Introduction: The Aedes aegypti mosquito is responsible for the transmission of Yellow Fever, Dengue, Chikungunya and Zikavirus, making it a deadly vector and global public health threat. Zikavirus and Chikungunya, which were previously restricted to smaller geographic areas, have both appeared in the Western Hemisphere in the past three years and spread to areas where A. aegypti are present. This means that the pathogens have now entered areas in which the population has no previous immunity, which can lead to extensive outbreaks and epidemics. As the effects of global climate change become apparent, the areas of the globe that are suitable for inhabitance by A. aegypti may change. Additionally, this vector prefers human hosts for blood meals and requires standing water to breed, which is often created by water storage containers. This means that increasing urbanization and human population density are likely to put populations at higher risk of exposure to this vector. Methods: To create maps of the future risk of exposure to Aedes aegypti globally, species occurrence data for the vector and the Maxent modeling approach were used. Current and projected climate data were downloaded from WorldClim.org for the four representative concentration pathways (RCPs) used to model future climate change. Human population density, projected to 2050, the same timeframe as the future climate data, were used to model changes in human populations. To identify areas at high risk for future presence of A. aegypti populations, current and future models were compared across areas with at least a 50% probability of increased risk. These results where then used to create maps displaying high risk areas. Results: The AUC, an indicator of model fit, signaled that the models had high predictive power. However, high omission rates indicated that the trade-off of risk mapping may be a need to decrease probability thresholds below 50% to capture the full at-risk population. Future high-risk areas were most often those surrounding current cities, which supports the idea that the combination of urbanization and increasing human population density will work synergistically to increase the disease burden within and around urban centers. Additionally, expansion at the current geographic margins of this species shows that incursion into currently non-endemic areas is possible. Conclusions: Urban and peri-urban populations are likely to be at higher risk of exposure compared to rural areas due to global climate change and changes in population density. Attempts to model expansion of vector habitats should consider how these human population characteristics will change the risk to populations and how to best identify the areas at highest risk. Thresholds for the probability of a population being at risk of exposure to a vector may need to be different from those required to determine whether or not a habitat is suitable for a species. Appropriately determining which areas are high-risk results in maps and models can then be used to identify areas where climate change mitigation and vector control efforts are likely to have the highest impacts.

Background: Exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) have been associated with higher circulating concentrations of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C). ApoB is the primary apolipoprotein component of LDL-C, and acts as a ligand for LDL-C receptors in various cells throughout the body. Circulating concentrations of ApoB are considered to be a better indicator of heart disease risk than TC or LDL-C. Objectives: Explore associations of concentrations of PFOA and PFOS with serum ApoB in adults. Methods: We analyzed data from 2744, 20-80 years old participants in the 2005–2006 National Health and Nutrition Examination Survey (NHANES). Linear regression models were used to estimate adjusted predicted means of serum ApoB (in g/L) for quartiles of PFOA and PFOS (in ng/mL) to describe patterns of associations. Results: Adjusted predicted mean concentrations of serum ApoB did not appear to vary meaningfully with increasing concentrations of PFOA (Q1 1.11, Q2 1.02, Q3 1.01, Q4 1.02) or increasing concentrations of PFOS (Q1 1.06, Q2 1.05, Q3 1.07, Q4 0.99) in study participants. Conclusions: Exposure to PFOA or PFOS does not appear to alter Apo B concentrations in adults.

We miss summer time during winter especially when it snows heavily resulting in cancelation of classes but we turn to ignore high temperature and its associated health impacts during summer. Several studies have shown that high temperatures during summer are associated with morbidity and mortality in many cities in the United States over the past decade. Gradual increase in temperature over the past years raises public health concerns about the impacts of heat on human health in future and the role of adaptation. Our study aimed at assessing future heat-related mortality due to climate change in the United States. We hypothesized that incidence of premature death will increase with future temperature rise and population adaptation will reduce the mortality rate. We reviewed research articles on temperature-related premature death. The literature search was limited to studies conducted in United States and seven studies which demonstrated positive association between temperature and premature death were selected for this study. We predicted future high temperature-related mortality using BenMap benefit model designed to estimate 2015 Appalachian Student Research Forum Page 111 air pollution impacts on public health. Based on the selected studies, BenMap model projected 2020-2050 temperature scenario using modeled daily mean apparent temperature to estimate future heat-related mortality. Our results showed that high temperatures would cause an increase in heat-related mortality and adaptation would minimize the effects of climate change as people get used to high temperatures. The outcome of our study confirms the positive association between high temperature and mortality which emphasizes the need for policy makers to take appropriate actions such as greenhouse gas emission reduction to protect public health.

Public health is an increasingly important issue addressed from both environmental and public health sectors for the future development of urban environments. From a planning perspective, one possible solution is to increase walkability throughout the cities. Many assessment methods are being developed and administered to evaluate the quality of existing urban environments to promote walkable cities/communities. The results from using these methods provide policymakers and stakeholders with valuable information regarding the existing physical conditions of the environment. Although several US cities started to develop and refocus plans toward pedestrian-oriented policies approaches, results from this particular study determined that the quality of pedestrian environments cannot solely be determined by using available assessment tools and recommend additional analytical methods used in conjunction with source data to provide a complete perspective to successfully increase the quality of life. The condition of the physical environment – high, average, and low quality – was important contributing factors to increase walkability, yet, it is equally important to understand and consider the needs, preferences and perceptions of end users when public officials are charged with the task of developing plan proposals for pedestrian neighborhoods. This study addresses these issues through a case study examining the quality of pedestrian environment and how people perceive those surroundings of downtown San Luis Obispo.

The overall objective of this dissertation was to examine exposures to the estrogenic endocrine disrupting chemicals (EEDCs), phthalates, bisphenol-A (BPA), and the metalloestrogens cadmium (Cd), arsenic (As), and manganese (Mn) in an older geriatric aged-population and examine associations with brain health. Given the evidence that EEDCs affect brain health and play a role in the development of cognitive dysfunction and neurodegenerative disease, and the constant environmental exposure through foods and everyday products has led this to becoming a great public health concern. Using a bioinformatic approach to find nuclear respiratory factor 1 (NRF1) gene targets involved in mitochondrial dysfunction, that are both estrogen and EEDC-sensitive, we found several genes involved in the gene pathways of Alzheimer’s disease (AD): APBB2, EIF2S1, ENO1, MAPT, and PAXIP1. Using the Center for Disease Control and Prevention (CDC), National Health and Nutrition Examination Survey (NHANES) 2011-2014 datasets to assess EEDC bioburden and associations with surrogate indicators of brain health, which include cognitive scores, memory questions, and taste and smell data, we found phthalate bioburden to be significantly higher in those with adverse brain health vii and significantly higher in females. In our logistic regression model when controlling for all known and suspected covariates in AD, in females, the phthalates in females ECP, MBP, MOH, MZP, and MIB in males and the phthalates COP, ECP, MBP, MC1, MEP, MHH, MOH, and MIB were significantly associated with poor cognitive test scores, poor memory, and taste and smell dysfunction. Among the metalloestrogens, Cd bioburden was higher in those with poor cognitive performance, poor memory, and taste and smell dysfunction, with the trend more significant in males. Among oral contraceptive (OC) and HRT (hormone replacement therapy) use, in our logistic regression model when controlling for all known and suspected covariates in AD, past OC and HRT use was associated with better cognitive test scores. The study provides further evidence of the complex role EEDCs play in overall brain health through other biological mechanisms and fills a gap in knowledge that demonstrates EEDCs effects on brain health in a geriatric age population.

En los Estados Unidos, los latinos suelen tener menos acceso a la educación, el trabajo, y el seguro médico en comparación con los blancos no-latinos, pero aun así el grupo parece superar ciertos obstáculos de la salud. Las estadísticas de la población latina muestran mayor longevidad y otras tasas favorables en comparación con los blancos no-latinos. Los expertos han titulado esta contradicción “La Paradoja Hispana Epidemiológica”. Desafortunadamente, la investigación de la paradoja está llena de generalizaciones y presuposiciones erróneas sobre la población latina diversa. Esta tesis investiga los participantes que producen generalizaciones sobre la supuesta paradoja para mostrar que estas generalizaciones impiden un entendimiento claro. Antes de llegar a conclusiones e implicaciones, es necesario diseccionar la paradoja para poder entender esta diversidad y especificar los aspectos que realmente necesitan explicaciones. El análisis de la aparente paradoja tiene mucho que decirnos no sólo sobre la población latina, sino también sobre las maneras en que se estudia la salud y cómo se presenta información sobre la salud al público. Una examinación de las investigaciones de la paradoja puede dar luz a estos discursos generales.

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus that establishes a life-long latent infection of B cells. It is usually asymptomatic in healthy individuals; however, individuals with compromised immunity often develop EBV-induced lymphoma. EBV also encodes potential oncogenes that can contribute to tumorigenesis. Therefore, vaccine and immunotherapeutic strategies targeting EBV are desirable. Recent studies have shown that infusion of EBV-specific CD8+T cells can elicit remission of lymphomas arising after administration of immunosuppressive drugs during transplantation, suggesting an important role for T cells in the prevention of EBV-induced malignancy. A better understanding of the cellular immune components involved in the control of EBV will aid in the development of methods to prevent infection and/or treat EBV-associated disease. While EBV infection is usually acquired asymptomatically during childhood, primary infection of adolescents and young adults can result in an illness termed acute infectious mononucleosis (AIM). Because of the characteristic symptoms of the illness, individuals with AIM can be readily identified and diagnosed with acute EBV infection. Thus, primary CD4+ and CD8+ T cell responses against the virus can be evaluated. It has been previously found that there is a marked expansion of lytic EBV protein-specific CD8+ T cells early during AIM, with delayed detection of lower frequencies of latent EBV protein-specific CD8+ T cells. The magnitude and specificity of CD4+T cell responses during AIM has been less well characterized. This thesis dissertation presents data from both functional assays and direct staining experiments documenting the timing, magnitude, and antigen-specificity of CD4+ T cells over the course of primary EBV infection. Lytic and latent protein-specific CD4+ T cells were readily detected by intracellular IFN-γ production at presentation with AIM and declined rapidly thereafter. Blood EBV load was also quantitated and found to decrease over time following AIM. By contrast, CD8+T cell IFN-y responses remained high for several weeks following presentation with AIM. Direct staining of lytic epitope-specific CD4+ T cells during AIM revealed high frequencies of virus-specific cells with low proliferative and IFN-γ-producing potential. Blood EBV load in these patients was persistently high through 6 wk following AIM. These data suggest a relationship between high EBV load during acute infection and impaired EBV-specific CD4+ T cell responses, which are compatible with impaired CD4+ T cell responses reported during high viremia associated with other viral infections. This may represent a mechanism by which persistent viruses, such as EBV, are able to establish a life-long infection in their hosts.

High frequencies of CTL recognizing laboratory strains of HIV-1 are present in HIV-1 infected adults as early as preseroconversion. The presence of HIV-1 specific CTL during primary infection has been correlated with better control of early viremia and a more delayed onset of CD4 lymphocyte loss. Previous experiments in our laboratory have demonstrated that, unlike HIV-1 infected adults, the majority of vertically infected infants lack CTL which recognize laboratory strains of HIV-1 within the first year of life. ADCC antibody responses against laboratory strains of HIV-1 env gene products are also delayed until at least two years of age. As a possible correlate, disease progression is also more rapid in vertically infected infants. We hypothesized that HIV-1-specific CTL are type-specific in early infancy and that the use of target cells expressing laboratory strain gene products might limit the detection of HIV-1-specific CTL. To address this hypothesis, HIV-1 env genes from early isolates of four infants were PCR amplified, cloned, and used to generate recombinant vaccinia vectors (vv). The frequencies of CTL precursors (CTLp) recognizing env gene products from autologous isolates and the IIIB strain of HIV-1 were measured at time points from early infancy to 19 months using limiting dilution analysis (LDA). ADCC titers were also measured against autologous and IIIB env gene products at 4 time points spanning 2 months to 2 years of age. CTL precursors from 3 of 4 of these patients were specific only for autologous HIV-1 env gene products during the first 6 to 12 months of age. A pattern of CTL responsiveness was observed in these 3 patients in which type-specific CTL precursors observed in early infancy were replaced by cross-reactive, group-specific CTL by 6 to 12 months of age. CTL precursors from a fourth patient at 12 months of age recognized IIIB env and 1 out of 2 envs derived from 2 autologous viral isolates. High titers titers of ADCC antibodies against autologous env were detected in two infants prior to the detection of ADCC antibodies to IIIB. In two other infants, group specific ADCC antibody responses were detected in late infancy. Our results demonstrate that young infants can mount HIV-1 specific CTL and ADCC responses. The ability of young infants to mount cellular immune responses to HIV-1 also provides support for the concept of perinatal vaccination to prevent HIV-1 transmission. Furthermore. the lack of broadly-reactive CTL in early infancy suggests that the use of vaccines based on laboratory strains of HIV-1 may not afford protection from vertical infection.

This study proposes to directly test the hypothesis that antibody-dependent enhancement (ADE) is the critical factor in the development of dengue hemorrhagic fever (DHF) in infants. DHF occurs in two distinct clinical settings: a) in children and adults with secondary DENV infection, and b) in infants with primary DENV infection born to mothers with prior DENV infection. The ADE hypothesis proposes that pre-existing serotype-cross-reactive non-neutralizing anti-DENV antibodies bind the heterotypic DENV during secondary infection and enhance its uptake into immune cells, leading to increased viral load and DHF. This model suggests that DHF in DENV-infected infants is caused by the enhancing effect of waning maternal anti-DENV antibodies, thus causing a “physiologic secondary infection” during an infant’s primary infection and thereby increasing the infant’s risk for DHF. The effect of maternal immunity on DHF in infants has been studied exclusively in Southeast Asia. However, the maternal DENV seroprevalence approaches 100% in this part of the world. As a consequence, the ADE model of infant DHF cannot truly be tested in Southeast Asia, because all infants possess anti-DENV antibody at birth. In the Western Hemisphere, by contrast, women may have experienced either a single DENV infection, more than one DENV infection, or no DENV infection at all. The ability to include DENV-seronegative mothers as controls allows for the ADE hypothesis to be directly tested in a clinical study. To our knowledge, no such study has been previously conducted. This thesis presents a case-control study designed to evaluate the influence of positive maternal dengue seroprevalence on the risk of DHF in infants. As the MSCI program provides instruction in study design, this thesis does not present findings. The clinical trial described herein began in May 2010 and enrollment is expected to continue through May 2012 (see Table 4).

Disasters are complex events characterized by damage to key infrastructure and population displacements into disaster shelters. Assessing the living environment in shelters during disasters is a crucial health security concern. Until now, jurisdictional knowledge and preparedness on those assessment methods, or deficiencies found in shelters is limited. A cross-sectional survey (STUSA survey) ascertained knowledge and preparedness for those assessments in all 50 states, DC, and 5 US territories. Descriptive analysis of overall knowledge and preparedness was performed. Fisher’s exact statistics analyzed differences between two groups: jurisdiction type and population size. Two logistic regression models analyzed earthquakes and hurricane risks as predictors of knowledge and preparedness. A convenience sample of state shelter assessments records (n=116) was analyzed to describe environmental health deficiencies found during selected events. Overall, 55 (98%) of jurisdictions responded (states and territories) and appeared to be knowledgeable of these assessments (states 92%, territories 100%, p = 1.000), and engaged in disaster planning with shelter partners (states 96%, territories 83%, p = 0.564). Few had shelter assessment procedures (states 53%, territories 50%, p = 1.000); or training in disaster shelter assessments (states 41%, 60% territories, p = 0.638). Knowledge or preparedness was not predicted by disaster risks, population size, and jurisdiction type in neither model. Knowledge: hurricane (Adjusted OR 0.69, 95% C.I. 0.06-7.88); earthquake (OR 0.82, 95% C.I. 0.17-4.06); and both risks (OR 1.44, 95% C.I. 0.24-8.63); preparedness model: hurricane (OR 1.91, 95% C.I. 0.06-20.69); earthquake (OR 0.47, 95% C.I. 0.7-3.17); and both risks (OR 0.50, 95% C.I. 0.06-3.94). Environmental health deficiencies documented in shelter assessments occurred mostly in: sanitation (30%); facility (17%); food (15%); and sleeping areas (12%); and during ice storms and tornadoes. More research is needed in the area of environmental health assessments of disaster shelters, particularly, in those areas that may provide better insight into the living environment of all shelter occupants and potential effects in disaster morbidity and mortality. Also, to evaluate the effectiveness and usefulness of these assessments methods and the data available on environmental health deficiencies in risk management to protect those at greater risk in shelter facilities during disasters.