Cardiometabolic profiles and proteomics associated with obesity phenotypes in a longitudinal cohort of young adults.

To assess cardiometabolic profiles and proteomics to identify biomarkers associated with the metabolically healthy and unhealthy obesity. Young adults (N = 156) enrolled were classified as not having obesity, metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO) based on NCEP ATP-III criteria. Plasma proteomics at study entry were measured using Olink Cardiometabolic Explore panel. Linear regression was used to assess associations between proteomics and obesity groups as well as cardiometabolic traits of glucose, insulin, and lipid profiles at baseline and follow-up visits. Enriched biological pathways were further identified based on the significant proteomic features. Among the baseline 95 (61%) and 61 (39%) participants classified as not having obesity and having obesity (8 MHO and 53 MUHO), respectively. Eighty of the participants were followed-up with an average 4.6 years. Forty-one proteins were associated with obesity (FDR < 0.05), 29 of which had strong associations with insulin-related traits and lipid profiles (FDR < 0.05). Inflammation, immunomodulation, extracellular matrix remodeling and endoplasmic reticulum lumen functions were enriched by 40 proteins. In this study population, obesity and MHO were associated with insulin resistance and dysregulated lipid profiles. The underlying mechanism included elevated inflammation and deteriorated extracellular matrix remodeling function.

Exposure to per- and polyfluoroalkyl substances and high-throughput proteomics in Hispanic youth.

BACKGROUND: Strong epidemiological evidence shows positive associations between exposure to per- and polyfluoroalkyl substances (PFAS) and adverse cardiometabolic outcomes (e.g., diabetes, hypertension, and dyslipidemia). However, the underlying cardiometabolic-relevant biological activities of PFAS in humans remain largely unclear. AIM: We evaluated the associations of PFAS exposure with high-throughput proteomics in Hispanic youth. MATERIAL AND METHODS: We included 312 overweight/obese adolescents from the Study of Latino Adolescents at Risk (SOLAR) between 2001 and 2012, along with 137 young adults from the Metabolic and Asthma Incidence Research (Meta-AIR) between 2014 and 2018. Plasma PFAS (i.e., PFOS, PFOA, PFHxS, PFHpS, PFNA) were quantified using liquid-chromatography high-resolution mass spectrometry. Plasma proteins (n = 334) were measured utilizing the proximity extension assay using an Olink Explore Cardiometabolic Panel I. We conducted linear regression with covariate adjustment to identify PFAS-associated proteins. Ingenuity Pathway Analysis, protein-protein interaction network analysis, and protein annotation were used to investigate alterations in biological functions and protein clusters. RESULTS: Results after adjusting for multiple comparisons showed 13 significant PFAS-associated proteins in SOLAR and six in Meta-AIR, sharing similar functions in inflammation, immunity, and oxidative stress. In SOLAR, PFNA demonstrated significant positive associations with the largest number of proteins, including ACP5, CLEC1A, HMOX1, LRP11, MCAM, SPARCL1, and SSC5D. After considering the mixture effect of PFAS, only SSC5D remained significant. In Meta-AIR, PFAS mixtures showed positive associations with GDF15 and IL6. Exploratory analysis showed similar findings. Specifically, pathway analysis in SOLAR showed PFOA- and PFNA-associated activation of immune-related pathways, and PFNA-associated activation of inflammatory response. In Meta-AIR, PFHxS-associated activation of dendric cell maturation was found. Moreover, PFAS was associated with common protein clusters of immunoregulatory interactions and JAK-STAT signaling in both cohorts. CONCLUSION: PFAS was associated with broad alterations of the proteomic profiles linked to pro-inflammation and immunoregulation. The biological functions of these proteins provide insight into potential molecular mechanisms of PFAS toxicity.

Critical windows of greenness exposure during preconception and gestational periods in association with birthweight outcomes.

Few studies have examined the association between greenness exposure and birth outcomes. This study aims to identify critical exposure time windows during preconception and pregnancy for the association between greenness exposure and birth weight. A cohort of 13 890 pregnant women and newborns in Shanghai, China from 2016-2019 were included in the study. We assessed greenness exposure using Normalized Difference Vegetation Index (NDVI) during the preconception and gestational periods, and evaluated the association with term birthweight, birthweight z-score, small-for-gestational age, and large-for-gestational age using linear and logistic regressions adjusting for key maternal and newborn covariates. Ambient temperature, relative humidity, ambient levels of fine particles (PM2.5) and nitrogen dioxide (NO2) assessed during the same period were adjusted for as sensitivity analyses. Furthermore, we explored the potential different effects by urbanicity and park accessibility through stratified analysis. We found that higher greenness exposure at the second trimester of pregnancy and averaged exposure during the entire pregnancy were associated with higher birthweight and birthweight Z-score. Specifically, a 0.1 unit increase in second trimester averaged NDVI value was associated with an increase in birthweight of 10.2 g (95% CI: 1.8-18.5 g) and in birthweight Z-score of 0.024 (0.003-0.045). A 0.1 unit increase in an averaged NDVI during the entire pregnancy was associated with 10.1 g (95% CI: 1.0-19.2 g) increase in birthweight and 0.025 (0.001-0.048) increase in birthweight Z-score. Moreover, the associations were larger in effect size among urban residents than suburban residents and among residents without park accessibility within 500 m compared to those with park accessibility within 500 m. Our findings suggest that increased greenness exposure, particularly during the second trimester, may be beneficial to birth weight in a metropolitan area.

Identifying critical windows of air pollution exposure during preconception and gestational period on birthweight: a prospective cohort study.

BACKGROUND: Few studies have assessed air pollution exposure association with birthweight during both preconception and gestational periods. METHODS: Leveraging a preconception cohort consisting of 14220 pregnant women and newborn children in Shanghai, China during 2016-2018, we aim to assess associations of NO2 and PM2.5 exposure, derived from high-resolution spatial-temporal models, during preconception and gestational periods with outcomes including term birthweight, birthweight Z-score, small-for-gestational age (SGA) and large-for-gestational age (LGA). Linear and logistic regressions were used to estimate 3-month preconception and trimester-averaged air pollution exposure associations; and distributed lag models (DLM) were used to identify critical exposure windows at the weekly resolution from preconception to delivery. Two-pollutant models and children's sex-specific associations were explored. RESULTS: After controlling for covariates, one standard deviation (SD) (11.5 µg/m3, equivalent to 6.1 ppb) increase in NO2 exposure during the second and the third trimester was associated with 13% (95% confidence interval: 2 - 26%) and 14% (95% CI: 1 - 29%) increase in SGA, respectively; and one SD (9.6 µg/m3) increase in PM2.5 exposure during the third trimester was associated with 15% (95% CI: 1 - 31%) increase in SGA. No association have been found for outcomes of birthweight, birthweight Z-score and LGA. DLM found that gestational weeks 22-32 were a critical window, when NO2 exposure had strongest associations with SGA. The associations of air pollution exposure tended to be stronger in female newborns than in male newborns. However, no significant associations of air pollution exposure during preconception period on birthweight outcomes were found. CONCLUSION: Consistent with previous studies, we found that air pollution exposure during mid-to-late pregnancy was associated with adverse birthweight outcomes.

Age, pelvic incidence, facet joint angle and pedicle-facet angle as correlative factors for isthmic spondylolisthesis: a retrospective case control study.

BACKGROUND: Isthmic spondylolisthesis (IS) is a common clinical disease with a high incidence rate. However, most current researches explain the clear pathogenesis from a single perspective. The aim of our study was to explore the relationships between multiple parameters in patients and find the potential risk factors of this disease. METHODS: Our study retrospectively included 115 patients who were diagnosed with isthmic spondylolisthesis and the same number of individuals without spondylolisthesis. The following parameters were measured or collected: age, pelvic incidence (PI), facet joint angle (FJA) and pedicle-facet angle (P-F angle). The radiographic files were imported into Mimics Medical 20.0 and all collected data were analyzed using SPSS, version 26.0, statistical software. RESULTS: The age was higher in IS group than in control group. PI was also higher in the IS group (50.99 ± 7.67) than in the control group (43.77 ± 9.30) significantly (P = 0.009). There was significant difference in cranial and average FJA tropism in L3-L4 level (P = 0.002, P = 0.006, respectively) and in L4-L5 level (P < 0.001). P-F angle of L4-L5 level showed significantly larger in IS group than in control group (P = 0.007).The logistic regression analysis showed a larger age, a greater L3-L4 cranial FJA tropism, and a greater L4-L5 cranial FJA tropism were potential predictors of IS, with an OR of 1.07, 1.28, and 1.39 respectively. The thresholds of the predictors were 60 years, 5.67°, and 8.97° according to the ROC curve. The linear regression equation was established: degree of slippage (%) = 0.220*age - 0.327* L3-4 cranial FJA tropism - 0.346* L4-5 average FJA tropism (F = 3.460, P = 0.011, r = 0.659). CONCLUSIONS: Our study revealed that isthmic spondylolisthesis may be related to multiple factors rather than a single factor. Age, PI, PJA and P-F angle are potentially associated with spondylolisthesis.

Metabolic pathways altered by air pollutant exposure in association with lipid profiles in young adults.

Mounting evidence suggests that air pollution influences lipid metabolism and dyslipidemia. However, the metabolic mechanisms linking air pollutant exposure and altered lipid metabolism is not established. In year 2014-2018, we conducted a cross-sectional study on 136 young adults in southern California, and assessed lipid profiles (triglycerides, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, very-low-density lipoprotein (VLDL)-cholesterol), and untargeted serum metabolomics using liquid chromatography-high-resolution mass spectrometry, and one-month and one-year averaged exposures to NO2, O3, PM2.5 and PM10 air pollutants at residential addresses. A metabolome-wide association analysis was conducted to identify metabolomic features associated with each air pollutant. Mummichog pathway enrichment analysis was used to assess altered metabolic pathways. Principal component analysis (PCA) was further conducted to summarize 35 metabolites with confirmed chemical identity. Lastly, linear regression models were used to analyze the associations of metabolomic PC scores with each air pollutant exposure and lipid profile outcome. In total, 9309 metabolomic features were extracted, with 3275 features significantly associated with exposure to one-month or one-year averaged NO2, O3, PM2.5 and PM10 (p < 0.05). Metabolic pathways associated with air pollutants included fatty acid, steroid hormone biosynthesis, tryptophan, and tyrosine metabolism. PCA of 35 metabolites identified three main PCs which together explained 44.4% of the variance, representing free fatty acids and oxidative byproducts, amino acids and organic acids. Linear regression indicated that the free fatty acids and oxidative byproducts-related PC score was associated with air pollutant exposure and outcomes of total cholesterol and LDL-cholesterol (p < 0.05). This study suggests that exposure to NO2, O3, PM2.5 and PM10 contributes to increased level of circulating free fatty acids, likely through increased adipose lipolysis, stress hormone and response to oxidative stress pathways. These alterations were associated with dysregulation of lipid profiles and potentially could contribute to dyslipidemia and other cardiometabolic disorders.

Interventions to improve sanitation for preventing diarrhoea.

BACKGROUND: Diarrhoea is a major contributor to the global disease burden, particularly amongst children under five years in low- and middle-income countries (LMICs). As many of the infectious agents associated with diarrhoea are transmitted through faeces, sanitation interventions to safely contain and manage human faeces have the potential to reduce exposure and diarrhoeal disease. OBJECTIVES: To assess the effectiveness of sanitation interventions for preventing diarrhoeal disease, alone or in combination with other WASH interventions. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, and Chinese language databases available under the China National Knowledge Infrastructure (CNKI-CAJ). We also searched the metaRegister of Controlled Trials (mRCT) and conference proceedings, contacted researchers, and searched references of included studies. The last search date was 16 February 2022. SELECTION CRITERIA: We included randomized controlled trials (RCTs), quasi-RCTs, non-randomized controlled trials (NRCTs), controlled before-and-after studies (CBAs), and matched cohort studies of interventions aimed at introducing or expanding the coverage and/or use of sanitation facilities in children and adults in any country or population. Our primary outcome of interest was diarrhoea and secondary outcomes included dysentery (bloody diarrhoea), persistent diarrhoea, hospital or clinical visits for diarrhoea, mortality, and adverse events. We included sanitation interventions whether they were conducted independently or in combination with other interventions. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligible studies, extracted relevant data, assessed risk of bias, and assessed the certainty of evidence using the GRADE approach. We used meta-analyses to estimate pooled measures of effect, described results narratively, and investigated potential sources of heterogeneity using subgroup analyses. MAIN RESULTS: Fifty-one studies met our inclusion criteria, with a total of 238,535 participants. Of these, 50 studies had sufficient information to be included in quantitative meta-analysis, including 17 cluster-RCTs and 33 studies with non-randomized study designs (20 NRCTs, one CBA, and 12 matched cohort studies). Most were conducted in LMICs and 86% were conducted in whole or part in rural areas. Studies covered three broad types of interventions: (1) providing access to any sanitation facility to participants without existing access practising open defecation, (2) improving participants' existing sanitation facility, or (3) behaviour change messaging to improve sanitation access or practices without providing hardware or subsidy, although many studies overlapped multiple categories. There was substantial heterogeneity amongst individual study results for all types of interventions. Providing access to any sanitation facility Providing access to sanitation facilities was evaluated in seven cluster-RCTs, and may reduce diarrhoea prevalence in all age groups (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.73 to 1.08; 7 trials, 40,129 participants, low-certainty evidence). In children under five years, access may have little or no effect on diarrhoea prevalence (RR 0.98, 95% CI 0.83 to 1.16, 4 trials, 16,215 participants, low-certainty evidence). Additional analysis in non-randomized studies was generally consistent with these findings. Pooled estimates across randomized and non-randomized studies provided similar protective estimates (all ages: RR 0.79, 95% CI 0.66 to 0.94; 15 studies, 73,511 participants; children < 5 years: RR 0.83, 95% CI 0.68 to 1.02; 11 studies, 25,614 participants).  Sanitation facility improvement Interventions designed to improve existing sanitation facilities were evaluated in three cluster-RCTs in children under five and may reduce diarrhoea prevalence (RR 0.85, 95% CI 0.69 to 1.06; 3 trials, 14,900 participants, low-certainty evidence). However, some of these interventions, such as sewerage connection, are not easily randomized. Non-randomized studies across participants of all ages provided estimates that improving sanitation facilities may reduce diarrhoea, but may be subject to confounding (RR 0.61, 95% CI 0.50 to 0.74; 23 studies, 117,639 participants, low-certainty evidence). Pooled estimates across randomized and non-randomized studies provided similar protective estimates (all ages: RR 0.65, 95% CI 0.55 to 0.78; 26 studies, 132,539 participants; children < 5 years: RR 0.70, 95% CI 0.54 to 0.91, 12 studies, 23,353 participants).  Behaviour change messaging only (no hardware or subsidy provided) Strategies to promote behaviour change to construct, upgrade, or use sanitation facilities were evaluated in seven cluster-RCTs in children under five, and probably reduce diarrhoea prevalence (RR 0.82, 95% CI 0.69 to 0.98; 7 studies, 28,909 participants, moderate-certainty evidence). Additional analysis from two non-randomized studies found no effect, though with very high uncertainty. Pooled estimates across randomized and non-randomized studies provided similar protective estimates (RR 0.85, 95% CI 0.73 to 1.01; 9 studies, 31,080 participants). No studies measured the effects of this type of intervention in older populations.  Any sanitation intervention A pooled analysis of cluster-RCTs across all sanitation interventions demonstrated that the interventions may reduce diarrhoea prevalence in all ages (RR 0.85, 95% CI 0.76 to 0.95, 17 trials, 83,938 participants, low-certainty evidence) and children under five (RR 0.87, 95% CI 0.77 to 0.97; 14 trials, 60,024 participants, low-certainty evidence). Non-randomized comparisons also demonstrated a protective effect, but may be subject to confounding. Pooled estimates across randomized and non-randomized studies provided similar protective estimates (all ages: RR 0.74, 95% CI 0.67 to 0.82; 50 studies, 237,130 participants; children < 5 years: RR 0.80, 95% CI 0.71 to 0.89; 32 studies, 80,047 participants). In subgroup analysis, there was some evidence of larger effects in studies with increased coverage amongst all participants (75% or higher coverage levels) and also some evidence that the effect decreased over longer follow-up times for children under five years. There was limited evidence on other outcomes. However, there was some evidence that any sanitation intervention was protective against dysentery (RR 0.74, 95% CI 0.54 to 1.00; 5 studies, 34,025 participants) and persistent diarrhoea (RR 0.57, 95% CI 0.43 to 0.75; 2 studies, 2665 participants), but not against clinic visits for diarrhoea (RR 0.86, 95% CI 0.44 to 1.67; 2 studies, 3720 participants) or all-cause mortality (RR 0.99, 95% CI 0.89 to1.09; 7 studies, 46,123 participants). AUTHORS' CONCLUSIONS: There is evidence that sanitation interventions are effective at preventing diarrhoea, both for young children and all age populations. The actual level of effectiveness, however, varies by type of intervention and setting. There is a need for research to better understand the factors that influence effectiveness.

Hybrid event-triggered tracking control for unmanned autonomous helicopter under disturbance and deception attacks.

This paper studies the hybrid event-triggered tracking control based on an unmanned autonomous helicopter (UAH) and an unmanned ground vehicle (UGV) under unmeasurable states, transmission delay, external disturbance, and deception attacks. By designing a switching condition, a hybrid event-triggered scheme (ETS) is proposed to realize an elegant trade-off between less data transmissions and control performance. Then, based on the designs of the observer and tracking controller, an augmented closed-loop system is established, and a sufficient condition on uniform ultimate boundedness is presented. Moreover, a co-design method of the hybrid ETS, observer, and controller is obtained via linear matrix inequalities (LMIs), which is further extended by utilizing an improved adaptive hybrid ETS. Finally, some simulation and comparisons are exploited to illustrate the proposed method.

A systematic review of evidence for maternal preconception exposure to outdoor air pollution on Children's health.

The preconception period is a critical window for gametogenesis, therefore preconception exposure to air pollutants may have long-term effects on children. We systematically reviewed epidemiological evidence concerning the effects of preconception ambient air pollution exposure on children's health outcomes and identified research gaps for future investigations. We searched PubMed and Web of Science from journal inception up to October 2022 based on an established protocol (PROSPERO: CRD42022277608). We then identified 162 articles based on searching strategy, 22 of which met the inclusion criteria. Studies covered a wide range of health outcomes including birth defects, preterm birth, birthweight, respiratory outcomes, and developmental outcomes. Findings suggested that exposure to outdoor air pollutants during maternal preconception period were associated with various health outcomes, of which birth defects has the most consistent findings. A meta-analysis revealed that during 3-month preconception period, a 10 µg/m3 increase in PM10 and PM2.5 was associated with relative risk (RR) of birth defects of 1.06 (95% confidence interval (CI): 1.00, 1.02) and 1.14 (95% CI: 0.82, 1.59), respectively. Preterm birth, low birthweight, and autism have also been associated with maternal preconception exposure to PM2.5, PM10, O3 and SO2. However, the significance of associations and effect sizes varied substantially across studies, partly due to the heterogeneity in exposure and outcome assessments. Future studies should use more accurate exposure assessment methods to obtain individual-level exposures with high temporal resolution. This will allow the exploration of which specific time window (weeks or months) during the preconception period has the strongest effect. In future epidemiologic studies, integrating pathophysiologic biomarkers relevant to clinical outcomes may help improve the causal inference of associations between preconception exposure and health outcomes suggested by the current limited literature. Additionally, potential effects of paternal preconception exposure need to be studied.

High Performance Polarization-Resolved Photodetectors Based on Intrinsically Stretchable Organic Semiconductors.

Polarization-sensitive photodetectors based on anisotropic semiconductors sense both the intensity and polarization state information without extra optical components. Here, a self-powered organic photodetector (OPD) composed of intrinsically stretchable polymer donor PNTB6-Cl and non-fullerene acceptor Y6 is reported. The PNTB6-Cl:Y6 photoactive film accommodates a remarkable 100% strain without fracture, exhibiting a high optical anisotropy of 1.8 after strain alignment. The resulting OPD not only shows an impressive faint-light detection capability (high spectral responsivity of 0.45 A W-1 and high specific detectivity of 1012 Jones), but also has a high anisotropic responsivity ratio of 1.42 under the illumination of parallel and traversed polarized light. To the best of the authors' knowledge, both the detector performance and polarization features are among the best-performing OPDs and polarization-sensitive photodetectors. As a proof-of-concept, polarization-sensitive OPDs are also utilized to set up a polarimetric imaging system and full-Stokes polarimeter. This work explores the potential of highly stretchable organic semiconductors for state-of-art polarization imaging and spectroscopy applications.

Health Outcomes in Children Associated with Prenatal and Early-Life Exposures to Air Pollution: A Narrative Review.

(1) Background: The developmental origins of health and disease (DOHaD) hypothesis links adverse fetal exposures with developmental mal-adaptations and morbidity later in life. Short- and long-term exposures to air pollutants are known contributors to health outcomes; however, the potential for developmental health effects of air pollution exposures during gestation or early-childhood have yet to be reviewed and synthesized from a DOHaD lens. The objective of this study is to summarize the literature on cardiovascular and metabolic, respiratory, allergic, and neuropsychological health outcomes, from prenatal development through early childhood, associated with early-life exposures to outdoor air pollutants, including traffic-related and wildfire-generated air pollutants. (2) Methods: We conducted a search using PubMed and the references of articles previously known to the authors. We selected papers that investigated health outcomes during fetal or childhood development in association with early-life ambient or source-specific air pollution exposure. (3) Results: The current literature reports that prenatal and early-childhood exposures to ambient and traffic-related air pollutants are associated with a range of adverse outcomes in early life, including cardiovascular and metabolic, respiratory and allergic, and neurodevelopmental outcomes. Very few studies have investigated associations between wildfire-related air pollution exposure and health outcomes during prenatal, postnatal, or childhood development. (4) Conclusion: Evidence from January 2000 to January 2022 supports a role for prenatal and early-childhood air pollution exposures adversely affecting health outcomes during development. Future studies are needed to identify both detrimental air pollutants from the exposure mixture and critical exposure time periods, investigate emerging exposure sources such as wildfire, and develop feasible interventional tools.

Effects of a Liquefied Petroleum Gas Stove Intervention on Gestational Blood Pressure: Intention-to-Treat and Exposure-Response Findings From the HAPIN Trial.

BACKGROUND: Approximately 3 to 4 billion people worldwide are exposed to household air pollution, which has been associated with increased blood pressure (BP) in pregnant women in some studies. METHODS: We recruited 3195 pregnant women in Guatemala, India, Peru, and Rwanda and randomly assigned them to intervention or control groups. The intervention group received a gas stove and fuel during pregnancy, while the controls continued cooking with solid fuels. We measured BP and personal exposure to PM2.5, black carbon and carbon monoxide 3× during gestation. We conducted an intention-to-treat and exposure-response analysis to determine if household air pollution exposure was associated with increased gestational BP. RESULTS: Median 24-hour PM2.5 dropped from 84 to 24 µg/m3 after the intervention; black carbon and carbon monoxide decreased similarly. Intention-to-treat analyses showed an increase in systolic BP and diastolic BP in both arms during gestation, as expected, but the increase was greater in intervention group for both systolic BP (0.69 mm Hg [0.03-1.35]; P=0.04) and diastolic BP (0.62 mm Hg [0.05-1.19]; P=0.03). The exposure-response analyses suggested that higher exposures to household air pollution were associated with moderately higher systolic BP and diastolic BP; however, none of these associations reached conventional statistical significance. CONCLUSIONS: In intention-to-treat, we found higher gestational BP in the intervention group compared with controls, contrary to expected. In exposure-response analyses, we found a slight increase in BP with higher exposure, but it was not statistically significant. Overall, an intervention with gas stoves did not markedly affect gestational BP.

Transcriptomic and metabolomic associations with exposures to air pollutants among young adults with childhood asthma history.

Ambient air pollutants are well-known risk factors for childhood asthma and asthma exacerbation. It is unknown whether different air pollutants individually or jointly affect pathophysiological mechanisms of asthma. In this study, we aim to integrate transcriptome and untargeted metabolome to identify dysregulated genetic and metabolic pathways that are associated with exposures to a mixture of ambient and traffic-related air pollutants among adults with asthma history. In this cross-sectional study, 102 young adults with childhood asthma history were enrolled from southern California in 2012. Whole blood transcriptome was measured with 20,869 expression signatures, and serum untargeted metabolomics including 937 metabolites were analyzed by Metabolon, Inc. Participants' exposures to regional air pollutants (NO2, O3, PM10, PM2.5) and near-roadway air pollutants averaged at one month and one year before study visit were estimated based on residential addresses. xMWAS network analysis and joint-pathway analysis were performed to identify subnetworks and genetic and metabolic pathways that were associated with exposure to air pollutants adjusted for socio-characteristic covariates. Network analysis found that exposures to air pollutants mixture were connected to 357 gene markers and 92 metabolites. One-year and one-month averaged PM2.5 and NO2 were associated with several amino acids related to serine, glycine, and beta-alanine metabolism. Lower serum levels of carnosine and aspartate, which are involved in the beta-alanine metabolic pathway, as well as choline were also associated with worse asthma control (p < 0.05). One-year and one-month averaged PM10 and one-month averaged O3 were associated with higher gene expression levels of HSPA5, LGMN, CTSL and HLA-DPB1, which are involved in antigen processing and presentation. These results indicate that exposures to various air pollutants are associated with altered genetic and metabolic pathways that affect anti-oxidative capacity and immune response and can potentially contribute to asthma-related pathophysiology.

Child Survival and Early Lifetime Exposures to Ambient Fine Particulate Matter in India: A Retrospective Cohort Study.

BACKGROUND: Ambient fine particulate matter [PM ≤2.5µm in aerodynamic diameter (PM2.5)] is a major health risk for children, particularly in South Asia, which currently experiences the highest PM2.5 levels globally. Nevertheless, there is comparatively little epidemiological evidence from this region to quantify the effects of PM2.5 on child survival. OBJECTIVES: We estimated the association between PM2.5 exposure and child survival in India. METHODS: We constructed a large, retrospective, and nationally representative cohort of children <5 years of age, born between 2009-2016, from the publicly available, cross-sectional 2015-2016 Demographic Health Surveys in India. In utero and post-delivery lifetime average ambient PM2.5 exposures were estimated with data from satellite remote sensing, meteorology, and land use information (model R2= 0.82). We used Cox proportional hazards regression to estimate the association between both average in utero and post-delivery lifetime PM2.5 and all-cause child mortality, controlling for individual- and household-level covariates, seasonality, location, and meteorology. RESULTS: Over 7,447,724 child-months of follow-up, there were 11,559 deaths at <5 years of age reported by the children's mothers. The mean concentrations of 9-month in utero and post-delivery lifetime average ambient PM2.5 exposure were 71.1 µg/m3 (range: 20.9-153.5 µg/m3) and 73.7 µg/m3 (range: 14.0-247.3 µg/m3), respectively. Estimated child mortality adjusted hazard ratios were 1.023 [95% confidence interval (CI): 1.008, 1.038] and 1.013 (95% CI: 1.001, 1.026) per 10-µg/m3 increase of in utero and post-delivery lifetime PM2.5, with both exposures in the model. DISCUSSION: This study adds to the growing body of evidence about the adverse health effects of PM2.5 by demonstrating the association between exposure, both in utero and post-delivery, on child survival at the national level in India. Strategies to reduce ambient air pollution levels, including steps to minimize in utero and early life exposures, are urgently needed in India and other countries where exposures are above recommended guideline values. https://doi.org/10.1289/EHP8910.

LPG stove and fuel intervention among pregnant women reduce fine particle air pollution exposures in three countries: Pilot results from the HAPIN trial.

The Household Air Pollution Intervention Network trial is a multi-country study on the effects of a liquefied petroleum gas (LPG) stove and fuel distribution intervention on women's and children's health. There is limited data on exposure reductions achieved by switching from solid to clean cooking fuels in rural settings across multiple countries. As formative research in 2017, we recruited pregnant women and characterized the impact of the intervention on personal exposures and kitchen levels of fine particulate matter (PM2.5) in Guatemala, India, and Rwanda. Forty pregnant women were enrolled in each site. We measured cooking area concentrations of and personal exposures to PM2.5 for 24 or 48 h using gravimetric-based PM2.5 samplers at baseline and two follow-ups over two months after delivery of an LPG cookstove and free fuel supply. Mixed models were used to estimate PM2.5 reductions. Median kitchen PM2.5 concentrations were 296 µg/m3 at baseline (interquartile range, IQR: 158-507), 24 µg/m3 at first follow-up (IQR: 18-37), and 23 µg/m3 at second follow-up (IQR: 14-37). Median personal exposures to PM2.5 were 134 µg/m3 at baseline (IQR: 71-224), 35 µg/m3 at first follow-up (IQR: 23-51), and 32 µg/m3 at second follow-up (IQR: 23-47). Overall, the LPG intervention was associated with a 92% (95% confidence interval (CI): 90-94%) reduction in kitchen PM2.5 concentrations and a 74% (95% CI: 70-79%) reduction in personal PM2.5 exposures. Results were similar for each site. CONCLUSIONS: The intervention was associated with substantial reductions in kitchen and personal PM2.5 overall and in all sites. Results suggest LPG interventions in these rural settings may lower exposures to the WHO annual interim target-1 of 35 µg/m3. The range of exposure contrasts falls on steep sections of estimated exposure-response curves for birthweight, blood pressure, and acute lower respiratory infections, implying potentially important health benefits when transitioning from solid fuels to LPG.

Sex hormone levels in females of different ages suffering from depression.

BACKGROUND: There are only a few studies on sex hormones in females of different ages suffering from depression, and their conclusions are not uniform until now. This study aimed to investigate the correlation between the severity of depression in females and factors such as sex hormones and differences in sex hormone levels in females of different ages, exploring variations after treatment. METHODS: A total of 169 females with depression were selected and divided into the first-episode (91 cases) and recurrent (78 cases) groups. Then, on the basis of their age, the first-episode patients were divided into the young (48 cases, age < 45 years), perimenopausal (20 cases, 45-55 years), and elderly groups (23 cases, age > 55 years); the patients with recurrent depression were classified into the young (37 cases, age < 45 years), perimenopausal (19 cases, 45-55 years), and elderly groups (22 cases, age > 55 years). The patients were assessed in accordance with the International Classification of Diseases of mental and behavioral disorders. The serum progesterone, prolactin, estradiol, and testosterone levels in the patients were measured, and differences in sex hormone levels of the groups were analyzed. RESULTS: The estradiol level was negatively correlated with age and the prolactin level was positively correlated with occupation. The severity of depression in females was found to be negatively correlated with age. The serum progesterone and estradiol levels in the young group were significantly higher than those in the elderly group, regardless of the first episode or recurrence. Estradiol levels in the perimenopausal and elderly groups with first-episode depression were significantly higher than those in the same group with recurrent depression. However, there was no significant difference in the serum progesterone, prolactin, estradiol, and testosterone levels in the recurrent group before and after treatment. CONCLUSIONS: Sex hormone levels, especially estradiol, varied among females of different ages suffering from depression. Recurrent depression also has a certain effect on sex hormone levels in females. Not only should the age and relapse be considered when studying the sex hormone levels of females with depression, but also attention should be paid to whether the patients have used antidepressants before their sexual hormonal testing.

Estimating climate change-related impacts on outdoor air pollution infiltration.

BACKGROUND: Rising temperatures due to climate change are expected to impact human adaptive response, including changes to home cooling and ventilation patterns. These changes may affect air pollution exposures via alteration in residential air exchange rates, affecting indoor infiltration of outdoor particles. We conducted a field study examining associations between particle infiltration and temperature to inform future studies of air pollution health effects. METHODS: We measured indoor fine particulate matter (PM2.5) in Atlanta in 60 homes (810 sampling-days). Indoor-outdoor sulfur ratios were used to estimate particle infiltration, using central site outdoor sulfur concentrations. Linear and mixed-effects models were used to examine particle infiltration ratio-temperature relationships, based on which we incorporated projected meteorological values (Representative Concentration Pathways intermediate scenario RCP 4.5) to estimate particle infiltration ratios in 20-year future (2046-2065) and past (1981-2000) scenarios. RESULTS: The mean particle infiltration ratio in Atlanta was 0.70 ± 0.30, with a 0.21 lower ratio in summer compared to transition seasons (spring, fall). Particle infiltration ratios were 0.19 lower in houses using heating, ventilation, and air conditioning (HVAC) systems compared to those not using HVAC. We observed significant associations between particle infiltration ratios and both linear and quadratic models of ambient temperature for homes using natural ventilation and those using HVAC. Future temperature was projected to increase by 2.1 °C in Atlanta, which corresponds to an increase of 0.023 (3.9%) in particle infiltration ratios during cooler months and a decrease of 0.037 (6.2%) during warmer months. DISCUSSION: We estimated notable changes in particle infiltration ratio in Atlanta for different 20-year periods, with differential seasonal patterns. Moreover, when stratified by HVAC usage, increases in future ambient temperature due to climate change were projected to enhance seasonal differences in PM2.5 infiltration in Atlanta. These analyses can help minimize exposure misclassification in epidemiologic studies of PM2.5, and provide a better understanding of the potential influence of climate change on PM2.5 health effects.

Exposure contrasts associated with a liquefied petroleum gas (LPG) intervention at potential field sites for the multi-country household air pollution intervention network (HAPIN) trial in India: results from pilot phase activities in rural Tamil Nadu.

BACKGROUND: The Household Air Pollution Intervention Network (HAPIN) trial aims to assess health benefits of a liquefied petroleum gas (LPG) cookfuel and stove intervention among women and children across four low- and middle-income countries (LMICs). We measured exposure contrasts for women, achievable under alternative conditions of biomass or LPG cookfuel use, at potential HAPIN field sites in India, to aid in site selection for the main trial. METHODS: We recruited participants from potential field sites within Villupuram and Nagapattinam districts in Tamil Nadu, India, that were identified during a feasibility assessment. We performed. (i) cross-sectional measurements on women (N = 79) using either biomass or LPG as their primary cookfuel and (ii) before-and-after measurements on pregnant women (N = 41), once at baseline while using biomass fuel and twice - at 1 and 2 months - after installation of an LPG stove and free fuel intervention. We involved participants to co-design clothing and instrument stands for personal and area sampling. We measured 24 or 48-h personal exposures and kitchen and ambient concentrations of fine particulate matter (PM2.5) using gravimetric samplers. RESULTS: In the cross-sectional analysis, median (interquartile range, IQR) kitchen PM2.5 concentrations in biomass and LPG using homes were 134 µg/m3 [IQR:71-258] and 27 µg/m3 [IQR:20-47], while corresponding personal exposures were 75 µg/m3 [IQR:55-104] and 36 µg/m3 [IQR:26-46], respectively. In before-and-after analysis, median 48-h personal exposures for pregnant women were 72 µg/m3 [IQR:49-127] at baseline and 25 µg/m3 [IQR:18-35] after the LPG intervention, with a sustained reduction of 93% in mean kitchen PM2.5 concentrations and 78% in mean personal PM2.5 exposures over the 2 month intervention period. Median ambient concentrations were 23 µg/m3 [IQR:19-27). Participant feedback was critical in designing clothing and instrument stands that ensured high compliance. CONCLUSIONS: An LPG stove and fuel intervention in the candidate HAPIN trial field sites in India was deemed suitable for achieving health-relevant exposure reductions. Ambient concentrations indicated limited contributions from other sources. Study results provide critical inputs for the HAPIN trial site selection in India, while also contributing new information on HAP exposures in relation to LPG interventions and among pregnant women in LMICs. TRIAL REGISTRATION: ClinicalTrials.Gov. NCT02944682 ; Prospectively registered on October 17, 2016.

Air Pollutant Exposure and Stove Use Assessment Methods for the Household Air Pollution Intervention Network (HAPIN) Trial.

BACKGROUND: High quality personal exposure data is fundamental to understanding the health implications of household energy interventions, interpreting analyses across assigned study arms, and characterizing exposure-response relationships for household air pollution. This paper describes the exposure data collection for the Household Air Pollution Intervention Network (HAPIN), a multicountry randomized controlled trial of liquefied petroleum gas stoves and fuel among 3,200 households in India, Rwanda, Guatemala, and Peru. OBJECTIVES: The primary objectives of the exposure assessment are to estimate the exposure contrast achieved following a clean fuel intervention and to provide data for analyses of exposure-response relationships across a range of personal exposures. METHODS: Exposure measurements are being conducted over the 3-y time frame of the field study. We are measuring fine particulate matter [PM < 2.5µm in aerodynamic diameter (PM2.5)] with the Enhanced Children's MicroPEM™ (RTI International), carbon monoxide (CO) with the USB-EL-CO (Lascar Electronics), and black carbon with the OT21 transmissometer (Magee Scientific) in pregnant women, adult women, and children <1 year of age, primarily via multiple 24-h personal assessments (three, six, and three measurements, respectively) over the course of the 18-month follow-up period using lightweight monitors. For children we are using an indirect measurement approach, combining data from area monitors and locator devices worn by the child. For a subsample (up to 10%) of the study population, we are doubling the frequency of measurements in order to estimate the accuracy of subject-specific typical exposure estimates. In addition, we are conducting ambient air monitoring to help characterize potential contributions of PM2.5 exposure from background concentration. Stove use monitors (Geocene) are being used to assess compliance with the intervention, given that stove stacking (use of traditional stoves in addition to the intervention gas stove) may occur. CONCLUSIONS: The tools and approaches being used for HAPIN to estimate personal exposures build on previous efforts and take advantage of new technologies. In addition to providing key personal exposure data for this study, we hope the application and learnings from our exposure assessment will help inform future efforts to characterize exposure to household air pollution and for other contexts. https://doi.org/10.1289/EHP6422.

Correction: The use of bluetooth low energy Beacon systems to estimate indirect personal exposure to household air pollution.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.