Investigating geographic differences in environmental chemical exposures in maternal and cord sera using non-targeted screening and silicone wristbands in California.

BACKGROUND: Differential risks for adverse pregnancy outcomes may be influenced by prenatal chemical exposures, but current exposure methods may not fully capture data to identify harms and differences. METHODS: We collected maternal and cord sera from pregnant people in Fresno and San Francisco, and screened for over 2420 chemicals using LC-QTOF/MS. We matched San Francisco participants to Fresno participants (N = 150) and compared detection frequencies. Twenty-six Fresno participants wore silicone wristbands evaluated for over 1500 chemicals using quantitative chemical analysis. We assessed whether living in tracts with higher levels of pollution according to CalEnviroScreen correlated with higher numbers of chemicals detected in sera. RESULTS: We detected 2167 suspect chemical features across maternal and cord sera. The number of suspect chemical features was not different by city, but a higher number of suspect chemicals in cosmetics or fragrances was detected in the Fresno versus San Francisco participants' sera. We also found high levels of chemicals used in fragrances measured in the silicone wristbands. Fresno participants living in tracts with higher pesticide scores had higher numbers of suspect pesticides in their sera. CONCLUSIONS: Multiple exposure-assessment approaches can identify exposure to many chemicals during pregnancy that have not been well-studied for health effects.

Regulation of protective autophagy in anoikis-resistant glioma stem cells by SDCBP/MDA-9/Syntenin.

Glioblastoma multiforme (GBM) is a frequent and aggressive glial tumor, containing a small population of therapy-resistant cells, glioma stem cells (GSCs). Current dogma suggests that tumors regrow from GSCs, and these cells contribute to therapy resistance, poor prognosis, and recurrence; highlighting the importance of GSCs in glioma pathophysiology and therapeutic targeting. Macroautophagy/autophagy-based cellular homeostasis can be changed from pro-survival to pro-cell death by modulating SDCBP/MDA-9/Syntenin (syndecan binding protein)-mediated signaling. In nonadherent conditions, GSCs display protective autophagy and anoikis-resistance, which correlates with expression of SDCBP/MDA-9/Syntenin. Conversely, SDCBP/MDA-9/Syntenin silencing induces autophagic death in GSCs, indicating that SDCBP/MDA-9/Syntenin regulates protective autophagy in GSCs under anoikis conditions. This process is mediated through phosphorylation of the anti-apoptotic protein BCL2 accompanied with suppression of high levels of autophagic proteins (ATG5, LAMP1, LC3B) through EGFR signaling. SDCBP/MDA-9/Syntenin-mediated regulation of BCL2 and EGFR phosphorylation is achieved through PTK2/FAK and PRKC/PKC signaling. When SDCBP/MDA-9/Syntenin is absent, this protective mechanism is deregulated, leading to highly elevated and sustained levels of autophagy and consequently decreased cell survival. Our recent paper reveals a novel functional link between SDCBP/MDA-9/Syntenin expression and protective autophagy in GSCs. These new insights into SDCBP/MDA-9/Syntenin-mediated regulation and maintenance of GSCs present leads for developing innovative combinatorial cancer therapies.

Investigation of association between environmental and socioeconomic factors and preterm birth in California.

BACKGROUND: Preterm birth (PTB),2 defined as birth at gestational age <37 weeks, is a major public health concern. Infants born prematurely, comprising of about 10% of the US newborns, have elevated risks of neonatal mortality and a wide array of health problems. Although numerous clinical, genetic, environmental and socioeconomic factors have been implicated in PTB, very few studies investigate the impacts of multiple pollutants and social factors on PTB using large scale datasets. OBJECTIVES: To evaluate association between environmental and socioeconomic factors and PTB in California. METHODS: We linked the birth cohort file maintained by the California Office of Statewide Health Planning and Development from 2009 to 2012 years across 1.8 million births and the CalEnviroScreen 3.0 dataset from California Communities Environmental Health Screening Tool at the census tract level for 56 California counties. CalEnviroScreen contains 7 exposure and 5 environmental effects variables that constitute the Pollution Burden variable, and 5 socioeconomic variables. We evaluated relationships between environmental exposures and the risk of PTB using hierarchical clustering analyses and GIS-based visualization. We also used logistic regression to evaluate the relationship between specific pollutant and exposure indicators and PTB, accounted for socio-demographic determinants such as maternal race/ethnicity, maternal age, maternal education and payment of delivery costs. RESULTS: There exists geographic variability in PTB for groups of counties with similar environmental and social exposure profiles. We found an association between Pollution Burden, particulate matter ≤2.5 µm (PM2.5), and Drinking Water Scores and PTB (adjusted odds ratios were 1.03 (95% Confidence Interval (CI): 1.01, 1.04), 1.03 (95% CI: 1.02,1.04), and 1.04 (95% CI: 1.03,1.05), respectively). Additional findings suggest that certain drinking water contaminants such as arsenic and nitrate are associated with PTB in California. CONCLUSIONS: CalEnviroScreen data combined with birth records offer great opportunity for revealing novel exposures and evaluating cumulative exposures related to PTB by providing useful environmental and social information. Certain drinking water contaminants such as arsenic and nitrate are potentially associated with PTB in California and should be investigated further. Small association signals may involve sizeable population impacts.

Environmental pollution and social factors as contributors to preterm birth in Fresno County.

BACKGROUND: Environmental pollution exposure during pregnancy has been identified as a risk factor for preterm birth. Most studies have evaluated exposures individually and in limited study populations. METHODS: We examined the associations between several environmental exposures, both individually and cumulatively, and risk of preterm birth in Fresno County, California. We also evaluated early (< 34 weeks) and spontaneous preterm birth. We used the Communities Environmental Health Screening Tool and linked hospital discharge records by census tract from 2009 to 2012. The environmental factors included air pollution, drinking water contaminants, pesticides, hazardous waste, traffic exposure and others. Social factors, including area-level socioeconomic status (SES) and race/ethnicity were also evaluated as potential modifiers of the relationship between pollution and preterm birth. RESULTS: In our study of 53,843 births, risk of preterm birth was associated with higher exposure to cumulative pollution scores and drinking water contaminants. Risk of preterm birth was twice as likely for those exposed to high versus low levels of pollution. An exposure-response relationship was observed across the quintiles of the pollution burden score. The associations were stronger among early preterm births in areas of low SES. CONCLUSIONS: In Fresno County, we found multiple pollution exposures associated with increased risk for preterm birth, with higher associations among the most disadvantaged. This supports other evidence finding environmental exposures are important risk factors for preterm birth, and furthermore the burden is higher in areas of low SES. This data supports efforts to reduce the environmental burden on pregnant women.

MDA-9/Syntenin regulates protective autophagy in anoikis-resistant glioma stem cells.

Glioma stem cells (GSCs) comprise a small subpopulation of glioblastoma multiforme cells that contribute to therapy resistance, poor prognosis, and tumor recurrence. Protective autophagy promotes resistance of GSCs to anoikis, a form of programmed cell death occurring when anchorage-dependent cells detach from the extracellular matrix. In nonadherent conditions, GSCs display protective autophagy and anoikis-resistance, which correlates with expression of melanoma differentiation associated gene-9/Syntenin (MDA-9) (syndecan binding protein; SDCBP). When MDA-9 is suppressed, GSCs undergo autophagic death supporting the hypothesis that MDA-9 regulates protective autophagy in GSCs under anoikis conditions. MDA-9 maintains protective autophagy through phosphorylation of BCL2 and by suppressing high levels of autophagy through EGFR signaling. MDA-9 promotes these changes by modifying FAK and PKC signaling. Gain-of-function and loss-of-function genetic approaches demonstrate that MDA-9 regulates pEGFR and pBCL2 expression through FAK and pPKC. EGFR signaling inhibits autophagy markers (ATG5, Lamp1, LC3B), helping to maintain protective autophagy, and along with pBCL2 maintain survival of GSCs. In the absence of MDA-9, this protective mechanism is deregulated; EGFR no longer maintains protective autophagy, leading to highly elevated and sustained levels of autophagy and consequently decreased cell survival. In addition, pBCL2 is down-regulated in the absence of MDA-9, leading to cell death in GSCs under conditions of anoikis. Our studies confirm a functional link between MDA-9 expression and protective autophagy in GSCs and show that inhibition of MDA-9 reverses protective autophagy and induces anoikis and cell death in GSCs.

Racial/Ethnic Disparities in Cumulative Environmental Health Impacts in California: Evidence From a Statewide Environmental Justice Screening Tool (CalEnviroScreen 1.1).

OBJECTIVES: We used an environmental justice screening tool (CalEnviroScreen 1.1) to compare the distribution of environmental hazards and vulnerable populations across California communities. METHODS: CalEnviroScreen 1.1 combines 17 indicators created from 2004 to 2013 publicly available data into a relative cumulative impact score. We compared cumulative impact scores across California zip codes on the basis of their location, urban or rural character, and racial/ethnic makeup. We used a concentration index to evaluate which indicators were most unequally distributed with respect to race/ethnicity and poverty. RESULTS: The unadjusted odds of living in one of the 10% most affected zip codes were 6.2, 5.8, 1.9, 1.8, and 1.6 times greater for Hispanics, African Americans, Native Americans, Asian/Pacific Islanders, and other or multiracial individuals, respectively, than for non-Hispanic Whites. Environmental hazards were more regressively distributed with respect to race/ethnicity than poverty, with pesticide use and toxic chemical releases being the most unequal. CONCLUSIONS: Environmental health hazards disproportionately burden communities of color in California. Efforts to reduce disparities in pollution burden can use simple screening tools to prioritize areas for action.

Methodological considerations in screening for cumulative environmental health impacts: lessons learned from a pilot study in California.

Polluting facilities and hazardous sites are often concentrated in low-income communities of color already facing additional stressors to their health. The influence of socioeconomic status is not considered in traditional models of risk assessment. We describe a pilot study of a screening method that considers both pollution burden and population characteristics in assessing the potential for cumulative impacts. The goal is to identify communities that warrant further attention and to thereby provide actionable guidance to decision- and policy-makers in achieving environmental justice. The method uses indicators related to five components to develop a relative cumulative impact score for use in comparing communities: exposures, public health effects, environmental effects, sensitive populations and socioeconomic factors. Here, we describe several methodological considerations in combining disparate data sources and report on the results of sensitivity analyses meant to guide future improvements in cumulative impact assessments. We discuss criteria for the selection of appropriate indicators, correlations between them, and consider data quality and the influence of choices regarding model structure. We conclude that the results of this model are largely robust to changes in model structure.

A screening method for assessing cumulative impacts.

The California Environmental Protection Agency (Cal/EPA) Environmental Justice Action Plan calls for guidelines for evaluating "cumulative impacts." As a first step toward such guidelines, a screening methodology for assessing cumulative impacts in communities was developed. The method, presented here, is based on the working definition of cumulative impacts adopted by Cal/EPA: "Cumulative impacts means exposures, public health or environmental effects from the combined emissions and discharges in a geographic area, including environmental pollution from all sources, whether single or multi-media, routinely, accidentally, or otherwise released. Impacts will take into account sensitive populations and socio-economic factors, where applicable and to the extent data are available." The screening methodology is built on this definition as well as current scientific understanding of environmental pollution and its adverse impacts on health, including the influence of both intrinsic, biological factors and non-intrinsic socioeconomic factors in mediating the effects of pollutant exposures. It addresses disparities in the distribution of pollution and health outcomes. The methodology provides a science-based tool to screen places for relative cumulative impacts, incorporating both the pollution burden on a community- including exposures to pollutants, their public health and environmental effects- and community characteristics, specifically sensitivity and socioeconomic factors. The screening methodology provides relative rankings to distinguish more highly impacted communities from less impacted ones. It may also help identify which factors are the greatest contributors to a community's cumulative impact. It is not designed to provide quantitative estimates of community-level health impacts. A pilot screening analysis is presented here to illustrate the application of this methodology. Once guidelines are adopted, the methodology can serve as a screening tool to help Cal/EPA programs prioritize their activities and target those communities with the greatest cumulative impacts.