Associations between race and ethnicity and treatment setting among gynecologic cancer patients.

INTRODUCTION: Racial and ethnic disparities in gynecologic cancer care have been documented. Treatment at academic facilities is associated with improved survival, yet no study has examined independent associations between race and ethnicity with facility type among gynecologic cancer patients. MATERIALS & METHODS: We used the National Cancer Database and identified 484,455 gynecologic cancer (cervix, ovarian, uterine) patients diagnosed between 2004 and 2020. Facility type was dichotomized as academic vs. non-academic, and we used logistic regression to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) between race and ethnicity and facility type. Secondarily, we examined joint effects of race and ethnicity and facility type on overall survival using Cox proportional hazards regression. RESULTS: We observed higher odds of treatment at academic (vs. non-academic) facilities among American Indian/Alaska Native (OR = 1.42, 95% CI = 1.28-1.57), Asian (OR = 1.64, 95% CI = 1.59-1.70), Black (OR = 1.69, 95% CI = 1.65-1.72), Hispanic (OR = 1.70, 95% CI = 1.66-1.75), Native Hawaiian/Pacific Islander (OR = 1.74, 95% CI = 1.57-1.93), and other race (OR = 1.29, 95% CI = 1.20-1.40) patients compared with White patients. In the joint effects survival analysis with White, academic facility-treated patients as the reference group, Asian, Hispanic, and other race patients treated at academic or non-academic facilities had improved overall survival. Conversely, Black patients treated at academic facilities [Hazard Ratio (HR) = 1.10, 95% CI = 1.07-1.12] or non-academic facilities (HR = 1.19, 95% CI = 1.16-1.21) had worse survival. DISCUSSION: Minoritized gynecologic cancer patients were more likely than White patients to receive treatment at academic facilities. Importantly, survival outcomes among patients receiving care at academic institutions differed by race, requiring research to investigate intra-facility survival disparities.

Risk of dementia due to Co-exposure to air pollution and neighborhood disadvantage.

BACKGROUND: Co-exposure to air pollution and neighborhood disadvantage may influence cognition decline. We tested these associations in the context of dementia risk. METHODS: We leveraged a cohort of adults ≥65 years (n = 5397) enrolled from 2011 to 2018 in the National Health and Aging Trends Study (NHATS). Particulate matter (PM) ≤ 10 µm in diameter, PM ≤ 2.5 µm in diameter, carbon monoxide, nitric oxide, and nitrogen dioxide - and neighborhood disadvantage were tested for joint associations with dementia risk. Pollutant concentrations at the 2010 census tract level were assigned using the US Environmental Protection Agency's Community Multiscale Air Quality Modeling System. Neighborhood disadvantage was defined using the tract Social Deprivation Index (SDI). Dementia was determined through self- or proxy-report or scores indicative of "probable dementia" according to NHATS screening tools. Joint effects of air pollutants and SDI were tested using quantile g-computation Cox proportional hazards models. We also stratified joint air pollution effects across SDI tertiles. Analyses adjusted for age at enrollment, sex, education, partner status, urbanicity, income, race and ethnicity, years at residence, census segregation, and census region. RESULTS: SDI score (aHR = 1.08; 95% CI 0.96, 1.22), joint air pollution (aHR = 1.03, 95% CI 0.92, 1.16) and joint SDI with air pollution (aHR = 1.04, 95% CI 0.89, 1.22) were not associated with dementia risk. After accounting for competing risk of death, joint SDI with air pollution was not associated with dementia risk (aHR = 1.06; 95% CI 0.87, 1.29). In stratified models, joint air pollution was associated with greater risk of dementia at high (aHR = 1.19; 95% CI 0.87, 1.63), but not at medium or low SDI. CONCLUSION: Air pollution was associated with greater dementia risk in disadvantaged areas after accounting for competing risks. Air pollution associations with dementia incidence may be attenuated when other risk factors are more prominent in disadvantaged neighborhoods.

Spatial variation in the joint effect of extreme heat events and ozone on respiratory hospitalizations in California.

Extreme heat and ozone are co-occurring exposures that independently and synergistically increase the risk of respiratory disease. To our knowledge, no joint warning systems consider both risks; understanding their interactive effect can warrant use of comprehensive warning systems to reduce their burden. We examined heterogeneity in joint effects (on the additive scale) between heat and ozone at small geographical scales. A within-community matched design with a Bayesian hierarchical model was applied to study this association at the zip code level. Spatially varying relative risks due to interaction (RERI) were quantified to consider joint effects. Determinants of the spatial variability of effects were assessed using a random effects metaregression to consider the role of demographic/neighborhood characteristics that are known effect modifiers. A total of 817,354 unscheduled respiratory hospitalizations occurred in California from 2004 to 2013 in the May to September period. RERIs revealed no additive interaction when considering overall joint effects. However, when considering the zip code level, certain areas observed strong joint effects. A lower median income, higher percentage of unemployed residents, and exposure to other air pollutants within a zip code drove stronger joint effects; a higher percentage of commuters who walk/bicycle, a marker for neighborhood wealth, showed decreased effects. Results indicate the importance of going beyond average measures to consider spatial variation in the health burden of these exposures and predictors of joint effects. This information can be used to inform early warning systems that consider both heat and ozone to protect populations from these deleterious effects in identified areas.

Extending the elemental defence hypothesis in the light of plant chemodiversity.

Some plant species tolerate and accumulate high levels of metals or metalloids in their tissues. The elemental defence hypothesis posits that metal(loid) hyperaccumulation by these plants can serve as protection against antagonists. Numerous studies support this hypothesis. In addition, as other plant species, hyperaccumulators synthesise specialised metabolites that can act as organic defences. In principle, the composition and concentration of plant-specialised metabolites vary pronouncedly not only among species, but also within species and within individuals. This variation is called chemodiversity. Surprisingly, the role of chemodiversity has received little attention in elemental defence. Thus, we advocate that the concept of the elemental defence hypothesis should be extended and linked to the multifunctionality of plant chemodiversity to better understand the eco-evolutionary dynamics and maintenance of metal(loid) hyperaccumulation. Comprehensive literature studies revealed that both metal(loid)s and specialised metabolites acting as defences are highly diverse in some hyperaccumulators and the biosynthetic pathways of these two types of defences are partly intertwined. Several edaphic-, population-, temporal- and spatial-related factors were found to influence metal(loid) diversity, which should be considered in the elemental defence hypothesis. We thus present a novel synthesis and outlook to extend the elemental defence hypothesis in the light of chemodiversity.

Epigenome-wide DNA methylation in leukocytes and toenail metals: The normative aging study.

BACKGROUND: Environmental metal exposures have been associated with multiple deleterious health endpoints. DNA methylation (DNAm) may provide insight into the mechanisms underlying these relationships. Toenail metals are non-invasive biomarkers, reflecting a medium-term time exposure window. OBJECTIVES: This study examined variation in leukocyte DNAm and toenail arsenic (As), cadmium (Cd), lead (Pb), manganese (Mn), and mercury (Hg) among elderly men in the Normative Aging Study, a longitudinal cohort. METHODS: We repeatedly collected samples of blood and toenail clippings. We measured DNAm in leukocytes with the Illumina HumanMethylation450 K BeadChip. We first performed median regression to evaluate the effects of each individual toenail metal on DNAm at three levels: individual cytosine-phosphate-guanine (CpG) sites, regions, and pathways. Then, we applied a Bayesian kernel machine regression (BKMR) to assess the joint and individual effects of metal mixtures on DNAm. Significant CpGs were identified using a multiple testing correction based on the independent degrees of freedom approach for correlated outcomes. The approach considers the effective degrees of freedom in the DNAm data using the principal components that explain >95% variation of the data. RESULTS: We included 564 subjects (754 visits) between 1999 and 2013. The numbers of significantly differentially methylated CpG sites, regions, and pathways varied by metals. For example, we found six significant pathways for As, three for Cd, and one for Mn. The As-associated pathways were associated with cancer (e.g., skin cancer) and cardiovascular disease, whereas the Cd-associated pathways were related to lung cancer. Metal mixtures were also associated with 47 significant CpG sites, as well as pathways, mainly related to cancer and cardiovascular disease. CONCLUSIONS: This study provides an approach to understanding the potential epigenetic mechanisms underlying observed relations between toenail metals and adverse health endpoints.

Joint Effects Between CDKN2B/P15 Methylation and Environmental Factors on the Susceptibility to Gastric Cancer.

BACKGROUND: The incidence of gastric cancer has long been at a high level in China, seriously affecting the health of Chinese people. AIMS: This case‒control study was performed to identify gene methylation biomarkers of gastric cancer susceptibility. METHODS: A total of 393 gastric cancer cases and 397 controls were included in this study. Gene methylation in peripheral blood leukocytes was detected by a methylation-sensitive high-resolution melting method, and the Helicobacter pylori antibody presence was semi-quantified in serum by ELISA. RESULTS: Individuals with total methylation of CDKN2B/P15 had a 1.883-fold (95%CI: 1.166-3.040, P = 0.010) risk of gastric cancer compared with unmethylated individuals. Individuals with both CDKN2B/P15 and NEUROG1 methylation had a higher risk of gastric cancer (OR = 2.147, 95% CI: 1.137-4.073, P = 0.019). The interaction between CDKN2B/P15 and NEUROG1 total methylation on gastric cancer risk was affected by the pattern of adjustment. In addition, the joint effects between CDKN2B/P15 total methylation and environmental factors, such as freshwater fish intake (OR = 6.403, 95% CI = 2.970-13.802, P < 0.001), irregular diet (OR = 5.186, 95% CI = 2.559-10.510, P < 0.001), unsanitary water intake (OR = 2.238, 95% CI = 1.144-4.378, P = 0.019), smoking (OR = 2.421, 95% CI = 1.456-4.026, P = 0.001), alcohol consumption(OR = 2.163, 95% CI = 1.309-3.576, P = 0.003), and garlic intake(OR = 0.373, 95% CI = 0.196-0.709, P = 0.003) on GC risk were observed, respectively. However, CDKN2B/P15 and NEUROG1 total methylation were not associated with gastric cancer prognosis. CONCLUSION: CDKN2B/P15 methylation in peripheral blood may be a potential biomarker for evaluating susceptibility to gastric cancer. The joint effects between CDKN2B/P15 methylation and environmental factors may also contribute to gastric cancer susceptibility.

Joint effects of recent stressful life events and adverse childhood experiences on perinatal comorbid anxiety and depression.

BACKGROUND: Stressful life events (SLEs) and adverse childhood experiences (ACEs) have been reported to be associated with perinatal depression (PND) or perinatal anxiety (PNA) alone; however, in most cases, majority of PND and PNA coexist and could lead to more serious health consequences. The independent effect of recent SLEs and their joint effects with ACEs on perinatal comorbid anxiety and depression (CAD) remain inadequately explored. METHODS: Based on a longitudinal study, 1082 participants receiving prenatal care in Ma'anshan, China were included. Women were recruited in the first trimester (T1: ≤14+ 6 weeks) and followed up at 15 ~ 27 weeks (T2), 28 ~ 40 weeks (T3), and postpartum (T4). Depression and anxiety status were assessed at all time points, while recent SLEs and ACEs were measured at T1. Logistic regression was conducted to examine the associations of SLEs with the risks of CAD at different time points, as well as their joint effects with ACEs on CAD. RESULTS: Approximately 38.5% of women experienced at least one SLE, which was significantly associated with higher risks of CAD at all time points (p < 0.05). As the number of SLEs increased, the risk of CAD increased (p for trend < 0.05). Specific types of SLEs were associated with CAD in different periods, while only interpersonal events were consistently associated with risks of CAD throughout the whole perinatal period. The joint effects of SLEs with ACEs on CAD were identified throughout the perinatal period, with the highest observed in the first trimester (aOR = 7.47, 95% CI: 3.73-14.95; p for trend < 0.001). CONCLUSION: Our study demonstrated independent associations of recent SLEs and their joint effects with ACEs with risks of perinatal CAD. SLEs combined with ACEs should be recognized as a major risk factor for perinatal CAD and managed at the earliest time to prevent and control CAD.

Walking against traffic and pedestrian injuries in the United Kingdom: new insights.

BACKGROUND: Studies from Finland and Taiwan have shown that walking against traffic was beneficial for reducing pedestrian crashes and fatalities. This study examined whether such beneficial effects are consistent across various circumstances. METHODS: This study aimed to investigate pedestrian fatalities in walking-against or with-traffic crashes by analysing the UK STATS19 crash data for the period between 1991 and 2020. We firstly employed Chi-square tests to examine risk factors for pedestrian injury severity. These variables were then incorporated into stepwise logistic regression models with multiple variables. We subsequently conducted joint effect analysis to investigate whether the beneficial effects of walking against traffic on injury severity vary across different situations. RESULTS: Our data contained 44,488 pedestrian crashes, of which 16,889 and 27,599 involved pedestrians walking against and with traffic, respectively. Pedestrians involved in with-traffic crashes were more likely to sustain fatalities (adjusted odds ratio [AOR] = 1.542; confidence interval [CI] = 1.139-1.927) compared with those in walking against-traffic crashes. The detrimental effect of walking with traffic on fatalities appeared to be more pronounced in darkness-unlit conditions (AOR = 1.48; CI = 1.29-1.70), during midnight hours (00:00-06:59 am) (AOR = 1.60; CI = 1.37-1.87), in rural areas (AOR = 2.20; CI = 1.92-2.51), when pedestrians were elderly (≥ 65 years old) (AOR = 2.65, CI = 2.16-3.26), and when heavy goods vehicles were crash partners (AOR = 1.51, CI = 1.28-1.78). CONCLUSIONS: Walking against traffic was beneficial in reducing pedestrian fatalities compared with walking with traffic. Furthermore, such a beneficial effect was more pronounced in darkness-unlit conditions, at midnights (00:00-06:59 am), in rural areas, when pedestrians were elderly, and when heavy goods vehicles struck pedestrians.

Quantitative analysis of dose interval effect of Pb-Cd interaction on Oryza sativa L. root.

Combined pollution of cadmium (Cd) and lead (Pb) occurs frequently in agriculture lands, which has received increasing research attention. However, little is known about the interaction behaviors of Cd and Pb at various concentrations in the mixture. This study evaluated the single and combined effects of Cd and Pb on rice (Oryza sativa L.) root elongation through acute exposure test. The combined pollution was analyzed with the concentration addition (CA) model, independent action (IA) model and mathematical statistical methods. The dose-response results revealed that the interaction could weaken the toxicity of both Pb and Cd, and Cd had a more significant inhibitory effect on Pb toxicity. The predicted values of CA and IA models were consistently lower than the observed values in the relative root elongation range of 0-60%. Further, combining the CA or IA model with mathematical statistical methods, the interaction of Pb and Cd at similar concentrations showed a significant antagonistic effect on rice root elongation. At low Pb concentrations (Cd > 0.0195, Pb < 0.015 mg/L), there was a synergistic effect of the mixture on rice root; at high Pb concentrations (Cd < 0.225, Pb ≥ 1.25 mg/L), Pb dominated the toxicity on rice root. This is the first report of a systematic method for assessing heavy metal interaction at different concentration levels, which may facilitate the formulation of control standards of heavy metal combined pollution in agricultural land.

Long-term exposure to ambient PM2.5 constituents is associated with dyslipidemia in Chinese adults.

BACKGROUND: Ambient particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5) consists of various toxic constituents. However, the health effect of PM2.5 may differ depending on its constituents, but the joint effect of PM2.5 constituents remains incompletely understood. OBJECTIVE: Our goal was to evaluate the joint effect of long-term PM2.5 constituent exposures on dyslipidemia and identify the most hazardous chemical constituent. METHODS: This study included 67,015 participants from the China Multi-Ethnic Cohort study. The average yearly levels of PM2.5 constituents for all individuals at their residences were assessed through satellite remote sensing and chemical transport modeling. Dyslipidemia was defined as one or more following abnormal blood lipid concentrations: total cholesterol (TC) ≥ 6.22 mmol/L, triglycerides (TG) ≥ 2.26 mmol/L, high-density lipoprotein cholesterol (HDL-C) < 1.04 mmol/L, and low-density lipoprotein cholesterol (LDL-C) ≥ 4.14 mmol/L. The logistic regression model was utilized to examine the single effect of PM2.5 constituents on dyslipidemia, while the weighted quantile sum regression model for the joint effect. RESULTS: The odds ratio with a 95 % confidence interval for dyslipidemia positively related to per-SD increase in the three-year average was 1.29 (1.20-1.38) for PM2.5 mass, 1.25 (1.17-1.34) for black carbon, 1.24 (1.16-1.33) for ammonium, 1.33 (1.24-1.43) for nitrate, 1.34 (1.25-1.44) for organic matter, 1.15 (1.08-1.23) for sulfate, 1.30 (1.22-1.38) for soil particles, and 1.12 (1.05-1.92) for sea salt. Stronger associations were observed in individuals < 65 years of age, males, and those with low physical activity. Joint exposure to PM2.5 constituents was positively related to dyslipidemia (OR: 1.09, 95 %CI: 1.05-1.14). Nitrate was identified as the constituent with the largest weight (weighted at 0.387). CONCLUSIONS: Long-term exposure to PM2.5 constituents poses a significant risk to dyslipidemia and nitrate might be the most responsible for the risk. These findings indicate that reducing PM2.5 constituent exposures, especially nitrate, could be beneficial to alleviate the burden of disease attributed to PM2.5-related dyslipidemia.

[Combined effect of active smoking history and passive smoking during pregnancy on postpartum depression and anxiety].

OBJECTIVE: To explore the independent and combined effects of smoking and passive smoking during pregnancy on maternal depression, anxiety and depressive anxiety comorbidities. METHODS: From August 2020 to February 2022, women who underwent 42-day postpartum examination in Changfeng Women's Center and Shuangfeng Hospital of Hefei were recruited. Their depression and anxiety symptoms were assessed using EPDS Scale and GAD Scale, respectively, and smoking and passive smoking status during pregnancy were collected. Multivariate Logistic regression was used to analyze the independent and combined effects of smoking and passive smoking during pregnancy on postpartum depression, anxiety and depression and anxiety comorbidities. RESULTS: A total of 2 447 parturients were included, whose mean age was(29.23±4.20) years old.58.6% of parturients lived in urban areas.97.2% parturients had unassisted reproduction and 73.5% pregnancy intention was spontaneous. Among them, 362(14.8%) had depression, 523(21.4%) had anxiety, and 270(11.0%) had depression and anxiety comorbidities. In an independent analysis of effects, maternal smoking during pregnancy was statistically associated with postpartum depression(OR=3.86, 95%CI 2.37-6.28), anxiety(OR =2.58, 95%CI 1.60-4.17) and depressive anxiety comorbidity(OR = 3.34, 95%CI 2.00-5.71). Maternal passive smoking during pregnancy was also positively associated with the risk of postpartum depression(OR = 1.56, 95%CI 2.00-5.71), anxiety(OR=1.71, 95%CI 1.24-2.37) and depression and anxiety comorbidities(OR = 1.52, 95%CI 1.02-2.28), and the higher the frequency of exposure to passive smoking, the higher risk of depression, anxiety, and depressive and anxiety comorbidities. No interaction between smoking during pregnancy and passive smoking exposure on postpartum depression(RERI = 0.69, 95%CI-4.62-6.00; AP = 10.84, 95%CI-73.37-95.04; S= 0.58, 95%CI 0.02-15.18), anxiety(RERI=0.27, 95%CI 0.05-0.49; AP=4.02, 95%CI-0.52-8.57; S=0.78, 95%CI 0.64-0.94) and depression and anxiety comorbidities(RERI = 0.07, 95%CI-0.25-0.39; AP=1.74, 95%CI-6.03-9.52; S=0.93, 95%CI 0.68-1.27)was observed. CONCLUSION: Both smoking and passive smoking during pregnancy were positively associated with the risk of postpartum depression, anxiety and depressive anxiety comorbidity.

Super-taxon in human microbiome are identified to be associated with colorectal cancer.

BACKGROUND: Microbial communities in the human body, also known as human microbiota, impact human health, such as colorectal cancer (CRC). However, the different roles that microbial communities play in healthy and disease hosts remain largely unknown. The microbial communities are typically recorded through the taxa counts of operational taxonomic units (OTUs). The sparsity and high correlations among OTUs pose major challenges for understanding the microbiota-disease relation. Furthermore, the taxa data are structured in the sense that OTUs are related evolutionarily by a hierarchical structure. RESULTS: In this study, we borrow the idea of super-variant from statistical genetics, and propose a new concept called super-taxon to exploit hierarchical structure of taxa for microbiome studies, which is essentially a combination of taxonomic units. Specifically, we model a genus which consists of a set of OTUs at low hierarchy and is designed to reflect both marginal and joint effects of OTUs associated with the risk of CRC to address these issues. We first demonstrate the power of super-taxon in detecting highly correlated OTUs. Then, we identify CRC-associated OTUs in two publicly available datasets via a discovery-validation procedure. Specifically, four species of two genera are found to be associated with CRC: Parvimonas micra, Parvimonas sp., Peptostreptococcus stomatis, and Peptostreptococcus anaerobius. More importantly, for the first time, we report the joint effect of Parvimonas micra and Parvimonas sp. (p = 0.0084) as well as that of Peptostrepto-coccus stomatis and Peptostreptococcus anaerobius (p = 8.21e-06) on CRC. The proposed approach provides a novel and useful tool for identifying disease-related microbes by taking the hierarchical structure of taxa into account and further sheds new lights on their potential joint effects as a community in disease development. CONCLUSIONS: Our work shows that proposed approaches are effective to study the microbiota-disease relation taking into account for the sparsity, hierarchical and correlated structure among microbes.

Association between Helicobacter pylori infection and the risk of type 2 diabetes mellitus based on a middle-aged and elderly Chinese population.

Evidence about the relationship between Helicobacter pylori (Hp) infection and type 2 diabetes mellitus (T2DM) is inconsistent and contradictory. This study attempted to investigate this association in the middle-aged and elderly Chinese population and analyze the joint effects of Hp infection and some risk factors on T2DM. Following a cross-sectional design, participants were recruited from the First Affiliated Hospital of Anhui Medical University in Hefei City, China. Hp status was measured using a 14C urea breath test. A total of 1,288 participants, including 90 diabetic patients and 1,198 nondiabetic subjects, were recruited in the current study. The participants with T2DM had a greater prevalence of Hp infection than participants without T2DM (26.67% versus 18.11%, p = 0.045). Furthermore, we found that Hp infection was closely associated with an incremental risk of T2DM [odds ratio (OR) = 1.77, 95% confidence intervals (CI): 1.04-3.00] after adjustment for potential confounders. In addition, we observed that the participants who were Hp-positive and ≥60 years old (OR = 9.16, 95% CI: 3.29-25.52), Hp-positive and obese (OR = 3.35, 95% CI: 1.57-7.14) or Hp-positive and hypertensive (OR = 6.10, 95% CI: 3.10-12.01) had a significantly higher risk for T2DM than those who were Hp-negative and ≤50 years old, Hp-negative and nonobese or Hp-negative and nonhypertensive. These findings imply that Hp infection is associated with an increased risk of T2DM in the middle-aged and elderly Chinese population. The association could be further elevated by the combination of Hp infection and some traditional risk factors.

The joint effects of physical activity and air pollution on type 2 diabetes in older adults.

BACKGROUND: Older adults with type 2 diabetes are at higher risk of developing common geriatric syndromes and have a lower quality of life. To prevent type 2 diabetes in older adults, it's unclear whether the health benefits of physical activity (PA) will be influenced by the harms caused by increased exposure to air pollution during PA, especially in developing countries with severe air pollution problem. We aimed to investigate the joint effects of PA and long-term exposure to air pollution on the type 2 diabetes in older adults from China. METHODS: This cross-sectional study was based on the China Multi-Ethnic cohort (CMEC) study. The metabolic equivalent of PA was calculated according to the PA scale during the CMEC baseline survey. High resolution air pollution datasets (PM10, PM2.5 and PM1) were collected from open products. The joint effects were assessed by the marginal structural mean model with generalized propensity score. RESULTS: A total of 36,562 participants aged 50 to 79 years were included in the study. The prevalence of type 2 diabetes was 10.88%. The mean (SD) level of PA was 24.93 (18.60) MET-h/d, and the mean (SD) level of PM10, PM2.5, and PM1 were 70.00 (23.32) µg/m3, 40.45 (15.66) µg/m3 and 27.62 (6.51) µg/m3, respectively. With PM10 < 92 µg/m3, PM2.5 < 61 µg/m3, and PM1 < 36 µg/m3, the benefit effects of PA on type 2 diabetes was significantly greater than the harms due to PMs when PA levels were roughly below 80 MET-h/d. With PM10 ≥ 92 µg/m3, PM2.5 ≥ 61 µg/m3, and PM1 ≥ 36 µg/m3, the odds ratio (OR) first decreased and then rose rapidly with confidence intervals progressively greater than 1 and break-even points close to or even below 40 MET-h/d. CONCLUSIONS: Our findings implied that for the prevention of type 2 diabetes in older adults, the PA health benefits outweighed the harms of air pollution except in extreme air pollution situations, and suggested that when the air quality of residence is severe, the PA levels should ideally not exceed 40 MET-h/d.

The associations of serum metals concentrations with the intermediate and pregnancy outcomes in women undergoing in vitro fertilization (IVF).

BACKGROUND: Toxic and essential trace elements are reported to have impact on female fertility. However, studies on the potential synergistic or antagonistic effects of metal mixtures on IVF outcomes remain limited. OBJECTIVE: To evaluate whether serum concentrations of metals, individually and as mixtures, are associated with pregnancy outcomes in women undergoing IVF. METHODS: In a prospective birth cohort study about IVF from the First Affiliated Hospital of Anhui Medical University (n = 1184), we measured the concentrations of serum metals by ICP-MS according to a previously established method. Oocyte/embryo development indicators and follow-up results were also collected. The individual and joint effects of metals were estimated using logistic regressions and Bayesian kernel machine regressions (BKMR). RESULTS: At embryonic stage, we found negative associations between the serum lead (Pb) (ß = -0.14, 95%CI: -0.32, -0.04) and cadmium (Cd) (ß = -0.24, 95%CI: -0.39, -0.09) concentrations and the high-quality embryos rate; and positive associations between the serum cobalt (Co) (ß = 0.18, 95%CI: 0.05, 0.31) and selenium (Se) (ß = 0.17, 95%CI: 0.06, 0.41) concentrations and the MII rate. Regarding to the pregnancy outcomes, the serum Pb was negatively related with successful implantation (OR=0.85, 95%CI: 0.77, 0.94) and clinical pregnancy (OR=0.95, 95%CI: 0.91, 0.99); and positively associated with spontaneous abortion (OR=1.39, 95% CI: 1.02, 1.91). The BKMR analysis showed linear or parabolic associations between the metal mixtures and pregnancy outcomes, with Pb showing the highest posterior inclusion probabilities. CONCLUSIONS: The toxic (Pb, Cd) and essential (Co, Se) metals could be incorporated as simultaneous predictors of IVF outcomes including potential antagonistic effects, in which Pb exhibits major contributions.

Risk of maternal exposure to mixed air pollutants during pregnancy for congenital heart diseases in offspring.

OBJECTIVE: To explore the risk of maternal exposure to mixed air pollutants of particulate matter 1 (PM 1), particulate matter 2.5 (PM 2.5), particulate matter 10 (PM 10) and NO 2 for congenital heart disease (CHD) in offspring, and to estimate the ranked weights of the above pollutants. METHODS: 6038 CHD patients and 5227 healthy controls from 40 medical institutions in 21 cities in Guangdong Registry of Congenital Heart Disease (GRCHD) from 2007 to 2016 were included. Logistic regression model was used to estimate the effect of maternal exposure to a single air pollutant on the occurrence of CHD in offspring. Spearman correlation coefficient was used to analyze the correlation between various pollutants, and Quantile g-computation was used to evaluate the joint effects of mixed exposure of air pollutants on CHD and the weights of various pollutants. RESULTS: The exposure levels of PM 1, PM 2.5, PM 10 and NO 2 in the CHD group were significantly higher than those in the control group (all P<0.01). The correlation coefficients among PM 1, PM 2.5, PM 10 and NO 2 were greater than 0.80. PM 1, PM 2.5, PM 10 and NO 2 exposure were associated with a significantly increased risk of CHD in offspring. Mixed exposure of these closely correlated pollutants presented much stronger effect on CHD than exposure of any single pollutants. There was a monotonic increasing relationship between mixed exposure and CHD risk. For each quantile increase in mixed exposure, the risk of CHD increased by 47% ( OR=1.47, 95% CI: 1.34-1.61). Mixed exposure had greater effect on CHD in the early pregnancy compared with middle and late pregnancy, but the greatest effect was the exposure in the whole pregnancy. The weight of PM 10 is the highest in the mixed exposure (81.3%). CONCLUSIONS: Maternal exposure to the mixture of air pollutants during pregnancy increases the risk of CHD in offspring, and the effect is much stronger than that of single exposure of various pollutants. PM 10 has the largest weights and the strongest effect in the mixed exposure.

Long-term exposure to ambient PM1 strengthened the association of depression/anxiety symptoms with poor sleep quality: The Henan Rural Cohort study.

Evidence from numerous epidemiological studies for the relationship between mental disorder and sleep quality was inconclusive and few studies assessed the modification effect of exposure to ambient air PM1 (particulate matter with an aerodynamic diameter ≤ 1.0 µm) on this association. In this study, 27,572 participants aged 18-79 years from The Henan Rural Cohort study were included in the final analyses. The Patient Health Questionnaire-2 (PHQ-2) and Generalized Anxiety Disorder-2 (GAD-2) scales were used to estimate the frequency of depression and anxiety symptoms of all participants, respectively. The Pittsburgh Sleep Quality Index (PSQI) scale was used to assess night sleep quality and PSQI global score (GSC) ≥ 6 was classified as poor sleep quality. The three-year average exposure concentration of PM1 before the baseline survey was determined as long-term exposure concentration of ambient PM1. Logistic regression model was conducted to estimate the independent or joint effect of depression/anxiety symptoms and ambient PM1 exposure on poor sleep quality. In the adjusted models, the odds ratios (ORs) and 95% confidence intervals (95% CIs) of poor sleep quality associated with depression and anxiety symptoms were 3.75 (3.37, 4.17) and 3.42 (3.06, 3.81), respectively, and that associated with long-term exposure to PM1 was 1.06 (1.03, 1.09). An interaction effect was observed between anxiety symptoms score and PM1 concentration on poor sleep quality. With the increment of PM1 concentration, the association was strengthened between depression/anxiety symptoms and poor sleep quality. Besides, compared with the reference group, the ORs (95% CIs) of poor sleep quality in those with comorbidity of depression and anxiety symptoms were 4.98 (3.95, 6.29), 5.23 (3.98, 6.87), 5.76 (4.42, 7.49), and 5.58 (3.83, 8.14), respectively, from the first to the fourth quartile level of the PM1 concentration. These findings suggested that long-term exposure to PM1 strengthened the association of depression/anxiety symptoms with poor sleep quality in rural China.

Graphene-triphenyl phosphate (TPP) co-exposure in the marine environment: Interference with metabolism and immune regulation in mussel Mytilus galloprovincialis.

Both immune regulation and endocrine systems are great challenges to marine organisms, and effective protocols for determining these adverse outcome pathways are limited, especially in vivo. The increasing usage of graphene nanomaterials can lead to the frequent exposure to marine organisms. Triphenyl phosphate (TPP), an organophosphate flame retardant, is frequently detected in natural environments. In this study, the combined toxic effects of co-exposure to graphene and TPP was investigated in Mytilus galloprovincialis using computational toxicology and multi-omics technology. Noticeably, graphene could disturb the membrane stability and increase the tissue accumulation of TPP. The adsorption behavior of TPP on graphene could inhibit the surface activity of graphene. In the digestive gland, transcriptomics analysis revealed the down-regulated genes in graphene + TPP treatment, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH), sorbitol dehydrogenase (SORD), glutathione s-transferase mu 3 (GSTM3) and 4-aminobutyrate aminotransferase (ABAT), were mainly associated with oxidative stress and energy metabolism. Moreover, metabolic responses indicated that graphene + TPP could cause disturbances in energy metabolism and osmotic regulation marked by differentially altered ATP, glucose and taurine in mussels. These data underline the need for further knowledge on the potential interactions of nanomaterials with existing contaminants in marine organisms.

Causal inference in perioperative medicine observational research: part 2, advanced methods.

Although RCTs represent the gold standard in clinical research, most clinical questions cannot be answered using this technique, because of ethical considerations, time, and cost. The goal of observational research in clinical medicine is to gain insight into the relationship between a clinical exposure and patient outcome, in the absence of evidence from RCTs. Observational research offers additional benefit when compared with data from RCTs: the conclusions are often more generalisable to a heterogenous population, which may be of greater value to everyday clinical practice. In Part 2 of this methods series, we will introduce the reader to several advanced methods for supporting the case for causality between an exposure and outcome, including: mediation analysis, natural experiments, and joint effects methods.

Combined toxic effects and DNA damage to two plant species exposed to binary metal mixtures (Cd/Pb).

Acute and long-term (3-, 10- and 56-day exposure) laboratory toxicity tests were carried out to assess the individual and combined toxic effects of cadmium (Cd) and lead (Pb) in Brassica oleracea and Trifolium repens. In addition to morphological parameters, this work also used comet assay to address endpoints in relation to genotoxicity. Bioaccumulation was measured to demonstrate the influence of the mixture on the concentrations of each metal in the plant. The statistical method reported by Ince et al. (1999) was used to evaluate the types of interaction between Cd and Pb in each treatment and concerning their combined effect. This study concludes that the combined effects of binary metal combinations of Cd/Pb on morphological parameters are most often additive, sometimes antagonistic and more rarely synergistic, thus extending the findings of previous publications on this subject. DNA damage analysis revealed concentration- and time-dependent interactions. Synergistic effects of mixed metals (more breaks than individually applied metals) are observed in T. repens after a short exposure. Antagonistic effects are statistically significant after 10 days-exposure, suggesting competition between metals. At 56 days, the rate of DNA damage observed in plants exposed to the Cd/Pb mixture was similar to that measured in plants exposed to lead only and was significantly lower than the rate of DNA damage induced by Cd. This supports the idea that there may be competition between metals and also strengthens the hypothesis that long-term reparation mechanisms may be implemented. Cd/Pb co-exposure does not significantly influence the bioaccumulation of each metal. It is nevertheless important to note that a statistically significant 'interaction' is not necessarily biologically relevant and should therefore be considered with caution when assessing heavy metals combined effects.