Functional studies of *Ras and Bcl-2 oncoproteins in keratinocyte homeostasis and multistep skin carcinogenesis

To assess the effect of deregulated Ha-ras and bcl-2, individually and in combination on epidermal keratinocyte homeostasis and during multistep skin carcinogenesis, we generated skin-specific transgenic mice and keratinocyte transfectants constitutively expressing oncogenic Ha-ras and bcl-2 proteins. The deregulated Ha-ras and bcl-2 expression contributing to homeostatic imbalances in the skin had an additive effect on the probability of tumor development. They were also cooperative in incidence, growth, and latency of tumor formation, and they exhibited synergistic cooperation in malignant transformation of benign papillomas. To explain the homeostatic imbalances by Ha-ras and bcl-2 overexpression in the skin, we investigated the three major cellular processes of proliferation, cell death, and differentiation. Epidermal expression of Bcl-2 retarded keratinocyte proliferation in the epidermis of neonatal mice compared with results for control littermates. Constitutive expression of Ha-ras increased keratinocyte proliferation, and co-expression of bcl-2 modestly suppressed the ras-mediated abnormal proliferation of neonatal keratinocytes. Bcl-2 proteins in keratinocytes protected UV-treated cells from apoptotic cell death regardless of oncogenic ras expression in both non-neoplastic neonatal epidermis and human keratinocyte cell lines. The spontaneous apoptotic index (AI) was also lower in papillomas constitutively expressing bcl-2 compared with the ones that developed in control mice. Ras-overexpressing epidermis, including that in ras/bcl-2 double transgenic mice, had abnormal differentiation patterns compared with controls. The oncogenic ras protein had alterations in both epidermal distribution and the extent of cytokeratin 14 and involucrin expression. Abnormal expression of the hyperproliferation marker cytokeratin 6 and modest down regulation of cytokeratin 1 were also detected. Late appearance of filaggrin was another abnormal phenotype of the ras-expressing epidermis. Overexpression of bcl-2 had no effect on epidermal differentiation. Together, these findings suggest that constitutive expression of oncogenic Ha-ras and bcl-2 are important determinants of epidermal proliferation, viability and differentiation. In summary, our results demonstrated that the disruption of epidermal homeostasis by overexpressed ras and bcl-2 predisposes to hyperplastic growth of the epidermis and to papilloma development and that these proteins with distinct mechanisms for oncogenesis are functionally synergistic for malignant transformation of chemically induced skin carcinogenesis. ^

Traumatisme craniocérébral, services de santé mentale et suicide de l'enfance à l'âge adulte : une étude épidémiologique et qualitative de la situation québécoise (1987 à 2013)

Introduction et recension des écrits : Récemment, les suicides de vétérans et d’athlètes professionnels ont attiré l’attention sur l’association entre le TCC et le suicide. Les lignes directrices concernant la prise en charge en santé mentale dans cette population demeurent fragmentaires. Les objectifs de cette thèse sont de 1) déterminer si une association existe entre le TCC subi dans l’enfance et le suicide futur, 2) explorer si les personnes qui se sont suicidées ont consulté un psychiatre dans l’année précédant le suicide et évaluer si cela diffère selon que la personne ait eu un TCC ou non, 3) décrire et qualifier l’offre québécoise de santé mentale offerte en réadaptation aux enfants et aux adultes ayant subi un TCC. Méthodologie : Le volet épidémiologique consiste en une étude de cohorte rétrospective sur un échantillon de 135 703 enfants ayant reçu des services médicaux au Québec en 1987 et suivis jusqu’en 2008. Le volet qualitatif comprend un sondage auprès des gestionnaires des programmes de réadaptation TCC du Québec, des groupes de discussion avec des cliniciens et des entrevues avec des survivants de TCC et leurs proches. Résultats : Notre étude épidémiologique confirme une association significative entre le TCC subi dans l’enfance (HR 1,49 IC95% 1,04- 2,14), dans l’adolescence (HR 1,57, IC 95% 1,09-2,26) et à l’âge adulte (HR 2,53, IC95% 1,79-3,59) et le suicide. Malgré un risque de suicide plus élevé, les personnes avec un TCC et qui se sont suicidées n’ont pas consulté de psychiatre plus fréquemment que les personnes sans TCC (OR 1,29, IC 95% 0,75- 2,24). Par ailleurs, notre étude qualitative révèle que les forces du système actuel incluent une bonne qualité des services, mais qu’il existe des faiblesses au niveau de l’accès aux médecins spécialisés, du dépistage systématique et de l’accès aux services à long terme. Nos recommandations incluent le développement d’une approche coordonnée en santé mentale, l’implication automatique d’un gestionnaire de cas et l’amélioration des mécanismes d’accès après le congé.

Host and Environmental Correlates of Multi-Drug Resistance in Kenyan Children with Acute Bacterial Diarrhea

Thesis (Master's)--University of Washington, 2016-06

Establishment of a PCR and restriction enzyme assay for the detection of the hemochromatosis gene in normal subjects and diabetic patients

The purpose of this study was to establish a polymerase chain reaction (PCR)-restriction enzyme assay for detecting the hereditary hemochromatosis (HHC) mutation, C282Y, in gestational and gestational diabetic subjects in South Florida. DNA samples from 43 gestational subjects were amplified by PCR, digested with RsaI, and analyzed by electrophoresis. An allelic frequency of 2.33%, or 4.65% heterozygosity, was observed. The assay is successful and applicable to future studies on HHC and gestational diabetes. ^

Preimplantation genetic diagnosis: Analysis of gene expression, nuclear DNA and cytoplasmic DNA

Preimplantation genetic diagnosis (PGD) following in vitro fertilization (IVF) offers couples at risk for transmitting genetic disorders the opportunity to identify affected embryos prior to replacement. In particular, embryo gender determination permits screening for X-linked diseases of unknown etiology. Analysis of embryos can be performed by polymerase chain reaction (PCR) amplification of material obtained by micromanipulation. This approach provides an alternative to the termination of an established pregnancy following chorionic villi sampling or amniocentesis. ^ Lately, the focus of preimplantation diagnosis and intervention has been shifting toward an attempt to correct cytoplasmic deficiencies. Accordingly, it is the aim of this investigation to develop methods to permit the examination of single cells or components thereof for clinical evaluation. In an attempt to lay the groundwork for precise therapeutic intervention for age related aneuploidy, transcripts encoding proteins believed to be involved in the proper segregation of chromosomes during human oocyte maturation were examined and quantified. Following fluorescent rapid cycle RT-PCR analysis it was determined that the concentration of cell cycle checkpoint gene transcripts decreases significantly as maternal age increases. Given the well established link between increasing maternal age and the incidence of aneuploidy, these results suggest that the degradation of these messages in aging oocytes may be involved with inappropriate chromosome separation during meiosis. ^ In order to investigate the cause of embryonic rescue observed following clinical cytoplasmic transfer procedures and with the objective of developing a diagnostic tool, mtDNA concentrations in polar bodies and subcellular components were evaluated. First, the typical concentration of mtDNA in human and mouse oocytes was determined by fluorescent rapid cycle PCR. Some disparity was noted between the copy numbers of individual cytoplasmic samples which may limit the use of the current methodology for the clinical assessment of the corresponding oocyte. ^

Evaluation of the cytotoxic and cytostatic activities of medicinal plants used by Peruvian healers against cancer-related symptoms

Twelve plants used medicinally in Callejon de Huaylas, Department of Ancash, northeastern Peru were selected and screened in vitro for cytotoxic and cytostatic activities. Traditional preparations, aqueous extracts and organic extracts (methanol:dimethyl chloride) were tested against murine leukemia P388 cells using flow cytometry. Seventy-five percent or more of the traditional and aqueous extracts were cytostatic at concentrations of 1mg/ml. For organic extracts, cytostatic activity ranged from 8.3% (at 6.25 μg/ml) to 58.3% (at 100 μg/ml). Quinchamalium procumbens, Ophryosporus chilca and Baccharis genistelloides showed strong activity. Extracts of Brachyotum rostratum, Monnina salicifolia, and Orthrosanthus chimboracensis were particularly interesting, since they were cytostatic but not cytotoxic at concentrations of 0.5 mg/ml. These Andean plants merit further analysis. The high percentage of activity found among the traditional preparations suggests that the traditional medical knowledge of Callejon de Huaylas healers deserves respect and merits further research. ^

Cytokine analysis in Atlantic bottlenose dolphins: Molecular characterization of IL-4, IL-6, and IL-10

The health status of wild and captive Atlantic Bottlenose dolphins ( Tersiops truncatis) is difficult to ascertain. Mass strandings of these animals have been attributed to pollutants, as well as bacterial infections. Using human Enzyme Linked Immuno-Assays (ELISA) for immunological cytokines, I measured soluble cytokine levels with respect to their health status. In a retrospective analysis of dolphin sera, there was a trend of higher cytokine levels in “sick” animals. I cultured dolphin lymphocytes in the presence of a mitogen (PHA), a super antigen (Staph-A), Lipopolysaccharide (LPS), and a calcium flux inducer (PMA). Levels of messenger RNA, from these cultured cells, were assayed with Polymerase Chain Reaction (PCR) using primers for the human cytokines IL-2, IL-4, IL-6, IL-10, Tumor Necrosis Factor, and Interferon gamma. Only IL-4, IL-6, and IL-10 messages were obtained, inferring similar nucleotide homology to the human primer sequences. The PCR products were sequenced. Sixteen IL-4 sequences, twelve IL-6 sequences and seven IL-10 sequences were obtained and analyzed. Each cytokine exhibited the same nucleotide sequence in all dolphins examined. There was no difference in the cytokine profile in response to the various stimuli. The derived amino acid composition for each of the dolphin cytokines was used for molecular modeling, which showed that dolphin IL-4, IL-6, and IL-10 were structurally similar to the corresponding proteins of Perissodactyla. ^

Risk factors of type 2 diabetes and cardiovascular diseases among Jamaican adolescents

Purpose. The purpose of the study was to examine Jamaican adolescents in a school setting, for risk factors of type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVDs). Methods. A descriptive epidemiological cross-sectional study of 276 Jamaican adolescents (112 males and 164 females) ages 14-19 years (15.6±1.2), randomly selected from grades 9-12 from ten high schools on the island. Thirteen risk factors were examined. Risk factors were compared with BMI levels and demographics. A sub-study validated finger prick testing of fasting blood glucose, total cholesterol, and HbA1c versus venous testing in 59 subjects. Results. Prevalence of overweight was 33.0% (n=91) with mean BMI of 23.74±7.74. Approximately 66.7% of subjects reported ≥ 3 risk factors. The number of T2DM and CVDs risk factors increased for subjects with BMI above 25. One third of the overweight subjects were classified with the metabolic syndrome. High BMI was associated with high waist circumference (r = .767, p < .01), high waist-to-hip ratio (r = .180, p < .01), presence of Acanthosis Nigricans (r = .657, p < .01), high total cholesterol (r = .158, p < .01), family history of T2DM (r = .157, p < .01), and hypertension (r = .422, p < .01). Regression analyses significantly predicted gender and physical activity (p < .001), and total number of risk factors for T2DM and CVDs (p < .001). Paired samples t-tests revealed no significant differences between methods of testing for TC and HbA1c (p < .01) but not for FBG (p > .05). Percentage bias for the methods of blood testing met the reference standards for fasting blood glucose but not for total cholesterol and HbA1c. Bland Altman tests of agreement between the two methods indicated good agreement for all three tests. Conclusion. Jamaican adolescents are at high risk for T2DM and CVDs as seen in other study populations. Effective programs to prevent T2DM and CVDs are needed. Family history of diseases, anthropometric measures, and gender identified more subjects at risk than did the biochemical measures. Comparison between finger prick and venous blood methods suggested that finger prick is an adequate method to screen for risk factors in children and adolescents.

Glycemic control: Risk factors, quality of life, workforce participation, and mortality among US adults with type 2 diabetes

Despite research showing the benefits of glycemic control, it remains suboptimal among adults with diabetes in the United States. Possible reasons include unaddressed risk factors as well as lack of awareness of its immediate and long term consequences. The objectives of this study were to, using cross-sectional data, (1) ascertain the association between suboptimal (Hemoglobin A1c (HbA1c) .7%), borderline (HbA1c 7-8.9%), and poor (HbA1c .9%) glycemic control and potentially new risk factors (e.g. work characteristics), and (2) assess whether aspects of poor health and well-being such as poor health related quality of life (HRQOL), unemployment, and missed-work are associated with glycemic control; and (3) using prospective data, assess the relationship between mortality risk and glycemic control in US adults with type 2 diabetes. Data from the 1988-1994 and 1999-2004 National Health and Nutrition Examination Surveys were used. HbA1c values were used to create dichotomous glycemic control indicators. Binary logistic regression models were used to assess relationships between risk factors, employment status and glycemic control. Multinomial logistic regression analyses were conducted to assess relationships between glycemic control and HRQOL variables. Zero-inflated Poisson regression models were used to assess relationships between missed work days and glycemic control. Cox-proportional hazard models were used to assess effects of glycemic control on mortality risk. Using STATA software, analyses were weighted to account for complex survey design and non-response. Multivariable models adjusted for socio-demographics, body mass index, among other variables. Results revealed that being a farm worker and working over 40 hours/week were risk factors for suboptimal glycemic control. Having greater days of poor mental was associated with suboptimal, borderline, and poor glycemic control. Having greater days of inactivity was associated with poor glycemic control while having greater days of poor physical health was associated with borderline glycemic control. There were no statistically significant relationships between glycemic control, self-reported general health, employment, and missed work. Finally, having an HbA1c value less than 6.5% was protective against mortality. The findings suggest that work-related factors are important in a person’s ability to reach optimal diabetes management levels. Poor glycemic control appears to have significant detrimental effects on HRQOL.^

Use of structural equation modeling to examine the association between breast cancer risk perception and repeat screening mammography among United States women

Breast cancer is the second leading cause of cancer death in United States women, estimated to be diagnosed in 1 out of 8 women in their lifetime. Screening mammography detects breast cancer in its pre-clinical stages when treatment strategies have the greatest chance of success, and is currently the only population-wide prevention method proven to reduce the morbidity and mortality associated with breast cancer. Research has shown that the majority of women are not screened annually, with estimates ranging front 6% - 30% of eligible women receiving all available annual mammograms over a 5-year or greater time frame. Health behavior theorists believe that perception of risk/susceptibility to a disease influences preventive health behavior, in this case, screening mammography The purpose of this dissertation is to examine the association between breast cancer risk perception and repeat screening mammography using a structural equation modeling (SEM) framework. A series of SEM multivariate regressions were conducted using self-reported, nationally representative data from the 2005 National Health Interview Survey. Interaction contrasts were tested to measure the potential moderating effects of variables which have been shown to be predictive of mammography use (physician recommendation, economic barriers, structural barriers, race/ethnicity) on the association between breast cancer risk perception and repeat mammography, while controlling for the covariates of age, income, region, nativity, and educational level. Of the variables tested for moderation, results of the SEM analyses identify physician recommendation as the only moderator of the relationship between risk perception and repeat mammography, thus the potentially most effective point of intervention to increase mammography screening, and decrease the morbidity and mortality associated with breast cancer. These findings expand the role of the physician from recommendation to one of attenuating the effect of risk perception and increasing repeat screening. The long range application of the research is the use of the SEM methodology to identify specific points of intervention most likely to increase preventive behavior in population-wide research, allowing for the most effective use of intervention funds.^

Immunomodulation by shark cartilage extracts

The immune system is composed of innate and adaptive mechanisms. Innate immune responses are significantly modulated by immunomodulatory factors that act through the induction of specific patterns of cytokine production in responding cells. Human leukocytes have been shown to respond to substance(s) present in acid extracts of commercial shark cartilage (SC). Shark cartilage is a food supplement taken by consumers as a prophylaxis and for the treatment of conditions ranging from arthritis to cancer. No reliable scientific evidence in the literature supports the alleged usefulness of shark cartilage supplements, but their use remains popular. Cartilage extracts exhibit immunomodulatory properties by inducing various inflammatory, Th1-type cytokines and potent chemokines in human peripheral blood leukocytes (HPBL) in vitro. The objectives of the study were to (1) to determine the nature of the active component(s), (2) to define the scope of cellular response to SC extract, and (3) to elucidate the molecular mechanisms underlying bioactivity. Results showed that there are at least two cytokine-inducing components which are acid stable. One anionic component has been identified as a small (14-21 kDa) glycoprotein with at least 40% carbohydrate content. Shark cartilage stimulated HPBL to produce cytokines resembling an inflammatory, Th1 polarized response. Leukocyte-specific responses consist of both initial cytokine responses to SC directly (i.e., TNF-α) and secondary responses such as the IFN-γ response by lymphocytes following initial SC stimulation. Response of RAW cells, a murine macrophage cell line, indicated that TNF-á could be induced in macrophages of another mammalian species in the absence of other cell types. The results suggest that the human monocyte/macrophage is most likely to be the initial responding cell to SC stimulation. Stimulation of cells appears to engage at least one ligand-receptor interaction with TLR 4, although the role of TLR 2 cannot be ruled out. Initial activation is likely followed by the activation of the JNK and p38 MAPK signal transduction pathways resulting in activation, release, and translocation of transcription factor nuclear factor κB (Nf-κB). This dissertation research study represents the first in-depth study into characterizing the bioactive component(s) of commercial shark cartilage responsible for its immunomodulating properties and defining cellular responses at the molecular level.

Anti-diarrheal plants of central Anatolia: Do they inhibit diarrhea-causing bacteria?

Infectious diarrhea results in 2 to 5 million deaths worldwide per year, and treatments that are safe, effective, and readily available are under investigation. The field of medicinal ethnobotany focuses on plants that are used by different cultural groups for treating various diseases and evaluates these plants for efficacy and cytotoxicity. In the present study, ethnobotanical research was conducted with Central Anatolian villagers in Turkey. Folk concepts and etiologies surrounding diarrhea were analyzed, as were salient plant-based remedies for diarrhea. Reviewing the literature, 91 plant species were described as anti-diarrheal in all of Turkey. In Central Anatolia, villagers described 35 species. For continued research via bactericidal and bacteriostatic bioassays, 15 plants were selected. Methanolic and aqueous extracts of medicinally used plant parts were evaluated for inhibitory properties against 10 diarrhea-causing bacteria in the first bioassay, and later 21 bacteria in a second assay utilizing spectrophotometry. The cytotoxic properties were also evaluated in an Alamar Blue Assay using HepG-2, PC-3, and SkMEL-5 human cell lines. While several extracts showed bactericidal and bacteriostatic properties, the methanolic extract of R. canina galls inhibited the most bacteria at the lowest concentrations. They were not cytotoxic. Thus, R. canina methanolic gall extracts were selected for bio-assay guided fractionation. Antibacterial activity was maintained in the third fraction which was composed of almost pure ellagic acid. The bioassay was repeated with standard ellagic acid, and the polyphenol retained potency in inhibiting multiple bacterial strains. Several other extracts showed promise for safe, effective anti-bacterial remedies for diarrhea.

Black band disease: Elucidating origins and disease mechanisms

Coral diseases were unknown in the scientific community fifty years ago. Since the discovery of a coral disease in 1965, there has been an exponential increase in the number of known coral diseases, as the abundance, prevalence, distribution, and number of host species affected has also significantly increased. Coral diseases are recognized as contributing significantly to the dramatic losses of coral cover on a global basis, particularly in the Caribbean. The apparent sudden emergence of coral diseases suggests that they may be a symptom of an overall trend associated with changing environmental conditions. However, not much evidence has been gathered to address this question. The following studies were designed to build a comprehensive argument to support this hypothesis for one important coral disease—black band disease (BBD). A meta-analysis of clone libraries identifying the microbial communities associated with BBD reveal important information including that a single cyanobacterial operational taxonomic unit (OTU) was by far the most prevalent OTU in diseased samples, and that the alphaproteobacteria, which include some of the most common bacteria in marine waters, were the most diversely represented. The analysis also showed that samples exhibited regional similarities. An fine and ultrastructural characterization of the disease revealed that the cyanobacteria are prolific borers through the coral skeleton, and that the cyanobacteria penetrate coral tissue, leading to their presence ahead of the main migrating disease band. It was further found that apparently healthy corals exposed to toxins found in BBD, exhibited similar tissue degradation to those infected with BBD. Comparing the disease progression to biofilm formation, it was determined that scouting cyanobacteria may contribute to the migration of the disease through progressive biofilm development over intact coral tissue. Together, these studies provide significant evidence for the hypothesis that BBD is an opportunistic disease, caused by common environmental bacteria, facilitated by the changing environmental conditions associated with climate change.

Aedes aegypti pharate first instar aseasonal quiescence cues anticipatory plasticity with implications for urban vector ecology and control

The eggs of the dengue fever vector Aedes aegypti possess the ability to undergo an extended quiescence period hosting a fully developed first instar larvae within its chorion. As a result of this life history stage, pharate larvae can withstand months of dormancy inside the egg where they depend on stored reserves of maternal origin. This adaptation known as pharate first instar quiescence, allows A. aegypti to cope with fluctuations in water availability. An examination of this fundamental adaptation has shown that there are trade-offs associated with it. ^ Aedes aegypti mosquitoes are frequently associated with urban habitats that may contain metal pollution. My research has demonstrated that the duration of this quiescence and the extent of nutritional depletion associated with it affects the physiology and survival of larvae that hatch in a suboptimal habitat; nutrient reserves decrease during pharate first instar quiescence and alter subsequent larval and adult fitness. The duration of quiescence compromises metal tolerance physiology and is coupled to a decrease in metallothionein mRNA levels. My findings also indicate that even low levels of environmentally relevant larval metal stress alter the parameters that determine vector capacity. ^ My research has also demonstrated that extended pharate first instar quiescence can elicit a plastic response resulting in an adult phenotype distinct from adults reared from short quiescence eggs. Extended pharate first instar quiescence affects the performance and reproductive fitness of the adult female mosquito as well as the nutritional status of its progeny via maternal effects in an adaptive manner, i.e., anticipatory phenotypic plasticity results as a consequence of the duration of pharate first instar quiescence and alternative phenotypes may exist for this mosquito with quiescence serving as a cue possibly signaling the environmental conditions that follow a dry period. M findings may explain, in part, A. aegypti's success as a vector and its geographic distribution and have implications for its vector capacity and control.^

Social capital, HIV risk behavior and substance use among recent Latino immigrants in South Florida

Social capital, or social cohesion or group connectedness, can influence both HIV risk behavior and substance use. Because recent immigrants undergo a change in environment, one of the consequences can be a change in social capital. There may be an association among changes in social capital, and HIV risk behavior and substance use post immigration. The dissertation focused on the interface of these three variables among recent Latino immigrants (RLIs) in South Florida. The first manuscript is a systematic review of social capital and HIV risk behavior, and served as a partial background for the second and third manuscripts. Twelve papers with a measure of social capital as an independent variable and HIV risk as the dependent variable were included in the analysis. Eleven studies measured social capital at the individual level, and one study measured social capital at the group level. HIV risk was influenced by social capital, but the type of influence was dependent on the type of social capital and on the study population. Cognitive social capital, or levels of collective action, was protective against HIV in both men and women. The role of structural social capital, or levels of civic engagement/group participation, on HIV risk was dependent on the type of structural social capital and varied by gender. Microfinance programs and functional group participation were protective for women, while dysfunctional group participation and peer-level support may have increased HIV risk among men. The second manuscript was an original study assessing changes in social capital and HIV risk behavior pre to post immigration among RLIs in South Florida (n=527). HIV risk behavior was assessed through the frequency of vaginal-penile condom use, and the number of sexual partners. It was a longitudinal study using secondary data analysis to assess changes in social capital and HIV risk behavior pre immigration to two years post immigration, and to determine if there was a relationship between the two variables. There was an 8% decrease in total social capital (p < .05). Reporting of 'Never use' of condoms in the past 90 days increased in all subcategories (p < .05). Single men had a decrease in number of sexual partners (p < .05). Lower social capital measured on the dimension of 'friend and other' was marginally associated with fewer sexual partners. The third manuscript was another original study looking at the association between social capital and substance use among RLIs in South Florida (n=527). Substance use with measured by frequency of hazardous alcoholic drinking, and illicit drug use. It was a longitudinal study of social capital and substance-use from pre to two years post immigration. Post-immigration, social capital, hazardous drinking and illicit drug use decreased (p<.001). After adjusting for time, compared to males, females were less likely to engage in hazardous drinking (OR=.31, p<.001), and less likely to engage in illicit drug use (OR=.67, p=.01). Documentation status was a moderator between social capital and illicit drug use. 'Business' and 'Agency' social capital were associated with changes in illicit drug use for documented immigrants. After adjusting for gender and marital status, on average, documented immigrants with a one-unit increase in 'business' social capital were 1.2 times more likely to engage in illicit drug use (p<.01), and documented immigrants with one-unit increase in 'agency' social capital were 38% less likely to engage in illicit drug use (p<.01). 'Friend and other' social capital was associated with a decrease in illicit drug use among undocumented immigrants. After adjusting for gender and marital status, on average, undocumented immigrants with a one-unit increase in 'friend and other' social capital were 45% less likely to engage in hazardous drinking and 44% less likely to use illicit drugs (p<.01, p<.05). Studying these three domains is relevant because HIV continues to be a public health issue, particularly in Miami-Dade County, which is ranked among other U.S. regions with high rates of HIV/AIDS prevalence. Substance use is associated with HIV risk behavior; in most studies, increased substance use is associated with increased chances of HIV risk behavior. Immigration, which is the hypothesized catalyst for the change in social capital, has an impact on the dynamic of a society. Greater immigration can be burdensome on the host country's societal resources; however immigrants are also potentially a source of additional skilled labor for the workforce. Therefore, successful adaption of immigrants can have a positive influence on receiving communities. With Florida being a major receiver of immigrants to the U.S, this dissertation attempts to address an important public health issue for South Florida and the U.S. at large.