Associations of multiple blood metals with cardiac structure and function: A cross-sectional study in a CAD population.

Coronary artery disease (CAD) is often accompanied by abnormal cardiac structure and function, leading to an increased prognostic risk. However, less is known about the associations of mixed metals with abnormal cardiac structure and function in CAD patients. Here, we aimed to investigate the associations of exposure to metal mixtures with cardiac structure and function and potential interactions in a CAD population. We conducted a cross-sectional study from Southwest China that included 1555 CAD patients. The blood concentrations of 14 metals were measured via inductively coupled plasma spectrometry. CAD was defined as at least one vessel having stenosis ≥ 50% the vessel diameter. Echocardiography was used for cardiac structural and functional measurements. Bayesian kernel machine regression was applied to explore the overall effect, metal weight, and dose effect. Linear regression analysis was used to analyze the effects of single metals, metal‒metal interactions and metal‒traditional interactions. Finally, we found that the negative associations of mixed metals with cardiac structure was significant when the levels of all metals were below the 60th percentile. For cardiac function, changes in metals from 50th to 75th were associated with 0.954% and 0.683% decrease in left ventricular ejection fraction and left ventricular fractional shortening, respectively. Negative associations of copper and manganese with cardiac structure and function, whereas positive associations of titanium, selenium and molybdenum with several parameters were found. Antagonistic interactions between copper and tin and between selenium and several metals (manganese, copper and aluminum) (all Pinteraction terms < 0.05) were found. In conclusion, mixed metal exposure was negatively associated with cardiac structure and function in CAD patients. The main metals contributing to this negative associations were copper and manganese. Selenium or tin supplementation may reduce the adverse associations of copper and manganese with cardiac structure and function.

Associations of prenatal exposure to PM2.5 and its components with offsprings' neurodevelopmental and behavioral problems: A prospective cohort study from China.

Prenatal exposure to fine particulate matter (PM2.5) has been linked with increased neurodevelopmental disorders. However, the most detrimental component of PM2.5 and the most vulnerable exposure time windows remain undetermined, especially in areas with high PM2.5 levels. In a prospective cohort study involving 4494 mother-child dyads, we examined the associations of prenatal exposure to PM2.5 and its four main components with children's neurodevelopmental and behavioral problems (NBPs), separately in three pregnancy trimesters. Poisson regression and generalized additive models were used to depict the linear and nonlinear associations, respectively. Weighted quantile sum and Bayesian kernel machine regression models were applied to examine the effects of exposure to both mixed and individual components. Results showed that exposure to PM2.5 and its components throughout the three trimesters increased the risk of children's NBPs (Risk ratio for PM2.5: 1.16, 95 % confidence interval 1.14-1.18 per µg/m3 in the first trimester; 1.15, 1.12-1.17 in the second trimester; 1.06, 1.04-1.08 in the third trimester), with associations gradually diminishing as pregnancy progressed (P values for trends < 0.05). Among the four main components of PM2.5, exposure to SO42- posed the highest risks on children's NBPs, while organic matter contributed the largest proportion to the overall impacts of PM2.5 exposure. These results underscore the significance of mitigating PM2.5 exposure in pregnant women to reduce the risk of neurodevelopmental disorders in offspring. Our findings would inform risk assessment of PM2.5 exposure and facilitate the development of precision preventive strategies targeting specific components of PM2.5 in similar areas with high levels of exposure.

Unveiling the link: Neonicotinoids and elevated cardiometabolic risks in Chinese rural residents-from a prospective cohort study combing mendelian randomization study.

PURPOSE: This study aimed to evaluate the relationships of separate and mixed exposure of neonicotinoids on cardiometabolic risk at baseline and follow-up and its change over 3 years, and further explore whether inflammatory markers levels and platelet traits (PLT) mediate these relationships. METHODS: In this prospective cohort study from the Henan Rural Cohort Study, 2315 participants were involved at baseline, and 1841 participants completed cardiometabolic risk predictors determinations during the 3-year follow-up. Each neonicotinoid pesticide was normalized to imidacloprid (IMIeq) using the relative potency factor approach. Quantile-based g-computation (Qgcomp) regression was used to evaluate the effect of the mixtures of neonicotinoids mediation analysis was employed to explore whether inflammatory markers levels and platelet traits mediated these relationships. A two-sample mendelian randomization (MR) study was further used to causal association. RESULTS: Qgcomp regression revealed a statistically positive relationship between neonicotinoids mixture exposure and cardiometabolic risk score at baseline and follow-up over 3 years. Both neutrophils/monocytes and PLT were mediators in the relationship between IMIeq and cardiometabolic risk score at baseline and follow-up over 3 years. The causal risk effect of pesticide exposure were 2.50 (0.05, 4.95) and 5.24 (1.28, 9.19) for cardiometabolic risk indicators including insulin resistance and triglyceride, respectively. Nevertheless, there was no correlation discovered between pesticide exposure and other markers of cardiometabolic risk. CONCLUSION: Neonicotinoid insecticides exposure was connected to an increased cardiometabolic risk, especially in individuals with T2DM. Furthermore, inflammatory markers and PLT seem to be two vital mediators of these associations. Additionally, genetic evidence on pesticide exposure and cardiometabolic risk still needs to be validated by multiregional and multiethnic GWAS studies.

Association between organophosphate esters individual and mixed exposure with the risk of hyperlipidemia and serum lipid levels among adults in Wuhan, China.

Toxicologic studies reported that organophosphate esters (OPEs) may disrupt lipid metabolism, thus affecting serum lipid levels. However, epidemiological evidence regarding the association between OPEs and the risk of hyperlipidemia (HPL) as well as serum lipid levels is scarce. In the present study, our aim was to investigate the impact of individual and mixed OPE exposure on HPL. A total of 1981 Chinese adults were involved based on a cross-sectional design. Overall, we found a positive association between bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and the risk of HPL. Bis(1-chloro-2-propyl) phosphate (BCIPHIPP) showed a positive association with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). BDCIPP, diphenyl phosphate (DPHP), di-ocresyl phosphate and di-p-cresyl phosphate (Docp&Dpcp), and 4-hydroxyphenyl-diphenyl phosphate (4-OH-DPHP) exhibited a negative association with high-density lipoprotein cholesterol (HDL-C). In stratified analyses, BDCIPP and BCIPHIPP were significantly correlated with the increased risk of HPL in the age ≤ 45 group. Bis(2-butoxyethyl) phosphate (BBOEP) was in relationship with an elevated risk of HPL in the subgroup of BMI < 24 kg/m2. BDCIPP was also positively associated with HPL in men. Quantile-based g computation (qgcomp) and generalized weighted quantile sum regression (gWQS) models demonstrated a negative association between OPEs mixed exposure and HDL-c in the total population, as well as a positive effect of them on HPL in the subgroup of age ≤ 45 years, which is consistent with the individual analyses. Furthermore, joint effect analyses revealed that participants with detected BDCIPP urinary levels and unhealthy lifestyles had the highest risk of HPL. Our findings offer evidence supporting the correlation between exposure to OPE and the risk of HPL, necessitating further prospective studies for validation.

Prenatal exposure to polycyclic aromatic hydrocarbons and phthalate acid esters and gestational diabetes mellitus: A prospective cohort study.

BACKGROUND: Polycyclic aromatic hydrocarbons and phthalate acid esters (PAHs & PAEs), known as endocrine disrupting chemicals (EDCs), widely exist in daily life and industrial production. Previous studies have suggested that PAHs & PAEs may modify the intrauterine homeostasis and have adverse effects on fetal development. However, epidemiological evidence on the associations between PAHs & PAEs and gestational diabetes mellitus (GDM) is still limited. OBJECTIVE: To investigate the effects of prenatal PAHs &PAEs exposure on the risk of GDM and hyperglycemia in pregnant women. METHODS: The study population was a total of 725 pregnant women from a prospective birth cohort study conducted from December 2019 to December 2021. Blood glucose levels were collected by the hospital information system. Urinary PAHs & PAEs concentrations were determined by gas chromatography tandem mass spectrometry. The Poisson regression in a generalized linear model (GLM), multiple linear regression, quantile-based g-computation method (qgcomp), and Bayesian kernel machine regression (BKMR) were applied to explore and verify the individual and overall effects of PAHs & PAEs on glucose homeostasis. Potential confounders were adjusted in all statistical models. RESULTS: A total of 179 (24.69%) women were diagnosed with GDM. The Poisson regression suggested that a ln-unit increment of 4-OHPHE (4-hydroxyphenanthrene) (adjusted Risk Ratio (aRR) = 1.13; 1.02-1.26) was associated with the increased GDM risk. Mixed-exposure models showed similar results. We additionally found that MBZP (mono-benzyl phthalate) (aRR = 1.19; 1.02-1.39) was positively related to GDM risk in qgcomp model. Although neither model demonstrated that 2-OHNAP (2-hydroxynaphthalene) and 9-OHFLU (9-hydroxyfluorene) increased the risk of GDM, 2-OHNAP and 9-OHFLU exposure significantly increased blood glucose levels. BKMR model further confirmed that overall effects of PAHs & PAEs were significantly associated with the gestational hyperglycemia and GDM risk. CONCLUSIONS: Our study presents that environmental exposure to PAHs & PAEs was positively associated with gestational glucose levels and the risks of developing GDM. In particular, 2-OHNAP, 9-OHFLU, 4-OHPHE and MBZP may serve as important surveillance markers to prevent the development of GDM.

Association between mixed metal exposure and stroke risk in Shanxi Province: a case-control study.

BACKGROUND: Stroke is the second leading cause of death for all human beings and poses a serious threat to human health. Environmental exposure to a mixture of metals may be associated with the occurrence and development of stroke, but the evidence in the Chinese population is not yet conclusive. OBJECTIVES: This study evaluated the association between stroke risk and 13 metals METHODS: Metal concentrations in whole blood samples from 100 stroke cases and 100 controls were measured by ICP-MS. The cumulative impact of mixed metal on stroke risk was investigated by using three statistical models, BKMR, WQS and QGC. RESULTS: The case group had higher concentrations of Mg, Mn, Zn, Se, Sn, and Pb than the control group (p<0.05). BKMR model indicated a correlation between the risk of stroke and exposure to mixed metals. WQS model showed that Mg (27.2 %), Se (25.1 %) and Sn (14.8 %) were positively correlated with stroke risk (OR=1.53; 95 %Cl: 1.03-2.37, p=0.013). The QGC model showed that Mg (49.2 %) was positively correlated with stroke risk, while Ti (31.7 %) was negatively correlated with stroke risk. CONCLUSIONS: Mg may be the largest contributor to the cumulative effect of mixed metal exposure on stroke risk, and the interaction between metals requires more attention. These findings could provide scientific basis for effectively preventing stroke by managing metals in the environment.

Association between exposure to organophosphorus pesticide and suicidal ideation among U.S. adults: A population-based study.

OBJECTIVE: This study aims to investigate the potential link between exposure to organophosphorus pesticides (OPPs) and suicidal ideation (SI) among adults. METHODS: This study encompassed four cycles of the National Health and Nutrition Examination Survey (NHANES), involving 5244 participants aged 20 and above. SI was assessed using the Patient Health Questionnaire-9. The levels of exposure to OPPs were estimated by analyzing concentrations of OPP metabolites in urine samples. Multivariate logistic regression models were used to explore the association between exposure to each OPP and SI. Stratified analyses and interaction tests were conducted across various groups, including pairwise combinations of gender and age, as well as body mass index, smoking status, hypertension, and diabetes. Weighted Quantile Sum (WQS) regression and Bayesian Kernel Machine Regression (BKMR) models were applied to assess the cumulative impact of exposure to the four OPPs on SI, along with their respective contributions. Additionally, the potential interactions among these four OPPs were evaluated. RESULTS: Multivariate logistic regression revealed that only dimethylthiophosphate (DMTP) among OPPs demonstrated a statistically significant positive association with SI [OR: 1.18; 95 % CI: 1.02-1.37]. Stratified analyses indicated that the influence of OPPs on SI was particularly pronounced in young and older men. The WQS regression analysis revealed a statistically significant association between the mixed metabolites of OPPs and SI [OR = 1.10, 95 % CI: 1.04-1.16], with DMTP (weighted 0.63) contributing the most. Furthermore, the BKMR model supported a positive trend in the overall impact of these OPP metabolites on SI, displaying notable individual exposure-response relationships for DMTP (PIP: 0.77). CONCLUSIONS: Our study suggests an association between exposure to DMTP and an increased risk of SI. Specifically, young adult males and older males appear particularly susceptible to the effects of OPP exposure.

Association between single and mixed exposure to polycyclic aromatic hydrocarbons and biological aging.

Background: Aging is one of the most important public health issues. Previous studies on the factors affecting aging focused on genetics and lifestyle, but the association between polycyclic aromatic hydrocarbons (PAHs) and aging is still unclear. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2003-2010. A total of 8,100 participants was used to construct the biological age predictors by using recent advanced algorithms Klemera-Doubal method (KDM) and Mahalanobis distance. Two biological aging indexes, recorded as KDM-BA acceleration and PhenoAge acceleration, were used to investigate the relationship between single PAHs and biological age using a multiple linear regression analysis, and a weighted quantile sum (WQS) model was constructed to explore the mixed effects of PAHs on biological age. Finally, we constructed the restricted cubic spline (RCS) model to assess the non-linear relationship between PAHs and biological age. Results: Exposure to PAHs was associated with PhenoAge acceleration. Each unit increase in the log10-transformed level of 1-naphthol, 2-naphthol, and 2-fluorene was associated with a 0.173 (95% CI: 0.085, 0.261), 0.310 (95% CI: 0.182, 0.438), and 0.454 (95% CI: 0.309, 0.598) -year increase in PhenoAge acceleration, respectively (all corrected P < 0.05). The urinary PAH mixture was relevant to KDM-BA acceleration (ß = 0.13, 95% CI: 0, 0.26, P = 0.048) and PhenoAge acceleration (ß = 0.59, 95% CI: 0.47, 0.70, P < 0.001), and 2-naphthol had the highest weight in the weighted quantile sum (WQS) regression. The RCS analyses showed a non-linear association between 2-naphthol and 2-fluorene with KDM-BA acceleration (all P < 0.05) in addition to a non-linear association between 1-naphthol, 2-naphthol, 3-fluorene, 2-fluorene, and 1-pyrene with PhenoAge acceleration (all P < 0.05). Conclusion: Exposure to mixed PAHs is associated with increased aging, with 2-naphthol being a key component of PAHs associated with aging. This study has identified risk factors in terms of PAH components for aging.

Associations of phthalates with accelerated aging and the mitigating role of physical activity.

Phthalates are positioned as potential risk factors for health-related diseases. However, the effects of exposure to phthalates on accelerated aging and the potential modifications of physical activity remain unclear. A total of 2317 participants containing complete study-related information from the National Health and Nutrition Examination Survey 2007-2010 were included in the current study. We used two indicators, the Klemera-Doubal method biological age acceleration (BioAgeAccel) and phenotypic age acceleration (PhenoAgeAccel), to assess the accelerated aging status of the subjects. Multiple linear regression (single pollutant models), weighted quantile sum (WQS) regression, Quantile g-computation, and Bayesian kernel machine regression (BKMR) models were utilized to explore the associations between urinary phthalate metabolites and accelerated aging. Three groups of physical activity with different intensities were used to evaluate the modifying effects on the above associations. Results indicated that most phthalate metabolites were significantly associated with BioAgeAccel and PhenoAgeAccel, with effect values (ß) ranging from 0.16 to 0.21 and 0.16-0.37, respectively. The WQS indices were positively associated with BioAgeAccel (0.33, 95% CI: 0.11, 0.54) and PhenoAgeAccel (0.50, 95% CI: 0.19, 0.82). Quantile g-computation indicated that phthalate mixtures were associated with accelerated aging, with effect values of 0.15 (95% CI: 0.02, 0.28) for BioAgeAccel and 0.39 (95% CI: 0.12, 0.67) for PhenoAgeAccel respectively. The BKMR models indicated a significant positive association between the concentrations of urinary phthalate mixtures with the two indicators. In addition, we found that most phthalate metabolites showed the strongest effects on accelerated aging in the no physical activity group and that the effects decreased gradually with increasing levels of physical activity (P < 0.05 for trend). Similar results were also observed in the mixed exposure models (WQS and Quantile g-computation). This study indicates that phthalates exposure is associated with accelerated aging, while physical activity may be a crucial barrier against phthalates exposure-related aging.

Associations between organophosphate esters and bone mineral density in adults in the United States: 2011-2018 NHANES.

BACKGROUND: Organophosphate esters (OPEs) are used extensively as flame retardants and plasticizers. Laboratory studies have shown that OPEs exhibit osteotoxicity by inhibiting osteoblast differentiation; however, little is known about how OPEs exposure is associated with bone health in humans. OBJECTIVES: We conducted a cross-sectional study to investigate the association between OPEs exposure and bone mineral density (BMD) in adults in the United States using data from the 2011-2018 National Health and Nutrition Examination Survey (NHANES). METHODS: Multivariate linear regression models were used to assess the association between concentrations of individual OPE metabolites and BMDs. We also used the Bayesian kernel machine regression (BKMR) and quantile g-computation (qgcomp) models to estimate joint associations between OPE mixture exposure and BMDs. All the analyses were stratified according to gender. RESULTS: A total of 3546 participants (median age, 40 years [IQR, 30-50 years]; 50.11% male) were included in this study. Five urinary OPE metabolites with a detection rate of > 50% were analyzed. After adjusting for the potential confounders, OPE metabolite concentrations were associated with decreased total-body BMD and lumbar spine BMD in males, although some associations only reached significance for bis(1-chloro-2-propyl) phosphate (BCPP), dibutyl phosphate (DBUP), and bis(2-chloroethyl) phosphate (BCEP) (ß = -0.013, 95% CI: -0.026, -0.001 for BCPP and total-body BMD; ß = -0.022, 95% CI: -0.043, -0.0001 for DBUP and lumbar spine BMD; ß=-0.018, 95% CI: -0.034, -0.002 for BCEP and lumbar spine BMD). OPE mixture exposure was also inversely associated with BMD in males, as demonstrated in the BMKR and qgcomp models. CONCLUSIONS: This study provides preliminary evidence that urinary OPE metabolite concentrations are inversely associated with BMD. The results also suggested that males were more vulnerable than females. However, further studies are required to confirm these findings.

Associations of essential metals with the risk of aortic arch calcification: a cross-sectional study in a mid-aged and older population of Shenzhen, China.

Vascular calcification is a strong predictor of cardiovascular events. Essential metals play critical roles in maintaining human health. However, the association of essential metal levels with risk of aortic arch calcification (AoAC) remains unclear. We measured the plasma concentrations of nine essential metals in a cross-sectional population and evaluated their individual and combined effects on AoAC risk using multiple statistical methods. We also explored the mediating role of fasting glucose. In the logistic regression model, higher quartiles of magnesium and copper were associated with the decreased AoAC risk, while higher quartile of manganese was associated with higher AoAC risk. The least absolute shrinkage and selection operator penalized regression analysis identified magnesium, manganese, calcium, cobalt, and copper as key metals associated with AoAC risk. The weighted quantile sum regression suggested a combined effect of metal mixture. A linear and positive dose-response relationship was found between manganese and AoAC in males. Moreover, blood glucose might mediate a proportion of 9.38% of the association between manganese exposure and AoAC risk. In summary, five essential metal levels were associated with AoAC and showed combined effect. Fasting glucose might play a significant role in mediating manganese exposure-associated AoAC risk.

Genetic and epigenetic modulations in toxicity: The two-sided roles of heavy metals and polycyclic aromatic hydrocarbons from the environment.

This study emphasizes the importance of considering the metabolic and toxicity mechanisms of environmental concern chemicals in real-life exposure scenarios. Furthermore, environmental chemicals may require metabolic activation to become toxic, and competition for binding sites on receptors can affect the severity of toxicity. The multicomplex process of chemical toxicity is reflected in the activation of multiple pathways during toxicity of which AhR activation is major. Real-life exposure to a mixture of concern chemicals is common, and the composition of these chemicals determines the severity of toxicity. Nutritional essential elements can mitigate the toxicity of toxic heavy metals, while the types and ratio of composition of PAH can either increase or decrease toxicity. The epigenetic mechanisms of heavy metals and PAH toxicity involves either down-regulation or up-regulation of some non-coding RNAs (ncRNAs) whereas specific small RNAs (sRNAs) may have dual role depending on the tissue and circumstance of expression. Similarly, decrease DNA methylation and histone modification are major players in heavy metals and PAH mediated toxicity and FLT1 hypermethylation is a major process in PAH induced carcinogenesis. Overall, this review provides the understanding of the metabolism of environmental concern chemicals, emphasizing the importance of considering mixed compositions and real-life exposure scenarios in assessing their potential effects on human health and diseases development as well as the dual mechanism of toxicity via genetic or epigenetic axis.

Association between multiple-heavy-metal exposures and systemic immune inflammation in a middle-aged and elderly Chinese general population.

BACKGROUND: Exposure to heavy metals alone or in combination can promote systemic inflammation. The aim of this study was to investigate potential associations between multiple plasma heavy metals and markers of systemic immune inflammation. METHODS: Using a cross-sectional study, routine blood tests were performed on 3355 participants in Guangxi, China. Eight heavy metal elements in plasma were determined by inductively coupled plasma mass spectrometry. Immunoinflammatory markers were calculated based on peripheral blood WBC and its subtype counts. A generalised linear regression model was used to analyse the association of each metal with the immunoinflammatory markers, and the association of the metal mixtures with the immunoinflammatory markers was further assessed using weighted quantile sum (WQS) regression. RESULTS: In the single-metal model, plasma metal Fe (log10) was significantly negatively correlated with the levels of immune-inflammatory markers SII, NLR and PLR, and plasma metal Cu (log10) was significantly positively correlated with the levels of immune-inflammatory markers SII and PLR. In addition, plasma metal Mn (log10 conversion) was positively correlated with the levels of immune inflammatory markers NLR and PLR. The above associations remained after multiple corrections. In the mixed-metal model, after WQS regression analysis, plasma metal Cu was found to have the greatest weight in the positive effects of metal mixtures on SII and PLR, while plasma metals Mn and Fe had the greatest weight in the positive effects of metal mixtures on NLR and LMR, respectively. In addition, blood Fe had the greatest weight in the negative effects of the metal mixtures for SII, PLR and NLR. CONCLUSION: Plasma metals Cu and Mn were positively correlated with immunoinflammatory markers SII, NLR and PLR. While plasma metal Fe was negatively correlated with immunoinflammatory markers SII, NLR, and PLR.

New findings on the risk of hypertension from organophosphorus exposure under different glycemic statuses: The key role of lipids?

BACKGROUND AND OBJECTIVE: Considering the widespread use of organophosphorus pesticides (OPs) and the global prevalence of hypertension (HTN), as well as studies indicating that different glycemic statuses may respond differently to the biological effects of OPs. Therefore, this study, based on the Henan rural cohort, aims to investigate the association between OPs exposure and HTN, and further explores whether lipids mediate these associations. METHODS: We measured the plasma levels of OPs in 2730 participants under different glycemic statuses using gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS). A generalized linear model, Quantile g-computation (QGC), adaptive elastic net (AENET), and Bayesian kernel machine regression (BKMR) models were used to assess the impact of OPs exposure on HTN, with least absolute shrinkage and selection operator (LASSO) penalty regression identifying main OPs. Mediation models were used to evaluate the intermediary role of blood lipids in the OPs-HTN relationship. RESULTS: The detection rates for all OPs were high, ranging from 76.35 % to 99.17 %. In the normal glucose tolerance (NGT) population, single exposure models indicated that malathion and phenthoate were associated with an increased incidence of HTN (P-FDR < 0.05), with corresponding odds ratios (ORs) and 95 % confidence intervals (CIs) of 1.624 (1.167,2.260) and 1.290 (1.072,1.553), respectively. QGC demonstrated a positive association between OP mixtures and HTN, with malathion and phenthoate being the primary contributors. Additionally, the AENET model's Exposure Response Score (ERS) suggested that the risk of HTN increases with higher ERS (P < 0.001). Furthermore, BKMR revealed that co-exposure to OPs increases HTN risk, with phenthoate having a significant impact. Furthermore, triglycerides (TG) mediated 6.55 % of the association between phenthoate and HTN. However, no association was observed in the impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM) populations. CONCLUSIONS: Our findings suggest that in the NGT population, OPs may significantly contribute to the development of HTN, proposing TG as a potential novel target for HTN prevention.

Mixture effects of trace element levels on cardiovascular diseases and type 2 diabetes risk in adults using G-computation analysis.

There is an increasing concern about the health effects of exposure to a mixture of pollutants. This study aimed to evaluate the associations between serum levels of heavy/essential metals ([Arsenic (As), Cadmium (Cd), Mercury (Hg), Lead (Pb), Nickel (Ni), Chromium (Cr), Copper (Cu), Iron (Fe), and Zinc (Zn)]) and the risk of developing cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2D). Data were collected from 450 participants (150 with CVDs, 150 with T2D, and 150 healthy subjects) randomly selected from the Ravansar Non-Communicable Disease (RaNCD) cohort in Western Iran, covering the years 2018-2023. Trace element levels in the serum samples were assayed using ICP-MS. Logistic regression was performed to estimate the adjusted risk of exposure to single and multi-metals and CVD/T2D. Odds ratios were adjusted for age, sex, education, residential areas, hypertension, and BMI. The mixture effect of exposure to multi-metals and CVD/T2D was obtained using Quantile G-computation (QGC). In the logistic regression model, chromium, nickel, and zinc levels were associated with CVD, and significant trends were observed for these chemical quartiles (P < 0.001). Arsenic, chromium, and copper levels were also associated with T2D. The weight quartile sum (WQS) index was significantly associated with both CVD (OR 4.17, 95% CI 2.16-7.69) and T2D (OR 11.96, 95% CI 5.65-18.26). Cd, Pb, and Ni were the most heavily weighed chemicals in these models.The Cd had the highest weight among the metals in the CVD model (weighted at 0.78), followed by Hg weighted at 0.197. For T2D, the serum Pb (weighted at 0.32), Ni (weighted at 0.19), Cr (weighted at 0.17), and Cd (weighted at 0.14) were the most weighted in the G-computation model. The results showed the significant role of toxic and essential elements in CVDs and T2D risk. This association may be driven primarily by cadmium and mercury for CVDs and Pb, Ni, Cr, and Cd for T2D, respectively. Prospective studies with higher sample sizes are necessary to confirm or refute our preliminary results as well as to determine other important elements.

Association between per- and polyfluoroalkyl substances exposure and prevalence of chronic obstructive pulmonary disease: The mediating role of serum albumin.

BACKGROUND: No study has examined the association between per- and polyfluoroalkyl substances (PFAS) exposure and chronic obstructive pulmonary disease (COPD) risk. This study aims to explore this relationship. METHODS: This study enrolled 4541 individuals who had available data on PFAS, COPD, and covariates from NHANES 2007-2018. Serum PFAS including perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS) were analyzed, because of high detective rates. Considering the skew distribution of PFAS levels, the natural logarithm-transformed PFAS (Ln-PFAS) was used. Logistic regression analysis, restricted cubic spline (RCS), and weighted quantile sum (WQS) regression were performed to explore the single, nonlinear, and mixed effects. A mediating analysis was used to evaluate the mediated effects of albumin. RESULTS: Individuals with COPD had higher levels of PFHxS, PFNA, PFOA, and PFOS compared to those without COPD. Ln-PFNA (OR males: 1.92, 95 % CI:1.31 to 2.80, P: <0.001; OR females: 1.07, 95 % CI: 0.81 to 1.40, P: 0.636) and ln-PFOA (OR males: 2.17, 95 % CI:1.38 to 3.41, P: <0.001; OR females: 1.49, 95 % CI: 1.08 to 2.05, P: 0.016) were associated with COPD risk especially in males. The interaction between PFNA exposure and sex on COPD risk was significant (P interaction: <0.001). The RCS curve demonstrated the nonlinear relationship between the ln-PFOA (P nonlinear:0.001), ln-PFNA (P nonlinear:0.045), and COPD risk in males. WQS analysis showed mixed PFAS exposure was correlated with COPD risk in males (OR: 1.44, 95 % CI:1.18 to 1.75, P: <0.001). Albumin mediated the relationship between PFOA and COPD (mediated proportion: -17.94 %). CONCLUSION: This study concludes PFOA and PFNA are linked to a higher COPD risk in males, and serum albumin plays a mediating role in the relationship between PFOA and COPD. Thess findings are beneficial for the prevention of COPD. Further studies are required to explore potential mechanisms.

Co-exposure to phthalates and polycyclic aromatic hydrocarbons and the risk of gestational hypertension in Chinese women.

Phthalates (PAEs) and polycyclic aromatic hydrocarbons (PAHs) are frequently detected in females of reproductive age. Many studies have found that environmental PAE and PAH levels are independent risk factors for gestational hypertension. However, exposure to both components is a more realistic scenario. To better assess the health effects of PAEs and PAHs in pregnant women, we explored the associations of exposure to both individual and combined PAEs and PAHs with gestational hypertension. This nested case-control study was a component of a prospective cohort study conducted in Beijing, China. We included 206 women with gestational hypertension and 214 pregnant controls. We used gas chromatography/tandem mass spectrometry (GC-MS/MS) to detect 8 PAEs and 13 PAHs in > 80 % of all collected hair samples. Multiple linear regression models were employed to test the individual associations between each component and gestational hypertension. A quantile-based g-computation (qgcomp) model and a weighted quantile sum (WQS) regression model were used to estimate whether exposure to both PAEs and PAHs increased the risk of gestational hypertension. The individual exposure analyses revealed that diethyl phthalate (DEP), diisobutyl phthalate (DIBP) (both PAEs), benzo(k)fluoranthene (BKF), anthracene, (ANT), and benzo(a)pyrene (BAP) (all PAHs) were positively associated with increased risk of gestational hypertension. In mixed-effect analyses, the qgcomp model indicated that co-exposure to PAEs and PAHs increased the risk of gestational hypertension (odds ratio = 2.01; 95 % confidence interval: 1.02, 3.94); this finding was verified by the WQS regression model. Our findings support earlier evidence that both PAEs and PAHs increase the risk of gestational hypertension, both individually and in combination. This suggests that reductions in exposure to endocrine system-disrupting chemicals such as PAEs and PAHs might reduce the risk of gestational hypertension.

Combined association of urinary volatile organic compounds with chronic bronchitis and emphysema among adults in NHANES 2011-2014: The mediating role of inflammation.

Evidence on the association of volatile organic compounds (VOCs) with chronic bronchitis (CB) and emphysema is spare and defective. To evaluate the relationship between urinary metabolites of VOCs (mVOCs) with CB and emphysema, and to identify the potential mVOC of paramount importance, data from NHANES 2011-2014 waves were utilized. Logistic regression was conducted to estimate the independent association of mVOCs with respiratory outcomes. Least absolute shrinkage and selection operator (LASSO) regression was performed to screen a parsimonious set of CB- and emphysema-relevant mVOCs that were used for further co-exposure analyses of weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR). Mediation analysis was employed to detect the mediating role of inflammatory makers in such associations. In single exposure analytic model, nine mVOCs were individually and positively associated with CB, while four mVOCs were with emphysema. In WQS regression, positive association between LASSO selected mVOCs and CB was identified (OR = 1.82, 95% CI: 1.25 to 2.69), and N-acetyl-S-(4-hydroxy-2-butenyl)-l-cysteine (MHBMA3) weighted the highest. Results from BKMR further validated such combined association and the significance of MHBMA3. As for emphysema, significantly positive overall trend of mVOCs was only observed in BKMR model and N-acetyl-S-(N-methylcarbamoyl)-l-cysteine (AMCC) contributed most to the mixed effect. White blood cell count (WBC) and lymphocyte number (LYM) were mediators in the positive pattern of mVOCs mixture with CB, while association between mVOCs mixture and emphysema was significantly mediated by LYM and segmented neutrophils num (NEO). This study demonstrated that exposure to VOCs was associated with CB and emphysema independently and combinedly, which might be partly speculated that VOCs were linked to activated inflammations. Our findings shed novel light on VOCs related respiratory illness, and provide a new basis for the contribution of certain VOCs to the risk of CB and emphysema, which has potential public health implications.

[Association analysis between mixed exposure to phenols and semen quality].

Phenols such as bisphenols, parabens, and triclosan are common environmental endocrine disruptors. Previous epidemiological studies have suggested that phenols may affect semen quality, but the results were inconsistent. In addition, most existing studies have been limited to the effects of a single chemical compound, ignoring the health effects of mixed exposure to multiple chemicals. Thus, we aimed to explore the associations between individual and mixed exposure to phenols and various semen quality parameters. In this study, a rapid and sensitive method was used to determine 18 phenolic compounds in urine samples of 799 volunteers who donated sperm samples to the Shanghai Human Sperm Bank. A spot urine sample was collected from each subject on the day of their clinic visit and stored at -20 ℃ until testing. Urine samples (200 µL) were extracted and added with 20 µL of an internal standard and 50 µL of ß-glucuronidase solution. The mixtures were then incubated for 12 h at 37 ℃. After hydrolysis, the samples were extracted twice using ethyl acetate (500 µL). The concentrations of the 18 phenolic compounds were measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Semen quality parameters were analyzed using a computer-aided semen analyzer. Multiple linear regressions were used to detect the associations between individual phenol exposure and semen quality parameters. In addition, weighted quantile sum (WQS) models were used to explore the associations between mixed-phenol exposure and semen quality parameters. After adjusting for potential covariates, the results of multiple linear regressions showed that exposure to ethyl paraben (EtP) was significantly negatively associated with sperm concentration and total sperm count (P<0.05). In addition, exposure to mixed phenols was significantly associated with decreased sperm concentration; methyl paraben (MeP) and EtP were identified as the main contributors to this decrease. Thus, phenol exposure may be associated with decreased semen quality in young males, particularly with respect to sperm concentration and total sperm count.

Association between urinary organophosphate ester metabolite exposure and thyroid disease risk among US adults: National Health and Nutrition Examination Survey 2011-2014.

Background: Organophosphate esters (OPEs) may interfere with thyroid function, but the relationship between OPEs and thyroid disease remains unclear. This study aims to elucidate the relationship between OPEs exposure and thyroid disease risk in the general population in the United States. Method: Data were obtained from the 2011-2014 National Health and Nutrition Examination Survey cycle. All participants were tested for seven OPE metabolites in their urine and answered questions about whether they had thyroid disease through questionnaires. Logistic regression was employed to analyze the association between exposure to individual OPE metabolites and thyroid disease. Weighted Quantile Sum (WQS) regression modeling was utilized to assess exposure to mixed OPE metabolites and risk of thyroid disease. Bayesian kernel machine regression(BKMR) models to analyze the overall mixed effect of OPE metabolites. Result: A total of 2,449 participants were included in the study, 228 of whom had a history of thyroid disease. Bis(1,3-dichloro-2-propyl) phos (BDCPP), Diphenyl phosphate (DPHP) and Bis(2-chloroethyl) phosphate (BCEP) were the top three metabolites with the highest detection rates of 91.75%, 90.77% and 86.57%, respectively. In multivariate logistic regression models, after adjustment for confounding variables, individuals with the highest tertile level of BCEP were significantly and positively associated with increased risk of thyroid disease (OR=1.57, 95% CI=1.04-2.36), using the lowest tertile level as reference. In the positive WQS regression model, after correcting for confounding variables, mixed exposure to OPE metabolites was significantly positively associated with increased risk of thyroid disease (OR=1.03, 95% CI=1.01-1.06), with BCEP and DPHP having high weights. In the BKMR model, the overall effect of mixed exposure to OPE metabolites was not statistically significant, but univariate exposure response trends showed that the risk of thyroid disease decreased and then increased as BCEP exposure levels increased. Conclusion: The study revealed a significant association between exposure to OPE metabolites and an increased risk of thyroid disease, with BCEP emerging as the primary contributor. The risk of thyroid disease exhibits a J-shaped pattern, whereby the risk initially decreases and subsequently increases with rising levels of BCEP exposure. Additional studies are required to validate the association between OPEs and thyroid diseases.