Medicine and Health Sciences Commons^™

Resolution Of Inflammation Rescues Axon Initial Segment Disruption, Nicholas M. George

Theses and Dissertations

Axonal domains are required for proper neuron function. These domains are unstable and degenerate concurrent with the inflammation in multiple sclerosis (MS) and the inflammatory disease models experimental autoimmune encephalomyelitis (EAE) and lipopolysaccharide (LPS) induced inflammation. Previous studies from our laboratory have shown that the axon initial segment (AIS) is maintained independently of the presence of myelin, but that AIS disruption is seen in MS as well as EAE and LPS-mediated inflammation. AIS loss can be interrupted in the early stage of EAE using the anti-inflammatory drug Didox. However, the potential for Didox directed repair of the AIS in later …

Sulfated Dehydropolymer Of Caffeic Acid For Repair Of Lung Damage And Emphysema, Tien M. Truong

Theses and Dissertations

The complex pathobiologic mechanisms of emphysema are not fully understood, leaving this deadly disease without effective pharmacotherapy for a cure. This project hypothesized that the sulfated dehydropolymer of caffeic acid (CDSO3) exhibits Fe²⁺ chelation-based hypoxia inducible factor-1a (HIF-1a) up-regulatory protective activities against in vitro emphysematous cell death and for in vivo reversal of emphysema induced with SU5416, a vascular endothelial growth factor blocker.

Using in vitro chromogenic competitive inhibition assays, CDSO3 was shown to chelate Fe²⁺ (IC₅₀ of 23 µM), but not Fe³⁺ ions. The trypan blue exclusion and lactate

dehydrogenase assays were then employed to …

Methcathinone Analogue Activity At The Human Serotonin Transporter, William Drake Varn

Theses and Dissertations

In the last few years, there has been continued concern about synthetic drug abuse in both the United States and worldwide. Small adjustments in drug compound structure often allow synthetic drug makers to manufacture a legal product that can produce the same highs as illegal counterparts. Unfortunately, this is happening faster than the government can outlaw the drug compounds, and a wide variety of synthetics are now appearing on the street. This study evaluated the effects on the human serotonin transporter of six different 4-para substituted methcathinone compounds. Using a Xenopus oocyte model, the efficacy of each MCAT analogue …

Examining Genetic And Environmental Influences On Alcohol Use And Externalizing Behaviors In African American Adolescents, Neeru Goyal

Theses and Dissertations

The aim of this thesis is to expand our understanding of the etiology of alcohol misuse and related disorders in African Americans using genetically informative study designs. Specifically, we take advantage of the candidate-gene approach and polygenic score analysis to extend the literature specific to African American populations. Chapter 2 explores gene x environment (GxE) interactions through the candidate gene approach to explore the relationship between two genes chosen on their potential relevance to stress response and adolescent alcohol use and misuse, among African American youth living in highly impoverished neighborhoods, as moderated by stressful life events. Chapter 3 implements …

Quantitative Analysis Of 5-Chloro-2-Methoxy-N-[2-(4-Sulfamoylphenyl)Ethyl]Benzamide (Glyburide Analogue, Ga) In Mouse Plasma And Whole Blood Using A Micro-Extraction And Liquid Chromatography-Tandem Mass Spectrometry, Ankit Zalavadia

Theses and Dissertations

Pharmacokinetic evaluation of 5-chloro-2-methoxy-N-[2-(4- sulfamoylphenyl)ethyl]benzamide in mouse plasma demanded for a suitable bioanalytical method. No reported bioanalytical method exists to-date that can quantify concentration of this compound in any biological matrix. The purpose of this study was 1) to develop and validate a new bioanalytical method using a micro-extraction and LC-MS/MS to quantify the target analyte in mouse plasma and 2) to partially validate the method in whole blood. A bioanalytical method was developed and validated in both matrices for a linear concentration range of 2-1000 ng/ml. For both matrices, the reverse predicted concentration of calibration standards (-8.95% to 12.16% …

Response Adaptive Randomization Using Surrogate And Primary Endpoints, Hui Wang

Theses and Dissertations

In recent years, adaptive designs in clinical trials have been attractive due to their efficiency and flexibility. Response adaptive randomization procedures in phase II or III clinical trials are proposed to appeal ethical concerns by skewing the probability of patient assignments based on the responses obtained thus far, so that more patients will be assigned to a superior treatment group. General response-adaptive randomizations usually assume that the primary endpoint can be obtained quickly after the treatment. However, in real clinical trials, the primary outcome is delayed, making it unusable for adaptation. Therefore, we utilize surrogate and primary endpoints simultaneously to …

Human Neural Progenitor Cells Are Productively Infected By R5-Tropic Hiv-1: Opiate Interactions On Infection And Function Involve Cdk5 Signaling, Joyce Magat Balinang

Theses and Dissertations

Human immunodeficiency virus type 1 (HIV-1) is known to cause a spectrum of neurological, behavioral and motor deficits collectively termed as HIV-1 associated neurocognitive impairments (HAND). Opiates augment HIV-related CNS complications through both direct and indirect mechanisms that disrupt glial and neuronal function. All CNS macroglia and neurons derive from neural progenitor cells (NPCs) during development, and NPCs in the adult brain contribute to repair processes. Since disruptions in NPC function are known to impact CNS populations and brain function in a number of disease/injury conditions, we determined whether HIV ± opiate exposure affected the maturation and fate of human …

Behaviorally Induced Insufficient Sleep Syndrome And Insomnia: Prevalence And Relationship To Depression In College Students, Allison Baylor

Theses and Dissertations

Background: College students are at increased risk for general sleep issues as well as specific disorders, including Behaviorally Induced Insufficient Sleep Syndrome (BISS) and insomnia. These disorders can have deleterious daytime consequences, which can be compounded by exacerbating depression. The present study aims to establish college prevalence of BISS/insomnia, to characterize sleep characteristics in this sample, and to compare depression across BISS/insomnia.

Methods: Data from a college risk behaviors and health study (n=989) was used. Insomnia and BISS were defined as mutually exclusive disorders, using ICD-10/DSM-5 criteria, and Pittsburg Sleep Quality Index items.

Results: Overall, the results of this study …

Genetic And Epigenetic Mechanisms Of Complex Reproductive Disorders, Bhavi P. Modi

Theses and Dissertations

Common, complex disorders are polygenic and multifactorial traits representing interactions between environmental, genetic and epigenetic risk factors. More often than not, contributions of these risk factors have been studied individually and this is especially true for complex reproductive traits where application of genomic technologies has been challenging and slow to progress. This thesis explores the potential of genetic and epigenetic components contributing to a better understanding of the biological pathways underlying disease risk in two specific female complex reproductive traits - polycystic ovary syndrome (PCOS) and preterm premature rupture of membranes (PPROM). The PCOS projects focus on characterization of a …

Resource Utilization And Costs Associated With Off-Label Use Of Atypical Antipsychotics In An Adult Population, Della Varghese

Theses and Dissertations

Introduction: Atypical Antipsychotics (AAPs) are approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia and bipolar disorder. AAPs are commonly used off-label to treat depression, post-traumatic stress disorder and neuropsychiatric symptoms in dementia due to lack of alternative treatment options and treatment resistance. Concerns for off-label use arise since AAPs increase the risk of cardiovascular events and death. The objectives were 1) describe patterns of RU and costs among off-label AAPs users in a nationally representative population 2) identify prevalence of off-label use in the Medicare population 3) compare RU and costs between off-label AAPs …

Curcumin/Melatonin Hybrids As Neuroprotective Agents For Alzheimer's Disease, John Saathoff

Theses and Dissertations

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia, affecting ~5.2 million Americans. Current FDA approved medications provide mainly symptomatic relief and there are no agents available to delay or cure this disease. Multiple factors such as amyloid-β aggregates, dyshomeostasis of biometals, oxidative stress, and neuroinflammation have been implicated in the development of AD. Even though significant advances have been made in understanding the mechanisms leading to AD, the exact etiology still remains elusive. Given AD’s multifactorial nature, a multifunctional strategy of small molecule design would help to identify novel chemical templates. Recently our lab …

Exploring The Concept Of Human Oct3 Inhibitors As A Novel Class Of Antidepressants, Kavita A. Iyer

Theses and Dissertations

The Dukat laboratory developed 2-amino-6-chloro-3,4-dihydroquinazoline (A6CDQ) as a 5-HT₃ receptor ligand. A6CDQ and one of its positional isomers, the 7-chloro analog A7CDQ, produced antidepressant-like effects in the mouse tail suspension test (TST). We investigated and systematically ruled out a solely 5-HT₃ receptor or hSERT mediated mechanism of antidepressant-like effect for both A6CDQ and A7CDQ.

The role of organic cation transporter 3 (OCT3) as an alternative mechanism in the regulation of neurotransmitters including serotonin (5-HT) and the therapeutic potential of targeting hOCT3 to achieve antidepressant effects has been established. By virtue of possessing protonatable nitrogen atoms, 2-aminodihyroquinazolines could potentially …

Exploring The Role Of Intersectionality On Cardiovascular Disease Risk In Sexual Minorities, Leia Harper

Theses and Dissertations

Background: Previous research has shown that sexual minority individuals (SM) are twice as likely to smoke, twice as likely to be overweight or obese, and less likely to be physically active than heterosexual persons; all of which place SMs at an increased risk for cardiovascular disease (CVD). While information on CVD risk by race/ethnicity and socioeconomic status is well documented, there is scant literature examining race, gender, and the potential CVD risk in SMs. The purpose of this study was to examine CVD risk in sexual minorities.

Method: The current study used data from the National Longitudinal Study of Adolescent …

Role Of Vav2 In Podocyte Inflammasome Activation And Glomerular Injury During Hyperhomocysteinemia, Sabena Conley

Theses and Dissertations

Hyperhomocysteinemia (hHcys) is a widely known pathogenic factor in the progression of end-stage renal disease (ESRD) and it is also associated with an increased risk for injurious cardiovascular pathologies during ESRD. HHcys is linked to the formation and activation of the NOD-like receptor protein 3 (NLRP3) inflammasome, characterized as a critical early mechanism initiating the inflammatory response. NADPH oxidase (NOX)-derived reactive oxygen species (ROS) mediate the activation of the NLRP3 inflammasome in podocytes in response to elevated levels of homocysteine (Hcys) in vitro and in vivo. However, it remains unknown how NLRP3 inflammasome activation is triggered by NOX. The …

Eeg Interictal Spike Detection Using Artificial Neural Networks, Howard J. Carey Iii

Theses and Dissertations

Epilepsy is a neurological disease causing seizures in its victims and affects approximately 50 million people worldwide. Successful treatment is dependent upon correct identification of the origin of the seizures within the brain. To achieve this, electroencephalograms (EEGs) are used to measure a patient’s brainwaves. This EEG data must be manually analyzed to identify interictal spikes that emanate from the afflicted region of the brain. This process can take a neurologist more than a week and a half per patient. This thesis presents a method to extract and process the interictal spikes in a patient, and use them to reduce …

The Role Of Enteric Glia In Opioid-Induced Constipation, Sukhada Bhave

Theses and Dissertations

Morphine is one of the most widely used drugs for the treatment of pain but its clinical efficacy is limited by adverse effects including persistent constipation and colonic inflammation. Morphine-induced colonic inflammation is facilitated by microbial dysbiosis and bacterial translocation. In this study, we demonstrate that secondary inflammation and persistent constipation are modulated by enteric glia. In chronic morphine treated mice (75 mg morphine pellet/5 days), ATP-induced currents were significantly enhanced in enteric glia isolated from the mouse colon myenteric plexus. Chronic morphine resulted in significant disruption of the colonic epithelium and increased Il-1β in the myenteric plexus. The increase …

Exploring The Factors Of Persistence For African American Senior Nursing Students, Yolanda Nelson

Theses and Dissertations

African American nursing students experience commonalities within their college experience. Often these students may be faced with challenges, barriers, and/or struggles that may place a hindrance on their success in meeting their educational goals. This qualitative study used a phenomenological approach to explore African American female nursing students perceptions of faculty-student relationships and its implications for persistence. Four African American female nursing students and two nursing faculty agreed to participate in this study. This research study offers an examination of past and present research regarding the history of African American nursing students, health disparity, social justice and diversity within the …

Genetic And Epigenetic Variations In Asthma And Wheeze Illnesses, Todd M. Everson

Theses and Dissertations

Asthma, a chronic respiratory condition, is common worldwide with no cure and limited effective prevention strategies. It is well recognized that asthma has a multifaceted etiology, though many of the underlying mechanisms involved in asthma development, persistence and remission are still convoluted. Epigenetic mechanisms, such as DNA methylation, regulate gene-expression but are not related to changes in the actual DNA sequence. Recently, differential patterns of DNA methylation within many genes have been associated with asthma, particularly within genes involved in the differentiation of pro-inflammatory T-helper 2 (Th2) cells. DNA methylation patterns within less known biologic pathways undoubtedly are involved in …

Dietary Patterns And Prostate Cancer Aggressiveness In African-American And European-American Men, Lara Ryan Schneider

Theses and Dissertations

Several foods and nutrients have been linked to prostate cancer risk, but the effect of overall diet on prostate cancer outcomes is not well understood. Previous research has primarily examined a posteriori dietary patterns in relation to prostate cancer; studies that have used a priori dietary patterns and their relationship with prostate cancer have been inconclusive. Furthermore, racial differences in prostate cancer incidence and aggressiveness are not well understood. Data from the case-only North Carolina-Louisiana Prostate Cancer Project (PCaP) was used to examine the association between overall dietary pattern, as measured by the Mediterranean Diet (MED) score and the Dietary …

Dental Insurance As A Mitigating Factor In Reducing The Risk Of Mortality Among Working-Age Adults With Dental Caries And Periodontitis, Naveed Sadiq

Theses and Dissertations

Background Poor oral health had been associated with increased risk of having systemic diseases and thus mortality. The purpose of this research was to find if dental coverage with health insurance could mitigate the risk of death due to untreated dental caries and periodontitis among working age U.S. adults. Methods Data were drawn from NHANES III (1988-1994) and linked to mortality updated till Dec. 31st, 2011. It was restricted to those in the age range of 20-64 years adults. Furthermore, it was restricted to those who had complete data collection on all measures. Unweighted propensity scores were calculated to control …

Low-Intensity Physical Activity And Cardiometabolic Risk Factors Among Older Adults With Multiple Chronic Conditions, Yueyao Li

Theses and Dissertations

Introduction Cardiovascular disease (CVD) is the leading cause of death among older adults in the Unites States and is driven largely by cardiometabolic risk factors including elevated blood pressure and blood glucose. Studies have found the protective effect of moderate intensity physical activity (MIPA) and vigorous intensity physical activity (VIPA) on cardiometabolic risk factor; however, the association between light physical activity (LIPA) and cardiometabolic risk factor among older adults is not clear. Objectives 1). Examine the association between LIPA and cardiometabolic risk factors. 2). Examine whether the association between LIPA and cardiometabolic risk factor is moderated by multiple chronic conditions. …

Framing Risk, Responsibility, And Resolution: A Mixed-Methods Study Exploring Traditional And Social Media Coverage Of The 2014 Elk River Chemical Spill, Tracey Thomas

Theses and Dissertations

Background: The 2014 Elk River Chemical Spill raised policy questions concerning chemical safety and revealed an immediate need for improved emergency communication. This two-phase study explored how media presented causes of and longterm solutions to the spill through an examination of media frames. The study also explored how health risks were communicated through traditional and social media. The specific aims of Phase I were to examine media coverage in the days following the spill and compare coverage across media channels. The specific aims of Phase II were to understand how public health stakeholders perceived coverage of the spill and how …

Refinement And Pilot Testing Social Networks For Encouraging Healthy Behaviors: The Social Pounds Off Digitally (Social Pod) Study, Sarah B. Hales

Theses and Dissertations

Currently about 71% of adults in the US are considered overweight or obese. Overweight and obesity are associated with higher risk of developing many chronic diseases; however, health risks associated with overweight and obesity can be reduced by as little as a 3% to 5% reduction in weight. Mobile health (mHealth) has shown promise as a way to deliver weight loss interventions, yet maintaining participant engagement over time has been a challenge. The purpose of this study was to develop, refine, and pilot test the Social Pounds Off Digitally (POD) Android app for personalized health monitoring and interaction; revise the …

Nurses Utilizing The V.O.I.C.E.S. Hiv Prevention Intervention In The Black Church Community, Jason Richard

Theses and Dissertations

The Human Immunodeficiency Virus (HIV) epidemic is a significant problem in the United States, especially in the “Bible Belt” Deep South where the epidemic is hitting this region the hardest. The HIV epidemic in the state of South Carolina is very real, significant, and quite alarming. In fact, the Center for Disease Control and Prevention (CDC) labels South Carolina as an HIV “hot spot.” All racial and ethnic groups are susceptible and impacted by HIV. However, evidence shows that African Americans – especially young adults 18-35, bear the brunt of the burden to the extent that the “new face” of …

Physical Activity And Breast Cancer In South Carolina, Chisom Onyeuku

Theses and Dissertations

This study examined the relationship between breast cancer incidence and recreational physical activity. It was one of the first studies in the southeastern US to examine incident breast cancer and physical activity in an ethnically diverse cohort of women. In terms of physical activity, both lifetime and recent physical activity were analyzed. All physical activity data were from validated self-reported surveys. The study examined BMI, menopausal status and race as key confounders and effect modifiers. The study found evidence that for Black women, there was a positive relationship between the amount of lifetime physical activity and the odds of incident …

Post-Fall Decision Making Among Older Women Living In Continuing Care Retirement Communities: A Mixed Methods Study, Caroline D. Bergeron

Theses and Dissertations

Introduction: One in every three adults over the age of 65 experiences a fall every year, with women experiencing more falls than men. Falls can affect how older women perceive themselves and their independence. The purpose of this study was to examine older women's health decision making after experiencing a fall. Methods: I conducted semi-structured interviews with 17 older women living independently in continuing care retirement communities (CCRCs) who had experienced a fall within the previous six months and 11 individuals the women identified as being involved in their post-fall decision making. I also conducted an exploratory survey on post-fall …

A Qualitative Study Of The Massage Therapy Foundation's Best Practices Symposium: Clarifying Definitions And Creating A Framework For Practice, Ann Blair Kennedy

Theses and Dissertations

Large numbers of individuals seek massage therapy for wellness/disease prevention purposes and research supports consumer reported benefits including physical and psychological improvements. However, challenges within the profession may be hindering the advancement of the field. To better understand the process and outcomes and ultimately develop best practices for massage therapy as well as better inform education, policy and research, it is necessary to investigate how massage and/or massage therapy are defined and operationalized in practice. This study entailed qualitative analysis of cross-sectional data using a grounded theory approach to examine the data gathered from a two-day symposium held in 2010 …

Relationship Between Job Satisfaction Among Frontline Staff And Patient Satisfaction: Evidence From Community Health Centers In South Carolina, Ashley Lynn Barnes

Theses and Dissertations

The role of frontline staff (FLS) is vital to the success of health delivery organizations as they are often the main point of patient contact and the primary source of feedback regarding the patient experience and satisfaction. Anecdotal evidence suggests that FLS have among the highest turnover rates in health delivery organizations, resulting in high recruitment and training costs as well as disruptions in day-to-day operations. However, few studies have examined the role of FLS and the factors affecting job satisfaction among FLS. Researchers have also not examined the impact of FLS satisfaction on patient satisfaction. To address these research …

Individual- And Neighborhood-Level Determinants Of Emergency Department Utilization Among Patients With Diabetes In South Carolina, Charity B. Breneman

Theses and Dissertations

AIM: The primary aim of this study was to evaluate the geographic variation in emergency department (ED) use in South Carolina using geographical information systems (GIS) and to examine the effects of both individual- and neighborhood-level characteristics on frequent ED use among patients with diabetes. METHODS: ED discharge data for 2013 was geocoded based on patients’ residential ZIP code using GIS. Frequent ED use among patients with diabetes was defined as three or more ED visits between January 1, 2013 and December 31, 2013. The boundaries for each neighborhood were defined by the U.S. Census Bureau ZIP Code Tabulation Areas …

Metabotropic Receptor Modulation Of Kainate Receptors In The Hippocampus, C'Iana Patrice Cooper

Theses and Dissertations

Kainate receptors (KARs) are glutamate-gated ion channels that mediate synaptic transmission, modulate transmitter release, and mediate excitation in the brain. Potentiation in their function predisposes the hippocampus to hyperexcitability and seizures. These receptors are widely expressed throughout the central nervous system as tetramers composed of various combinations of GluK1-5 subunits. In the hippocampus (a brain region commonly associated with seizure initiation), GluK2-, GluK4-, and GluK5-containing receptors are highly expressed in the CA3 pyramidal cell layer, whereas GluK1 is barely detectable. The lack of pharmacological tools hinders identifying the functional contribution of each kainate receptor subtype in normal CA3 synaptic transmission. …