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Design Of Novel Inhibitors For Infectious Diseases Using Structure-Based Drug Design: Virtual Screening, Homology Modeling And Molecular Dynamics, Divya Ramamoorthy

USF Tampa Graduate Theses and Dissertations

The main aim of the study in this thesis was to use structure-based protocols to design new drugs for enzymes, DXS and DXR in the non mevalonate pathway. Another aim of this study was to identify the dimer interface in E.coli FabH as an allosteric binding site for designing new class of anti-infective drugs. We have attempted to identify potential inhibitors for DXS by docking the NCI Diversity set compounds, compound libraries available from GSK-MMV and St. Jude's Children's research center. FabH dimer interface has been identified as a potential target using SiteMap, Alanine mutagenesis and docking studies.

The first …

Perceived Barriers For Implementing Primary Sexually Transmitted Infection Prevention, Rachel Monique Stewart-Campbell

USF Tampa Graduate Theses and Dissertations

Adolescents continue to be at increased risk for contracting sexually transmitted infections (STI's). This research study describes the perception of barriers that providers in the Tampa Bay area encounter when implementing primary STI prevention programs for adolescents within the community context. This study used semi structured interviews to explore perceived barriers for implementing primary such programs for adolescents in the Tampa Bay area programs. Participants reported faith based institutions/churches and schools as common sectors for presenting a variety of barriers for implementing their program. Perceptions of barriers were described as, the need to tailor program messages and presentations based on …

The Yellow Flag Of Quarantine: An Analysis Of The Historical And Prospective Impacts Of Socio-Legal Controls Over Contagion, Peter Oliver Okin

USF Tampa Graduate Theses and Dissertations

Under the ancient threat of morbidity and mortality from infectious diseases, human societies have responded for thousands of years by imposing social containment measures. Even before theorists and laymen recognized the existence of pathogenic organisms, or fully understood the principles of contagion, many societies and individuals did empirically infer that such diseases were transmissible from human to human (as well as sometimes between animals and humans). Having few effective technological measures to prevent or treat contagions, they did devise a variety of socio-behavioral procedures for separating overtly ill persons or suspected disease-carriers from nominally uninfected people. These methods included various …

Occupational Stressors Among Providers Of Hiv Prevention And Support Services, Mackenzie Kaye Rapp

USF Tampa Graduate Theses and Dissertations

Much literature has documented the high levels of burnout, stress, and grief in HIV physicians and nurses due to the challenging nature of the chronic, fatal disease with which they deal on a daily basis. Providers of social and HIV prevention services face similar challenges while working with stigmatized, terminally ill clients. However, since these latter occupations deal with social, rather than clinical interventions, their experiences may differ from those of medical personnel. Through open-ended interviews with HIV counselors, educators, case managers, and outreach workers, this exploratory study assesses the occupational stressors of providers of social and HIV prevention services …

Stochastic Modeling Of Network-Centric Epidemiological Processes, Divine Wanduku

USF Tampa Graduate Theses and Dissertations

The technological changes and educational expansion have created the heterogeneity in the human species. Clearly, this heterogeneity generates a structure in the population

dynamics, namely: citizen, permanent resident, visitor, and etc. Furthermore, as the heterogeneity in the population increases, the human mobility between meta-populations patches

also increases. Depending on spatial scales, a meta-population patch can be decomposed into sub-patches, for examples: homes, neighborhoods, towns, etc. The dynamics of human

mobility in a heterogeneous and scaled structured population is still its infancy level. We develop and investigate (1) an algorithmic two scale human mobility dynamic model for a meta-population. Moreover,the two …

Therapeutic Peptide-Based Vaccination Strategies Against Hpv-Induced Cancers, Kelly Barrios Marrugo

USF Tampa Graduate Theses and Dissertations

There is an urgent need for the development of an effective therapeutic vaccine against cancer caused by human papilloma virus (HPV). We focused on HPV-induced malignancies because of their high worldwide prevalence (e.g., cervical carcinoma and head & neck cancer). A successful therapeutic vaccine could prevent the 250 000 deaths/year worldwide and the 2.25 billion dollars that

are expended in related care in the US.

We used an HPV-induced mouse cancer model to test vaccines

composed of a CD8 T cell peptide epitope administered with potent adjuvants designed to generate vast numbers of high avidity cytotoxic T lymphocytes specific for …

Behavioral And Immunological Phenotypes Of Transgenic Mice Overexpressing Human Secreted Amyloid Precursor Protein Alpha: Implications For Autism, Antoinette R. Bailey

USF Tampa Graduate Theses and Dissertations

Autism is a heterogeneous neurodevelopmental disorder that is characterized by impaired social interaction and communication as well as restricted and repetitive behaviors and focused interests. In addition to the cardinal behavioral characteristics observed for diagnosis, autistic individuals exhibit a number of comorbid conditions as well as a variety of aberrant immunological features. Recent studies report that plasma from autistic children contained elevated levels of secreted amyloid precursor protein alpha (sAPP-á), the á-secretase cleavage product of the amyloid precursor protein (APP) which is ubiquitously expressed in the brain, spleen, thymus and other organs. Interestingly, the sAPP-á fragment functions as a neurotrophic …

Drug Discovery From Floridian Mangrove Endophytes, Jeremy Beau

USF Tampa Graduate Theses and Dissertations

A significant challenge of the 21st century is the growing health threat stemming from drug-resistant infectious diseases. There is an undeniable need to discover new, safe and effective drugs with novel mechanisms of action to combat this threat. A study of drugs currently on the market showed that natural products account for approximately 75% of new anti-infective drugs, either as new agents or analogs based upon their structure. Unfortunately, major pharmaceutical companies have cut back tremendously in natural products research in part due to the frustrating obstacle of frequent rediscovery of compounds. Fungi in particular are difficult to work with …

The Effects Of Food Insecurity On Mental Wellbeing In Monteverde Costa Rica, Robert Eugene Cowherd

USF Tampa Graduate Theses and Dissertations

The rapid expansion of ecotourism in the Monteverde zone of Costa Rica has increased the incidence in food insecurity in the area. Changes in food preferences and availability have led to a more homogenized diet that is increasingly delocalized and reliant on processed foods. Additionally, there has been a rapid economic shift away from agricultural and dairy farming to an economy more reliant on tourism. This NSF supported study builds upon data from a longitudinal investigation (#BNS 0753017) examining the nutritional effects of this rapid economic transition. Using a mixed methods approach, a culturally appropriate scale of stress was developed …

Lenalidomide Targets The T-Cell Co-Stimulatory Pathway To Mediate Immune Modulation, Jessica Marie Mcdaniel

USF Tampa Graduate Theses and Dissertations

T-cells are lymphocytes that make up part of the adaptive arm of the immune system, and are essential for efficient protection from and eradication of viruses and pathogens. T-cells not only play an important role in protection from external agents, but also regulate and prevent activation towards self-peptides and detect and remove erratically growing cells. Alterations in T-cell activation and suppression contribute to auto-immunity, immunocompromised disorders, and cancer progression.

The immune system, and T-cells in particular, provides daily surveillance, recognition and destruction of aberrant cells. Although the immune system is proficient at suppressing malignant progression, tumor cells acquire various methods …

A Novel Device And Nanoparticle-Based Approach For Improving Diagnosis And Treatment Of Pelvic Inflammatory Disease, Natasha Faith Cover

USF Tampa Graduate Theses and Dissertations

Pelvic Inflammatory Disease (PID) is one of the most common causes of morbidity in women. PID is a polymicrobial infection of the female reproductive tract, and is associated with pelvic pain, abnormal uterine bleeding, and tubal damage that can lead to ectopic pregnancies and infertility. It is curable but the effects of PID can be permanent if not properly diagnosed and treated. PID presents as a spectrum of disease and is often missed at early stages; even acute PID can be difficult to diagnose, as there is no single conclusive diagnostic test. Currently, PID is identified and treated syndromically because …

Dengue Fever In Tegucigalpa, Honduras: Use Of The Explanatory Model In A Sample Of Urban Neighborhoods To Contextualize And Define Dengue Fever Among Community Participants, Jose Enrique Hasemann

USF Tampa Graduate Theses and Dissertations

This project elucidated the explanatory model of dengue fever held by members of urban communities in Tegucigalpa, Honduras. The study was conducted over a four-month period from May-August of 2011, and it was divided into two stages. The first stage of the project consisted of volunteer participation with dengue fever surveillance brigades in the three communities with the highest incidence of dengue fever during the beginning of 2011. This initial stage employed participant observation as its research method. The second stage was conducted in a different community within Tegucigalpa. The primary research methods employed during the second stage of the …

The Holistic Complementary Structure Of Western Bio-Medicine And Traditional Healing And Achieving Complete Health, Candace Gail Oubre

USF Tampa Graduate Theses and Dissertations

Achieving complete health requires a deep understanding of complementary cultural competency sensitivity between physician and patient. This may include but is not limited to access to preventative health care resources, access to health educational resources and access to cultural healing resources, for example, shamans, Ayurvedic physicians, and herbal healers. Advocates of cultural competency emphasize great importance on knowledge of the patients' cultural background; however, the transcendence of this knowledge can be explained further through complementary cultural competency sensitivity. This is when the cultures of the physician and patient complement each other in terms of understanding what is in the patients' …

Characterization Of The Serologic Responses To Plasmodium Vivax Dbpii Variants Among Inhabitants Of Pursat Province, Cambodia, Samantha Jones Barnes

USF Tampa Graduate Theses and Dissertations

The Plasmodium vivax Duffy Binding Protein (DBP) is the ligand in the major pathway for P. vivax invasion of human reticulocytes, making it an appealing vaccine candidate. Region II of DBP (DBP-RII) is the minimal portion of the ligand that mediates recognition of the Duffy Antigen Receptor for Chemokines (DARC receptor) on the reticulocyte surface and constitutes the primary vaccine target. Analysis of natural variation in the coding sequences of DBP-RII revealed signature evidence for selective pressure driving variation in the residues of the putative receptor-binding site. We hypothesize that anti-DBP immunity in P. vivax infections is strain-specific and hindered …

Modeling And Surveillance Of Pandemic Influenza Outbreaks, Diana Prieto

USF Tampa Graduate Theses and Dissertations

Pandemic outbreaks are unpredictable as to their virus strain, transmissibility, and impact on our quality of life. Hence, the decision support models for mitigation of pandemic outbreaks must be user-friendly and operational, and also incorporate valid estimates of disease transmissibility and severity. This dissertation research is aimed at 1) reviewing the existing pandemic simulation models to identify their implementation gaps with regard to usability and operability, and suggesting research remedies, 2) increasing operability of simulation models by calibrating them via an epidemiological model that estimates infection probabilities using viral shedding profiles of concurrent pandemic and seasonal influenza, and 3) developing …

Decision Aid Models For Resource Sharing Strategies During Global Influenza Pandemics, Alfredo Santana Reynoso

USF Tampa Graduate Theses and Dissertations

Pandemic influenza outbreaks have historically entailed significant societal and economic disruptions. Today, our quality of life is threatened by our inadequate preparedness for the imminent pandemic. The key challenges we are facing stem from a significant uncertainty in virus epidemiology, limited response resources, inadequate international collaboration, and the lack of appropriate science-based decision support tools. The existing literature falls short of comprehensive models for global pandemic spread and mitigation which incorporate the heterogeneity of the world regions and realistic travel networks. In addition, there exist virtually no studies which quantify the impact of resource sharing strategies among multiple countries. This …

Tarnished Golden Years: Older Offenders With Mental Health Problems And Late Life First Time Offenders, Brianne Stanback

USF Tampa Graduate Theses and Dissertations

Older offenders (offenders 50 years and older) are a distinct groups within the U.S. correctional system. Studies 1 and 2 were intended to investigate mental health and stressors among jailed older offenders.

Study 1 examined the prevalence rates of mental health disorders and explored the relationship between mental health disorders and stressors. Participants 50 years and older (N=330) from the 2002 wave of the Survey of Inmates in Local Jails (SILJ) were studied via descriptive analysis, factor analysis, and a logistic regression to determine which variables were related to the probability of having a mental health problem. 65.8% of participants …

Development Of An Elisa For Eastern Equine Encephalitis Virus That Can Differentiate Infected From Vaccinated Horses, Andrea Bingham

USF Tampa Graduate Theses and Dissertations

Eastern Equine Encephalitis virus (EEEV) causes a fatal mosquito-borne virus that is vaccine preventable for horses. The conventional serological tests measure antibodies to the structural proteins of EEEV which are also found in the vaccine. This makes it difficult to differentiate infected and vaccinated animals (DIVA). Detection of antibodies to non-structural proteins (NSPs) is a theoretical strategy that would allow you to survey natural infections among vaccinated populations. This test would also allow for more accurate representations of the natural infection rate, vaccination rate, and help identify vaccine failures. The potential uses of the NSPs of Eastern Equine Encephalitis virus …

Natural Product Drug Discovery Against Tropical Diseases, Wai Sheung Ma

USF Tampa Graduate Theses and Dissertations

This dissertation describes the isolation of secondary metabolites from natural origins through a series of chromatographic techniques and spectrometric characterization in the effort of drug discovery. The isolated compounds obtained were used as drug leads against tropical diseases, namely malaria and leishmaniasis. While first chapter offers an introduction on the use of a natural product by itself as an effective therapeutic and its role on inspiring the discovery of new drugs, the later chapters will concentrate on isolation and characterization of bioactive natural products from an Antarctic sponge and mangrove endophytic fungi during the dissertation work.

The second chapter describes …

Understanding The Psychosocial Aspects Of Waterpipe Smoking Among College Students, Mary Pautler Martinasek

USF Tampa Graduate Theses and Dissertations

Waterpipe tobacco smoking has migrated from being a custom of some cultures to becoming a staple around college campuses. The social nature and flavored tobacco encourage initiation in this tobacco naïve age group.

The study was a sequential mixed method design, employing primary data collection and analysis of a random sample of university students who live on campus at a single university. The study involved observations (N=6), intercept interviews with smokers and nonsmokers (N=63), three focus groups (N=31), and an online survey (N=288).

Findings were centered on the constructs of the Theory of Reasoned Action by Ajzen and Fishbein (1975), …

The Role Of Hiv-1 Proteins In Alzheimer's Disease Pathology, Brian Nelson Giunta

USF Tampa Graduate Theses and Dissertations

Prevalence of HIV-associated cognitive impairment is rising, the worst form of which is HIV-associated dementia (HAD). The disease is fuiled by a chronic innate type pro-inflammatory response in the brain which is highly dependent upon the activation of microglia. We first created an in vitro model of HAD composed of cultured microglial cells synergistically activated by the addition of IFN-gamma and the HIV-1 coat glycoprotein, gp120. This activation, as measured by TNF-alpha and NO release, is synergistically attenuated through the alpha7nAChR and p44/42 MAPK system by pretreatment with nicotine, and the cholinesterase inhibitor, galantamine. As these medications have been FDA …

Synthesis And Antimicrobial Activities Of S,S'-Heterosubstituted Disulfides, Praveen Ramaraju

USF Tampa Graduate Theses and Dissertations

Antibiotic resistance is a particularly critical health concern and has increased dramatically over the past two decades. For over a decade the Turos laboratory has been designing small molecules to target pathogenic microbes such as Staphylococcus aureus and the resistant variants like methicillin-resistant Staphylococcus aureus (MRSA). Previously, N-thiolated Β-lactams, N-thiolated 2-oxazolidinones and aromatic disulfides that were synthesized in Dr. Turos' lab have shown strong activity against these bacteria. The present work describes the synthesis and antimicrobial activities of a related structural class called S,S'-heterosubstituted disulfides. For ages, sulfur (elemental) has been used as an antibacterial for controlling infestation and bacterial …

Generation And Application Of Antigen-Specific Induced Regulatory T Cells In Allogeneic Bone Marrow Transplantation, Kenrick Semple

USF Tampa Graduate Theses and Dissertations

CD28 co-stimulation is required for the generation of naturally occurring regulatory T cells (nTregs) in the thymus through Lck-signaling. However, high level of CD28 suppresses the generation of induced Tregs (iTregs) from naïve CD4 T cells, although underlying mechanism(s) has not been defined. Here we investigated the role of CD28-mediated signaling pathways in the suppression of Treg generation. We used a series of transgenic (Tg) mice on CD28-deficient background that bears WT CD28 or mutated CD28 in its cytosolic tail incapable of binding to Lck, PI3K or Itk. Regardless of exogenous IL-2, strong CD28 costimulation suppressed iTreg generation through Lck …

Novel Roles For The Transcriptional Repressor Prdm1 In Human Natural Killer Cells And Identification Of An Inhibitor Of Its Interacting Methyltransferase G9a, Matthew Adams Smith

USF Tampa Graduate Theses and Dissertations

The studies presented within this dissertation provide the first description of PRDM1 (also known as Blimp-1 or PRDI-BF1) function in natural killer cells. NK cells are major effectors of the innate immune response via antigen-independent cytotoxicity and link to the adaptive immune response through cytokine release. Molecular mechanisms mediating NK activation are relatively well-studied; however, much less is known about the mechanisms that restrain activation.

In the first study, the transcriptional repressor PRDM1 is shown to be a critical negative regulator of NK function. Microarray analysis was used to characterize transcriptional changes associated with cytokine-mediated activation. PRDM1 is expressed at …

Growing Up With Hiv: Disease Management Among Perinatally Infected Adolescents, Barbara J. Szelag

USF Tampa Graduate Theses and Dissertations

Children born with HIV in the 1980s and 1990s are surviving into adolescence and adulthood, due to the availability of highly active antiretroviral therapy (HAART). Growing up with a chronic and stigmatized disease presents considerable challenges as young people explore their sexuality, develop relationships, and take steps to become independent and productive adults. Adherence to HAART is an essential and life-long practice for the maintenance of health and longevity. For adolescents born with HIV, a daily medication schedule is one aspect of disease management that also includes medical visits, HIV status acceptance, bouts of illness, and disclosure of HIV status …

Assessment Of Fertility Potential In Bottlenose Dolphins (Tursiops Truncatus): An Elisa-Based Biomarker Analysis, Leslie Schwierzke Wade

USF Tampa Graduate Theses and Dissertations

As apex predators in coastal systems, bottlenose dolphins (Tursiops truncatus) are susceptible to persistent organic pollutant (POP) accumulation and retention over time, which has prompted continued interest in understanding the extent to which contaminant body burdens or other stressors are sufficient to cause adverse sublethal effects on energetic fitness, immune function, or reproduction. Increasing our knowledge of reproductive endocrinology in bottlenose dolphins may provide insight into changes in reproductive rates, thereby expanding the capacity to assess conservation status. This study used the Enzyme-Linked ImmunoSorbent Assay (ELISA) technique to examine peptide fertility hormones [inhibin A, inhibin B and anti-Müllerian …

Sharps Injuries In Medical Training: Higher Risk For Residents Than For Medical Students, Rachel Williams

USF Tampa Graduate Theses and Dissertations

Because of their relative inexperience in performing procedures and handling sharps devices, medical students and resident physicians are considered to be at high risk for sharps injuries. A higher rate of sharps injuries for medical trainees implies a higher risk for occupationally-acquired infection with bloodborne pathogens and may have financial and legal implications for training institutions. This study examines the prevalence of sharps injuries among US medical students and resident physicians. A systematic review of the literature yielded 10 studies that gave data on sharps injuries for US medical students or residents, and those data were combined with data from …

Assessing The Relationship Of Monocytes With Primary And Secondary Dengue Infection Among Hospitalized Dengue Patients In Malaysia, 2010: A Cross-Sectional Study, Benjamin Glenn Klekamp

USF Tampa Graduate Theses and Dissertations

Dengue, a group of four similar viruses transmitted through the bite of a mosquito, is estimated to infect upwards of 100 million annually in over 100 nations throughout the global equatorial belt. Distribution of global dengue is highly skewed as Southeast Asian and Western Pacific regions endure 75% of the global dengue burden. Similar to other regional countries, Malaysia has been rapidly urbanizing, which has supported a hyperendemic dengue state.

The biological pathway by which dengue infection causes a wide range of clinical manifestations, spanning asymptomatic to life-threatening severe complications, is not comprehensively understood. Historically, severe dengue complications have primarily …

Evaluating The Get Into Fitness Today (Gift) Program: Weight Loss And The Roles Of Education And Empowerment, Emily Koby Novicki

USF Tampa Graduate Theses and Dissertations

This study investigated the effects of Get Into Fitness Today (GIFT), a health program for adults that promotes balanced nutrition, physical activity, and weight loss through weekly meetings that provide education and social support. In addition to investigating the effects of GIFT, this evaluation sought to better understand explanatory models used by participants and program staff, and the roles of education and empowerment in weight loss and health education. This mixed methods, case study evaluation consisted of quantitative analysis of existing program records for 664 participants, 40 hours of participant observation of class sessions with ten GIFT groups, and follow-up …

Environmental Health In The Latin American And Caribbean Region: Use Of Water Storage Containers, Water Quality, And Community Perception, Erlande Omisca

USF Tampa Graduate Theses and Dissertations

Water quality and availability are important issues in many developing countries where portions of populations still lack access to potable water. Throughout the English-speaking Caribbean and parts of Latin America, households and businesses invest in water supply systems even when they are connected to and pay for water services from a private or state owned provider. Inconsistent supplies of water from the water companies have led many people to invest in storage tanks which, if operated correctly, can provide water throughout the day even when the supply from the main is low or zero. While these individual systems help to …