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Geographic Disparities Associated With Stroke And Myocardial Infarction In East Tennessee, Ashley Pedigo Golden

Doctoral Dissertations

Stroke and myocardial infarction (MI) are serious conditions whose burdens vary by socio-demographic and geographic factors. Although several studies have investigated and identified disparities in burdens of these conditions at the county and state levels, little is known regarding their geographic epidemiology at the neighborhood level. Both conditions require emergency treatments and therefore timely geographic accessibility to appropriate care is critical. Investigation of disparities in geographic accessibility to stroke and MI care and the role of Emergency Medical Services (EMS) in reducing treatment delays are vital in improving health outcomes. Therefore, the objectives of this work were to: (i) classify …

Detection Of Two Pathogens Of High Importance To The National Poultry Improvement Plan: Salmonella Spp. And Mycoplasma Spp., Robin Levi Jarquin

Graduate Theses and Dissertations

In 1935, the National Poultry Improvement Plan (NPIP) was created to control Salmonella gallinarum and Salmonella pullorum . These two pathogens were devastating economically for poultry producers. Through cooperative efforts using vaccination and strict biosecurity, these two pathogens were eradicated from the United States. Currently, the NPIP program is targeting two other poultry pathogens, Salmonella enterica serovar Enteritidis and Mycoplasma . In the broiler industry it targets 2 specific Mycoplasma species (synoviae, gallisepticum). Vaccinations for these bacteria are available, but are not fully effective at controlling all strains and serovars. Thus, constant monitoring systems and strict biosecurity measures are necessary …

Methodological Quality Of Quantitative Nursing Lesbian, Gay, Bisexual, And Transgender Research From 2000 To 2010, Michael Johnson

UNLV Theses, Dissertations, Professional Papers, and Capstones

Lesbian, gay, bisexual, and transgender (LGBT) people constitute one of the largest underserved populations in any nursing setting. Despite the large LGBT populations, very little nursing research has been conducted on these populations. Nurse researchers have recommended that nursing researchers end the silence on LGBT research. To accomplish this, the methodological rigor of LGBT nursing research must be evaluated and improved upon. Currently, no literature examines the methodological quality of quantitative nursing LGBT research. Using a cross-sectional design, it was the purpose of this study to evaluate the methodological quality of quantitative nursing LGBT research from 2000 to 2010 using …

The Role Of Cell Sterilization In Population Based Studies Of Radiogenic Second Cancers Following Radiation Therapy, Annelise Giebeler

Dissertations & Theses (Open Access)

Advances in radiotherapy have generated increased interest in comparative studies of treatment techniques and their effectiveness. In this respect, pediatric patients are of specific interest because of their sensitivity to radiation induced second cancers. However, due to the rarity of childhood cancers and the long latency of second cancers, large sample sizes are unavailable for the epidemiological study of contemporary radiotherapy treatments. Additionally, when specific treatments are considered, such as proton therapy, sample sizes are further reduced due to the rareness of such treatments. We propose a method to improve statistical power in micro clinical trials. Specifically, we use a …

Role Of The Gcn5 Histone Acetyltransferase In Spinocerebellar Ataxia Type 7 And In Immature Neurons, Yi Chun Chen

Dissertations & Theses (Open Access)

Spinocerebellar Ataxia type 7 (SCA7) is a neurodegenerative disease caused by expansion of a CAG repeat encoding a polyglutamine tract in ATXN7, a component of the SAGA histone acetyltransferase (HAT) complex. Previous studies provided conflicting evidence regarding the effects of polyQ-ATXN7 on the activity of Gcn5, the HAT catalytic subunit of SAGA. Here I showed that reducing Gcn5 expression accelerates both cerebellar and retinal degeneration in a mouse model of SCA7. Deletion of Gcn5 in Purkinje cells in mice expressing wild type Atxn7, however, causes only mild ataxia and does not lead to the early lethality observed in SCA7 mice. …

Characterization Of The Mechanism Of Pparγ-Mediated Neointima Formation In Rodents, Ryoko Tsukahara

Theses and Dissertations (ETD)

Lysophosphatidic acid (LPA) and its ether analog alkyl glycerophosphate (AGP) elicit arterial wall remodeling when applied intralumenally into the uninjured carotid artery. LPA is the ligand of eight GPCRs and the peroxisome proliferator-activated receptor γ (PPARγ). We pursued a gene knockout strategy to identify the LPA receptor subtypes necessary for the neointimal response in a non-injury model of carotid remodeling and also compared the effects of AGP and the PPARγ agonist rosiglitazone (ROSI) on balloon injury-elicited neointima development. In the balloon injury model AGP significantly increased neointima; however, rosiglitazone application attenuated it. AGP and ROSI were also applied intralumenally for …

Compound 49b: A Novel Beta-Adrenergic Receptor Agonist In The Treatment Of Diabetic Retinopathy, Kimberly Williams-Guy

Theses and Dissertations (ETD)

Diabetic retinopathy is the leading cause of blindness in working Americans. While there are therapeutic regimens for the disease, more effective methods are needed. We have previously shown that a non-specific beta-adrenergic receptor agonist, isoproterenol, was effective in preventing functional and morphological changes associated with diabetic retinopathy in the rat. Isoproterenol also produced left ventricle remodeling suggesting it entered the systemic circulation. We therefore synthesized various novel beta-adrenergic receptor compounds and screened these compounds in vitro for their ability to reduce markers of inflammation and apoptosis. Of the various compounds tested, Compound 49b was able to reduce both inflammation and …

Autoimmune Consequences Of Histone Deimination During Neutrophil Activation, Nishant Dwivedi

Theses and Dissertations (ETD)

Tolerance blocks the expression of autoantibodies, whereas autoimmunity promotes it. How tolerance breaks and autoantibody production begins, thus, are crucial questions for the understanding and treatment of autoimmune diseases. Evidence implicates cell death and autoantigen modifications in the initiation of autoimmune reactions. One form of neutrophil cell death deserves attention because it occurs as a consequence of neutrophil activation, requires the post-translational modification of histones and results in the extracellular release of chromatin. The extracellular chromatin incorporates histones in which arginines have been converted to citrullines by peptidylarginine deiminase IV (PAD4) creating structures that capture or "trap" bacterial pathogens. Neutrophil …

Can Antioxidant-Rich Berries Improve Risk Factors Associated With Cardiovascular Disease In Postmenopausal Smokers?, Jordan Alaine Teeple

Graduate Theses and Dissertations

The purpose of this study was to examine the effects of smoking on risk factors associated with cardiovascular disease (CVD) and determine the efficacy of antioxidant-rich berries in ameliorating these risk factors in postmenopausal smokers. Menopause and cigarette smoking have been identified as major risk factors for CVD due to a decrease in antioxidant protection, increase in inflammation and oxidative stress, and adverse changes in serum lipids. Antioxidants, specifically flavonoid compounds found in blackberries and blueberries, have been shown to prevent low-density lipoprotein cholesterol oxidation and thus prevent downstream inflammation and oxidative stress. Healthy, postmenopausal nonsmokers (n=14) and smokers (n=31) …

The Incidence Of Plexiform Lesion Formation In Lines Divergently Selected For Ascites, James Grant Mason

Graduate Theses and Dissertations

Complex Vascular Lesions, (CVL) are a common vascular change associated with idiopathicpulmonary arterial hypertension (IPAH). CVL have been characterized in studies using animal models involving, but not limited to, Sprague-Dawley rats and poultry (Abe et al., 2010; Wideman et al., 2011).IPAH has been documented in poultry although no connection has been made with CVLs. The current study characterizes CVL in the lungs from broilers derived from lines divergently selected for 15 generations for ascites susceptibility under conditions of simulated high altitude. The ascites RES and SUS lines were sampled for CVL incidence over time. Both lines were reared in a …

Spatial Distribution Of Obesity Among West Virginia 5th Grade Children: Analysis Of The Socioeconomic, Physical, And Personal Environment, Sherry Roper

Theses and Dissertations (ETD)

Childhood obesity defined as a body mass index (BMI) at or above the 95th percentile for children of the same age and sex, is considered an epidemic in the United States. Biology and lifestyle behaviors have been identified as important factors in the development of childhood obesity; however, researchers are beginning to place more emphasis upon the impact that continual environmental exposures have upon obesity development. Environmental risk factors associated with obesity are distributed continuously over space, yet evidence suggests that burden of risk may not be evenly dispersed across a community. West Virginia (WV), a rural Appalachian community has …

Evaluation Of The Pilot Program, Pediatric Early Warning Sentinel Surveillance Program (Pewss), And Its Efficacy In Monitoring Pediatric Illness In Clark County, Nevada, Michelle Lee Lutman

UNLV Theses, Dissertations, Professional Papers, and Capstones

The influenza outbreak that occurred during 2009 stimulated the formation of several surveillance programs throughout the country. The majority monitor only influenza; however, there are several other circulating respiratory pathogens, especially within the pediatric community. These other respiratory pathogens cause a variety of illnesses, such as bronchitis, pneumonia, croup, etc. Prior research has provided the medical community with valuable information about respiratory illnesses, especially those which afflict pediatric patients. Areas of knowledge including seasonality, demographics, signs and symptoms, prevention measures, and pathogenicity, have been greatly expanded over the years. This information has been of tremendous help to the medical community …

A Brief Content Analysis Of Attachment And Sexual Relationships In Sex Therapy And Research Journals, Kathryn Zambrano Devis

UNLV Theses, Dissertations, Professional Papers, and Capstones

A surge of scholarly publications on attachment within couple relationships prompted this content analysis of attachment articles published in six sex therapy and sex research journals. This study investigates the extent to which these journals attend to attachment in the context of adult sexual relationships. The researcher found 2257 articles published within these journals; 64 of which attend to attachment and 9 of which attend to attachment and sex. Implications for couples therapy in the field of sex therapy and future directions are discussed.

Maternal And Fetal Plasma Protein Changes In Fetal Growth Restriction, Maxim D. Seferovic

Electronic Thesis and Dissertation Repository

Fetal Growth Restriction (FGR) is caused by impaired maternal-fetal exchange of oxygen and nutrients causing fetal hypoxia and starvation. A functional failure of the placenta is the underlying cause, however the pathophysiology remains unknown. The fetus adapts by limiting growth, reducing demand for metabolic substrates. Monitoring the fetal size is the primary clinical method of FGR detection, though it does not distinguish a constitutionally small fetus from a pathological. Proteomic profiling of fetal and maternal plasma was therefore undertaken for discovery of biomarkers and pathological mechanisms. As a model of hepatic secreted fetal plasma proteins, HepG2 cell secretion changes in …

Autoimmune Responses To Atherosclerotic Lipids: A Study In Murine Models Of Atherosclerosis And Obesity, Hanjing Wu

Dissertations & Theses (Open Access)

Atherosclerosis is a chronic, complex arterial disease characterized by intimal lipid accumulation and inflammation. A unique lipid-binding molecule, namely cluster of differentiation 1d (CD1d), may impact atherosclerosis. Structurally, CD1d acts as a nonpolymorphic cell-surface receptor, resembling the major histocompatibility complex-I (MHC-I). While MHC-I restricts peptide antigen presentation to T cells, CD1d presents lipid antigens to T cells named CD1d-restrictedd T cells. Although increased expression of CD1d has been found in human plaques, the exact nature of CD1d-recognized lipids in atherosclerosis remains to be determined. Three groups of lipids may undergo oxidation in atherosclerosis producing atherogenic lipids: phospholipids, fatty acids, and …

Elucidating The Genetic Determinants Of The Archetypal Complex Disease Hypertriglyceridemia, Christopher T. Johansen

Electronic Thesis and Dissertation Repository

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Canada. Among non-traditional risk factors, plasma triglyceride (TG) concentration is re-emerging as a significant risk factor. Patients with hypertriglyceridemia (HTG) – an archetypal complex phenotype defined by fasting plasma TG concentration >95^th percentile – thus have significantly increased CVD risk, compounded by associated co-morbidities such as obesity, metabolic syndrome and type 2 diabetes. However, the molecular pathways contributing to HTG susceptibility are incompletely defined. A better understanding of the genetic determinants that underlie the phenotypic spectrum of plasma TG and HTG susceptibility is necessary to identify novel …

The Mechanism Of Tumorigenesis In The Immortalized Human Pancreatic Cell Lines: Cell Culture Models Of Human Pancreatic Cancer, Zhe Chang

Dissertations & Theses (Open Access)

The mechanism of tumorigenesis in the immortalized human pancreatic cell lines: cell culture models of human pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer in the world. The most common genetic lesions identified in PDAC include activation of K-ras (90%) and Her2 (70%), loss of p16 (95%) and p14 (40%), inactivation p53 (50-75%) and Smad4 (55%). However, the role of these signature gene alterations in PDAC is still not well understood, especially, how these genetic lesions individually or in combination contribute mechanistically to human pancreatic oncogenesis is still elusive. Moreover, a cell culture transformation model with sequential …

Gene By Bmi Interactions Influencing C-Reactive Protein Levels In European-Americans, Sarah Tudor

Dissertations & Theses (Open Access)

C-Reactive Protein (CRP) is a biomarker indicating tissue damage, inflammation, and infection. High-sensitivity CRP (hsCRP) is an emerging biomarker often used to estimate an individual’s risk for future coronary heart disease (CHD). hsCRP levels falling below 1.00 mg/l indicate a low risk for developing CHD, levels ranging between 1.00 mg/l and 3.00 mg/l indicate an elevated risk, and levels exceeding 3.00 mg/l indicate high risk. Multiple Genome-Wide Association Studies (GWAS) have identified a number of genetic polymorphisms which influence CRP levels. SNPs implicated in such studies have been found in or near genes of interest including: CRP, APOE, APOC, IL-6, …

Upregulation Of Reactive Oxygen Species During The Retrovirus Life Cycle And Their Roles In A Mutant Of Moloney Murine Leukemia Virus, Ts1-Mediated Neurodegeneration, Soo Jin Kim

Dissertations & Theses (Open Access)

Viral invasion of the central nervous system (CNS) and development of neurological symptoms is a characteristic of many retroviruses. The mechanism by which retrovirus infection causes neurological dysfunction has yet to be fully elucidated. Given the complexity of the retrovirus-mediated neuropathogenesis, studies using small animal models are extremely valuable. Our laboratory has used a mutant moloney murine leukemia retrovirus, ts1-mediated neurodegneration. We hypothesize that astrocytes play an important role in ts1-induced neurodegeneration since they are retroviral reservoirs and supporting cells for neurons. It has been shown that ts1 is able to infect astrocytes in vivo and in …

Mutant Cx43 In Skin Differentiation And Disease, Jared M. Churko

Electronic Thesis and Dissertation Repository

Connexin43 (Cx43) is expressed within keratinocytes, dermal fibroblasts, and the hair follicle epithelium. Since Cx43 is so widely expressed in resident cells of the skin, we speculated that this connexin would play an essential role in skin homeostasis, hair growth and wound healing. Mutations in the gene which encodes Cx43 lead to a disease called oculodentodigital dysplasia (ODDD) and patients expressing the frame-shift mutants (fs230 or fs260) develop a skin disease called palmar plantar hyperkeratosis. In addition, patients with ODDD often develop hair which is dry, sparse, and slow growing. To study skin abnormalities associated with ODDD, hair growth and …

Early Diagnosis Of Pulmonary Embolism: Review And Cost-Effectiveness Analysis, Efstathios Polychronopoulos

Health Services Research Dissertations

Pulmonary embolism (PE) is a serious, life-threatening thrombotic disease, which results in considerable health and economic consequences each year for the United States. These consequences include a toll of 83,000 deaths and an economic impact between 1,5 and 5 billion. Approaches to strategy selection by physicians and other health-care specialists are based mainly upon cost, technology availability, and cultural tolerance regarding radiation exposure. The purpose of this study was to determine the most cost-effective diagnostic strategy with patients suspected of PE among several strategies currently used by examining their detection failure rates. This objective was met by (a) assessing parameter …

The Role Of Protein Kinase C Epsilon In Hydrogen Peroxide And Nitric Oxide Release During Oxidative Stress Caused By Extracorporeal Shockwave Lithotripsy, Edward S. Iames

PCOM Biomedical Studies Student Scholarship

Clinical extracorporeal shock wave lithotripsy (ESWL) treatment to ablate kidney stones can cause acute damage to the renal microvasculature. Accumulation of continued treatment with shockwave therapy can lead to chronic damage to the kidney, and lead to clinical hypertension. Shockwaves have been shown to stimulate endothelial cells to release superoxide (SO), which is converted to hydrogen peroxide (H₂O₂), and reacts with nitric oxide (NO) to produce peroxynitrite anion (OONO^-), creating a powerful oxidant that increases oxidative stress while simultaneously reducing NO bioavailability. Increased oxidative stress during events such as ESWL, also uncouples NO production …

Ischemia Impairs Vasodilation In Skeletal Muscle Resistance Artery, Kyle Remington Struthers

Master's Theses

Functional vasodilation in arterioles is impaired with chronic ischemia. We sought to examine the impact of chronic ischemia and age on skeletal muscle resistance artery function. To examine the impact of chronic ischemia, the femoral artery was resected from young (2-3mo) and adult (6-7mo) mice and the profunda femoris artery diameter was measured at rest and following gracilis muscle contraction 14 days later using intravital microscopy. Functional vasodilation was significantly impaired in ischemic mice (14.4±4.6% vs. 137.8±14.3%, p<0.0001 n=8) and non-ischemic adult mice (103.0±9.4% vs. 137.8±14.3%, p=0.05 n=10). In order to analyze the cellular mechanisms of the impairment, a protocol was developed to apply pharmacological agents to the experimental preparation while maintaining tissue homeostasis. Endothelial and smooth muscle dependent vasodilation were impaired with ischemia, 39.6 ± 13.6% vs. 80.5 ± 11.4% and 43.0 ± 11.7% vs. 85.1 ± 10.5%, respectively. From this data, it can be supported that smooth muscle dysfunction is the reason for the observed impairment in arterial vasodilation.

Repetitive Transcranial Magnetic Stimulation Used For Tinnitus Suppression: A Voxel-Based Morphometry Study, Lauren E. Laitman

Honors Theses

Tinnitus is a debilitating disorder with unknown underlying mechanisms, often induced by loud noises. Tinnitus symptoms include the conscious perception of constant sound absent an external source. This study sought to determine effectiveness of treatment with repetitive transcranial magnetic stimulation (rTMS), and to use voxel-based morphometry (VBM) to identify treatment related neuronal reorganization. One hertz rTMS was delivered for 20 minutes on each of 5 consecutive days. Tinnitus suppression was measured with the Tinnitus Handicap Questionnaire (THQ), and VBM was carried out on structural Magnetic Resonance images collected before and after sham-treatment and rTMS. Findings indicate the effectiveness of rTMS …

The Effects Of Computer-Based Education On Children's Knowledge About Asthma, Matyt L. Adler

Evidence-Based Practice Project Reports

Asthma is a global health problem affecting people of all ages that can cause severe limitations when uncontrolled. In the United States, asthma was the most prevalent chronic disease among children and youth in 2008 (U.S. Department of Health and Human Services, 2009). Because day-to-day management of asthma is the responsibility of the child or the parent, education of patients is one of four crucial components to effectively provide quality asthma care. Changes in workload complexities with primary care visits has increased and visit duration decreased, resulting in less available time to address individual patient needs including the education aspect …

Characterization Of Quadriceps Neuromuscular Function In Knee Osteoarthritis, Michael James Berger

Electronic Thesis and Dissertation Repository

PURPOSE: The purpose of this thesis was to characterize quadriceps neuromuscular dysfunction in patients with knee osteoarthritis (OA). Concerns pertaining to study design in this patient population (e.g. disease severity criteria and muscle imaging outcome measures) were also addressed.

METHODS: Five studies were undertaken using data acquired from volunteers recruited at the local institution and from participants in the public source dataset of the Osteoarthritis Initiative (http://oai.epi-ucsf.org/datarelease/). Clinical disease severity was evaluated with the Western Ontario and McMaster Osteoarthritis Index (WOMAC). Radiographic severity was evaluated with Kellgren-Lawrence Grading (KLG). Quadriceps muscle isometric strength and isotonic power were measured …

Examining The Role Of Specific Virulence Mechanisms During Pseudomonas Aeruginosa Infection In A Zebrafish Model Of Cystic Fibrosis, Ryan T. Phennicie

Electronic Theses and Dissertations

Cystic fibrosis (CF) is the most common lethal hereditary disease. CF is caused by recessive mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene and is associated with multi-­-organ defects resulting from improper ion transport across epithelial membranes. Chronic lung infection by the environmentally ubiquitous opportunistic human pathogen Pseudomonas aeruginosa and the subsequent hyperinflammation that occurs as the host immune system combats the bacterium cause substantial morbidity and mortality in CF. Despite numerous studies that have sought to elucidate the role of CFTR in the innate immune response, the links between CFTR, innate immunity, and P. aeruginosa infection remain …

Natural History Study Of Arthrogryposis Multiplex Congenita, Amyoplasia Type, Trisha Nichols

Dissertations & Theses (Open Access)

Arthrogryposis or Arthrogrypsosis Multiplex Congenita (AMC) are terms used to describe the clinical finding of multiple congenital contractures. There are more than 300 distinct disorders associated with arthrogryposis. Amyoplasia is the most common type of arthrogryposis and is often referred to as the “classic” type. There is no known cause of amyoplasia and no risk factors have been identified. Moreover, there is no established diagnostic criteria, which has led to inconsistency and confusion in the medical literature. The purpose of this study was to describe the natural history of amyoplasia, to determine if there are any identifiable risk factors and …

The Effects Of Curcumin On Body Composition Of Patients With Advanced Pancreatic Cancer, Henrique A. Parsons Md

Dissertations & Theses (Open Access)

Cachexia is very common among patients with advanced pancreatic cancer and is a marker of poor prognosis. Weight loss in cachexia is due to both adipose and muscle compartments, and sarcopenia (severe muscle depletion) is associated with worse outcomes. Curcumin has shown a myriad of biological effects, including anti-cancer and anti-inflammatory. The ability of curcumin to attenuate cachexia and muscle loss has been tested in animal models, with conflicting results so far. The hypothesis of this study was that patients with advanced pancreatic cancer treated with curcumin for two months have less fat and muscle loss as compared to matched …

Insights Into P53-Dependent Apoptotic Signaling And Cell Fate Vis-A-Vis Functional Cooperation Among Bcl-Xl, Cytoplasmic P53, And Puma, John C. Fisher

Theses and Dissertations (ETD)

Following DNA damage, nuclear p53 induces the expression of PUMA (p53 upregulated modulator of apoptosis), a BH3‑only protein that binds and inhibits the anti‑apoptotic BCL‑2 repertoire, including BCL‑xL. Structural investigations of PUMA and the BCL‑xL×PUMA BH3 domain complex by X‑ray crystallography and nuclear magnetic resonance (NMR) spectroscopy reveal a novel, PUMA‑induced, domain‑swapped dimerization of BCL‑xL that requires a π‑stacking interaction between PUMA W71 and BCL‑xL H113. PUMA is an intrinsically disordered protein, but upon interaction with BCL‑xL, PUMA W71 and the PUMA BH3 domain residues fold into an alpha helix and subtly remodel BCL‑xL to trigger its dimerization. Wild type …