U-shaped Dose-response Relationship Research Articles

Association of Blood Metals and Metal Mixtures with the Myocardial Enzyme Profile: An Occupational Population-Based Study in China.

To investigate a cross-sectional association between blood metal mixture and myocardial enzyme profile, we quantified creatine kinase (CK), creatine kinase-MB (CK-MB), lactate dehydrogenase (LD), α-hydroxybutyrate dehydrogenase (α-HBD), and aspartate transaminase (AST) levels among participants from the manganese-exposed workers healthy cohort (MEWHC) (n = 544). The levels of 22 metals in blood cells were determined using inductively coupled plasma mass spectrometry. The least absolute shrinkage and selection operator (LASSO) penalized regression model was utilized for screening metals. The exposure-response relationship between specific metal and myocardial enzyme profile was identified by general linear regression and restricted cubic spline analyses. The overall effect and interactions were evaluated using Bayesian kernel machine regression (BKMR). Manganese was linearly and positively associated with CK (Poverall = 0.019, Pnon-linearity = 0.307), dominating the positive overall effect of mixture exposure (manganese, arsenic, and rubidium) on CK level. Calcium and zinc were linearly and negatively associated with LD levels (Poverall < 0.05, Pnon-linearity > 0.05), and asserted dominance in the negative overall effect of metal mixtures (rubidium, molybdenum, zinc, nickel, cobalt, calcium, and magnesium) on LD level. Interestingly, we observed a U-shaped dose-response relationship of molybdenum with LD level (Poverall < 0.001, Pnon-linearity = 0.015), an interaction between age and calcium on LD level (Pinteration = 0.041), and an interaction between smoking and molybdenum on LD level (Pinteration = 0.035). Our study provides evidence that metal mixture exposure affects the myocardial enzyme profile. Additional investigation is required to confirm these associations, and to reveal the fundamental mechanisms involved.

Associations between 4 lipid biomarkers and cardiometabolic multimorbidity development in middle aged and old adults in China

Objective: To estimate the longitudinal association between serum lipid biomarkers and the development of cardiometabolic multimorbidity (CMM) in middle-aged and old adults (≥45) in China, while examining effect differences among degree of dyslipidemia aggregation and various dyslipidemia combination patterns. Methods: Based on data from the China Health and Retirement Longitudinal Study (2011-2018), logistic regression analysis was used to evaluate the associations of TC, LDL-C, HDL-C, TG (4 forms of dyslipidemias), degree and pattern of dyslipidemia combination with CMM. We also used restricted cubic splines to show the dose-response associations between 4 lipid biomarkers and CMM development. Results: Of the 6 522 participants included, 590 (9.05%) developed CMM. After adjusting for covariates, all 4 forms of dyslipidemias were positively associated with CMM development (high TC: OR=1.33, 95%CI: 1.03-1.71; high LDL-C: OR=1.35, 95%CI: 1.05-1.75; low HDL-C: OR=1.45, 95%CI: 1.19-1.77; high TG: OR=1.50, 95%CI: 1.20-1.88). The U-shaped dose-response relationship between LDL-C and CMM development was observed (P for non-linear =0.022). The odds of CMM increased with the increase of dyslipidemias forms, which was highest in those with ≥3 forms of dyslipidemias (OR=2.02, 95%CI: 1.33-3.06). In various dyslipidemia form combinations, the possibility of CMM development was highest in those with high TC, high LDL-C and low HDL-C (OR=3.54, 95%CI: 1.40-8.67). High TC and high LDL-C were significantly associated with CMM development in people without cardiometabolic diseases. Low HDL-C was positively associated with diabetes and CMM development in participants without cardiometabolic diseases, cardiovascular disease (CVD) followed by diabetes, and diabetes followed by CVD. High TG was positively associated with diabetes and CMM in participants without cardiometabolic diseases, and diabetes followed by CVD. Conclusions: A total of 4 forms of dyslipidemia were all independently associated with CMM development in middle-aged and old adults in China. The dose-response relationship between LDL-C level and CMM development was U-shaped. The aggregation of 4 forms of dyslipidemia were associated with the development of CMM. Low HDL-C and high TG were significantly associated with multiple patterns of cardiometabolic diseases development.

Nonlinear dose-response association of moderate-to-vigorous physical activity with hyperuricemia in US adults: NHANES 2007-2018.

The relationship between physical activity and hyperuricemia (HUA) remains inconsistent, and the dose-response association between moderate-to- vigorous physical activity (MVPA) level and HUA still unclear. In this study, we aimed to investigate the dose-response association of MVPA with HUA, and to explore an appropriate range of MVPA level for preventing HUA. Data from the US National Health and Nutrition Examination Survey (NHANES) 2007-2018 were used, including 28740 non-gout adult Americans. MVPA level was self-reported using the Global Physical Activity Questionnaire and serum uric acid was measured using timed endpoint method. The dose-response relationship between MVPA level and HUA was modeled with restricted cubic spline analysis. Logistic regression analysis were applied to estimate odd ratios (ORs) and 95% confidence intervals (CIs) of the relationships between MVPA level and HUA. A total of 28740 adults were included in the study (weighted mean age, 47.3 years; 46.5% men), with a prevalence rate of HUA was 17.6%. The restricted cubic spline functions depicted a general U-shaped relationship between MVPA level and HUA. The MVPA level of 933 and 3423 metabolic equivalent (MET) -min/wk were the cut-off discriminating for the risk of HUA. Participants with MVPA levels in the range of 933-3423 MET-min/wk had lower risk of HUA and they had the lowest risk when MVPA levels at around 1556 MET-min/wk. Compared with the moderate-activity group (600-2999 Met-min/wk), the low-activity group (< 600 Met-min/wk) had a greater risk of HUA (OR, 1.13 [95%CI, 1.02-1.26]) after fully adjusting for potential confounders. Compared with the moderate MVPA level, the low MVPA level was associated with the higher risk of HUA. And there may be a U-shaped dose-response relationship between MVPA level and HUA. When MVPA level was approximately 933-3423 MET-min/wk, the risk of HUA may at a lower level and the risk reached the lowest when MVPA level at around 1556 MET-min/wk.

Associations between static and dynamic changes of platelet counts and in-hospital mortality in critical patients with acute heart failure

To investigate the predictive value of baseline platelet count and its short-term dynamic changes in the prognosis of patients with acute heart failure (AHF) in the intensive care unit. Patients diagnosed with AHF in the medical information mart for intensive care III and their clinical data were retrospectively filtered. Patients were divided into survivor and non-survivor groups based on their prognosis during hospitalization, and differences in baseline data between groups were compared. Logistic regression models and restricted cubic spline (RCS) plots were performed to evaluate the relationship between baseline platelet counts and in-hospital mortality. Changes and trends in platelet counts were compared between the survivor and non-survivor groups after adjusting for confounders with the generalized additive mixing model (GAMM). A total of 2930 critical patients with acute heart failure were included, of which 2720 were survivors and 210 were non-survivors. Multiple logistic regression models revealed that baseline platelet count was an independent factor in hospital mortality (OR 0.997, 95% CI 0.994–0.999, P-value = 0.018). The RCS plot demonstrated a U-shaped dose–response relationship between baseline platelet count and in-hospital mortality. GAMM analysis suggested that the platelet counts decreased and then increased in the survivor group and gradually decreased in the non-survivor group, with a gradual increase of difference between two groups. After adjusting for confounders, the mean daily increase was −6.014 (95% CI −7.076–4.953, P-value < 0.001). Baseline platelet demonstrated a U-shaped dose–response relationship with adverse outcomes in critical patients with AHF. Early elevation of platelet was correlated with higher in-hospital mortality, indicating that tracking early changes in platelet might help determine the short-term prognosis of critical patients with AHF.

Urinary haloacetic acid concentrations and thyroid function among women: Results from the TREE study

BackgroundDisinfection byproducts (DBPs) have been shown to impair thyroid function in experimental models. However, epidemiological evidence is scarce. MethodsThis study included 1190 women undergoing assisted reproductive technology (ART) treatment from the Tongji Reproductive and Environmental (TREE) cohort from December 2018 to August 2021. Serum thyrotropin (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured as indicators of thyroid function. FT4/FT3 and TSH/FT4 ratios were calculated as markers of thyroid hormone homeostasis. Dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), the two most abundant HAAs, in urine were detected to assess individual DBP exposures. ResultsAfter adjusting for relevant covariates, positive associations were observed between urinary TCAA concentrations and serum TSH and TSH/FT4 levels (e.g., percent change = 5.82 %, 95 % CI: 0.70 %, 11.21 % for TSH), whereas inverse associations were found for serum FT3 and FT4 (e.g., percent change = −1.29 %, 95 % CI: −2.49 %, −0.07 % for FT3). There also was a negative association between urinary DCAA concentration and serum FT4/FT3 (percent change = −2.49 %, 95 % CI: −4.71 %, −0.23 %). These associations were further confirmed in the restricted cubic spline and generalized additive models with linear or U-shaped dose-response relationships. ConclusionUrinary HAAs were associated with altered thyroid hormone homeostasis among women undergoing ART treatment.

Spicy food consumption reduces the risk of ischaemic stroke: a prospective study.

Previous studies revealed that consuming spicy food reduced mortality from CVD and lowered stroke risk. However, no studies reported the relationship between spicy food consumption, stroke types and dose–response. This study aimed to further explore the association between the frequency of spicy food intake and the risk of stroke in a large prospective cohort study. In this study, 50174 participants aged 30–79 years were recruited. Spicy food consumption data were collected via a baseline survey questionnaire. Outcomes were incidence of any stroke, ischaemic stroke (IS) and haemorrhagic stroke (HS). Multivariable-adjusted Cox proportional hazard models estimated the association between the consumption of spicy food and incident stroke. Restricted cubic spline analysis was used to examine the dose–response relationship. During the median 10·7-year follow-up, 3967 strokes were recorded, including 3494 IS and 516 HS. Compared with those who never/rarely consumed spicy food, those who consumed spicy food monthly, 1–2 d/week and 3–5 d/week had hazard ratio (HR) of 0·914 (95 % CI 0·841, 0·995), 0·869 (95 % CI 0·758, 0·995) and 0·826 (95 % CI 0·714, 0·956) for overall stroke, respectively. For IS, the corresponding HR) were 0·909 (95 % CI 0·832, 0·994), 0·831 (95 % CI 0·718, 0·962) and 0·813 (95 % CI 0·696, 0·951), respectively. This protective effect showed a U-shaped dose–response relationship. For obese participants, consuming spicy food ≥ 3 d/week was negatively associated with the risk of IS. We found the consumption of spicy food was negatively associated with the risk of IS and had a U-shaped dose–response relationship with risk of IS. Individuals who consumed spicy food 3–5 d/week had a significantly lowest risk of IS.

Correlation between essential and toxic elements in maternal blood during early pregnancy and atrial septal defects/ventricular septal defects/patent ductus arteriosus in offspring.

Congenital heart defects (CHDs) are the most common congenital malformation in the world. Recent studies have found that essential and toxic trace element levels may play a crucial role in the risk of neonatal malformation. However, the relationships between element levels in early pregnancy and CHD risk among humans remain unclear. This study investigates the association between maternal essential element (copper [Cu], zinc [Zn], calcium [Ca], manganese [Mg] and iron [Fe]) and toxic element (lead [Pb] and cadmium [Cd]) levels during early pregnancy and CHDs. A hospital-based case-control study was conducted, including 181 cases and 218 controls. Eligible participants underwent antenatal examination during gestational weeks 11-14 and trace element levels were detected by the atomic absorption method. Multi-variable logistic regression was used to examine the associations between the level of maternal trace elements and CHD risks. Higher levels of Ca in early pregnancy were associated with lower risk of ASD/VSD risks. Moreover, higher Fe, Pb, and Cd levels in the first trimester were associated with higher risks of all CHD and the subtypes risks, and the tests for trend were significant (all p < .05). The restricted cubic spline analysis showed that there was a nonlinear inverted u-shaped dose-response relationship between levels of Zn, Pb, and Cd in the first trimester and risk of CHDs (non-linearity test p < .05). A moderate increase in Zn and Ca levels and a decrease in Pb and Cd levels during early pregnancy are needed to reduce the incidence of CHDs in the Chinese population.

Association of Sleep Duration with Risk of All-Cause and Cause-Specific Mortality Among American Adults: A Population-Based Cohort Study.

To examine potential factors affecting sleep duration and explore its association with the risk of mortality among adults in the United States. The study population consisted of adults aged 26 to 79 years who participated in the National Health and Nutrition Examination Survey (NHANES) conducted from 2007 to 2016. Sleep duration was classified into three categories: short (<7 hours), optimal (7-8 hours), and long (≥9 hours). The associations between sleep duration and both all-cause mortality and cause-specific mortality (including heart disease, tumors, cerebrovascular disease, and others) were examined in the overall population and subgroups using weighted Cox regression models. Dose-response associations between sleep duration and risk of all-cause mortality were explored using restricted cubic spline (RCS) analyses. Additionally, a multinomial logistic regression analysis was conducted to investigate potential factors that influence sleep duration in adults. The study included a total of 24,141 subjects, with a population-weighted mean age of 48.93 years. Over 30% of the subjects exhibited unhealthy sleep habits. Fully adjusted models revealed that both short sleep duration (HR=1.169, 95% CI 1.027-1.331) and long sleep duration (HR=1.286, 95% CI 1.08-1.531), were associated with an increased risk of all-cause mortality. The RCS curves showed a U-shaped relationship between sleep duration and risk of all-cause mortality. Subgroup analyses showed a significant association between poor sleep patterns and all-cause mortality among adults aged 26-64 years, males, and non-Hispanic whites. Furthermore, multinomial logistic regression identified several predictors associated with short and long sleep durations. Both short and long sleep duration are associated with an increased risk of all-cause mortality, with a U-shaped dose-response relationship. It is imperative to implement appropriate primary prevention strategies aimed at monitoring and providing health education to populations at risk of developing unhealthy sleep patterns.

Effects of prenatal single and mixed bisphenol exposure on bone mineral density in preschool children: A population-based prospective cohort study

Exposure to bisphenols can affect bone mineral density (BMD) in animals and humans. However, the effects of maternal exposure to bisphenols during pregnancy on bone health in preschool children remain unknown. We aimed to assess the effects of prenatal exposure to single and multiple bisphenols on bone health in preschool children. A total of 230 mother–child pairs were included in this study. Generalized linear regression, restricted cubic spline (RCS), principal component analysis (PCA), and Bayesian kernel machine regression (BKMR) were utilized to assess the relationship between bisphenol levels and bone health in preschool children. Each natural log (Ln) unit increase in tetrabromobisphenol A was related to a 0.007 m/s (95 % CI: –0.015, 0.000) decrease in Ln-transformed speed of sound (SOS) among girls. Decreased BMD Z scores in preschool children were found only in the high bisphenol S exposure group (β = -0.568; 95 % CI: –1.087, –0.050) in boys. The risk of low BMD (BMDL) was significantly higher in the middle-exposure group (OR = 4.695; 95 % CI: 1.143, 24.381) and high-exposure group of BPS (OR = 6.165, 95 % CI: 1.445, 33.789) compared with the low-exposure group in boys. In girls, the risk of BMDL decreased with increasing bisphenol A concentration (OR = 0.413, 95 % CI: 0.215, 0.721). RCS analysis revealed a U-shaped nonlinear correlation between BPB concentration and BMDL in girls (P-overall = 0.011, P-nonlinear = 0.009). In PCA, a U-shaped dose–response relationship was found between PC2 and the risk of BMDL (P-overall = 0.048, P-nonlinear = 0.032), and a significant association was only noted in girls when stratified by sex. The BKMR model revealed a horizontal S-shaped curve relationship between bisphenol mixtures and BMDL in girls. The results indicated that prenatal exposure to single and mixed bisphenols can affect BMD in preschool children, exerting nonmonotonic and child sex-specific effects.

The Joint Effects of Bisphenols and Iodine Exposure on Thyroid during Pregnancy.

The aim of this research was to study the combined effects of bisphenols and iodine exposure on the thyroid gland during pregnancy. We included 162 pregnant women from a cohort established in Shanghai. Urinary concentrations of bisphenol A, bisphenol B(BPB), bisphenol C(BPC), bisphenol F, bisphenol S, and bisphenol AF(BPAF) were examined. Bayesian kernel machine regression (BKMR) and quantile g-computation models were used. The geometric means of BPA, BPB, BPC, BPF, BPS, BPAF, and ΣBPs levels in urine were 3.03, 0.24, 2.66, 0.36, 0.26, 0.72, and 7.55 μg/g creatinine, respectively. We observed a positive trend in the cumulative effects of BPs and iodine on serum triiodothyronine (FT3) and free thyroxine (FT4), as well as a U-shaped dose-response relationship between BPs and the probability of occurrence of thyroperoxidase autoantibody positivity in women with low urinary iodine concentration. In addition, a synergistic effect on the probability of occurrence of thyroid autoantibody positivity was observed between BPF and BPB, as well as between BPC and BPAF in this study. There were adverse health effects on the thyroid after co-exposure to BPs and iodine. Even if pregnant women were exposed to lower levels of BPs, women with iodine deficiency remained vulnerable to thyroid autoimmune disease.

Toxicity and effects on anuran tadpole metamorphosis of the anthranilic diamide insecticides chlorantraniliprole and cyantraniliprole

ABSTRACT The present study examined the acute and chronic toxicity attributed to commercial formulations of the anthranilic diamide insecticides chlorantraniliprole (CHLO) and cyantraniliprole (CYAN) on the neotropical amphibian species Rhinella arenarum, Rhinella fernandezae and Scinax granulatus. The median lethal concentrations obtained after 96 hr exposure (96 hr-LC50) were generally greater than 100 mg/L, except for stage 25 S. Granulatus, which were the most sensitive animals tested with a 96 hr-LC50 value of 46.78 mg/L. In subchronic exposures of R. arenarum, the 21day-LC50 were 151.4 mg/L for CHLO and >160 mg/L for CYAN, the weight gain of the tadpoles during this period not being markedly affected in both cases. Finally, when tadpoles of R. arenarum were exposed to CHLO throughout the metamorphic process, an inverted U-shaped non-monotonic dose-response relationship was observed between exposure concentrations and both % of individuals transiting between stage 39 and 42 and the time required to accomplish this. Data obtained raise the hypothesis of an effect of CHLO on the hypothalamic-pituitary-thyroid (HPT) axis, either directly or through an interaction with the stress-hormone system, as metamorphic progression from stage 39 to S42 occurs under the strict control of thyroid hormones. These observations are important as the anthranilic diamide insecticides are not currently known as endocrine disruptors. Further investigations are needed to clarify the pathways leading to these effects and examine whether environmentally-relevant aquatic concentrations of anthranilic diamides might be impacting amphibian populations in the wild.

Standardized Centella asiatica (ECa 233) extract decreased pain hypersensitivity development in a male mouse model of chronic inflammatory temporomandibular disorder

Chronic inflammatory temporomandibular disorder (TMD) pain has a high prevalence, and available nonspecific treatments have adverse side effects. ECa 233, a standardized Centella asiatica extract, is highly anti-inflammatory and safe. We investigated its therapeutic effects by injecting complete Freund’s adjuvant (CFA) into right temporomandibular joint of mice and administering either ibuprofen or ECa 233 (30, 100, and 300 mg/kg) for 28 days. Inflammatory and nociceptive markers, bone density, and pain hypersensitivity were examined. CFA decreased ipsilateral bone density, suggesting inflammation localization, which ipsilaterally caused immediate calcitonin gene-related peptide elevation in the trigeminal ganglia (TG) and trigeminal subnucleus caudalis (TNC), followed by late increase of NaV1.7 in TG and of p-CREB and activation of microglia in TNC. Contralaterally, only p-CREB and activated microglia in TNC showed delayed increase. Pain hypersensitivity, which developed early ipsilaterally, but late contralaterally, was reduced by ibuprofen and ECa 233 (30 or 100 mg/kg). However, ibuprofen and only 100-mg/kg ECa 233 effectively mitigated marker elevation. This suggests 30-mg/kg ECa 233 was antinociceptive, whereas 100-mg/kg ECa 233 was both anti-inflammatory and antinociceptive. ECa 233 may be alternatively and safely used for treating chronic inflammatory TMD pain, showing an inverted U-shaped dose–response relationship with maximal effect at 100 mg/kg.

Sleep Behaviors and Progression of Multimorbidity in Middle-Aged and Older Adults: AProspective Cohort Study From China.

Sleep behavior (eg, sleep duration, sleep quality, and nap) is closely related to many chronic conditions. However, less is known about its association with multiple chronic conditions (multimorbidity), particularly evidence from cohort studies. Data were collected from a cohort of 8937 individuals aged 45 and older from the China Health and Retirement Longitudinal Study (2011-2018). Sleep duration, sleep quality, and nap duration were collected in 2011 and 2013. Progression of multimorbidity was defined as the first report of 2 or more chronic conditions for participants without multimorbidity or the new report of 1 or more conditions for those with multimorbidity. Cox regression models were performed to calculate the hazard ratios and 95% confidence intervals (CIs) of the associations between sleep behaviors and the progression of multimorbidity. Short sleep duration and poor sleep quality were associated with the progression of multimorbidity independently and jointly, especially in those less than 65years and females. The U-shaped dose-response relationships were observed between nighttime and total sleep duration and the progression of multimorbidity. Persistent short and unsteadily changed sleep behaviors increased the risk of multimorbidity progression. Individuals sleeping ≤5h/night with 5-7 restless days/week had 1.53 times higher risk of multimorbidity progression (95% CI: 1.37-1.71), compared to those sleeping 7-8h/night with <1 restless day/week. Short sleep duration and poor sleep quality were independently and jointly associated with a higher risk of multimorbidity progression in a mid-to-older population. Optimal sleep duration and sleep quality should be emphasized in multimorbidity prevention and control.

Association of Calcium, Magnesium, Zinc, and Copper Intakes with Diabetic Retinopathy in Diabetics: National Health and Nutrition Examination Survey, 2007–2018

Purpose To evaluate the associations between calcium, magnesium, zinc, and copper intakes and the risk of diabetic retinopathy (DR) in US diabetes adults. Methods Using data from the National Health and Nutrition Examination Survey (NHANES) 2007–2018. Multivariable logistic regression models and restricted cubic spline models were applied to examine the associations between total calcium, magnesium, zinc, and copper intakes and diabetic retinopathy. Results A total of 3794 adults aged 40 years or older were included. Higher quartile intake of calcium, magnesium, zinc, and copper was associated with a lower occurrence of DR, the multivariate adjusted ORs (95% CI) were 0.57 (0.38–0.86), 0.48 (0.32–0.73), 0.58 (0.39–0.88), and 0.48 (0.30–0.77), respectively. U-shaped dose-response relationships were found between calcium, magnesium, zinc, copper intake, and the risk of DR. Conclusion Higher total calcium, magnesium, zinc, and copper intake were inversely associated with the risk of DR in US diabetes adults.

Statistical modeling of hormesis quantities in inverted U-shaped dose-response relationships by reparameterization of a bilogistic model

Statistical procedures that allow quantitative determination of hormesis features are required for quantitative characterization of hormesis to provide information on the biphasic dose-response phenomenon and its variability. Only a direct estimate of individual effective doses in hormetic dose-response relationships is possible using prior extensions of the bilogistic model of Beckon and coworkers. This study presented further extensions of the model to determine the toxic potency and hormetic dose zone by estimating two effective doses simultaneously. In addition, the extended models allow for partitioning the hormetic dose zone through the dose of maximum stimulation. This study demonstrated a 4-step statistical modeling approach to quantify 20 hormesis quantities. The applicability and challenges of the mathematical procedures are discussed based on a few examples of hormetic dose-response relationships. The syntaxes for the analyses were provided as Appendix to demonstrate its implementation in SAS® statistical software. Given the variability of hormetic dose-responses generated from toxicological studies in many disciplines, the proposed approach cannot apply to all dose-response patterns. However, we hope the proposed extensions could provide versatile statistical tools for quantitatively exploring a variety of biphasic dose-response curves.

Association of serum bisphenol A levels with incident overweight and obesity risk and the mediating effect of adiponectin

BackgroundExisting cross-sectional studies indicated a positive association of bisphenol A (BPA) with overweight and obesity. However, the relationship and potential mechanisms underlying this association remain to be elucidated in prospective studies. ObjectiveThis study was designed to investigate whether serum BPA is associated with incident overweight and obesity risk, and to further explore whether adiponectin plays a mediating role in the association. MethodsWe measured blood BPA and adiponectin in Chinese populations. The association of serum BPA with overweight and obesity risk was evaluated using multivariable logistic regression models. We further examined the mediating effect of adiponectin by causal mediation analysis. ResultsAmong 796 participants free of overweight and obesity at baseline, 133 individuals developed overweight and obesity during the follow-up period. Compared with those in the lowest quartile of serum BPA, those in the second and third quartiles were positively associated with incident overweight and obesity risk adjusting for covariates (all P-values < 0.05), whereas this association was not observed in the fourth quartile. Further spline analysis showed an inverted U-shaped dose-response relationship (Pnon-linear = 0.04). Furthermore, each unit of serum log10-transformed BPA levels was associated with higher changes in waist-to-height ratio and body roundness index (all P-values < 0.05). Mediation analysis indicated significant indirect effects of adiponectin on the associations of BPA with overweight and obesity prevalence (mediation proportion: 46.08%; P = 0.02), and BMI levels (mediation proportion: 30.32%; P = 0.03). ConclusionSerum BPA displayed a positive association with incident overweight and obesity risk in a non-monotonic pattern, and adiponectin might mediate the association. Further mechanistic studies are warranted.

Associations of bisphenol exposure with thyroid hormones in pregnant women: a prospective birth cohort study in China.

Bisphenols are endocrine disruptor chemicals that disrupt thyroid hormone homeostasis. However, evidence on the effects of bisphenol mixtures on thyroid hormones are insufficient. Therefore, the present study aimed to explore the effects of bisphenol substitutes and bisphenol mixtures on thyroid hormones during pregnancy. The study was conducted among 446 pregnant women in the Guangxi Zhuang Birth Cohort (GZBC), China. In multiple linear regressions, compared with the low-exposure group, bisphenol S (BPS) concentrations in the middle-exposure group led to a 10.90% (95% CI: - 18.16%, - 2.99%) decrease in triiodothyronine (T3) levels in the first trimester; tetrabromobisphenol A (TBBPA) levels in the middle-exposure group led to an 8.26% (95% CI: - 15.82%, - 0.01%) decrease in T3 levels in the first trimester; bisphenol B (BPB) levels in the middle-exposure group led to higher free thyroxine (FT4) levels (9.84%; 95% CI: 1.73%, 18.60%) in the second trimester; bisphenol F (BPF) in the middle-exposure group led to higher FT4 levels (8.59%, 95% CI: 0.53%, 17.31%) in the second trimester; and TBBPA levels in the high-exposure group led to a 9.39% (95% CI: 1.46%, 17.93%) increase in FT4 levels in the second trimester. The Bayesian kernel machine regression (BKMR) and restricted cubic spline (RCS) models showed a U-shaped dose-response relationship between bisphenol A (BPA) and free triiodothyronine (FT3) (p < 0.01) as well as BPS and FT4 (p < 0.05). Nonlinear relationships were also observed between the bisphenol mixture and FT3. Overall, maternal bisphenol exposure affected thyroid hormone levels during pregnancy. This study provides evidence that BPB, BPF, BPS, and TBBPA are unsafe substitutes for BPA, as well as the overall effect of bisphenols on adverse health in human beings.

Pesticide Exposure in Relation to the Incidence of Abnormal Glucose Regulation: A Retrospective Cohort Study.

Diabetes and prediabetes (called abnormal glucose regulation (AGR)) are adverse health effects associated with exposure to pesticides. However, there are few epidemiological studies on the relationship between pesticide use and the incidence of AGR. We examined the causal relationship between pesticide use and AGR incidence in a rural population using data from a Korean Farmers’ Cohort study of 1076 participants. Poisson regression with robust error variance was used to calculate the relative risks (RR) and 95% confidence intervals (CI) to estimate the relationship between pesticide exposure and AGR. The incidence of AGR in the pesticide-exposed group was 29.1%. Pesticide use increased the RR of AGR (RR 1.32, 95% CI 1.03–1.69). We observed a low-dose effect related to exposure of pesticides to AGR and a U-shaped dose–response relationship in men. Pesticide exposure is related to the incidence of AGR, and the causal relationship differs between men and women.

Regular Physical Activities Inhibit Risk Factors of the Common Cold Among Chinese Adults.

BackgroundPhysical activity (PA) has a significant health impact worldwide and has been linked to a lower risk of the common cold.ObjectiveThe aim of this study was to estimate the form of PA among Chinese adults and the correlation between PA and number of the common cold in China's eastern, central, and western areas.DesignA cross-sectional study.SettingChina's eastern, central, and western regions from 30 November 2020 to 30 March 2021.PatientsA total of 1,920 healthy participants, who aged over 18 years old, with Internet access, were enrolled, and then self-reported PA behaviors and number of the common cold were collected.MeasurementsThe authors calculated preference, intensity, frequency, and duration of PA in Chinese based on gender, age, and broad occupational categories and explored the potential effect between these factors and the common cold.ResultsApproximately 20.4% of participants reported not participating in sports regularly. Except for gender, there were significant differences in PA preference and intensity among the remaining individuals (P <0.05). Sixteen common exercises were divided into three intensity levels by the Borg CR10 Scale: low- (5), moderate- (8), and high-intensity exercises (3), and the corresponding intensity, frequency, and duration were computed with significant differences (P <0.05). The most popular workouts are “Brisk walking” and “Running.” Age, sex, and occupation had no significant effect on colds (P > 0.05). However, intensity shows a U-shaped dose-response relationship with colds, whereas the frequency and duration have an inverse dose-response relationship (P <0.05). High intensity combined with high frequency increased colds the most. Nevertheless, non-exercise groups always have the most colds in each comparison.LimitationsThe result may be vulnerable to recall bias.ConclusionIntensity showed that U-shape, frequency, and duration showed inverse response to the number of colds last year, but age, sex, and occupation had no significant effects. High intensity and high frequency mixed increased colds the most, regardless of duration.

Association Between Water Intake and Mortality Risk-Evidence From a National Prospective Study.

BackgroundFew studies have explored the association between water intake and mortality risk, and the findings were inconsistent.ObjectiveThis study aimed to explore the water intake–mortality association, utilizing the data from the National Health and Nutrition Examination Survey (NHANES) and the 2015 public-linked mortality files released by the National Center for Health Statistics.MethodsWe used the diet- and mortality-linked data of a total of 35,463 adults (17,234 men) aged ≥20 years in the NHANESs 1999–2014 to perform a prospective study. The multivariate-adjusted Cox proportional hazards model was used to explore the associations of the amount of water intake (expressed by total water, plain water, beverage, and food water) and water intake proportion (expressed by the percentage of each kind of water) with mortality risks due to all causes, malignant neoplasms/cancer, and heart disease. The restricted cubic spline plots were adopted to clarify the dose–response relationships among them.ResultsWith a median of 88 months (interquartile range: 49–136 months) follow-up, a total of 4,915 all-cause deaths occurred, including 1,073 and 861 deaths from malignant neoplasms/cancer and heart disease, respectively. The amount of water intake in either type was negatively associated with all-cause mortality risk. Additionally, the negative linear dose–response relationships of water intake and all-cause mortality risk were found for all types of water except for food water, which followed a non-linear pattern. Similarly, compared to the lowest quartile (beverage water intake: <676 g/day; food water intake: <532 g/day), beverage and food water intakes in the range of 1,033–1,524 and 1,612–3,802 g/day were associated with decreased malignant neoplasms/cancer mortality risk. A U-shaped dose–response relationship was found for beverage water intake and malignant neoplasms/cancer mortality risk and a negative linear dose–response relationship was found for food water intake and malignant neoplasms/cancer mortality risk. Coffee and/or tea consumption was/were negatively associated with mortality risks due to all causes and malignant neoplasms/cancer. No significant associations of water intake proportion and mortality risks were found.ConclusionOur findings demonstrated that higher water intake is associated with lower mortality risks among the United States population.