The role of extreme heat exposure on premature rupture of membranes in Southern California: A study from a large pregnancy cohort.

BACKGROUND: Significant mortality and morbidity in pregnant women and their offspring are linked to premature rupture of membranes (PROM). Epidemiological evidence for heat-related PROM risk is extremely limited. We investigated associations between acute heatwave exposure and spontaneous PROM. METHODS: We conducted this retrospective cohort study among mothers in Kaiser Permanente Southern California who experienced membrane ruptures during the warm season (May-September) from 2008 to 2018. Twelve definitions of heatwaves with different cut-off percentiles (75th, 90th, 95th, and 98th) and durations (≥ 2, 3, and 4 consecutive days) were developed using the daily maximum heat index, which incorporates both daily maximum temperature and minimum relative humidity in the last gestational week. Cox proportional hazards models were fitted separately for spontaneous PROM, term PROM (TPROM), and preterm PROM (PPROM) with zip codes as the random effect and gestational week as the temporal unit. Effect modification by air pollution (i.e., PM2.5 and NO2), climate adaptation measures (i.e., green space and air conditioning [AC] penetration), sociodemographic factors, and smoking behavior was examined. RESULTS: In total, we included 190,767 subjects with 16,490 (8.6%) spontaneous PROMs. We identified a 9-14% increase in PROM risks associated with less intense heatwaves. Similar patterns as PROM were found for TPROM and PPROM. The heat-related PROM risks were greater among mothers exposed to a higher level of PM2.5 during pregnancy, under 25 years old, with lower education and household income level, and who smoked. Even though climate adaptation factors were not statistically significant effect modifiers, mothers living with lower green space or lower AC penetration were at consistently higher heat-related PROM risks compared to their counterparts. CONCLUSION: Using a rich and high-quality clinical database, we detected harmful heat exposure for spontaneous PROM in preterm and term deliveries. Some subgroups with specific characteristics were more susceptible to heat-related PROM risk.

Air quality improvement and cognitive decline in community-dwelling older women in the United States: A longitudinal cohort study.

BACKGROUND: Late-life exposure to ambient air pollution is a modifiable risk factor for dementia, but epidemiological studies have shown inconsistent evidence for cognitive decline. Air quality (AQ) improvement has been associated with improved cardiopulmonary health and decreased mortality, but to the best of our knowledge, no studies have examined the association with cognitive function. We examined whether AQ improvement was associated with slower rate of cognitive decline in older women aged 74 to 92 years. METHODS AND FINDINGS: We studied a cohort of 2,232 women residing in the 48 contiguous US states that were recruited from more than 40 study sites located in 24 states and Washington, DC from the Women's Health Initiative (WHI) Memory Study (WHIMS)-Epidemiology of Cognitive Health Outcomes (WHIMS-ECHO) study. They were predominantly non-Hispanic White women and were dementia free at baseline in 2008 to 2012. Measures of annual (2008 to 2018) cognitive function included the modified Telephone Interview for Cognitive Status (TICSm) and the telephone-based California Verbal Learning Test (CVLT). We used regionalized universal kriging models to estimate annual concentrations (1996 to 2012) of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) at residential locations. Estimates were aggregated to the 3-year average immediately preceding (recent exposure) and 10 years prior to (remote exposure) WHIMS-ECHO enrollment. Individual-level improved AQ was calculated as the reduction from remote to recent exposures. Linear mixed effect models were used to examine the associations between improved AQ and the rates of cognitive declines in TICSm and CVLT trajectories, adjusting for sociodemographic (age; geographic region; race/ethnicity; education; income; and employment), lifestyle (physical activity; smoking; and alcohol), and clinical characteristics (prior hormone use; hormone therapy assignment; depression; cardiovascular disease (CVD); hypercholesterolemia; hypertension; diabetes; and body mass index [BMI]). For both PM2.5 and NO2, AQ improved significantly over the 10 years before WHIMS-ECHO enrollment. During a median of 6.2 (interquartile range [IQR] = 5.0) years of follow-up, declines in both general cognitive status (ß = -0.42/year, 95% CI: -0.44, -0.40) and episodic memory (ß = -0.59/year, 95% CI: -0.64, -0.54) were observed. Greater AQ improvement was associated with slower decline in TICSm (ßPM2.5improvement = 0.026 per year for improved PM2.5 by each IQR = 1.79 µg/m3 reduction, 95% CI: 0.001, 0.05; ßNO2improvement = 0.034 per year for improved NO2 by each IQR = 3.92 parts per billion [ppb] reduction, 95% CI: 0.01, 0.06) and CVLT (ßPM2.5 improvement = 0.070 per year for improved PM2.5 by each IQR = 1.79 µg/m3 reduction, 95% CI: 0.02, 0.12; ßNO2improvement = 0.060 per year for improved NO2 by each IQR = 3.97 ppb reduction, 95% CI: 0.005, 0.12) after adjusting for covariates. The respective associations with TICSm and CVLT were equivalent to the slower decline rate found with 0.9 to 1.2 and1.4 to 1.6 years of younger age and did not significantly differ by age, region, education, Apolipoprotein E (ApoE) e4 genotypes, or cardiovascular risk factors. The main limitations of this study include measurement error in exposure estimates, potential unmeasured confounding, and limited generalizability. CONCLUSIONS: In this study, we found that greater improvement in long-term AQ in late life was associated with slower cognitive declines in older women. This novel observation strengthens the epidemiologic evidence of an association between air pollution and cognitive aging.

Exposure to air pollutant mixture and gestational diabetes mellitus in Southern California: Results from electronic health record data of a large pregnancy cohort.

BACKGROUND: Epidemiological findings are inconsistent regarding the associations between air pollution exposure during pregnancy and gestational diabetes mellitus (GDM). Several limitations exist in previous studies, including potential outcome and exposure misclassification, unassessed confounding, and lack of simultaneous consideration of air pollution mixtures and particulate matter (PM) constituents. OBJECTIVES: To assess the association between GDM and maternal residential exposure to air pollution, and the joint effect of the mixture of air pollutants and PM constituents. METHODS: Detailed clinical data were obtained for 395,927 pregnancies in southern California (2008-2018) from Kaiser Permanente Southern California (KPSC) electronic health records. GDM diagnosis was based on KPSC laboratory tests. Monthly average concentrations of fine particulate matter < 2.5 µm (PM2.5), <10 µm (PM10), nitrogen dioxide (NO2), and ozone (O3) were estimated using kriging interpolation of Environmental Protection Agency's routine monitoring station data, while PM2.5 constituents (i.e., sulfate, nitrate, ammonium, organic matter and black carbon) were estimated using a fine-resolution geoscience-derived model. A multilevel logistic regression was used to fit single-pollutant models; quantile g-computation approach was applied to estimate the joint effect of air pollution and PM component mixtures. Main analyses adjusted for maternal age, race/ethnicity, education, median family household income, pre-pregnancy BMI, smoking during pregnancy, insurance type, season of conception and year of delivery. RESULTS: The incidence of GDM was 10.9% in the study population. In single-pollutant models, we observed an increased odds for GDM associated with exposures to PM2.5, PM10, NO2 and PM2.5 constituents. The association was strongest for NO2 [adjusted odds ratio (OR) per interquartile range: 1.176, 95% confidence interval (CI): 1.147-1.205)]. In multi-pollutant models, increased ORs for GDM in association with one quartile increase in air pollution mixtures were found for both kriging-based regional air pollutants (NO2, PM2.5, and PM10, OR = 1.095, 95% CI: 1.082-1.108) and PM2.5 constituents (i.e., sulfate, nitrate, ammonium, organic matter and black carbon, OR = 1.258, 95% CI: 1.206-1.314); NO2 (78%) and black carbon (48%) contributed the most to the overall mixture effects among all krigged air pollutants and all PM2.5 constituents, respectively. The risk of GDM associated with air pollution exposure were significantly higher among Hispanic mothers, and overweight/obese mothers. CONCLUSION: This study found that exposure to a mixture of ambient PM2.5, PM10, NO2, and PM2.5 chemical constituents was associated with an increased risk of GDM. NO2 and black carbon PM2.5 contributed most to GDM risk.

Air Pollution Particulate Matter Exposure and Chronic Cerebral Hypoperfusion and Measures of White Matter Injury in a Murine Model.

BACKGROUND: Exposure to ambient air pollution particulate matter (PM) is associated with increased risk of dementia and accelerated cognitive loss. Vascular contributions to cognitive impairment are well recognized. Chronic cerebral hypoperfusion (CCH) promotes neuroinflammation and blood-brain barrier weakening, which may augment neurotoxic effects of PM. OBJECTIVES: This study examined interactions of nanoscale particulate matter (nPM; fine particulate matter with aerodynamic diameter ≤200 nm) and CCH secondary to bilateral carotid artery stenosis (BCAS) in a murine model to produce white matter injury. Based on other air pollution interactions, we predicted synergies of nPM with BCAS. METHODS: nPM was collected using a particle sampler near a Los Angeles, California, freeway. Mice were exposed to 10 wk of reaerosolized nPM or filtered air (FA) for 150 h. CCH was induced by BCAS surgery. Mice (C57BL/6J males) were randomized to four exposure paradigms: a) FA, b) nPM, c) FA + BCAS, and d) nPM + BCAS. Behavioral outcomes, white matter injury, glial cell activation, inflammation, and oxidative stress were assessed. RESULTS: The joint nPM + BCAS group exhibited synergistic effects on white matter injury (2.3× the additive nPM and FA + BCAS scores) with greater loss of corpus callosum volume on T2 magnetic resonance imaging (MRI) (30% smaller than FA group). Histochemical analyses suggested potential microglial-specific inflammatory responses with synergistic effects on corpus callosum C5 immunofluorescent density and whole brain nitrate concentrations (2.1× and 3.9× the additive nPM and FA + BCAS effects, respectively) in the joint exposure group. Transcriptomic responses (RNA-Seq) showed greater impact of nPM + BCAS than individual additive effects, consistent with changes in proinflammatory pathways. Although nPM exposure alone did not alter working memory, the nPM + BCAS cohort demonstrated impaired working memory when compared to the FA + BCAS group. DISCUSSION: Our data suggest that nPM and CCH contribute to white matter injury in a synergistic manner in a mouse model. Adverse neurological effects may be aggravated in a susceptible population exposed to air pollution. https://doi.org/10.1289/EHP8792.

Associations of Coffee and Tea Consumption With Survival to Age 90 Years Among Older Women.

BACKGROUND: Coffee and tea are two of the most widely consumed beverages worldwide and have been associated with reduced risk of mortality in some studies. However, it is unknown whether consumption of these beverages is associated with survival to an advanced age. OBJECTIVE: To examine associations of coffee and tea consumption with survival to age 90 years. DESIGN: Prospective cohort study among participants from the Women's Health Initiative, recruited during 1993 to 1998 and followed up until March 31, 2018. SETTING: The setting included 40 US clinical centers. PARTICIPANTS: A racially and ethnically diverse cohort of 27,480 older women, aged 65 to 81 years at baseline. MEASUREMENTS: Women were classified as having either survived to age 90 years or died before this age. Consumption of caffeinated and decaffeinated coffee and caffeinated tea was assessed at baseline and categorized as 0, 1, 2 to 3, or 4 or more cups/day. Associations of coffee and tea consumption with survival to age 90 years were examined using logistic regression models adjusted for sociodemographic characteristics, lifestyle behaviors, dietary quality, and chronic disease history. RESULTS: A total of 14,659 (53.3%) women survived to age 90 years during follow-up. Caffeinated coffee, decaffeinated coffee, or caffeinated tea consumption was not significantly associated with survival to age 90 years after adjusting for confounders. Findings did not significantly vary by smoking, body mass index, or race/ethnicity. CONCLUSION: No amount of coffee or tea consumption was associated with late-age survival among older women. These findings may be reassuring to older women who consume coffee and tea as part of their daily diets but do not support drinking these beverages to achieve longevity.

Source Characterization and Exposure Modeling of Gas-Phase Polycyclic Aromatic Hydrocarbon (PAH) Concentrations in Southern California.

Airborne exposures to polycyclic aromatic hydrocarbons (PAHs) are associated with adverse health outcomes. Because personal air measurements of PAHs are labor intensive and costly, spatial PAH exposure models are useful for epidemiological studies. However, few studies provide adequate spatial coverage to reflect intra-urban variability of ambient PAHs. In this study, we collected 39-40 weekly gas-phase PAH samples in southern California twice in summer and twice in winter, 2009, in order to characterize PAH source contributions and develop spatial models that can estimate gas-phase PAH concentrations at a high resolution. A spatial mixed regression model was constructed, including such variables as roadway, traffic, land-use, vegetation index, commercial cooking facilities, meteorology, and population density. Cross validation of the model resulted in an R2 of 0.66 for summer and 0.77 for winter. Results showed higher total PAH concentrations in winter. Pyrogenic sources, such as fossil fuels and diesel exhaust, were the most dominant contributors to total PAHs. PAH sources varied by season, with a higher fossil fuel and wood burning contribution in winter. Spatial autocorrelation accounted for a substantial amount of the variance in total PAH concentrations for both winter (56%) and summer (19%). In summer, other key variables explaining the variance included meteorological factors (9%), population density (15%), and roadway length (21%). In winter, the variance was also explained by traffic density (16%). In this study, source characterization confirmed the dominance of traffic and other fossil fuel sources to total measured gas-phase PAH concentrations while a spatial exposure model identified key predictors of PAH concentrations. Gas-phase PAH source characterization and exposure estimation is of high utility to epidemiologist and policy makers interested in understanding the health impacts of gas-phase PAHs and strategies to reduce emissions.

Whole blood lead levels are associated with biomarkers of joint tissue metabolism in African American and white men and women: the Johnston County Osteoarthritis Project.

PURPOSE: To examine associations between biomarkers of joint tissue metabolism and whole blood lead (Pb), separately for men and women in an African American and Caucasian population, which may reflect an underlying pathology. METHODS: Participants in the Johnston County Osteoarthritis Project Metals Exposure Sub-Study (329 men and 342 women) underwent assessment of whole blood Pb and biochemical biomarkers of joint tissue metabolism. Urinary cross-linked N telopeptide of type I collagen (uNTX-I) and C-telopeptide fragments of type II collagen (uCTX-II), serum cleavage neoepitope of type II collagen (C2C), serum type II procollagen synthesis C-propeptide (CPII), and serum hyaluronic acid (HA) were measured using commercially available kits; the ratio of [C2C:CPII] was calculated. Serum cartilage oligomeric matrix protein (COMP) was measured by an in-house assay. Multiple linear regression models were used to examine associations between continuous blood Pb and biomarker outcomes, adjusted for age, race, current smoking status, and body mass index. Results are reported as estimated change in biomarker level for a 5-unit change in Pb level. RESULTS: The median Pb level among men and women was 2.2 and 1.9µg/dL, respectively. Correlations were noted between Pb levels and the biomarkers uNTX-I, uCTX-II, and COMP in women, and between Pb and uCTX-II, COMP, CPII, and the ratio [C2C:CPII] in men. In adjusted models among women, a 5-unit increase in blood Pb level was associated with a 28% increase in uCTX-II and a 45% increase in uNTX-I levels (uCTX-II: 1.28 [95% CI: 1.04-1.58], uNTX-I: 1.45 [95% CI:1.21-1.74]). Among men, levels of Pb and COMP showed a borderline positive association (8% increase in COMP for a 5-unit change in Pb: 1.08 [95% CI: 1.00-1.18]); no other associations were significant after adjustment. CONCLUSIONS: Based upon known biomarker origins, the novel associations between blood Pb and biomarkers appear to be primarily reflective of relationships to bone and calcified cartilage turnover among women and cartilage metabolism among men, suggesting a potential gender-specific effect of Pb on joint tissue metabolism that may be relevant to osteoarthritis.

Glutamatergic neurons in rodent models respond to nanoscale particulate urban air pollutants in vivo and in vitro.

BACKGROUND: Inhalation of airborne particulate matter (PM) derived from urban traffic is associated with pathology in the arteries, heart, and lung; effects on brain are also indicated but are less documented. OBJECTIVE: We evaluated rodent brain responses to urban nanoscale (< 200 nm) PM (nPM). METHODS: Ambient nPM collected near an urban freeway was transferred to aqueous suspension and reaerosolized for 10-week inhalation exposure of mice or directly applied to rat brain cell cultures. RESULTS: Free radicals were detected by electron paramagnetic resonance in the nPM 30 days after initial collection. Chronic inhalation of reaerosolized nPM altered selected neuronal and glial activities in mice. The neuronal glutamate receptor subunit (GluA1) was decreased in hippocampus, whereas glia were activated and inflammatory cytokines were induced [interleukin-1α (IL-1α), tumor necrosis factor-α (TNFα)] in cerebral cortex. Two in vitro models showed effects of nPM suspensions within 24-48 hr of exposure that involved glutamatergic functions. In hippocampal slice cultures, nPM increased the neurotoxicity of NMDA (N-methyl-d-aspartic acid), a glutamatergic agonist, which was in turn blocked by the NMDA antagonist AP5 [(2R)-amino-5-phosphonopentanoate]. In embryonic neuron cultures, nPM impaired neurite outgrowth, also blocked by AP5. Induction of IL-1α and TNFα in mixed glia cultures required higher nPM concentrations than did neuronal effects. Because conditioned media from nPM-exposed glia also impaired outgrowth of embryonic neurites, nPM can act indirectly, as well as directly, on neurons in vitro. CONCLUSIONS: nPM can affect embryonic and adult neurons through glutamatergic mechanisms. The interactions of nPM with glutamatergic neuronal functions suggest that cerebral ischemia, which involves glutamatergic excitotoxicity, could be exacerbated by nPM.

Whole blood lead levels are associated with radiographic and symptomatic knee osteoarthritis: a cross-sectional analysis in the Johnston County Osteoarthritis Project.

INTRODUCTION: Lead (Pb) is known to affect bone, and recent evidence suggests that it has effects on cartilage as well. As osteoarthritis (OA) is a highly prevalent disease affecting bone and cartilage, we undertook the present analysis to determine whether whole blood Pb levels are associated with radiographic and symptomatic OA (rOA and sxOA, respectively) of the knee. METHODS: The analysis was conducted using cross-sectional data from the Johnston County Osteoarthritis Project, a rural, population-based study, including whole blood Pb levels, bilateral posteroanterior weight-bearing knee radiography and knee symptom data. rOA assessment included joint-based presence (Kellgren-Lawrence (K-L) grade 2 or higher) and severity (none, K-L grade 0 or 1; mild, K-L grade 2; moderate or severe, K-L grade 3 or 4), as well as person-based laterality (unilateral or bilateral). SxOA was deemed present (joint-based) in a knee on the basis of K-L grade 2 or higher with symptoms, with symptoms rated based on severity (0, rOA without symptoms; 1, rOA with mild symptoms; 2, rOA with moderate or severe symptoms) and in person-based analyses was either unilateral or bilateral. Generalized logit or proportional odds regression models were used to examine associations between the knee OA status variables and natural log-transformed blood Pb (ln Pb), continuously and in quartiles, controlling for age, race, sex, body mass index (BMI), smoking and alcohol drinking. RESULTS: Those individuals with whole blood Pb data (N = 1,669) had a mean (±SD) age of 65.4 (±11.0) years and a mean BMI of 31.2 (±7.1) kg/m2, including 66.6% women and 35.4% African-Americans, with a median blood Pb level of 1.8 µg/dl (range, 0.3 to 42.0 µg/dl). In joint-based analyses, for every 1-U increase in ln Pb, the odds of prevalent knee rOA were 20% higher (aOR, 1.20; 95% CI, 1.01 to 1.44), while the odds of more severe rOA were 26% higher (aOR, 1.26; 95% CI, 1.05 to 1.50, under proportional odds). In person-based analyses, the odds of bilateral rOA were 32% higher for each 1-U increase in ln Pb (aOR, 1.32; 95% CI, 1.03 to 1.70). Similarly for knee sxOA, for each 1-U increase in ln Pb, the odds of having sxOA were 16% higher, the odds of having more severe symptoms were 17% higher and the odds of having bilateral knee symptoms were 25% higher. Similar findings were obtained with regard to ln Pb in quartiles. CONCLUSIONS: Increases in the prevalence and severity measures for both radiographically and symptomatically confirmed knee OA (although statistically significant only for rOA) were observed with increasing levels of blood Pb, suggesting that Pb may be a potentially modifiable environmental risk factor for OA.

Insecticide use and risk of rheumatoid arthritis and systemic lupus erythematosus in the Women's Health Initiative Observational Study.

OBJECTIVE: Farming and agricultural pesticide use has been associated with 2 autoimmune rheumatic diseases, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, risk associated with other residential or work place insecticide use is unknown. METHODS: We analyzed data from the Women's Health Initiative Observational Study (n=76,861 postmenopausal women, ages 50-79 years). Incident cases (n=213: 178 for RA, 27 for SLE, and 8 for both) were identified based on self-report and use of disease-modifying antirheumatic drugs at year 3 of followup. We examined self-reported residential or work place insecticide use (personally mixing/applying by self and application by others) in relation to RA/SLE risk, overall and in relation to farm history. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were adjusted for age, race, region, education, occupation, smoking, reproductive factors, asthma, other autoimmune diseases, and comorbidities. RESULTS: Compared with never used, personal use of insecticides was associated with increased RA/SLE risk, with significant trends for greater frequency (HR 2.04, 95% CI 1.17-3.56 for ≥6 times/year) and duration (HR 1.97, 95% CI 1.20-3.23 for ≥20 years). Risk was also associated with long-term insecticide application by others (HR 1.85, 95% CI 1.07-3.20 for ≥20 years) and frequent application by others among women with a farm history (HR 2.73, 95% CI 1.10-6.78 for ≥6 times/year). CONCLUSION: These results suggest residential and work place insecticide exposure is associated with the risk of autoimmune rheumatic diseases in postmenopausal women. Although these findings require replication in other populations, they support a role for environmental pesticide exposure in the development of autoimmune rheumatic diseases.

Limited educational attainment and radiographic and symptomatic knee osteoarthritis: a cross-sectional analysis using data from the Johnston County (North Carolina) Osteoarthritis Project.

INTRODUCTION: Applying a cross-sectional analysis to a sample of 2,627 African-American and Caucasian adults aged > or = 45 years from the Johnston County Osteoarthritis Project, we studied the association between educational attainment and prevalence of radiographic knee osteoarthritis and symptomatic knee osteoarthritis. METHODS: Age- and race-adjusted associations between education and osteoarthritis outcomes were assessed by gender-stratified logistic regression models, with additional models adjusting for body mass index, knee injury, smoking, alcohol use, and occupational factors. RESULTS: In an analysis of all participants, low educational attainment (<12 years) was associated with higher prevalence of four knee osteoarthritis outcomes (unilateral and bilateral radiographic and symptomatic osteoarthritis). Women with low educational attainment had 50% higher odds of having radiographic knee osteoarthritis and 65% higher odds of symptomatic knee osteoarthritis compared with those with higher educational attainment (> or = 12 years), by using fully adjusted models. In the subset of postmenopausal women, these associations tended to be weaker but little affected by adjustment for hormone replacement therapy. Men with low educational attainment had 85% higher odds of having symptomatic knee osteoarthritis by using fully adjusted models, but the association with radiographic knee osteoarthritis was explained by age. CONCLUSIONS: After adjustment for known risk factors, educational attainment, as an indicator of socioeconomic status, is associated with symptomatic knee osteoarthritis in both men and women and with radiographic knee osteoarthritis in women.

Associations of occupational tasks with knee and hip osteoarthritis: the Johnston County Osteoarthritis Project.

OBJECTIVE: This cross-sectional study examined associations of occupational tasks with radiographic and symptomatic osteoarthritis (OA) in a community-based sample. METHODS: Participants from the Johnston County Osteoarthritis Project (n = 2729) self-reported the frequency of performing 10 specific occupational tasks at the longest job ever held (never/seldom/sometimes vs often/always) and lifetime exposure to jobs that required spending > 50% of their time doing 5 specific tasks or lifting 22, 44, or 110 pounds 10 times weekly. Multivariable logistic regression models examined associations of each occupational task separately with radiographic and symptomatic knee and hip OA, controlling for age, race, gender, body mass index, prior knee or hip injury, and smoking. RESULTS: Radiographic hip and knee OA were not significantly associated with any occupational tasks, but several occupational tasks were associated with increased odds of both symptomatic knee and hip OA: lifting > 10 pounds, crawling, and doing heavy work while standing (OR 1.4-2.1). More occupational walking and standing and less sitting were also associated with symptomatic knee OA, and more bending/twisting/reaching was associated with symptomatic hip OA. Exposure to a greater number of physically demanding occupational tasks at the longest job was associated with greater odds of both symptomatic knee and hip OA. CONCLUSION: Our results confirm an association of physically demanding occupational tasks with both symptomatic knee and hip OA, including several specific activities that increased the odds of OA in both joint groups. These tasks represent possibilities for identifying and targeting at-risk individuals with preventive interventions.

Prospective study of metal fume-induced responses of global gene expression profiling in whole blood.

Metal particulate inhalation causes pulmonary and cardiovascular diseases. Our previous results showed that systemic responses to short-term occupational welding-fume exposure could be assessed by microarray analyses in whole-blood total RNA sampled before and after exposure. To expand our understanding of the duration of particulate-induced gene expression changes, we conducted a study using a similar population 1 yr after the original study and extended our observations in the postexposure period. We recruited 15 individuals with welding fume exposure and 7 nonexposed individuals. Thirteen of the 22 individuals (9 in exposed group and 4 in nonexposed group) had been monitored in the previous study. Whole-blood total RNA was analyzed at 3 time points, including baseline, immediately following exposure (approximately 5 h after baseline), and 24 h after baseline, using cDNA microarray technology. We replicated the patterns of Gene Ontology (GO) terms associated with response to stimulus, cell death, phosphorus metabolism, localization, and regulation of biological processes significantly enriched with altered genes in the nonsmoking exposed group. Most of the identified genes had opposite expression changes between the exposure and postexposure periods in nonsmoking welders. In addition, we found dose-dependent patterns that were affected by smoking status. In conclusion, short-term occupational exposure to metal particulates causes systemic responses in the peripheral blood. Furthermore, the acute particulate-induced effects on gene expression profiling were transient in nonsmoking welders, with most effects diminishing within 19 h following exposure.

Sleep duration and risk of ischemic stroke in postmenopausal women.

BACKGROUND AND PURPOSE: Many studies have shown a U-shape association between sleep duration and mortality, but epidemiological evidence linking cardiovascular diseases with habitual sleep patterns is limited and mixed. METHODS: We conducted a prospective study on 93 175 older women (aged 50 to 79 years) in the Women's Health Initiative Observational study cohort to examine the risk of ischemic stroke in relation to self-reported sleep duration. Cox models were used to investigate the putative associations, adjusting for multiple sociodemographic and lifestyle factors, depression, snoring, sleepiness symptoms, and other cardiovascular disease-related clinical characteristics. RESULTS: At baseline, 8.3% of subjects had reported their sleep duration as or=9 hours/night). After an average of 7.5 years of follow-up, 1166 cases of ischemic stroke had occurred. Multivariable-adjusted relative risk (RR) and 95% CI for ischemic stroke (using a sleep time of 7 hours/night as the reference) were 1.14 (0.97, 1.33), 1.24 (1.04, 1.47), and 1.70 (1.32, 2.21) for women reporting or=9 hours of sleep. A modestly stronger association with sleep duration or=9 hours/night) need further elucidation.

Night heart rate variability and particulate exposures among boilermaker construction workers.

BACKGROUND: Although studies have documented the association between heart rate variability (HRV) and ambient particulate exposures, the association between HRV, especially at night, and metal-rich, occupational particulate exposures remains unclear. OBJECTIVE: Our goal in this study was to investigate the association between long-duration HRV, including nighttime HRV, and occupational PM(2.5) exposures. METHODS: We used 24-hr ambulatory electrocardiograms (ECGs) to monitor 36 male boilermaker welders (mean age of 41 years) over a workday and nonworkday. ECGs were analyzed for HRV in the time domain; rMSSD (square root of the mean squared differences of successive intervals), SDNN (SD of normal-to-normal intervals over entire recording), and SDNN(i) (SDNN for all 5-min segments) were summarized over 24-hr, day (0730-2130 hours), and night (0000-0700 hours) periods. PM(2.5) (particulate matter with an aerodynamic diameter

Global gene expression profiling in whole-blood samples from individuals exposed to metal fumes.

Accumulating evidence demonstrates that particulate air pollutants can cause both pulmonary and airway inflammation. However, few data show that particulates can induce systemic inflammatory responses. We conducted an exploratory study using microarray techniques to analyze whole-blood total RNA in boilermakers before and after occupational exposure to metal fumes. A self-controlled study design was used to overcome the problems of larger between-individual variation interferences with observations of relatively smaller changes caused by environmental exposure. Moreover, we incorporated the dichotomous data of absolute gene expression status in the microarray analyses. Compared with nonexposed controls, we observed that genes with altered expression in response to particulate exposure were clustered in biologic processes related to inflammatory response, oxidative stress, intracellular signal transduction, cell cycle, and programmed cell death. In particular, the preinflammatory cytokine interleukin 8 and one of its receptors, chemokine receptor 4, seemed to play important roles in early-stage response to heavy metal exposure and were down-regulated. Furthermore, most observed expression variations were from nonsmoking exposed individuals, suggesting that smoking profoundly affects whole-blood expression profiles. Our study is the first to demonstrate that with a paired sampling study design of pre- and postexposed individuals, small changes in gene expression profiling can be measured in whole-blood total RNA from a population-based study. This technique can be applied to evaluate the host response to other forms of environmental exposures.