 124 Slovenian children (CRP-SLO cohort). Children's total, externalizing and internalizing behavioral problems were assessed using the Child Behavior Checklist at 7 years of age (only available in the NACII-IT cohort). Adjusted linear and negative binomial regression models were fitted, together with weighted quantile sum (WQS) regression models to assess phthalate mixture associations. Results showed that, in boys but not girls of the NACII-IT cohort, each natural-log-unit increase in mono-n-butyl phthalate (MnBP) and Mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) was cross-sectionally associated with higher externalizing problems [incidence rate ratio (IRR): 1.20; 95% CI: 1.02, 1.42 and 1.26; 95% CI: 1.03, 1.55, respectively]. A suggestive mixture association with externalizing problems was also observed per each tertile mixture increase in the whole population (WQS-IRR = 1.15; 95% CI: 0.97, 1.36) and boys (IRR = 1.20; 95% CI: 0.96, 1.49). In NACII-IT, PCB-SK, InAirQ-HU and NEBII-NO cohorts together, urinary phthalate metabolites were strongly associated with higher urinary BDNF levels, with WQS regression confirming a mixture association in the whole population (percent change (PC) = 25.9%; 95% CI: 17.6, 34.7), in girls (PC = 18.6%; 95% CI: 7.92, 30.5) and mainly among boys (PC = 36.0%; 95% CI: 24.3, 48.9). Among CRP-SLO boys, each natural-log-unit increase in ∑DINCH concentration was associated with lower serum BDNF levels (PC: -8.8%; 95% CI: -16.7, -0.3). In the NACII-IT cohort, each natural-log-unit increase in urinary BDNF levels predicted worse internalizing scores among all children (IRR: 1.15; 95% CI: 1.00, 1.32). Results suggest that (1) children's exposure to di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP) metabolites is associated with more externalizing problems in boys, (2) higher exposure to DINCH may associate with lower systemic BDNF levels in boys, (3) higher phthalate exposure is associated with higher urinary BDNF concentrations (although caution is needed since the possibility of a "urine concentration bias" that could also explain these associations in noncausal terms was identified) and (4) higher urinary BDNF concentrations may predict internalizing problems. Given this is the first study to examine the relationship between phthalate metabolite exposure and BDNF biomarkers, future studies are needed to validate the observed associations.

Associations between exposure to brominated flame retardants and periodontitis in U.S. adults

BackgroundIncreasing evidence has shown that environmental factors play a crucial role in the pathogenesis of periodontitis. Humans are simultaneously exposed to a variety of environmental brominated flame retardants (BFRs). However, the relationship between BFRs in periodontitis remains unclear. This study aimed to investigate the overall association between BFRs and periodontitis in a nationally representative US population and to further identify important chemicals. MethodsData from 3322 NHANES participants from 2009 to 2016 were used. Serum BFRs were registered, including PBDE-28, PBDE-47, PBDE-85, PBDE-99, PBDE100, PBDE-153, PBDE-154, PBDE-183, PBDE-209 and PBB-153. Survey weighted generalized logistic regression models, restricted cubic splines (RCS) were conducted to assess single BFRs exposure with periodontitis. Meanwhile, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were used to evaluate the overall association of BFRs mixtures with periodontitis and to identify significant chemicals. ResultsA total of 3322 participants were included in the study, of whom 1795 had periodontitis. After adjusting for potential confounders, multiple logistic regression analysis revealed significant positive associations between serum levels of PBDE-28, PBDE-47, PBDE-85, PBDE-99, PBDE-100, PBDE-154, PBDE-183, and PBB-153 and the risk of periodontitis (all P < 0.05). A dose-response relationship was observed for many of these BFRs, with higher quantiles associated with an increased risk of periodontitis. WQS regression identified PBDE-183 (38.60%), PBDE-153 (21.20%), PBDE-209 (14.40%), and PBDE-99 (11.90%) as the BFRs with the largest weights contributing to the overall mixture effect on periodontitis risk. BKMR analysis further supported the positive association between serum BFRs and periodontitis, with most individual BFRs showing a positive trend, except for PBDE-153. Restricted cubic spline analysis revealed a generally increasing probability of periodontitis with increasing concentrations of BFRs, albeit with some nonlinear patterns for certain compounds. ConclusionIn conclusion, this study provides compelling evidence of a significant association between exposure to brominated flame retardants (BFRs) and an increased risk of periodontitis in a nationally representative sample of U.S. adults. Elevated serum levels of several BFRs, including PBDE-28, PBDE-47, PBDE-85, PBDE-99, PBDE-100, PBDE-154, PBDE-183, and PBB-153, were found to be positively associated with periodontitis, exhibiting a dose-response relationship.

Associations of environmental chemical exposures measured in personal silicone wristbands with sociodemographic factors, COVID-19 restrictions, and child respiratory health

BackgroundAlthough human biomonitoring of environmental chemicals has been considered a gold standard, these methods can be costly, burdensome, and prone to unwanted sources of variability that may cause confounding. Silicone wristbands have recently emerged as innovative passive samplers for measuring personal exposures. MethodsIn a pilot study from 2019 to 2021 involving 55 children aged 5–9 years in Seattle and Yakima, Washington, we utilized silicone wristbands to explore associations of sociodemographic variables and COVID-19-related restrictions, including school closures, with exposures to numerous chemicals including brominated and organophosphate ester (OPE) flame retardants, polychlorinated biphenyls, polycyclic aromatic hydrocarbons (PAHs), phthalates, and pesticides. We additionally conducted the first analysis testing silicone wristband chemicals as predictors of child wheeze, individually and in mixtures via logistic weighted quantile sum regression (WQS). ResultsAmong 109 semi-volatile organic compounds measured, we detected 40 in >60% of wristbands worn by children continuously for an average of 5 days. Chemicals were generally positively correlated, especially within the same class. Male sex and increasing age were linked with higher exposures across several chemical classes; Hispanic/Latino ethnicity was linked with higher exposures to some phthalates and OPEs. COVID-19 restrictions were associated with lower wristband concentrations of brominated and triaryl OPE flame retardants. Each one-decile higher WQS exposure index was suggestively associated with 2.11-fold [95% CI: 0.93–4.80] higher odds of child wheeze. Risk of child wheeze was higher per 10-fold increase in the PAH chrysene (RR = 1.93[1.07–3.49]), the pesticide cis-permethrin (3.31[1.23–8.91]), and di-isononyl phthalate (DINP) (5.40[1.22–24.0]) ConclusionsOur identification of demographic factors including sex, age, and ethnicity associated with chemical exposures may aid efforts to mitigate exposure disparities. Lower exposures to flame retardants during pandemic restrictions corroborates prior evidence of higher levels of these chemicals in school versus home environments. Future research in larger cohorts is needed to validate these findings.

Sex and obesity influence the relationship between perfluoroalkyl substances and lean body mass: NHANES 2011–2018

ObjectivePolyfluoroalkyl substances (PFAS) are known endocrine disruptors, that have been the subject of limited research regarding their impact on human lean body mass. The aim of this study was to investigate the effects of PFAS exposure on lean body mass. MethodsWe performed a cross-sectional data analysis involving 1022 adolescents and 3274 adults from the National Health and Nutrition Examination Survey (NHANES) 2011–2018, whose lean body mass was measured by dual-energy X-ray absorptiometry. The lean mass index (LMI) was calculated as lean body mass dividing by the square of height. The association between PFAS and LMI was examined through a multivariate-adjusted weighted generalized linear model. Moreover, weighted quantile sum (WQS) regression models were employed to futher examine the relationship between the mixture of PFAS and LMI. ResultsRegression analyses revealed an inverse correlation between PFAS exposure and LMI after adjusting for potential covariates. Adults with higher serum PFAS concentrations manifested a reduction in whole LMI (β = −0.193, 95 % confidence interval (CI): −0.325 to −0.06). Notably, this correlation was particularly significant in adult females and individuals with obesity, and it was observed across diverse anatomical regions, including lower limbs, right arm, trunk, and whole lean body mass. In adult females, the association between PFAS and whole LMI was statistically significant (β = −0.294, 95 % CI: −0.495 to −0.094), and a similar trend was found in obese individuals (β = −0.512, 95 % CI: −0.762 to −0.261). WQS regression analyses supported the results obtained from weighted linear regression analyses. ConclusionsOur study suggests that exposure to PFAS, whether individually or in combination, is associated with decreased lean body mass in specific body areas, with sex and obesity serving as major influencing factors.

Moderate BMI accumulation modified associations between blood benzene, toluene, ethylbenzene and xylene (BTEX) and phenotypic aging: mediating roles of inflammation and oxidative stress

The associations between blood benzene, toluene, ethylbenzene, and xylenes (BTEX) and biological aging among general adults remain elusive. The present study comprised 5780 participants from the National Health and Nutrition Examination Survey 1999–2010. A novel measure of biological aging, phenotypic age acceleration (PhenoAge.Accel), derived from biochemical markers was calculated. Weighted generalized linear regression and weighted quantile sum regression (WQS) were utilized to assess the associations between BTEX components and mixed exposure, and PhenoAge.Accel. The mediating roles of systemic immune-inflammation index (SII) and oxidative stress indicators (serum bilirubin and gamma-glutamyl transferase), along with the modifying effects of body mass index (BMI) were also examined. In the single-exposure model, the highest quantile of blood benzene (b = 0.89, 95%CI: 0.58 to 1.20), toluene (b = 0.87, 95%CI: 0.52 to 1.20), and ethylbenzene (b = 0.80, 95%CI: 0.46 to 1.10) was positively associated with PhenoAge.Accel compared to quantile 1. Mixed-exposure analyses revealed a consistent positive association between BTEX mixed exposure and PhenoAge.Accel (b = 0.88, 95%CI: 0.56 to 1.20), primarily driven by benzene (92.78%). The association between BTEX and PhenoAge.Accel was found to be partially mediated by inflammation and oxidative stress indicators (ranging from 3.2% to 13.7%). Additionally, BMI negatively modified the association between BTEX mixed exposure and PhenoAge.Accel, with a threshold identified at 36.2 kg/m^2. Furthermore, BMI negatively moderated the direct effect of BTEX mixed exposure on PhenoAge.Accel in moderated mediation models, while positively modified the link between SII and PhenoAge.Accel in the indirect path (binteraction = 0.04, 95%CI: 0.01 to 0.06). Overall, BTEX mixed exposure was associated with PhenoAge.Accel among US adults, with benzene may have reported most contribution, and inflammation and oxidative damage processes may partially explain this underlying mechanism. The study also highlighted the potential benefits of appropriate BMI increased. Additional large-scale cohort studies and experiments were necessary to substantiate these findings.

Mixture analysis of associations between environmental and workplace toxins and liver damage and telomere length, stratified by race/ethnicity

This study aimed to identify the worst “bad actors” in mixtures of pollutants contributing to liver damage and shorter telomeres in the U.S. population, using Weighted Quantile Sum (WQS) modeling with stratification by race/ethnicity. We conducted a comprehensive cross-sectional analysis of mixtures of pollutants in National Health and Nutrition Examination Survey datasets: a) 33,979 adults with blood levels of cadmium (Cd), lead (Pb), and mercury, including subsets with measurements of per-/polyfluoroalkyl substances (PFAS), and polychlorinated biphenyls (PCBs)/polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs); and b) 7360 adults with measurements of telomeres, Cd, and Pb. Multivariable-adjusted WQS regression examined associations between WQS mixture indices and liver injury [alanine aminotransferase (ALT)-elevation], advanced liver-fibrosis (LF), and telomere length. WQSmetal indices were associated with advanced-LF in all racial/ethnic groups. The top contributor was Cd in the total population and in non-Hispanic Whites (NHW), while Pb was the top contributor in non-Hispanic Blacks (NHB). The WQSmetal-PCB-PCDD/F index was associated with ALT-elevation, with PCB126, Cd and Pb as main contributors; the odds ratio (OR) per decile was 1.50 (95%CI, 1.26-1.78), while the OR per decile of the WQSmetal-PFAS index was 1.03 (95%CI, 0.98-1.05), not significant. WQSmetal indices were associated with shorter telomeres. Cd was main contributor associated with advanced-LF in NHW, while Pb was the major bad actor in NHB, suggesting that NHB may be especially susceptible to Pb toxicity. Metals were associated with shorter telomeres. Metal and PCB/PCDD/F mixtures were associated with ALT-elevation. Heavy metals and organic chemicals may contribute to liver-related morbidity and healthcare disparities.

Polycyclic aromatic hydrocarbons exposure associated with increased risk of psoriasis.

Psoriasis is considered to be multifactorial, with both genetic and environmental factors contributing to its development. Polycyclic aromatic hydrocarbons (PAHs) are widespread in the environment, originating from sources such as cigarette smoke, exhaust emissions, grilled foods, smoked foods and urban air. Researchs have established a link between PAHsexposure and autoimmune disorders; however, specific effects of PAHs on psoriasis remain underexplored. This study aims to evaluate the correlation between PAHs exposure and susceptibility to psoriasis. We analysed eight monohydroxy PAHs (1-Hydroxynaphthalene (1-NAP), 2-Hydroxynaphthalene (2-NAP), 3-Hydroxyfluorene (3-FLU), 2-Hydroxyfluorene (2-FLU), 1-Hydroxyphenanthrene (1-PHE), 1-Hydroxypyrene (1-PYR), 2-Hydroxyphenanthrene (2-PHE) and 3-Hydroxyphenanthrene (3-PHE)) in 5996 participants from the National Health and Nutrition Examination Survey (NHANES). We employed multivariate logistic regression, trend analysis, weighted quantile sum (WQS) regression and restricted cubic spline (RCS) analysis to investigate the relationship between PAHs exposure and psoriasis risk. Multivariate logistic regression and trend analysis revealed that monohydroxy PAHs, including 2-NAP, 3-FLU, 2-FLU and the mixture of 2-PHE and 3-PHE, are associated with an increased risk of psoriasis. Additionally, WQS regression showed a significant positive correlation between combined exposure to monohydroxy PAHs and psoriasis risk, with the mixture of 2-PHE and 3-PHE (47.3%) being the most influential factor. RCS regression further corroborated these findings. Specifically, 2-FLU can increase the expression of psoriasis-related inflammatory factors in HaCaT cells. In conclusion, PAHs exposure increases the risk of developing psoriasis. Efforts to reduce PAHs levels in the environment and minimise exposure are crucial for public health strategies aimed at preventing psoriasis.

The mediating role of chronic low-grade inflammation participation in the relationship between obesity and type 2 diabetes: findings from the NHANES

BackgroundChronic low-grade inflammation may mediate the relationship between obesity and diabetes, yet clinical research in this area remains scarce. Thus, this study aimed to explore the mediating role of chronic low-grade inflammation in this relationship using the National Health and Nutrition Examination Survey (NHANES).MethodsThis study involved 2,482 participants enrolled in the NHANES between 2005 and 2016. Based on the complex sampling survey weights of NHANES, logistic regression models were fitted, adjusting for various covariates to investigate the relationship between BMI, INFLA score, and diabetes. Moreover, weighted quantile sum (WQS) regression models were fitted to analyze the proportional contribution of individual components within the INFLA score. Finally, mediation analysis was conducted to quantitatively assess the magnitude of the mediating effect of the INFLA score on the relationship between BMI and diabetes.ResultsAfter adjusting for all potential confounding factors, a significant positive correlation was noted between INFLA score and diabetes [OR (95% CI), 1.038(1.003–1.075), p = 0.035]. Additionally, a significant positive correlation was observed between the high INFLA group and diabetes compared to the low INFLA group [OR (95% CI), 1.599(1.031–2.481), p = 0.037]. WQS regression models revealed that the proportional contributions of C-reactive protein, white blood cell count, platelet count, and neutrophil-to-lymphocyte ratio (NLR) were 55.5%, 34.8%, 8.46%, and 1.19%, respectively. Finally, the results of the mediation analysis indicated that the indirect effect of the INFLA score accounted for 10.20%.ConclusionsChronic low-grade inflammation was associated with diabetes and partially mediates the relationship between obesity and diabetes.

Association of Life’s Essential 8 with metabolic dysfunction-associated steatotic liver disease (MASLD), a cross-sectional study from the NHANES 2003–2018

There is limited research on the relationship between Life's Essential 8 (LE8) score and metabolic dysfunction-associated steatotic liver disease (MASLD). Our aim is to investigate the relationship between overall lifestyle assessed by LE-8 score and MASLD in a nationally representative sample. We employed the LE8 score to comprehensively evaluate cardiovascular health, the assessment of MASLD primarily utilized the Fatty Liver Index. The weighted logistic regression models, restrictive cubic splines (RCS), subgroup analyses and the weighted quantile sum (WQS) regression were used to evaluate the relationship between the cardiovascular health and MASLD. Logistic regression models revealed that higher LE8 scores were associated with lower odds of having MASLD. The RCS revealed a significant nonlinear dose–response relationship between LE8 scores and MASLD. The WQS regression model indicated that blood glucose contributed the most to the risk of MASLD. The subgroup analysis indicates that there are significant differences in this association across age, educational level, and poverty income ratio. Our study suggests that an inverse correlation between LE8 and the risk of MASLD. Our findings underscore the utility of the LE8 algorithm in MASLD risk assessment and provide support for MASLD prevention through the promotion of healthy lifestyles.

Association of plasma metals with resting-state functional connectivity in ischemic stroke

BackgroundMetal exposure has long been considered a significant risk factor for ischemic stroke. However, existing data on the effects of metal exposure on brain function in ischemic stroke are limited. Therefore, this study aimed to explore the correlation between exposure to various metals and changes in resting-state functional connectivity (rs-FC) in ischemic stroke patients. MethodsThis study included 28 acute ischemic stroke patients with hemiplegia and 28 matched healthy controls (HCs). All participants underwent T1-weighted MRI and 3.0 T resting-state functional magnetic resonance imaging (fMRI). After MRI acquisition, the rs-FC between 137 cortical and subcortical regions was extracted and preprocessed. Plasma levels of 19 metals were measured using inductively coupled plasma mass spectrometry (ICP-MS). The Bayesian kernel machine regression (BKMR) model and the weighted quantile sum regression (WQS) model were used to assess the overall effect of metal mixture exposure. The severity of neurological deficits in each acute ischemic stroke patient was evaluated using the National Institutes of Health Stroke Scale (NIHSS). Additionally, the associations between exposure to various metals and modifications in brain functional connectivity were determined using Pearson or Spearman correlation analysis. ResultsBilateral brain connectivity was significantly decreased compared to controls and was associated with neurological impairment in ischemic stroke. In patients with ischemic stroke, the plasma concentrations of Cr (p < 0.001), Cu (p = 0.004), As (p = 0.010), Cs (p = 0.046), Rb (p = 0.041), and Sb (p = 0.001) were significantly higher than those in the HCs, whereas the plasma Tl concentrations (p = 0.022) were significantly lower. The results of the BKMR and WQS models showed that combined exposure to metal mixtures was linked to a higher risk of ischemic stroke. Cr was positively correlated with the rs-FC between the left Rolandic_Oper and the left Supp_Motor_Area (r = 0.414, p = 0.029), while negatively correlated with the rs-FC between the right Parietal_Inf and the left supramarginal (r = −0.398, p = 0.037). Cu was negatively correlated with the rs-FC between the left paracentral lobule and the left thalamus (r = −0.409, p = 0.031). Tl was positively correlated with the rs-FC between the right Parietal_Inf and the left supramarginal cortex (r = 0.590, p = 0.001). A negative correlation was observed between Cs and rs-FC between the right Cingulate_Mid and left Occipital_Sup (r = −0.429, p = 0.024). Sb was negatively correlated with the rs-FC between the left Parietal_Inf and the right SupraMarginal (r = −0.384, p = 0.044), the right Parietal_Inf and the left SupraMarginal (r = −0.583, p = 0.001), and the left SupraMarginal and the right SupraMarginal (r = −0.377, p = 0.048). ConclusionPlasma levels of Cr, Cu, Tl, Cs, and Sb were associated with altered rs-FC in brain regions related to motor control, sensory integration, executive function, language processing, and emotional regulation in ischemic stroke patients with basal ganglia infarction.