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BackgroundMyeloid-derived suppressor cells (MDSCs), which include monocytic (mMDSCs) and granulocytic (gMDSCs) cells, are an immunosuppressive, heterogeneous population of cells upregulated in cancer and other pathologic conditions, in addition to normal conditions of stress. The origin of MDSCs is debated, and the regulatory pattern responsible for gMDSC differentiation remains unknown. Since DNA methylation (DNAm) contributes to lineage differentiation, we have investigated whether it contributes to the acquisition of the gMDSC phenotype.ResultsUsing the Illumina EPIC array to measure DNAm of gMDSCs and neutrophils from diverse neonatal and adult blood sources, we found 189 differentially methylated CpGs between gMDSCs and neutrophils with a core of ten differentially methylated CpGs that were consistent across both sources of cells. Genes associated with these loci that are involved in immune responses include VCL, FATS, YAP1, KREMEN2, UBTF, MCC-1, and EFCC1. In two cancer patient groups that reflected those used to develop the methylation markers (head and neck squamous cell carcinoma (HNSCC) and glioma), all of the CpG loci were differentially methylated, reaching statistical significance in glioma cases and controls, while one was significantly different in the smaller HNSCC group.ConclusionsOur findings indicate that gMDSCs have a core of distinct DNAm alterations, informing future research on gMDSC differentiation and function.

BackgroundDNA methylation alterations may underlie associations between gestational perfluoroalkyl substances (PFAS) exposure and later-life health outcomes. To the best of our knowledge, no longitudinal studies have examined the associations between gestational PFAS and DNA methylation.ObjectivesWe examined associations of gestational PFAS exposure with longitudinal DNA methylation measures at birth and in adolescence using the Health Outcomes and Measures of the Environment (HOME) Study (2003-2006; Cincinnati, Ohio).MethodsWe quantified serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) in mothers during pregnancy. We measured DNA methylation in cord blood (n=266) and peripheral leukocytes at 12 years of age (n=160) using the Illumina HumanMethylation EPIC BeadChip. We analyzed associations between log2-transformed PFAS concentrations and repeated DNA methylation measures using linear regression with generalized estimating equations. We included interaction terms between children's age and gestational PFAS. We performed Gene Ontology enrichment analysis to identify molecular pathways. We used Project Viva (1999-2002; Boston, Massachusetts) to replicate significant associations.ResultsAfter adjusting for covariates, 435 cytosine-guanine dinucleotide (CpG) sites were associated with PFAS (false discovery rate, q

Living near major roadways has been associated with increased risk of cardiovascular morbidity and mortality, presumably from exposure to elevated levels of traffic-related air and/or noise pollution. This association may potentially be mediated through increased risk of incident hypertension, but results from prior studies are equivocal. Using Cox proportional hazards models we examined residential proximity to major roadways and incident hypertension among 38,360 participants of the Women's Health Initiative (WHI) Clinical Trial cohorts free of hypertension at enrollment and followed for a median of 7.9 years. Adjusting for participant demographics and lifestyle, trial participation, and markers of individual and neighborhood socioeconomic status, the hazard ratios for incident hypertension were 1.13 (95% CI: 1.00, 1.28), 1.03 (0.95, 1.11), 1.05 (0.99, 1.11), and 1.05 (1.00, 1.10) for participants living ≤50, >50-200, >200-400, and >400-1000 m vs >1000 m from the nearest major roadway, respectively (ptrend=0.013). This association varied substantially by WHI study region with hazard ratios for women living ≤50 m from a major roadway of 1.61 (1.18, 2.20) in the West, 1.51 (1.22, 1.87) in the Northeast, 0.89 (0.70, 1.14) in the South, and 0.94 (0.75, 1.19) in the Midwest. In this large, national cohort of post-menopausal women, residential proximity to major roadways was associated with incident hypertension in selected regions of the U.S. If causal, these results suggest residential proximity to major roadways, as a marker for air, noise and other traffic-related pollution, may be a risk factor for hypertension.

BackgroundLiving near major roadways has been linked with increased risk of cardiovascular events and worse prognosis. Residential proximity to major roadways may also be associated with increased risk of hypertension, but few studies have evaluated this hypothesis.Methods and resultsWe examined the cross-sectional association between residential proximity to major roadways and prevalent hypertension among 5401 postmenopausal women enrolled into the San Diego cohort of the Women's Health Initiative. We used modified Poisson regression with robust error variance to estimate the association between prevalence of hypertension and residential distance to nearest major roadway, adjusting for participant demographics, medical history, indicators of individual and neighborhood socioeconomic status, and for local supermarket/grocery and fast food/convenience store density. The adjusted prevalence ratios for hypertension were 1.22 (95% CI: 1.07, 1.39), 1.13 (1.00, 1.27), and 1.05 (0.99, 1.12) for women living ≤100, >100 to 200, and >200 to 1000 versus >1000 m from a major roadway (P for trend=0.006). In a model treating the natural log of distance to major roadway as a continuous variable, a shift in distance from 1000 to 100 m from a major roadway was associated with a 9% (3%, 16%) higher prevalence of hypertension.ConclusionsIn this cohort of postmenopausal women, residential proximity to major roadways was positively associated with the prevalence of hypertension. If causal, these results suggest that living close to major roadways may be an important novel risk factor for hypertension.

BACKGROUND: DNA methylation alterations may underlie associations between gestational perfluoroalkyl substances (PFAS) exposure and later-life health outcomes. To the best of our knowledge, no longitudinal studies have examined the associations between gestational PFAS and DNA methylation. OBJECTIVES: We examined associations of gestational PFAS exposure with longitudinal DNA methylation measures at birth and in adolescence using the Health Outcomes and Measures of the Environment (HOME) Study (2003–2006; Cincinnati, Ohio). METHODS: We quantified serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) in mothers during pregnancy. We measured DNA methylation in cord blood (푛= 266) and peripheral leukocytes at 12 years of age (푛= 160) using the Illumina HumanMethylation EPIC BeadChip. We analyzed associations between log2-transformed PFAS concentrations and repeated DNA methylation measures using linear regression with generalized estimating equations. We included interaction terms between children’s age and gestational PFAS. We performed Gene Ontology enrichment analysis to identify molecular pathways. We used Project Viva (1999–2002; Boston, Massachusetts) to replicate significant associations. RESULTS: After adjusting for covariates, 435 cytosine–guanine dinucleotide (CpG) sites were associated with PFAS (false discovery rate, 푞< 0.05). Specifically, we identified 2 CpGs for PFOS, 12 for PFOA, 8 for PFHxS, and 413 for PFNA; none overlapped. Among these, 2 CpGs for PFOA and 4 for PFNA were replicated in Project Viva. Some of the PFAS-associated CpG sites annotated to gene regions related to cancers, cognitive health, cardiovascular disease, and kidney function. We found little evidence that the associations between PFAS and DNA methylation differed by children’s age. DISCUSSION: In these longitudinal data, PFAS biomarkers were associated with differences in several CpGs at birth and at 12 years of age in or near genes linked to some PFAS-associated health outcomes. Future studies should examine whether DNA methylation mediates associations between gestational PFAS exposure and health. [ABSTRACT FROM AUTHOR]

Introduction A large body of evidence has linked extreme heat events (i.e., 'heat waves') with higher mortality, especially from respiratory and cardiovascular diseases (Basagana et al. 2011; D'Ippoliti et al. [...], Background: Climate change is expected to cause increases in heat-related mortality, especially among the elderly and very young. However, additional studies are needed to clarify the effects of heat on morbidity across all age groups and across a wider range of temperatures. OBJECTIVES: We aimed to estimate the impact of current and projected future temperatures on morbidity and mortality in Rhode Island. METHODS: We used Poisson regression models to estimate the association between daily maximum temperature and rates of all-cause and heat-related emergency department (ED) admissions and all-cause mortality. We then used downscaled Coupled Model Intercomparison Project Phase 5 (CMIP5; a standardized set of climate change model simulations) projections to estimate the excess morbidity and mortality that would be observed if this population were exposed to the temperatures projected for 2046-2053 and 2092-2099 under two representative concentration pathways (RCP): RCP 8.5 and 4.5. RESULTS: Between 2005 and 2012, an increase in maximum daily temperature from 75 to 85°F was associated with 1.3% and 23.9% higher rates of all-cause and heat-related ED visits, respectively. The corresponding effect estimate for all-cause mortality from 1999 through 2011 was 4.0%. The association with all-cause ED admissions was strongest for those < 18 or ≥ 65 years of age, whereas the association with heat-related ED admissions was most pronounced among 18- to 64-year-olds. If this Rhode Island population were exposed to temperatures projected under RCP 8.5 for 2092-2099, we estimate that there would be 1.2% (range, 0.6-1.6%) and 24.4% (range, 6.9-41.8%) more all-cause and heat-related ED admissions, respectively, and 1.6% (range, 0.8-2.1%) more deaths annually between April and October. CONCLUSIONS: With all other factors held constant, our findings suggest that the current population of Rhode Island would experience substantially higher morbidity and mortality if maximum daily temperatures increase further as projected. http://dx.doi.org/10.1289/ehp.1408826

Introduction Depressive symptoms are highly prevalent in older adults (Thielke et al. 2010) and are an important risk factor for cardiovascular morbidity and mortality. Specifically, high levels of depressive symptoms [...], BACKGROUND: Exposure to ambient air pollution, particularly from traffic, has been associated with adverse cognitive outcomes, but the association with depressive symptoms remains unclear. OBJECTIVES: We investigated the association between exposure to ambient air and traffic pollution and the presence of depressive symptoms among 732 Boston-area adults [greater than or equal to] 65 years of age (78.1 [+ or -] 5.5 years, mean [+ or -] SD). METHODS: We assessed depressive symptoms during home interviews using the Revised Center for Epidemiological Studies Depression Scale (CESD-R). We estimated residential distance to the nearest major roadway as a marker of long-term exposure to traffic pollution and assessed short-term exposure to ambient fine particulate matter ([PM.sub.2.5]), sulfates, black carbon (BC), ultrafine particles, and gaseous pollutants, averaged over the 2 weeks preceding each assessment. We used generalized estimating equations to estimate the odds ratio (OR) of a CESD-R score [greater than or equal to] 16 associated with exposure, adjusting for potential confounders. In sensitivity analyses, we considered CESD-R score as a continuous outcome and mean annual residential BC as an alternate marker of long-term exposure to traffic pollution. RESULTS: We found no evidence of a positive association between depressive symptoms and long-term exposure to traffic pollution or short-term changes in pollutant levels. For example, we found an OR of CESD-R score [greater than or equal to] 16 of 0.67 (95% CI: 0.46, 0.98) per interquartile range (3.4 [micro]g/[m.sup.3]) increase in [PM.sub.2.5] over the 2 weeks preceding assessment. CONCLUSIONS: We found no evidence suggesting that ambient air pollution is associated with depressive symptoms among older adults living in a metropolitan area in attainment of current U.S. regulatory standards. http://dx.doi.org/10.1289/ehp.1205909.