Development of risk based treatability and engineering measures for reducing exposure to lead contaminated media in the Miami inner city, Florida

A major consequence of contamination at the local level’s population as it relates to environmental health and environmental engineering is childhood lead poisoning. Environmental contamination is one of the pressing environmental concerns facing the world today. Current approaches often focus on large contaminated industrial size sites that are designated by regulatory agencies for site remediation. Prior to this study, there were no known published studies conducted at the local and smaller scale, such as neighborhoods, where often much of the contamination is present to remediate. An environmental health study of local lead-poisoning data in Liberty City, Little Haiti and eastern Little Havana in Miami-Dade County, Florida accounted for a disproportionately high number of the county’s reported childhood lead poisoning cases. An engineering system was developed and designed for a comprehensive risk management methodology that is distinctively applicable to the geographical and environmental conditions of Miami-Dade County, Florida. Furthermore, a scientific approach for interpreting environmental health concerns, while involving detailed environmental engineering control measures and methods for site remediation in contained media was developed for implementation. Test samples were obtained from residents and sites in those specific communities in Miami-Dade County, Florida (Gasana and Chamorro 2002). Currently lead does not have an Oral Assessment, Inhalation Assessment, and Oral Slope Factor; variables that are required to run a quantitative risk assessment. However, various institutional controls from federal agencies’ standards and regulation for contaminated lead in media yield adequate maximum concentration limits (MCLs). For this study an MCL of .0015 (mg/L) was used. A risk management approach concerning contaminated media involving lead demonstrates that the linkage of environmental health and environmental engineering can yield a feasible solution.

Specific Increase in MDR1 Mediated Drug-Efflux in Human Brain Endothelial Cells following Co-Exposure to HIV-1 and Saquinavir

Persistence of HIV-1 reservoirs within the Central Nervous System (CNS) remains a significant challenge to the efficacy of potent anti-HIV-1 drugs. The primary human Brain Microvascular Endothelial Cells (HBMVEC) constitutes the Blood Brain Barrier (BBB) which interferes with anti-HIV drug delivery into the CNS. The ATP binding cassette (ABC) transporters expressed on HBMVEC can efflux HIV-1 protease inhibitors (HPI), enabling the persistence of HIV-1 in CNS. Constitutive low level expression of several ABC-transporters, such as MDR1 (a.k.a. P-gp) and MRPs are documented in HBMVEC. Although it is recognized that inflammatory cytokines and exposure to xenobiotic drug substrates (e.g HPI) can augment the expression of these transporters, it is not known whether concomitant exposure to virus and anti-retroviral drugs can increase drug-efflux functions in HBMVEC. Our in vitro studies showed that exposure of HBMVEC to HIV-1 significantly up-regulates both MDR1 gene expression and protein levels; however, no significant increases in either MRP-1 or MRP-2 were observed. Furthermore, calcein-AM dye-efflux assays using HBMVEC showed that, compared to virus exposure alone, the MDR1 mediated drug-efflux function was significantly induced following concomitant exposure to both HIV-1 and saquinavir (SQV). This increase in MDR1 mediated drug-efflux was further substantiated via increased intracellular retention of radiolabeled [3H-] SQV. The crucial role of MDR1 in 3H-SQV efflux from HBMVEC was further confirmed by using both a MDR1 specific blocker (PSC-833) and MDR1 specific siRNAs. Therefore, MDR1 specific drug-efflux function increases in HBMVEC following co-exposure to HIV-1 and SQV which can reduce the penetration of HPIs into the infected brain reservoirs of HIV-1. A targeted suppression of MDR1 in the BBB may thus provide a novel strategy to suppress residual viral replication in the CNS, by augmenting the therapeutic efficacy of HAART drugs.

Exposure to endocrine disrupting compounds and reproductive toxicity in women

The overall objective of the research presented in this dissertation was to assess exposure to endocrine disrupting chemicals (EDCs), polychlorinated biphenyls (PCBs), phthalates, and bisphenol A (BPA) in the general population and evaluate their associations with adverse reproductive health effects, including cancers, in women. Given the proven contribution of unopposed estrogens to the risk for endometrial neoplasia or breast cancer, renewed health concerns have aroused about estrogen mimicking EDCs found in food, personal care products or as environmental contaminants. Our meta-analysis showed that exposure to estrogen mimicking PCBs increased summary risk of breast cancer and endometriosis. We further evaluated the relationship between endometriosis and breast cancer, and EDCs using a bioinformatics method. Our bioinformatics approach was able to identify genes with the potential to be involved in interaction with PCB, phthalates and BPA that may be important to the development of breast cancer and endometriosis. Therefore, we hypothesized that exposure to EDCs such as PCBs, phthalates, and BPA, results in adverse reproductive health effects in women. Using subject data and biomarkers available from the Center for Disease Controls National Health and Nutrition Examination Survey database we conducted a cross-sectional study of EDCs in relation to self-reported history of endometriosis, uterine leiomyomas, breast cancer, cervical cancer, ovarian cancer, and uterine cancer. Significantly higher body burdens of PCBs were found in women diagnosed with breast cancer, ovarian cancer, and uterine cancer compared to women without cancer. PCB 138 was significantly associated with breast cancer, cervical cancer, and uterine cancer, while PCBs 74 and 118 were significantly associated with ovarian cancer. The sum of dioxin-like PCBs were significantly associated with ovarian cancer (OR of 2.02, 95% CI: 1.06-3.85) and the sum of non-dioxin-like PCBs were significantly associated with uterine cancer (OR of 1.12, 95%CI: 1.03-1.23). Significantly higher body burdens of PCBs were also found in women diagnosed with endometriosis and uterine leiomyomas. Documenting the exposure to EDCs among the general U.S. population, and identifying agents associated with reproductive toxicity have the potential to fill research gaps and facilitate our understanding of the complex role environmental chemicals play in producing toxicity in reproductive organs.^

Effects of Prenatal and Early Postnatal Exposure to Aversive Stimuli on Fearfulness and Exploratory Behavior in Bobwhite Qauil Neonates (Colinus virginianus)

Neophobia, the fear of novelty, is a behavioral trait found across a number of animal species, including humans. Neophobic individuals perceive novel environments and stimuli to have aversive properties, and exhibit fearful behaviors when presented with non-familiar situations. The present study examined how early life exposure to aversive novel stimuli could reduce neophobia in bobwhite quail chicks. Experiment 1 exposed chicks to a novel auditory tone previously shown to be aversive to naïve chicks (Suarez, 2012) for 24 hours immediately after hatching, then subsequently tested them in the presence of the tone within a novel maze task. Postnatally exposed chicks demonstrated decreased fearfulness compared to naïve chicks, and behaved more similarly to chicks tested in the presence of a known attractive auditory stimulus (a bobwhite maternal assembly call vocalization). Experiment 2 exposed chicks to the novel auditory tone for 24 hours prenatally, then subsequently tested them within a novel maze task. Prenatally exposed chicks showed decreased fearfulness to a similar degree as those postnatally exposed, revealing that both prenatal and postnatal exposure methods are capable of decreasing fear of auditory stimuli. Experiment 3 exposed chicks to a novel visual stimulus for 24 hours postnatally, then subsequently tested them within a novel emergence box / T-maze apparatus. Chicks exposed to the visual stimulus showed decreased fearfulness compared to naïve chicks, thereby demonstrating the utility of this method across sense modalities. Experiment 4 assessed whether early postnatal exposure to one novel stimulus could generalize and serve to decrease fear of novelty when chicks were tested in the presence of markedly different stimuli. By combining the methods of Experiments 1 and 3, this experiment revealed that chicks exposed to one type of stimulus (auditory or visual) demonstrated decreased fear when subsequently tested in the presence of the opposite type of novel stimulus. These results suggest that experience with novel stimuli can moderate the extent to which neophobia will develop during early development.

Exposure to Endocrine Disrupting Compounds and Reproductive Toxicity in Women

The overall objective of the research presented in this dissertation was to assess exposure to endocrine disrupting chemicals (EDCs), polychlorinated biphenyls (PCBs), phthalates, and bisphenol A (BPA) in the general population and evaluate their associations with adverse reproductive health effects, including cancers, in women. Given the proven contribution of unopposed estrogens to the risk for endometrial neoplasia or breast cancer, renewed health concerns have aroused about estrogen mimicking EDCs found in food, personal care products or as environmental contaminants. Our meta-analysis showed that exposure to estrogen mimicking PCBs increased summary risk of breast cancer and endometriosis. We further evaluated the relationship between endometriosis and breast cancer, and EDCs using a bioinformatics method. Our bioinformatics approach was able to identify genes with the potential to be involved in interaction with PCB, phthalates and BPA that may be important to the development of breast cancer and endometriosis. Therefore, we hypothesized that exposure to EDCs such as PCBs, phthalates, and BPA, results in adverse reproductive health effects in women. Using subject data and biomarkers available from the Center for Disease Controls National Health and Nutrition Examination Survey database we conducted a cross-sectional study of EDCs in relation to self-reported history of endometriosis, uterine leiomyomas, breast cancer, cervical cancer, ovarian cancer, and uterine cancer. Significantly higher body burdens of PCBs were found in women diagnosed with breast cancer, ovarian cancer, and uterine cancer compared to women without cancer. PCB 138 was significantly associated with breast cancer, cervical cancer, and uterine cancer, while PCBs 74 and 118 were significantly associated with ovarian cancer. The sum of dioxin-like PCBs were significantly associated with ovarian cancer (OR of 2.02, 95% CI: 1.06-3.85) and the sum of non-dioxin-like PCBs were significantly associated with uterine cancer (OR of 1.12, 95%CI: 1.03-1.23). Significantly higher body burdens of PCBs were also found in women diagnosed with endometriosis and uterine leiomyomas. Documenting the exposure to EDCs among the general U.S. population, and identifying agents associated with reproductive toxicity have the potential to fill research gaps and facilitate our understanding of the complex role environmental chemicals play in producing toxicity in reproductive organs.

An Analysis of the Potential Risk Exposure to Lead (Pb) through Urban Community Gardens

Community gardening in cities is increasing, driven by social interaction and food security. City soils are sinks for heavy metals; including neurotoxic lead (Pb). Exposure routes are primarily through inhalation/ingestion of soil, or second by ingestion of plants that have accumulated Pb. This research evaluates soil at three Liberty City, Florida sites estimating risk of Pb exposure through primary and secondary pathways. Soil cores were collected from Liberty City, and red Malabar spinach (Basella rubra) was grown in Pb soil treatments in a greenhouse. Total soil Pb levels and plant tissues were measured after acid digestion, by ICP-OES. In Liberty City, two sites had hotspots with areas of elevated soil Pb levels. Plants grown on Pb contaminated soil all accumulated statistically significant Pb concentrations. Therefore, there is a potential risk of Pb exposure to residents in Liberty City by exposure in hotspot sites through both the primary and secondary pathways.

Predicting posttraumatic stress reactions in children prior to traumatic exposure

The present study examined the relations among previously identified risk and protective variables associated with traumatic exposure and evaluated a model of resilience to traumatic events among Latino youth prior to traumatic exposure using structural equation modeling. Model tests were pursued in the context of Full Information Maximum Likelihood (FIML) methods as implemented in Mplus. The model evaluated the role of the following variables: (a) intervening life events; (b) child characteristics; (c) social support from significant others; and (d) children's coping. Data were collected from 181 Latino youth (M age = 9.22, SD = 1.38; 49.0% female) participants. Data analyses revealed that children's perceived available social support and use of coping strategies predicted low state anxiety following exposure to cues of disaster. Life events and preexisting depression symptoms did not significantly predict social support and coping, whereas preexisting anxiety was a significant predictor of perceived social support. This study represents an important initial step towards establishing and empirically evaluating a resilience model. Implications for preparedness interventions and a framework for the etiology of resilient reactions to disaster exposure are discussed.