Irregular Cycles, Ovulatory Disorders, and Cardiometabolic Conditions in a US-Based Digital Cohort.

Importance: Polycystic ovary syndrome (PCOS), characterized by irregular menstrual cycles and hyperandrogenism, is a common ovulatory disorder. Having an irregular cycle is a potential marker for cardiometabolic conditions, but data are limited on whether the associations differ by PCOS status or potential interventions. Objective: To evaluate the association of PCOS, time to regularity since menarche (adolescence), and irregular cycles (adulthood) with cardiometabolic conditions. Design, Setting, and Participants: This cross-sectional study used a large, US-based digital cohort of users of the Apple Research application on their iPhone. Eligibility criteria were having ever menstruated, living in the US, being at age of consent of at least 18 years (or 19 years in Alabama and Nebraska or 21 years in Puerto Rico), and being able to communicate in English. Participants were enrolled between November 14, 2019, and December 13, 2022, and completed relevant surveys. Exposures: Self-reported PCOS diagnosis, prolonged time to regularity (not spontaneously establishing regularity within 5 years of menarche), and irregular cycles. Main Outcomes and Measures: The primary outcome was self-reported cardiometabolic conditions, including obesity, prediabetes, type 1 and 2 diabetes, high cholesterol, hypertension, metabolic syndrome, arrhythmia, congestive heart failure, coronary artery disease, heart attack, heart valve disease, stroke, transient ischemic attack (TIA), deep vein thrombosis, and pulmonary embolism measured using descriptive statistics and logistic regression to estimate prevalence odds ratios (PORs) and 95% CIs. Effect modification by lifestyle factors was also estimated. Results: The study sample (N = 60 789) had a mean (SD) age of 34.5 (11.1) years, with 12.3% having PCOS and 26.3% having prolonged time to regularity. Among a subset of 25 399 participants who completed the hormonal symptoms survey, 25.6% reported irregular cycles. In covariate-adjusted logistic regression models, PCOS was associated with a higher prevalence of all metabolic and several cardiovascular conditions, eg, arrhythmia (POR, 1.37; 95% CI, 1.20-1.55), coronary artery disease (POR, 2.92; 95% CI, 1.95-4.29), heart attack (POR, 1.79; 95% CI, 1.23-2.54), and stroke (POR, 1.66; 95% CI, 1.21-2.24). Among participants without PCOS, prolonged time to regularity was associated with type 2 diabetes (POR, 1.24; 95% CI, 1.05-1.46), hypertension (POR, 1.09; 95% CI, 1.01-1.19), arrhythmia (POR, 1.20; 95% CI, 1.06-1.35), and TIA (POR, 1.33; 95% CI, 1.01-1.73), and having irregular cycles was associated with type 2 diabetes (POR, 1.36; 95% CI, 1.08-1.69), high cholesterol (POR, 1.17; 95% CI, 1.05-1.30), arrhythmia (POR, 1.21; 95% CI, 1.02-1.43), and TIA (POR, 1.56; 95% CI, 1.06-2.26). Some of these associations were modified by high vs low body mass index or low vs high physical activity. Conclusions and Relevance: These findings suggest that PCOS and irregular cycles may be independent markers for cardiometabolic conditions. Early screening and intervention among individuals with irregular menstrual cycles may be beneficial.

Non-persistent endocrine disrupting chemical mixtures and uterine leiomyomata in the study of environment, lifestyle and fibroids (SELF).

BACKGROUND: Results of studies investigating associations between individual endocrine-disrupting chemicals (EDCs) and incidence of uterine leiomyomata (UL), a hormone-dependent gynecological condition, have been inconsistent. However, few studies have evaluated simultaneous exposure to a mixture of EDCs with UL incidence. METHODS: We conducted a case-cohort analysis (n = 708) of data from the Study of the Environment, Lifestyle and Fibroids (SELF), a prospective cohort study. Participants were aged 23-35 years at enrollment, had an intact uterus, and identified as Black or African American. We measured biomarker concentrations of 21 non-persistent EDCs, including phthalates, phenols, parabens, and triclocarban, in urine collected at baseline, 20-month, and 40-month clinic visits. We ascertained UL incidence and characteristics using ultrasounds at baseline and approximately every 20 months through 60 months. We used probit Bayesian Kernel Machine Regression (BKMR-P) to evaluate joint associations between EDC mixtures with cumulative UL incidence. We estimated the mean difference in the probit of UL incidence over the study period, adjusting for baseline age, education, years since last birth, parity, smoking status and body mass index. We converted probit estimates to odds ratios for ease of interpretation. RESULTS: We observed that urinary concentrations of the overall EDC mixture were inversely associated with UL incidence in the overall mixtures model, with the strongest inverse associations at the 70th percentile of all biomarkers compared with their 50th percentile (odds ratio = 0.59; 95% confidence interval: 0.36, 0.96). Strongest contributors to the joint association for the mixture were bisphenol S (BPS), ethyl paraben (EPB), bisphenol F (BPF) and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP), which each demonstrated inverse associations except for MECPP. There was suggestive evidence of an interaction between MECPP and EPB. CONCLUSION: In this prospective ultrasound study, we observed evidence of an inverse association between the overall mixture of urinary biomarker concentrations of non-persistent EDCs with UL incidence.

Associations between solar and geomagnetic activity and cognitive function in the Normative Aging study.

BACKGROUND: Studies show that changes in solar and geomagnetic activity (SGA) influence melatonin secretion and the autonomic nervous system. We evaluated associations between solar and geomagnetic activity and cognitive function in the Normative Aging Study from 1992 to 2013. METHODS: We used logistic and linear generalized estimating equations and regressions to evaluate the associations between moving averages of sunspot number (SSN) and Kp index (a measure of geomagnetic activity) and a binary measure for Mini-Mental State Examination (MMSE) scores (≤25 or > 25) and six other cognitive tests as continuous measures, combined into one global composite score and considered separately. RESULTS: A one-IQR increase in same-day SSN and Kp index were associated with 17% (95% CI: 3%, 34%) and 19% (95% CI: 4%, 36%) increases in the odds of low MMSE score. We observed small increases in the global cognitive score with increasing SSN, although we observed decreases specifically in relation to the backwards digit span test. CONCLUSIONS: Periods of high SGA were associated with cognitive function. SGA may not equally impact all aspects of cognitive function, as evidenced by differences in associations observed for the MMSE, global cognitive score, and individual cognitive tests. Given that much of the pathology of cognitive decline in the elderly remains unexplained, studies specifically targeting decline and with longer follow-up periods are warranted.

Indoor and ambient black carbon and fine particulate matter associations with blood biomarkers in COPD patients.

BACKGROUND: Systemic inflammation contributes to cardiovascular risk and chronic obstructive pulmonary disease (COPD) pathophysiology. Associations between systemic inflammation and exposure to ambient fine particulate matter (PM ≤ 2.5 µm diameter; PM2.5), and black carbon (BC), a PM2.5 component attributable to traffic and other sources of combustion, infiltrating indoors are not well described. METHODS: Between 2012 and 2017, COPD patients completed in-home air sampling over one-week intervals, up to four times (seasonally), followed by measurement of plasma biomarkers of systemic inflammation, C-reactive protein (CRP) and interleukin-6 (IL-6), and endothelial activation, soluble vascular adhesion molecule-1 (sVCAM-1). Ambient PM2.5, BC and sulfur were measured at a central site. The ratio of indoor/ambient sulfur in PM2.5, a surrogate for fine particle infiltration, was used to estimate indoor BC and PM2.5 of ambient origin. Linear mixed effects regression with a random intercept for each participant was used to assess associations between indoor and indoor of ambient origin PM2.5 and BC with each biomarker. RESULTS: 144 participants resulting in 482 observations were included in the analysis. There were significant positive associations between indoor BC and indoor BC of ambient origin with CRP [%-increase per interquartile range (IQR);95 % CI (13.2 %;5.2-21.8 and 11.4 %;1.7-22.1, respectively)]. Associations with indoor PM2.5 and indoor PM2.5 of ambient origin were weaker. There were no associations with IL-6 or sVCAM-1. CONCLUSIONS: In homes of patients with COPD without major sources of combustion, indoor BC is mainly attributable to the infiltration of ambient sources of combustion indoors. Indoor BC of ambient origin is associated with increases in systemic inflammation in patients with COPD, even when staying indoors.

Early-Life Exposure to Air Pollution and Childhood Asthma Cumulative Incidence in the ECHO CREW Consortium.

Importance: Exposure to outdoor air pollution contributes to childhood asthma development, but many studies lack the geographic, racial and ethnic, and socioeconomic diversity to evaluate susceptibility by individual-level and community-level contextual factors. Objective: To examine early life exposure to fine particulate matter (PM2.5) and nitrogen oxide (NO2) air pollution and asthma risk by early and middle childhood, and whether individual and community-level characteristics modify associations between air pollution exposure and asthma. Design, Setting, and Participants: This cohort study included children enrolled in cohorts participating in the Children's Respiratory and Environmental Workgroup consortium. The birth cohorts were located throughout the US, recruited between 1987 and 2007, and followed up through age 11 years. The survival analysis was adjusted for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, neighborhood characteristics, and cohort. Statistical analysis was performed from February 2022 to December 2023. Exposure: Early-life exposures to PM2.5 and NO2 according to participants' birth address. Main Outcomes and Measures: Caregiver report of physician-diagnosed asthma through early (age 4 years) and middle (age 11 years) childhood. Results: Among 5279 children included, 1659 (31.4%) were Black, 835 (15.8%) were Hispanic, 2555 (48.4%) where White, and 229 (4.3%) were other race or ethnicity; 2721 (51.5%) were male and 2596 (49.2%) were female; 1305 children (24.7%) had asthma by 11 years of age and 954 (18.1%) had asthma by 4 years of age. Mean values of pollutants over the first 3 years of life were associated with asthma incidence. A 1 IQR increase in NO2 (6.1 µg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.25 [95% CI, 1.03-1.52]) and children younger than 11 years (HR, 1.22 [95% CI, 1.04-1.44]). A 1 IQR increase in PM2.5 (3.4 µg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.31 [95% CI, 1.04-1.66]) and children younger than 11 years (OR, 1.23 [95% CI, 1.01-1.50]). Associations of PM2.5 or NO2 with asthma were increased when mothers had less than a high school diploma, among Black children, in communities with fewer child opportunities, and in census tracts with higher percentage Black population and population density; for example, there was a significantly higher association between PM2.5 and asthma incidence by younger than 5 years of age in Black children (HR, 1.60 [95% CI, 1.15-2.22]) compared with White children (HR, 1.17 [95% CI, 0.90-1.52]). Conclusions and Relevance: In this cohort study, early life air pollution was associated with increased asthma incidence by early and middle childhood, with higher risk among minoritized families living in urban communities characterized by fewer opportunities and resources and multiple environmental coexposures. Reducing asthma risk in the US requires air pollution regulation and reduction combined with greater environmental, educational, and health equity at the community level.

Sensitive development windows of prenatal air pollution and cognitive functioning in preschool age Mexican children.

Introduction: Neurotoxicity resulting from air pollution is of increasing concern. Considering exposure timing effects on neurodevelopmental impairments may be as important as the exposure dose. We used distributed lag regression to determine the sensitive windows of prenatal exposure to fine particulate matter (PM2.5) on children's cognition in a birth cohort in Mexico. Methods: Analysis included 553 full-term (≥37 weeks gestation) children. Prenatal daily PM2.5 exposure was estimated using a validated satellite-based spatiotemporal model. McCarthy Scales of Children's Abilities (MSCA) were used to assess children's cognitive function at 4-5 years old (lower scores indicate poorer performance). To identify susceptibility windows, we used Bayesian distributed lag interaction models to examine associations between prenatal PM2.5 levels and MSCA. This allowed us to estimate vulnerable windows while testing for effect modification. Results: After adjusting for maternal age, socioeconomic status, child age, and sex, Bayesian distributed lag interaction models showed significant associations between increased PM2.5 levels and decreased general cognitive index scores at 31-35 gestation weeks, decreased quantitative scale scores at 30-36 weeks, decreased motor scale scores at 30-36 weeks, and decreased verbal scale scores at 37-38 weeks. Estimated cumulative effects (CE) of PM2.5 across pregnancy showed significant associations with general cognitive index (CE^ = -0.35, 95% confidence interval [CI] = -0.68, -0.01), quantitative scale (CE^ = -0.27, 95% CI = -0.74, -0.02), motor scale (CE^ = -0.25, 95% CI = -0.44, -0.05), and verbal scale (CE^ = -0.2, 95% CI = -0.43, -0.02). No significant sex interactions were observed. Conclusions: Prenatal exposure to PM2.5, particularly late pregnancy, was inversely associated with subscales of MSCA. Using data-driven methods to identify sensitive window may provide insight into the mechanisms of neurodevelopmental impairment due to pollution.

Exposure-response associations between chronic exposure to fine particulate matter and risks of hospital admission for major cardiovascular diseases: population based cohort study.

OBJECTIVE: To estimate exposure-response associations between chronic exposure to fine particulate matter (PM2.5) and risks of the first hospital admission for major cardiovascular disease (CVD) subtypes. DESIGN: Population based cohort study. SETTING: Contiguous US. PARTICIPANTS: 59 761 494 Medicare fee-for-service beneficiaries aged ≥65 years during 2000-16. Calibrated PM2.5 predictions were linked to each participant's residential zip code as proxy exposure measurements. MAIN OUTCOME MEASURES: Risk of the first hospital admission during follow-up for ischemic heart disease, cerebrovascular disease, heart failure, cardiomyopathy, arrhythmia, valvular heart disease, thoracic and abdominal aortic aneurysms, or a composite of these CVD subtypes. A causal framework robust against confounding bias and bias arising from errors in exposure measurements was developed for exposure-response estimations. RESULTS: Three year average PM2.5 exposure was associated with increased relative risks of first hospital admissions for ischemic heart disease, cerebrovascular disease, heart failure, cardiomyopathy, arrhythmia, and thoracic and abdominal aortic aneurysms. For composite CVD, the exposure-response curve showed monotonically increased risk associated with PM2.5: compared with exposures ≤5 µg/m3 (the World Health Organization air quality guideline), the relative risk at exposures between 9 and 10 µg/m3, which encompassed the US national average of 9.7 µg/m3 during the study period, was 1.29 (95% confidence interval 1.28 to 1.30). On an absolute scale, the risk of hospital admission for composite CVD increased from 2.59% with exposures ≤5 µg/m3 to 3.35% at exposures between 9 and 10 µg/m3. The effects persisted for at least three years after exposure to PM2.5. Age, education, accessibility to healthcare, and neighborhood deprivation level appeared to modify susceptibility to PM2.5. CONCLUSIONS: The findings of this study suggest that no safe threshold exists for the chronic effect of PM2.5 on overall cardiovascular health. Substantial benefits could be attained through adherence to the WHO air quality guideline.

Protocol for the air purification for eosinophilic COPD study (APECS): a randomised controlled trial of home air filtration by HEPA.

INTRODUCTION: Exposure to particulate matter (PM) pollution has been associated with lower lung function in adults with chronic obstructive pulmonary disease (COPD). Patients with eosinophilic COPD have been found to have higher levels of airway inflammation, greater responsiveness to anti-inflammatory steroid inhalers and a greater lung function response to PM pollution exposure compared with those with lower eosinophil levels. This study will evaluate if reducing home PM exposure by high-efficiency particulate air (HEPA) air filtration improves respiratory health in eosinophilic COPD. METHODS AND ANALYSIS: The Air Purification for Eosinophilic COPD Study (APECS) is a double-blinded randomised placebo-controlled trial that will enrol 160 participants with eosinophilic COPD living in the area of Boston, Massachusetts. Real and sham air purifiers will be placed in the bedroom and living rooms of the participants in the intervention and control group, respectively, for 12 months. The primary trial outcome will be the change in forced expiratory volume in 1 s (FEV1). Lung function will be assessed twice preintervention and three times during the intervention phase (at 7 days, 6 months and 12 months postrandomisation). Secondary trial outcomes include changes in (1) health status by St. George's Respiratory Questionnaire; (2) respiratory symptoms by Breathlessness, Cough and Sputum Scale (BCSS); and (3) 6-Minute Walk Test (6MWT). Inflammatory mediators were measured in the nasal epithelial lining fluid (NELF). Indoor PM will be measured in the home for the week preceding each study visit. The data will be analysed to contrast changes in outcomes in the intervention and control groups using a repeated measures framework. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Institutional Review Board of Beth Israel Deaconess Medical Centre (protocol #2019P0001129). The results of the APECS trial will be presented at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION: NCT04252235. Version: October 2023.

Association between gestational exposure to solar activity and pregnancy loss using live births from a Massachusetts-based medical center.

BACKGROUND: Solar activity has been linked to biological mechanisms important to pregnancy, including folate and melatonin levels and inflammatory markers. Thus, we aimed to investigate the association between gestational solar activity and pregnancy loss. METHODS: Our study included 71,963 singleton births conceived in 2002-2016 and delivered at an academic medical center in Eastern Massachusetts. We studied several solar activity metrics, including sunspot number, Kp index, and ultraviolet radiation, with data from the NASA Goddard Space Flight Center and European Centre for Medium-Range Weather Forecasts. We used a novel time series analytic approach to investigate associations between each metric from conception through 24 weeks of gestation and the number of live birth-identified conceptions (LBICs) -the total number of conceptions in each week that result in a live birth. This approach fits distributed lag models to data on LBICs, adjusted for time trends, and allows us to infer associations between pregnancy exposure and pregnancy loss. RESULTS: Overall, the association between solar activity during pregnancy and pregnancy loss varied by exposure metric. For sunspot number, we found that an interquartile range increase in sunspot number (78·7 sunspots) in all of the first 24 weeks of pregnancy was associated with 14·0 (95% CI: 6·5, 21·3) more pregnancy losses out of the average 92 LBICs in a week, and exposure in weeks ten through thirteen was identified as a critical window. Although not statistically significant, higher exposure to Kp index and to UV radiation across all 24 weeks of pregnancy was associated with more and less pregnancy losses, respectively. CONCLUSION: While exposure to certain metrics of solar activity (i.e., sunspot number) throughout the first 24 weeks of pregnancy may be associated with pregnancy losses, exposure to other metrics were not. Solar activity is a complex phenomenon, and more studies are needed to clarify underlying pathways.

Prenatal exposure to air pollution and BWGA Z-score: Modifying effects of placenta leukocyte telomere length and infant sex.

BACKGROUND: Air pollutants, such as fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3), have been associated with adverse birth outcomes, including low birth weight, often exhibiting sex-specific effects. However, the modifying effect of placental telomere length (TL), reflecting cumulative lifetime oxidative stress in mothers, remains unexplored. METHOD: Using data from a Northeastern U.S. birth cohort (n = 306), we employed linear regression and weighted quantile sum models to assess trimester-average air pollution exposures and birth weight for gestational age (BWGA) z-scores. Placental TL, categorized by median split, was considered as an effect modifier. Interactions among air pollutants, placental TL, infant sex, and BWGA z-score were evaluated. RESULTS: Without placental TL as a modifier, only 1st trimester O3 was significantly associated with BWGA z-scores (coefficient: 0.33, 95% CI: 0.03, 0.63). In models considering TL interactions, a significant modifying effect was observed between 3rd trimester NO2 and BWGA z-scores (interaction p-value = 0.02). Specifically, a one interquartile range (1-IQR) increase in 3rd trimester NO2 was linked to a 0.28 (95% CI: 0.06, 0.52) change in BWGA z-score among shorter placental TL group, with no significant association among longer TL group. Among male infants, there were significant associations between 3rd trimester PM2.5 exposure and BWGA z-scores in the longer TL group (coefficient: -0.34, 95% CI: -0.61, -0.02), and between 1st trimester O3 exposure and BWGA z-scores among males in the shorter TL group (coefficient: 0.59, 95% CI: 0.06, 1.08). For females, only a negative association in 2nd trimester mixture model was observed within the longer TL group (coefficient: -0.10, 95% CI: -0.21, -0.01). CONCLUSION: These findings highlight the need to consider the complex interactions among prenatal air pollutant exposures, placental TL, and fetal sex to better elucidate those at greatest risk for adverse birth outcomes.

Radon decay product particle radioactivity and oxidative stress biomarkers in patients with COPD.

Radon decay products include α-radiation emitting radionuclides that attach to airborne particles that have potential to promote oxidative tissue damage after inhalation. To assess associations between α-particle radioactivity (α-PR) with urinary biomarkers of oxidative tissue damage, 140 patients with chronic obstructive pulmonary disease (COPD) had up to four 1-week seasonal assessments (N = 413) of indoor (home) and ambient (central site) PM2.5 and black carbon (BC). Following environmental sampling, urine samples were analyzed for total and free malondialdehyde (MDA), biomarkers of lipid oxidation, and 8-hydroxyl-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage. Particle radioactivity was measured as α-activity on PM2.5 filter samples. Linear mixed-effects regression models adjusted for urinary creatinine and other personal characteristics were used to assess associations. Indoor α-PR was associated with an increase in 8-OhdG (8.53%; 95% CI: 3.12, 14.23); total MDA (5.59%; 95% CI: 0.20, 11.71); and free MDA (2.17%; 95% CI: 2.75, 7.35) per interquartile range (IQR) of α-PR [median 1.25 mBq/m3; IQR 0.64], similar adjusting for PM2.5 or BC. The ratio of indoor/ambient α-PR was positively associated with each biomarker and associations with ambient α-PR were positive but weaker than with indoor concentrations. These findings are consistent with a contribution of radon decay products as measured by α-PR to oxidative stress in patients with COPD, with a greater contribution of indoor radon decay products.

Pulmonary, inflammatory, and oxidative effects of indoor nitrogen dioxide in patients with COPD.

Introduction: Indoor nitrogen dioxide (NO2) sources include gas heating, cooking, and infiltration from outdoors. Associations with pulmonary function, systemic inflammation, and oxidative stress in patients with chronic obstructive pulmonary disease (COPD) are uncertain. Methods: We recruited 144 COPD patients at the VA Boston Healthcare System between 2012 and 2017. In-home NO2 was measured using an Ogawa passive sampling badge for a week seasonally followed by measuring plasma biomarkers of systemic inflammation (C-reactive protein [CRP] and interleukin-6 [IL-6]), urinary oxidative stress biomarkers (8-hydroxy-2'deoxyguanosine [8-OHdG] and malondialdehyde [MDA]), and pre- and postbronchodilator spirometry. Linear mixed effects regression with a random intercept for each subject was used to assess associations with weekly NO2. Effect modification by COPD severity and by body mass index (BMI) was examined using multiplicative interaction terms and stratum-specific effect estimates. Results: Median (25%ile, 75%ile) concentration of indoor NO2 was 6.8 (4.4, 11.2) ppb. There were no associations observed between NO2 with CRP, 8-OHdG, or MDA. Although the confidence intervals were wide, there was a reduction in prebronchodilator FEV1 and FVC among participants with more severe COPD (FEV1: -17.36 mL; -58.35, 23.60 and FVC: -28.22 mL; -91.49, 35.07) that was greater than in patients with less severe COPD (FEV1: -1.64 mL; -24.80, 21.57 and FVC: -6.22 mL; -42.16, 29.71). In participants with a BMI <30, there was a reduction in FEV1 and FVC. Conclusions: Low-level indoor NO2 was not associated with systemic inflammation or oxidative stress. There was a suggestive association with reduced lung function among patients with more severe COPD and among patients with a lower BMI.

Early-life manganese exposure during multiple developmental periods and adolescent verbal learning and memory.

BACKGROUND: Manganese (Mn) is both an essential and toxic metal, and associations with neurodevelopment depend on exposure timing. Prospective data examining early life Mn with adolescent cognition are sparse. METHODS: We enrolled 140 Italian adolescents (10-14 years old) from the Public Health Impact of Metals Exposure study. Mn in deciduous teeth was measured using laser ablation-mass spectrometry to represent prenatal, postnatal and early childhood exposure. The California Verbal Learning Test for Children (CVLT-C) was administered to assess adolescent verbal learning and memory. Multivariable regression models estimated changes in CVLT-C scores and the odds of making an error per doubling in dentine Mn in each exposure period. Multiple informant models tested for differences in associations across exposure periods. RESULTS: A doubling in prenatal dentine Mn levels was associated with lower odds of making an intrusion error (OR = 0.23 [95% CI: 0.09, 0.61]). This beneficial association was not observed in other exposure periods. A doubling in childhood Mn was beneficially associated with short delay free recall: (ß = 0.47 [95% CI: -0.02, 0.97]), which was stronger in males (ß = 0.94 [95% CI: 0.05, 1.82]). Associations were null in the postnatal period. CONCLUSION: Exposure timing is critical for understanding Mn-associated changes in cognitive function.

Disparities in joint exposure to environmental and social stressors in urban households in Greater Boston.

OBJECTIVES: Understanding how environmental and social stressors cluster is critical to explaining and addressing health disparities. It remains unclear how these stressors cluster at fine spatial resolution in low to medium-income, urban households. We explored patterns of environmental and social exposures at the household-level and potential predictors of these joint exposures in two environmental justice communities in the Greater Boston area. METHODS: We recruited 150 households in Chelsea, MA and the Dorchester neighborhood of Boston, MA, between 2016 and 2019 and collected data on two domains: environmental and social stressor. For each domain, we fit Latent Class Analysis (LCA) models to exposure data to assess intra-domain variability, and cross-classified the resultant classes to identify joint exposure profiles. We compared differences in the distribution of these profiles by participants' demographic and household characteristics using χ2, Fisher's exact, Analysis of Variance, and Kruskal-Wallis tests. RESULTS: We identified two latent classes in each domain: High environmental (n = 90; 60.4%), Low environmental (n = 59; 39.6%), High Social (n = 31; 20.8%), and Low Social (n = 118; 79.2%). Cross-classification yielded four joint exposure profiles: Both Low (n = 46, 30.9%); Both High (n = 18, 12.1%); High environmental-Low Social (n = 72, 48.3%); and Low environmental-High Social (n = 13, 8.7%). Significant group differences were found by housing type (e.g., single-family vs. multi-family) (Fisher's exact p = 0.0016), housing tenure (p = 0.0007), and study site (p < 0.0001). We also observed differences by race/ethnicity, income, and education: households that were Hispanic/Latinx, below the poverty level, and with lower education were more likely to be in the Both High group. CONCLUSIONS: Our analyses confirmed that environmental and social stressors cluster in socially disadvantaged households. Housing type, housing tenure, and location of the residence were also strong predictors of cluster membership, with renter and multi-family residents at risk of high exposures to environmental and social stressors.

Long-term exposure to ambient fine particulate components and leukocyte epigenome-wide DNA Methylation in older men: the Normative Aging Study.

BACKGROUND: Epigenome-wide association studies of ambient fine particulate matter (PM2.5) have been reported. However, few have examined PM2.5 components (PMCs) and sources or included repeated measures. The lack of high-resolution exposure measurements is the key limitation. We hypothesized that significant changes in DNA methylation might vary by PMCs and the sources. METHODS: We predicted the annual average of 14 PMCs using novel high-resolution exposure models across the contiguous U.S., between 2000-2018. The resolution was 50 m × 50 m in the Greater Boston Area. We also identified PM2.5 sources using positive matrix factorization. We repeatedly collected blood samples and measured leukocyte DNAm with the Illumina HumanMethylation450K BeadChip in the Normative Aging Study. We then used median regression with subject-specific intercepts to estimate the associations between long-term (one-year) exposure to PMCs / PM2.5 sources and DNA methylation at individual cytosine-phosphate-guanine CpG sites. Significant probes were identified by the number of independent degrees of freedom approach, using the number of principal components explaining > 95% of the variation of the DNA methylation data. We also performed regional and pathway analyses to identify significant regions and pathways. RESULTS: We included 669 men with 1,178 visits between 2000-2013. The subjects had a mean age of 75 years. The identified probes, regions, and pathways varied by PMCs and their sources. For example, iron was associated with 6 probes and 6 regions, whereas nitrate was associated with 15 probes and 3 regions. The identified pathways from biomass burning, coal burning, and heavy fuel oil combustion sources were associated with cancer, inflammation, and cardiovascular diseases, whereas there were no pathways associated with all traffic. CONCLUSIONS: Our findings showed that the effects of PM2.5 on DNAm varied by its PMCs and sources.

Impacts of census differential privacy for small-area disease mapping to monitor health inequities.

The U.S. Census Bureau will implement a modernized privacy-preserving disclosure avoidance system (DAS), which includes application of differential privacy, on publicly released 2020 census data. There are concerns that the DAS may bias small-area and demographically stratified population counts, which play a critical role in public health research, serving as denominators in estimation of disease/mortality rates. Using three DAS demonstration products, we quantify errors attributable to reliance on DAS-protected denominators in standard small-area disease mapping models for characterizing health inequities. We conduct simulation studies and real data analyses of inequities in premature mortality at the census tract level in Massachusetts and Georgia. Results show that overall patterns of inequity by racialized group and economic deprivation level are not compromised by the DAS. While early versions of DAS induce errors in mortality rate estimation that are larger for Black than non-Hispanic white populations in Massachusetts, this issue is ameliorated in newer DAS versions.

Minute level smartphone derived exposure to greenness and consumer wearable derived physical activity in a cohort of US women.

BACKGROUND: Inconsistent results have been found in the literature on associations of greenness, or vegetation quantity, and physical activity. However, few studies have assessed associations between mobility-based greenness and physical activity from mobile health data from smartphone and wearable devices with fine spatial and temporal resolution. METHODS: We assessed mobility-based greenness exposure and wearable accelerometer data from participants in the US-based prospective Nurses' Health Study 3 cohort Mobile Health (mHealth) Substudy (2018-2020). We recruited 500 female participants with instructions to wear devices over four 7-day sampling periods equally spaced throughout the year. After restriction criteria there were 337 participants (mean age 36 years) with n = 639,364 unique observations. Normalized Difference Vegetation Index (NDVI) data were derived from 30 m x 30 m Landsat-8 imagery and spatially joined to GPS points recorded every 10 min. Fitbit proprietary algorithms provided physical activity summarized as mean number of steps per minute, which we averaged during the 10-min period following a GPS-based greenness exposure assessment. We utilized Generalized Additive Mixed Models to examine associations (every 10 min) between greenness and physical activity adjusting for neighborhood and individual socioeconomic status, Census region, season, neighborhood walkability, daily mean temperature and precipitation. We assessed effect modification through stratification and interaction models and conducted sensitivity analyses. RESULTS: Mean 10-min step count averaged 7.0 steps (SD 14.9) and greenness (NDVI) averaged 0.3 (SD 0.2). Contrary to our hypotheses, higher greenness exposure was associated non-linearly with lower mean steps per minute after adjusting for confounders. We observed statistically significant effect modification by Census region and season. DISCUSSION: We utilized objective physical activity data at fine temporal and spatial scales to present novel estimates of the association between mobility-based greenness and step count. We found higher levels of greenness were inversely associated with steps per minute.

Indoor (residential) and ambient particulate matter associations with urinary oxidative stress biomarkers in a COPD cohort.

OBJECTIVES: Oxidative stress contributes to chronic obstructive pulmonary disease (COPD) pathophysiology. Associations between indoor (residential) exposure to particulate matter ≤2.5 µm in diameter (PM2.5) and one of its components, black carbon (BC), and oxidative stress are ill-defined. METHODS: Between 2012 and 2017, 140 patients with COPD completed in-home air sampling over one week intervals, followed by collection of urine samples to measure oxidative stress biomarkers, malondialdehyde (MDA), a marker of lipid peroxidation, and 8-hydroxy-2' -deoxyguanosine (8-OHdG), a marker of oxidative DNA damage. Ambient (central site) BC and PM2.5 were measured, and the ratio of indoor/ambient sulfur in PM2.5, a surrogate for residential ventilation and particle infiltration, was used to estimate indoor BC and PM2.5 of outdoor origin. Mixed effects linear regression models with a participant-specific random intercept were used to assess associations with oxidative biomarkers, adjusting for personal characteristics. RESULTS: There were positive associations (% increase per IQR; 95 % CI) of directly measured indoor BC with total MDA (6.96; 1.54, 12.69) and 8-OHdG (4.18; -0.67, 9.27), and similar associations with both indoor BC of outdoor origin and ambient BC. There were no associations with directly measured indoor PM2.5, but there were positive associations between indoor PM2.5 of outdoor origin and total MDA (5.40; -0.91, 12.11) and 8-OHdG (8.02; 2.14, 14.25). CONCLUSIONS: In homes with few indoor combustion sources, directly measured indoor BC, estimates of indoor BC and PM2.5 of outdoor origin, and ambient BC, were positively associated with urinary biomarkers of oxidative stress. This suggests that the infiltration of particulate matter from outdoor sources, attributable to traffic and other sources of combustion, promotes oxidative stress in COPD patients.