Weighted Quantile Sum Regression Research Articles

Association of postnatal exposure to mixture of bisphenol A, Di-n-butyl phthalate and Di-(2-ethylhexyl) phthalate with Children's IQ at 5 Years of age: Mothers and Children's environmental health (MOCEH) study

Early childhood is important for neurodevelopment, and exposure to endocrine disruptors such as bisphenol A (BPA) and phthalates in this period may cause neurodevelopmental disorders and delays. The present study examined the association between exposure to mixtures of BPA and three metabolites of phthalates in early childhood and IQ at 5 years of age. The Mother and Children's Environmental Health (MOCEH) study is a prospective birth cohort study conducted in Korea with 1751 pregnant women enrolled from 2006 to 2010. After excluding those without relevant data, 47 children were included in the final analysis. We measured children's urinary concentrations of metabolites of endocrine-disrupting chemicals (Bisphenol A, mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate and mono-(2-ethyl-5-butyl) phthalate) at ages of 24 and 36 months. We evaluated the children's IQ with the Korean Wechsler Intelligence Test at the age of 5 years. After adjusting for potential confounders, a multiple linear regression was conducted to examine the associations between individual endocrine-disrupting chemicals and the IQ of the children. Weighted Quantile Sum (WQS) regression and quantile-based g-computation were used to assess the association between IQ at age 5 and exposure to mixtures of BPA and phthalates. In the single-chemical analyses, mono-(2-ethyl-5-butyl) phthalate exposure at 36 months was adversely associated with children's IQ (β = −4.93, 95% confidence interval (CI): -9.22, −0.64). In the WQS regression and quantile-based g-computation analyses, exposure to the mixture of BPA and phthalates was associated with lower IQ [β = −9.13 (P-value = 0.05) and β = −9.18 (P-value = 0.05), respectively]. The largest contributor to the overall association was exposure to mono-(2-ethyl-5-butyl) phthalate at 36 months. In the present study, postnatal exposure to mixtures of BPA and three metabolites of phthalates was associated with decreased IQ of children at age 5.

Using machine learning methods to analyze the association between urinary polycyclic aromatic hydrocarbons and chronic bowel disorders in American adults

The etiology of chronic bowel disorders is multifaceted, with environmental exposure to harmful substances potentially playing a significant role in their pathogenesis. However, research on the correlation between polycyclic aromatic hydrocarbons (PAHs) and chronic bowel disorders remains limited. Using data from the National Health and Nutrition Examination Survey (NHANES) conducted in 2009–2010, we investigated the relationship between 9 PAHs and chronic diarrhea and constipation in U.S. adults. We employed unsupervised methods such as clustering and Principal Component Analysis (PCA) to identify participants with similar exposure patterns. Additionally, we used supervised learning techniques, namely weighted quantile sum (WQS) and Bayesian kernel machine (BKMR) regressions, to assess the association between PAHs and the occurrence of chronic diarrhea and chronic constipation. PCA identified three principal components in the unsupervised analysis, explaining 86.5% of the total PAH variability. The first component displayed a mild association with chronic diarrhea, but no correlation with chronic constipation. Participants were divided into three clusters via K-means clustering, based on PAH concentrations. Clusters with higher PAH exposure demonstrated an increased odds ratio for chronic diarrhea, but no meaningful connection with chronic constipation. In the supervised analysis, the WQS regression underscored a positive relationship between the PAH mixture and chronic diarrhea, with three PAHs significantly impacting the mixture effect. The mixture index showed no correlation with chronic constipation. BKMR analysis illustrated a positive trend in the impact of four specific PAHs on chronic diarrhea, given other metabolites were fixed at their 50th percentiles. Our results suggest a clear association between higher PAH exposure and an increased risk of chronic diarrhea, but not chronic constipation. It also underscores the potential role of specific PAHs in contributing to the risk of chronic diarrhea.

The Association between Prenatal Exposure to Per- and Polyfluoroalkyl Substances and Respiratory Tract Infections in Preschool Children: A Wuhan Cohort Study.

This study investigates the association between prenatal exposure to per- and polyfluoroalkyl substances (PFASs) and the incidence and frequency of respiratory tract infections (RTIs) in preschool children. We selected 527 mother-infant pairs from Wuhan Healthy Baby Cohort (WHBC), China. Ten PFASs were measured in umbilical cord serum, and we collected data on common RTIs in preschool children aged 4 years through a questionnaire. Associations of single PFASs with the incidence and frequency of RTIs were analyzed via Logistic regression and Poisson regression, while the collective effect was assessed by weighted quantile sum (WQS) regression. Furthermore, stratified and interaction analyses were performed to evaluate if there were sex-specific associations. We found a positive correlation between perfluorododecanoic acid (PFDoDA) and the incidence of tonsillitis, with several PFASs also showing positive associations with its frequency. Moreover, perfluorotridecanoic acid (PFTrDA) showed a positive link with the frequency of common cold. The results of WQS regression revealed that after adjusting for other covariates, PFASs mixture showed a positive association with the incidence of tonsillitis, the frequency of common cold, and episodes. In particular, perfluoroundecanoic acid (PFUnDA), PFDoDA, PFTrDA, perfluorodecanoic acid (PFDA) and 8:2 chlorinated polyfluorinated ether sulfonic acid (8:2 Cl-PFESA) had the most significant impact on this combined effect. The results suggest that both single and mixed exposures to PFASs may cause RTIs in preschool children. However, there was no statistically significant interaction between different PFASs and sex.

Individual and combined effects of phthalate metabolites on eczema in the United States population

Phthalates might trigger immune dysregulation. The relationship between a phthalate mixture exposure and eczema remains unclear. To address this research gap, four statistical models were used to investigate the individual, combined, and interaction relationships between monoesters of phthalates (MPAEs) and eczema, including the logistic regression, weighted quantile sum regression (WQS), quantile g computation (qg-computation), and bayesian kernel machine regression (BKMR). Moreover, subgroup analyses were performed by sex and age. After adjusting for all covariates, the logistic regression model suggested a positive correlation between mono-(3-carboxypropyl) phthalate (MCPP) and eczema. Subgroup analysis suggested that the effect of the MPAEs on eczema was predominantly present in men and children. In the WQS model, the joint effect of 11 MPAEs on eczema was marginally significant [odds ratio = 1.36, 95% confidence interval: 0.97–1.90]. Moreover, a positive association was observed between the combined exposure to 11 MPAEs and eczema in the BKMR model. MCPP and mono-(carboxynonyl) phthalate were the most substantial risk factors based on the results of WQS and qg-computation models. The exposure to a mixture of MPAEs may lead to an elevated prevalence of eczema in the United States population, with men and children being particularly vulnerable to their effects.

Associations of polychlorinated biphenyls and organochlorine pesticides with metabolic dysfunction-associated fatty liver disease among Chinese adults: Effect modification by lifestyle

Exposure to environmental pollutants and unhealthy lifestyles are key risk factors for metabolic dysfunction-associated fatty liver disease (MAFLD). While previous studies have suggested links between exposure to organochlorine pesticides (PCBs) and organochlorine pesticides (OCPs) and MAFLD, the results have been inconsistent. Furthermore, the combined effects of PCBs and OCPs on MAFLD and whether lifestyle factors can modify the associations remain unknown. Therefore, this study aimed to investigate the individual and joint effects of PCBs and OCPs on MAFLD and explore the potential modifying role of lifestyle. The study included 1923 participants from Wuhan, China. MAFLD was diagnosed based on ultrasonically diagnosed hepatic steatosis and the presence of overweight/obese, diabetes mellitus, or metabolic dysregulation. Healthy lifestyle score was determined by smoking, alcohol consumption, physical activity, and diet. Logistic regression and weighted quantile sum (WQS) were used to assess associations of individual and mixture of PCBs/OCPs with MAFLD. To explore the potential lifestyle modification, joint associations of PCBs/OCPs and lifestyle on MAFLD were conducted. Single-pollutant analysis showed positive associations of p,p′-DDE, β-HCH, PCB-153, and PCB-180 with MAFLD, with ORs (95% CIs) of 1.18 (1.05, 1.33), 1.57 (1.20, 2.05), 1.45 (1.14, 1.83), and 1.42 (1.12, 1.80), respectively. WQS regression demonstrated a harmful effect of PCBs/OCPs mixture on MAFLD (OR = 1.73, 95% CI = 1.24, 2.43), with β-HCH, p,p’-DDE, and PCB-180 being the major contributors. In the joint association analysis, participants with both high PCBs/OCPs exposure and unhealthy lifestyle have the highest odds of MAFLD. In conclusion, exposure to the mixture of PCBs and OCPs was positively correlated with MAFLD, and adopting a healthy lifestyle can mitigate the adverse impact.

Association of exposures to serum terpenes with the prevalence of dyslipidemia: a population-based analysis.

This study sought to examine hitherto unresearched relationships between serum terpenes and the prevalence of dyslipidemia. Serum terpenes such as limonene, α-pinene, and β-pinene from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) were used as independent variables in this cross-sectional study. Continuous lipid variables included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), residual cholesterol (RC), and apolipoprotein B (Apo B). Binary lipid variables (elevated TC, ≥5.18 mmol/L; lowered HDL-C, <1.04 mmol/L in men, and <1.30 mmol/L in women; elevated non-HDL-C, ≥4.2 mmol/L; elevated TG, ≥1.7 mmol/L; elevated LDL-C, ≥3.37 mmol/L; elevated RC, ≥1.0 mmol/L; and elevated Apo B, ≥1.3 g/L) suggest dyslipidemia. The relationships between the mixture of serum terpenes with lipid variables were investigated using weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR). The study for TC, HDL-C, and non-HDL-C included a total of 1,528 people, whereas the analysis for TG, LDL-C, RC, and Apo B comprised 714 participants. The mean age of the overall participants was 47.69 years, and 48.77% were male. We found that tertiles of serum terpene were positively associated with binary (elevated TC, non-HDL-C, TG, LDL-C, RC, Apo B, and lowered HDL-C) and continuous (TC, non-HDL-C, TG, LDL-C, RC, and Apo B, but not HDL-C) serum lipid variables. WQS regression and BKMR analysis revealed that the mixture of serum terpenes was linked with the prevalence of dyslipidemia. According to our data, the prevalence of dyslipidemia was correlated with serum concentrations of three terpenes both separately and collectively.

Exposure to polycyclic aromatic hydrocarbons increases the risk of poor sleep pattern in US adults: results from the NHANES (2005-2010).

Recently, polycyclic aromatic hydrocarbons (PAHs) were found to be linked to various diseases. The current study's objective was to explore whether or not there was a relation between PAH exposure and poor sleep pattern. We evaluated nine urine PAH metabolites as exposures in our cross-sectional research based on the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. Logistic regression, restricted cubic spline regression (RCS) model, weighted quantile sum (WQS) regression, subgroup analysis, and mediation analysis were used to assess the associations between PAH metabolism and poor sleep pattern risk. After controlling for all confounding variables, several primary PAH metabolites, namely 1-hydroxynapthalene (1-NAP, OR 1.32, 95% CI 1.04-1.68), 2-hydroxyfluorene (2-FLU, OR 1.34, 95% CI 1.05-1.71), 1-hydroxyphenanthrene (1-PHE, OR 1.30, 95% CI 1.03-1.64), 9-hydroxyfluorene (9-FLU, OR 1.38, 95% CI 1.09-1.74), and ∑PAHs (OR 1.33, 95% CI 1.05-1.69), compared to the bottom tertile, were associated with increased risk of poor sleep pattern. The WQS regression analysis showed that 9-FLU and 1-NAP comprised the two most important factors related to poor sleep pattern. Mediation analysis revealed that inflammation acted as a mediator between PAHs and the prevalence of poor sleep pattern. In conclusion, exposure to PAHs may be associated with poor sleep pattern. Inflammation is a mediator of the effects of PAH exposure on poor sleep pattern.

Synergistic impact of co-exposures to whole blood metals on chronic kidney disease in general US adults: a cross‑sectional study of the National Health and Nutrition Examination Survey 2011-2020.

The impact of exposure to metals on chronic kidney disease (CKD) has only been investigated in two-way or single metal interactions in previous studies. We investigated the associations between five single metals in blood and their mixed exposure and CKD by using the machine learning approach. Relevant data were extracted from the National Health and Nutrition Examination Survey (NHANES 2011-2020), and the level of five metals in blood detected by inductively coupled plasma mass spectrometry was considered as exposures, namely, cadmium (Cd), lead (Pb), total mercury (Hg), manganese (Mn), and selenium (Se). The correlations between individual metal and metal mixtures and CKD were then evaluated by survey-multivariable logistic regression (SMLR), generalized weighted quantile sum (WQS), and Bayesian kernel machine regression (BKMR). Altogether, our study included 12,412 participants representing 572.6 million non-institutionalized US adults. Several single metals with the high quartile of exposure showed a positive association with the CKD ratio including Cd [(AOR = 1.873, 95% CI: 1.537, 2.284), Q4], Pb [(AOR = 1.559, 95% CI: 1.295, 1.880), Q4], and total Hg [(AOR = 1.169, 95% CI: 1.018, 1.343), Q2], while Mn [(AOR = 0.796, 95% CI: 0.684, 0.927), Q2] and Se [(AOR = 0.805, 95% CI: 0.664, 0.976), Q4] were negatively associated with the CKD ratio. In light of the positive fit of the WQS regression model, a significantly positive correlation was found between mixed metals and CKD (AOR = 1.373, 95% CI: 1.224, 1.539) after full covariate adjustment, and a similar finding was also detected in the BKMR model. Our study revealed that each single metal including Cd, Pb, and total Hg might have a positive association with CKD while this association was negative for both Mn and Se. The five metals might have a positive joint effect on CKD.

OR06-06 Association Between Mixed Dioxin Exposure And Thyroid Functions In U.S. Adults: A Comparison Of Three Statistical Models

Abstract Disclosure: C. Han: None. S. Lee: None. E.N. Pearce: None. Background: Previous studies of the relationship between dioxin exposure and thyroid function have usually been based on multi-chemical linear models and results have been inconsistent. However, complex nonlinear relationships and interactions between mixed dioxin exposures and thyroid function have not been studied. We applied three different statistical models to assess the joint effect of 20 dioxins on thyroid function. Methods: A total of 6 polychlorinated dibenzo-p-dioxins (PCDDs), 10 polychlorinated dibenzofurans (PCDFs), 4 dioxin-like polychlorinated biphenyls (DL-PCBs) and serum TSH were measured in the serum of U.S. adults by the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2010. We fitted multivariable logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models to estimate the association of individual and mixed dioxin exposures with high TSH. Results: Among the 2818 individuals included in our analysis, 1.99% had TSH &amp;gt;5.6 uIU/mL. In the multivariable logistic regression established for each single dioxin, 1,2,3,7,8-pncdd, 1,2,3,4,7,8-hxcdd, 1,2,3,6,7,8-hxcdd, 1,2,3,7,8,9-hxcdd, 1,2,3,4,7,8-Hexachlorofuran, 1,2,3,6,7,8-Hexachlorofuran, 3,3',4,4',5,5'-hexachlorobiphenyl, 3,3',4,4',5-Pentachlorobiphenyl, and 2,3,7,8-Tetrachloro-p-dioxin were positively associated with high TSH, and 3,4,4',5-Tetrachlorobiphenyl was negatively associated with high TSH. In the WQS regression model, the WQS index was significantly associated (OR (95% CI): 2.03 (1.06, 3.88)) with high TSH, and 1,2,3,7,8-pncdd (weighted at 0.24) made the largest contribution. In the BKMR analysis, a significant positive association was found between mixed dioxin exposure and high TSH when all dioxins were at their 55 to 70th percentile, compared to their 50th percentile. TSH was lower when all dioxins were at their 30th to 45th percentile, compared to their 50th percentile. Conclusion: By comparing the three statistical models, we concluded that the whole-body burden of 20 dioxins was significantly positively associated with high TSH. 1,2,3,7,8-pncdd played the most important roles in hypothyroidism. Presentation: Thursday, June 15, 2023

Prenatal exposure to metal mixtures and lung function in children from the New Hampshire birth cohort study

Prenatal exposure to metals/metalloids, even at common US population levels, may pose risks to fetal health, and affect children's lung function. Yet, the combined effects of simultaneous prenatal exposures on children's lung function remain largely unexplored. This study analyzed 11 metals (As speciation, Cd, Co, Cu, Mo, Ni, Pb, Sb, Se, Sn, Zn) in maternal urine during weeks 24–28 of gestation and evaluated lung function, including forced vital capacity (FVC) and forced expiratory volume in the first second of expiration (FEV1), in 316 US mother-child pairs at around age 7. We used Bayesian Kernel Machine Regression (BKMR), weighted quantile sum regression (WQSR), and multiple linear regression to examine the association between metal mixture exposure and children's lung function, adjusting for maternal smoking, child age, sex, and height. In BKMR models assessing combined exposure effects, limited evidence of metal non-linearity or interactions was found. Nevertheless, Co, As species, and Pb showed a negative association, while Mo exhibited a positive association with children's FVC and FEV1, with other metals held constant at their medians. The weighted index, from WQSR analysis assessing the cumulative impact of all metals, highlighted prenatal Mo with the highest positive weight, and Co, As, and Sb with the most substantial negative weights on children's FVC and FEV1. Urinary Co and Pb were negatively associated with FVC (β = −0.09, 95% confidence interval (CI) (−0.18; −0.01) and β = −0.07, 95% CI (−0.13; 0.00), respectively). Co was also negatively associated with FEV1 (β = −0.09, 95% CI (−0.18; 0.00). There was a negative association between As and FVC, and a positive association between Mo and both FVC and FEV1, though with wide confidence intervals. Our findings suggest that prenatal trace element exposures may impact children's lung function, emphasizing the importance of reducing toxic exposures and maintaining adequate nutrient levels.

Associations of essential trace elements with epigenetic aging indicators and the potential mediating role of inflammation

BackgroundEssential trace elements (ETEs) play essential roles in vital functions, but their effects on epigenetic aging remain poorly understood. ObjectivesThis study aimed to investigate the associations of ETEs with four epigenetic aging indicators and assess the potential mediating role of inflammation. MethodsWe recruited 93 individuals from hospitals between October 2018 and August 2019. Plasma levels of cobalt, copper, iron, manganese, molybdenum, selenium, and zinc were measured by ICP-MS, and leukocyte DNA methylation levels were measured using Illumina MethylationEPIC beadchip. Linear regression was used to estimate the association between seven plasma ETEs and epigenetic aging indicators. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models were used to evaluate the effect of ETEs mixtures. Inflammatory status was assessed using four systemic inflammation indices (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII)) and three cytokines (IL-4, IL-6, and IL-13). Mediation analysis was performed to explore the role of inflammation in the above associations. ResultsPlasma Se levels were significantly negatively associated with DunedinPACE, whereas Cu levels were significantly positively associated with it. Both WQS regression and BKMR models suggested that Se and Cu dominate the effect of the ETEs mixture. MLR and interleukin 6 were significantly and positively associated with DunedinPACE. Further mediation analysis indicated that inflammation partially mediated the association between ETEs and DunedinPACE. DiscussionPlasma Se and Cu levels are closely associated to epigenetic aging, and inflammation might be a potential mechanism underlying this relationship. These findings contribute to the prevention of health hazards associated with population aging.

Association of Dietary Flavonoid Intake with Serum Cotinine Levels in the General Adult Population.

Cotinine, the primary metabolite of nicotine, can be utilized as a marker for active smoking and as an indicator of exposure to secondhand smoke. However, the direct relationship between dietary flavonoid intake and serum cotinine levels remains a subject of ongoing investigation. In this study, we utilized data from the National Health and Nutrition Examination Survey (NHANES) 2007-2010 and 2017-2018 to assess the association between dietary flavonoid intake and serum cotinine levels in adults through multiple linear regression analysis. A weighted quantile sum (WQS) regression model was used to assess the association of the mixture of six dietary flavonoids with serum cotinine levels in adults, which could represent the overall effect of the mixture of six dietary flavonoids. We also conducted stratified analyses by smoke status to explore multiple linear regression associations between different flavonoid intake and serum cotinine levels. A total of 14,962 adults were included in the study. Compared to the group with the lowest dietary flavonoid intake, total flavonoid intake in the second (β = -0.29 [-0.44, -0.14]), third (β = -0.41 [-0.58, -0.24]), and highest groups (β = -0.32 [-0.49, -0.16]) was inversely related to the levels of serum cotinine after adjusting the full model. An RCS model showed that when the total dietary flavonoid intake was less than 99.61 mg/day, there was a negative linear association between dietary flavonoid intake and the serum cotinine. The WQS regression model also showed that the intake of a mixture of six dietary flavonoids was significantly negatively correlated with serum cotinine levels (β = -0.54 [-0.61, -0.46], p <0.01), with anthocyanins having the greatest effect (weights = 32.30%). Our findings imply a significant correlation between dietary flavonoid intake and serum cotinine levels among adults. The consumption of a combination of six dietary flavonoids was consistently linked to lower serum cotinine levels, with anthocyanins displaying the most pronounced impact.

Associations of polychlorinated biphenyl and organochlorine pesticide exposure with hyperuricemia: modification by lifestyle factors.

Recent research has reported positive associations of exposure to polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) with hyperuricemia. However, most of these studies have primarily focused on the individual effects of PCB/OCP exposure. We aimed to explore the associations of both individual and combined PCB/OCP exposure with hyperuricemia and examine whether such associations could be modified by lifestyle factors. The cross-sectional study recruited 2032 adults between March and May 2019 in Wuhan, China. Logistic regression and weighted quantile sum (WQS) regression were applied to explore the relationship of individual and combined PCB/OCP exposure with hyperuricemia, while considering the modified effects of lifestyle factors. Of the 2032 participants, 522 (25.7%) had hyperuricemia. Compared with the non-detected group, the detected groups of PCB153 and PCB180 exhibited a positive association with hyperuricemia, with OR (95% CIs) of 1.52 (1.22, 1.91) and 1.51 (1.20, 1.90), respectively. WQS regression showed that PCB/OCP mixture was positively associated with hyperuricemia (OR: 1.31, 95% CI: 1.08, 1.58). PCB153/PCB180 exposure, combined with an unhealthy lifestyle, has a significant additive effect on hyperuricemia. Overall, PCB/OCP mixture and individual PCB153/PCB180 exposure were positively associated with hyperuricemia. Adherence to a healthy lifestyle may modify the potential negative impact of PCBs/OCPs on hyperuricemia.

Associations between agrichemical mixtures and childhood cancer in Nebraska counties- a Generalized Weighted Quantile Sum Regression based approach

Associations between agrichemical mixtures and childhood cancer in Nebraska counties- a Generalized Weighted Quantile Sum Regression based approach

Study on the correlation and interaction between metals and dyslipidemia: a case-control study in Chinese community-dwelling elderly.

Previous studies on the association between metals and dyslipidemia are not completely consistent. There are few studies investigating the relationship between mixed metal exposure and dyslipidemia as well as the effects of metals on dyslipidemia in community-dwelling elderly. To evaluate the correlations and interaction effect between the urinary concentrations of metals and the risk of dyslipidemia in community-dwelling elderly. We designed a case-control study to assess the correlation between urine metals and dyslipidemia in elderly people in the Yinchuan. The urinary levels of 13 metals, including calcium, vanadium, iron, cobalt, zinc, copper, arsenic, selenium, molybdenum, cadmium, tellurium, and thallium, were measured by inductively coupled plasma-mass spectrometry (ICP-MS), and the blood biochemical analyzer was used to measure the blood lipid levels of 3384 senior individuals from four different areas of Yinchuan city. Logistic regression and restricted cubic splines (RCS) were used to explore the correlation and dose-response relationship between urinary metals and the risk of dyslipidemia. Least absolute shrinkage and selection operator (LASSO) regression was used to select metals, and then weighted quantile sum (WQS) regression was used to explore the weight of each metal in mixed metals. Bayesian kernel machine regression (BKMR) was used to explore the interactions between metals on dyslipidemia risk. (1) After selection by LASSO regression, in the multi-metal model, compared with the lowest quartile, the adjusted ORs (95%CI) of the highest quartiles were 0.47 (0.37-0.60) for Fe, 1.43 (1.13-1.83) for Zn, 1.46 (1.11-1.92) for As, 0.59 (0.44-0.80) for Se, 1.53 (1.18-2.00) for Mo, and 1.36 (1.07-1.73) for Te. (2) In the WQS regression model, Fe and Mo accounted for the largest weight in the negative and positive effects of dyslipidemia, respectively. (3) In the BKMR model, there may be a positive interaction between Te and Se on dyslipidemia. Among the mixed metals, Fe, As, Se, Mo, and Te were associated with the prevalence of dyslipidemia, with Fe and Mo contributing the most. There may be certain interactions between Te and Se.

Association between co-exposure to phenols, phthalates, and polycyclic aromatic hydrocarbons with the risk of frailty.

The phenomenon of population aging has brought forth the challenge of frailty. Nevertheless, the contribution of environmental exposure to frailty remains ambiguous. Our objective was to investigate the association between phenols, phthalates (PAEs), and polycyclic aromatic hydrocarbons (PAHs) with frailty. We constructed a 48-item frailty index using data from the National Health and Nutrition Examination Survey (NHANES). The exposure levels of 20 organic contaminants were obtained from the survey circle between 2005 and 2016. The association between individual organic contaminants and the frailty index was assessed using negative binomial regression models. The combined effect of organic contaminants was examined using weighted quantile sum (WQS) regression. Dose-response patterns were modeled using generalized additive models (GAMs). Additionally, an interpretable machine learning approach was employed to develop a predictive model for the frailty index. A total of 1566 participants were included in the analysis. Positive associations were observed between exposure to MIB, P02, ECP, MBP, MHH, MOH, MZP, MC1, and P01 with the frailty index. WQS regression analysis revealed a significant increase in the frailty index with higher levels of the mixture of organic contaminants (aOR, 1.12; 95% CI, 1.05-1.20; p < 0.001), with MIB, ECP, COP, MBP, P02, and P01 identified as the major contributors. Dose-response relationships were observed between MIB, ECP, MBP, P02, and P01 exposure with an increased risk of frailty (both with p < 0.05). The developed predictive model based on organic contaminants exposure demonstrated high performance, with an R2 of 0.9634 and 0.9611 in the training and testing sets, respectively. Furthermore, the predictive model suggested potential synergistic effects in the MIB-MBP and P01-P02 pairs. Taken together, these findings suggest a significant association between exposure to phthalates and PAHs with an increased susceptibility to frailty.

Exposure to parabens and semen quality in reproductive-aged men

BackgroundParabens are common preservatives in personal care products, cosmetics, and medical goods. In the past few years, animal studies showed the male reproductive toxicity associated with some parabens. Yet, epidemiological studies have generated inconsistent findings and research rarely has focused on the mixture effects of the parabens. We aimed to explore the associations between individual paraben exposure as well as the mixture and semen quality parameters. MethodsA total of 795 male partners from preconception couples were included in the study. Their urine samples were analyzed for the concentrations of six parabens, namely methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP), butyl paraben (BuP), benzyl paraben (BzP) and heptyl paraben (HeP). Multiple linear regression models and weighted quantile sum regression (WQS) models were utilized to assess the relationships between individual paraben exposure and paraben mixture with semen quality parameters, respectively. ResultsAfter adjusting for covariates, exposure to a paraben mixture was significantly associated with declining sperm concentration, total sperm count, and progressive motility, among which BuP was identified as the main contributor to sperm concentration and total sperm count while MeP to progressive motility. Results from multiple linear regression models were generally in line with the WQS analysis. ConclusionsOur results suggest negative associations between paraben mixture and sperm concentration, total sperm count, and sperm motility among reproductive-aged men.

Associations between blood essential metal mixture and serum uric acid: a cross-sectional study.

Although several studies have explored the associations between single essential metals and serum uric acid (SUA), the study about the essential metal mixture and the interactions of metals for hyperuricemia remains unclear. We performed a cross-sectional study to explore the association of the SUA levels with the blood essential metal mixture, including magnesium (Mg), calcium (Ca), iron (Fe), copper (Cu), zinc (Zn), manganese (Mn) in Chinese community-dwelling adults (n=1039). The multivariable linear regression, the weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were conducted to estimate the associations of blood essential metals with SUA levels and the BKMR model was also conducted to estimate the interactions of the essential metals on SUA. In the multivariable linear regression, the association of blood Mg, Mn, and Cu with SUA was statistically significant, both in considering multiple metals and a single metal. In WQS regression [β=13.59 (95%CI: 5.57, 21.60)] and BKMR models, a positive association was found between the mixture of essential metals in blood and SUA. Specifically, blood Mg and Cu showed a positive association with SUA, while blood Mn showed a negative association. Additionally, no interactions between individual metals on SUA were observed. In conclusion, further attention should be paid to the relationship between the mixture of essential metals in blood and SUA. However, more studies are needed to confirm these findings.

The association between exposure to volatile organic compounds and serum lipids in the US adult population

Background and AimEpidemiological evidence on the relationship between exposure to volatile organic compounds (VOCs), both single and mixed, and serum lipid levels is limited, and their relationship remains unclear. Our study aimed to investigate the associations of exposure to VOCs with serum lipid levels in the US adult population.Methods and resultsThe study examined the association of 16 VOC levels (2-methylhippuric acid, 3- and 4-methylhippuric acid, N-acetyl-S-(2-carbamoylethyl)-L-cysteine, N-acetyl-S-(N-methylcarbamoyl)-L-cysteine, 2-aminothiazoline-4-carboxylic acid, N-acetyl-S-(benzyl)-L-cysteine, N-acetyl-S-(n-propyl)-L-cysteine, N-acetyl-S-(2-carboxyethyl)-L-cysteine, N-acetyl-S-(2-cyanoethyl)-L-cysteine, N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine, N-acetyl-S-(2-hydroxypropyl)-L-cysteine. N-Acetyl-S-(3-hydroxypropyl)-L-cysteine, mandelic acid, N-acetyl-S-(4-hydroxy-2-butenyl)-L-cysteine, phenylglyoxylic acid and N-acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine) with total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) using data from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2015, and a total of 1410 adults were enrolled. The association was evaluated by Bayesian kernel machine regression (BKMR), multiple linear regression and weighted quantile sum (WQS) regression. In BKMR analysis, exposure to VOCs is positively correlated with levels of TC, TG, and LDL-C. However, statistical significance was observed only for the impact on TG. Our linear regression analysis and WQS regression generally support the BKMR results. Several VOCs were positively associated with serum lipid profiles (e.g., the ln-transformed level of mandelic acid (MA) displayed an increase in estimated changes of 7.01 (95% CIs: 2.78, 11.24) mg/dL for TC level), even after the effective number of tests for multiple testing (P < 0.05).ConclusionsExposure to VOCs was associated with serum lipids, and more studies are needed to confirm these findings.

Exposure to multiple air pollutant mixtures and the subtypes of hypertensive disorders in pregnancy: A multicenter study

BackgroundHypertensive disorders in pregnancy (HDP) have heterogeneous etiologies. Previous studies have linked individual air pollutants to overall HDP with inconsistent results. Moreover, it has not been explored how exposure to a mixture of multiple air pollutants may affect the risks of the subtypes of the disorders. ObjectivesTo investigate the associations of exposure to air pollutant mixture in the 1st and 2nd trimesters of pregnancy with the risks of HDP and its subtypes. MethodsPregnancy data were obtained from the China Labor and Delivery Survey, a nationwide cross-sectional survey in 2015 and 2016. Levels of air pollutants [including fine particulate matter (PM2.5), carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), and sulfur dioxide (SO2)] in the 1st and 2nd trimesters were estimated based on the model developed by the Institution of Atmospheric Physics, Chinese Academy of Science. Generalized linear mixed models were built to assess the single-exposure effects of air pollutants in early gestation on HDP. The restricted cubic spline function was further applied to assess the potential non-linearity. The weighted quantile sum (WQS) regression was used to investigate the effects of co-exposure to multiple air pollutants. ResultsA total of 67,512 pregnancies were included, and 2,834 were HDP cases. The single-effect analysis showed that CO, PM2.5, and SO2 exposure in the 2nd trimester was positively associated with the risks of gestational hypertension (GH), with adjusted odds ratios (aORs) and 95% confidence intervals (CI) of 1.16 (1.04, 1.28), 1.19 (1.04, 1.37), and 1.13 (1.04, 1.22), respectively. The first-trimester O3 exposure was also associated with an increased preeclampsia/eclampsia (PE) risk (aOR = 1.17; 95%CI: 1.02, 1.33). WQS regression confirmed positive associations of air pollutant mixture with HDP subtypes, with PM2.5 as the main contributing pollutant to GH, and CO and O3 as the main pollutants to PE. ConclusionsExposure to multiple air pollutant mixtures in early pregnancy was associated with increased risks of hypertensive disorders in pregnancy.