Medicine and Health Sciences Commons^™

Determinants Of Pap Screening Among Sub-Saharan African Immigrant Women, Adebola Olamide Adegboyega

Theses and Dissertations--Nursing

The purpose of this dissertation was to explore the determinants of Pap screening completion among sub-Saharan African immigrant women. Cervical cancer is a public health problem globally. The risk of invasive cervical cancer remains high among sub- Saharan African immigrant women in the US despite being a preventable cancer. Early detection through Pap screening is crucial for prevention, treatment and prognosis. The specific aims of this dissertation were to 1) examine Pap screening practices among African immigrant women and to identify gaps to guide future research; 2) explore barriers and motivators that influence Pap screening decisions among African immigrant women; …

Social Determinants Of Health And Disparities In Outcomes Related To Cardiovascular Health In Vulnerable Populations, Jennifer L. Miller

Theses and Dissertations--Nursing

The purpose of this dissertation was to explore the mechanism of association between social determinants of health (SDH), particularly limited health literacy, and disparate outcomes related to cardiovascular disease in vulnerable populations. Specific aims were to 1) compare quality of life (QOL), anxiety, and depressive symptoms between genders in implantable cardioverter defibrillator (ICD) recipients; 2) examine the association between multi-morbidity burden and QOL; 3) determine whether health literacy levels independently predict CVD risk in the male prison population; 4) examine the relationship between health literacy and decisiveness regarding end of life (EOL) choices, and 5) examine SDH as predictors of …

Gastrointestinal Bleeding Events And Statin Use: A Large Propensity Score-Matched Retrospective Cohort Study, Ashley I. Martinez

Theses and Dissertations--Pharmacy

Literature is conflicting regarding the association between statin use and gastrointestinal (GI) bleeding. This study sought to determine whether there is an association between statin use and GI bleeding by comparing incidence of gastrointestinal events between statin users and an active comparator group.

Data was obtained from a large administrative claims database composed of subjects enrolled in a selection of insurance plans throughout the United States from 2009-2014. New statin users (exposed) and thyroid medication users (active comparator, unexposed) were followed from the baseline period (one year prior to medication initiation) until first event, discontinuation, or disenrollment. Subjects were matched …

Factors Regulating Features Of Metabolic Syndrome, Sonja S. Pijut

Theses and Dissertations--Pharmacy

The collective presence of central obesity, low HDL-cholesterol, and elevated triglycerides, blood pressure, and fasting blood glucose constitutes Metabolic Syndrome (MetS), a disease state that increases the risk of cardiovascular disease (CVD) and Type 2 Diabetes Mellitus (T2DM). Nonalcoholic fatty liver disease (NAFLD), present in up to 90% of obese adults, is also linked to MetS. As in CVD, disruptions in cholesterol metabolism play a contributing role in the development of T2DM and NAFLD. Genes involved in cholesterol synthesis, secretion, and catabolism are diurnally regulated in the liver and adipose. Disruptions in the sleep-wake cycle are thought to potentiate metabolic …

The Development Of Bsn272 From Prevention Of Diet-Induced Hyperlipidemia In Mice To A Potential Therapy For Prader-Willi Syndrome In Humans, Jarrod B. Williams

Theses and Dissertations--Pharmacy

While type 2 diabetes mellitus (T2DM) is distinguished as a disorder of blood glucose homeostasis, the vast majority of patients afflicted with this disease in the US present with the entire complement of the metabolic syndrome: abdominal obesity, hypertriglyceridemia, low HDL levels, elevated blood pressure, and elevated fasting plasma glucose. Current guidelines aim to treat each of these disorders, but do so individually even though they are manifestations of common pathologies. In other words, a patient will be prescribed different medications for diabetes, blood pressure, CVD prevention, etc., while the only single treatment aimed at the myriad of disorders together …

Effects Of Core And Shell Modification To Tethered Nanoassemblies On Sirna Therapy, Steven Rheiner

Theses and Dissertations--Pharmacy

siRNA therapy is an emerging technique that reduces protein expression in cells by degrading their mRNAs via the RNA interference pathway (RNAi). Diseases such as cancer often proliferate due to increased protein expression and siRNA therapy offers a new method of treatment for those diseases. Although siRNA therapy has shown success in vitro, it often fails in vivo due to instability in the blood stream. To overcome this limitation, delivery vehicles are necessary for successful transfection of siRNA into target cells and cationic polymers have been widely studied for this purpose. However, complexes between siRNA and delivery vehicles made …

Development Of Diverse Size And Shape Rna Nanoparticles And Investigation Of Their Physicochemical Properties For Optimized Drug Delivery, Daniel L. Jasinski

Theses and Dissertations--Pharmacy

RNA nanotechnology is an emerging field that holds great promise for advancing drug delivery and materials science. Recently, RNA nanoparticles have seen increased use as an in vivo delivery system. RNA was once thought to have little potential for in vivo use due to biological and thermodynamic stability issues. However, these issues have been solved by: (1) Finding of a thermodynamically stable three-way junction (3WJ) motif; (2) Chemical modifications to RNA confer enzymatic stability in vivo; and (3) the finding that RNA nanoparticles exhibit low immunogenicity in vivo.

In vivo biodistribution and pharmacokinetics are affected by the physicochemical …

Halo- And Solvato-Fluorochromic Polymer Nanoassemblies For Cancer Theranostics, Derek Alexander Reichel

Theses and Dissertations--Pharmacy

Theranostics is an emerging treatment approach that combines diagnostics with therapy in order to personalize treatment regimens for individual patients and decrease cancer mortality. Previously, nanoparticles entrapping conventional fluorescent dyes were developed for cancer theranostics, but fluorescent nanoparticles did not allow clinicians to significantly improve cancer treatments.

The use of fluorescent dyes that are sensitive to solvent acidity (halo-fluorochromism) and polarity (solvato-fluorochromism) may overcome the limitations of fluorescent nanoparticles and improve cancer therapy by enabling researchers to detect chemical properties within the nanoparticle core environment. The model halo- and solvato-fluorochromic dye Nile blue was attached to the core of nanoscale …

Pneumococcal Conjugate Vaccine 13 Coverage In Children, High-Risk Adults 19-64 Years Of Age, And Adults Over 65 Years Of Age In A Commercially Insured U.S. Population, Joseph C. Vanghelof

Theses and Dissertations--Pharmacy

This thesis aimed to elucidate the demographic characteristics associated with elevated or reduced rates of pneumococcal conjugate 13 (PCV13) vaccination.

A retrospective cohort study was performed using the Truven Health MarketScan® Database. Three cohorts were created corresponding to populations for which the CDC recommends PCV13 vaccination. Cohort 1: children < 36 months of age. Cohort 2: adults 19-64 years of age with high infection risk. Cohort 3: adults > 65 years of age. Odds of having a PCV13 claim were calculated for each cohort.

For Cohort 1, 78% out of a total of 353,214 subjects had a sufficient number of PCV13 doses to meet CDC recommendations. For Cohort 2, 3.7% out of a total of 673,157 subjects had a PCV13 …

Rational Design, Synthesis, And Characterization Of Novel Mpges-1 Inhibitors As Next Generation Of Anti-Inflammatory Drugs, Ziyuan Zhou

Theses and Dissertations--Pharmacy

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are currently widely used as fever and pain relief in patients with arthritis and other inflammatory symptoms. NSAIDs effect by inhibiting cyclooxygenase-1 (COX-1) and/or cyclooxygenase-2 (COX-2). COX isozymes (COXs) are key enzymes in the biosynthesis of prostaglandin H₂ (PGH₂) from arachidonic acid (AA). It is now clear that prostaglandin E₂ (PGE₂), one of the downstream products of PGH₂, is the main mediator in both chronic and acute inflammation. Microsomal prostaglandin E synthase (mPGES-1) is the terminal enzyme of COX-2 in the PGE₂ biosynthesis pathway. …

Effects Of In Utero Nicotine Exposure On Immune Cell Disposition After P. Aeruginosa Lung Infection, Nayon Kang

Theses and Dissertations--Pharmacy

Current smoking cessation guidelines recommend nicotine replacement therapy (NRT) to assist pregnant smokers to quit, but this is without strong evidence for effectiveness and safety. Nicotine, the main addictive component of tobacco, is known to exert physiological effects by binding to its receptor, the nicotinic acetylcholine receptor (nAChR). Recent studies have identified the presence of nAChRs in non-neuronal cells, and in macrophages, functional alteration upon stimulation with nicotine has been documented.

To understand the impact of in utero nicotine exposure on various immune cell disposition and function, we designed preliminary studies using an in vivo model of P. aeruginosa infection. …

Gene Expression Profiles Reveal Alternative Targets Of Therapeutic Intervention For The Treatment Of Drug-Resistant Non-Small Cell Lung Cancers, Madeline J. Krentz Gober

Theses and Dissertations--Pharmacy

More than 80% of lung cancer patients die from drug-resistant, metastatic disease. Our focus is to identify new drug targets and alternative therapeutic strategies to improve outcomes for this majority of lung cancer patients. We aimed to satisfy the need for new treatment approaches by leveraging the information gained from the development of two multigene biomarker predictors of Epidermal Growth Factor Receptor Inhibitors (EGFRI) response in Non-Small Cell Lung Cancer (NSCLC). From these data, we first identified TGFβ signaling as a possible modulator of EGFRI resistance and I hypothesized that TGFβ signaling participates in the development and maintenance of erlotinib-resistance …

An Exploratory Statistical Method For Finding Interactions In A Large Dataset With An Application Toward Periodontal Diseases, Joshua Lambert

Theses and Dissertations--Epidemiology and Biostatistics

It is estimated that Periodontal Diseases effects up to 90% of the adult population. Given the complexity of the host environment, many factors contribute to expression of the disease. Age, Gender, Socioeconomic Status, Smoking Status, and Race/Ethnicity are all known risk factors, as well as a handful of known comorbidities. Certain vitamins and minerals have been shown to be protective for the disease, while some toxins and chemicals have been associated with an increased prevalence. The role of toxins, chemicals, vitamins, and minerals in relation to disease is believed to be complex and potentially modified by known risk factors. A …

Statistical Analyses To Detect And Refine Genetic Associations With Neurodegenerative Diseases, Yuriko Katsumata

Theses and Dissertations--Epidemiology and Biostatistics

Dementia is a clinical state caused by neurodegeneration and characterized by a loss of function in cognitive domains and behavior. Alzheimer’s disease (AD) is the most common form of dementia. Although the amyloid β (Aβ) protein and hyperphosphorylated tau aggregates in the brain are considered to be the key pathological hallmarks of AD, the exact cause of AD is yet to be identified. In addition, clinical diagnoses of AD can be error prone. Many previous studies have compared the clinical diagnosis of AD against the gold standard of autopsy confirmation and shown substantial AD misdiagnosis Hippocampal sclerosis of aging (HS-Aging) …

Promotion Of Early Pediatric Hearing Detection Through Patient Navigation, Matthew L. Bush

Theses and Dissertations--Clinical and Translational Science

Congenital hearing loss is the most common neonatal sensory disorder and it is crucial to diagnose hearing loss as soon as possible after birth in order to facilitate rapid treatment. Universal standards of infant hearing healthcare dictate that infant hearing screening should be completed by one month of age and abnormal screening tests should be followed with definitive audiological testing by three months of age. Obtaining diagnostic testing can be complicated by limited access to care in rural areas, breakdowns in communication, lack of parental support, and poor coordination of care. There is no established method to address appointment non-adherence …

Vocal Function Exercises For Normal Voice: With And Without Semi-Occlusion, Megan Suzanne Brown

Theses and Dissertations--Communication Sciences and Disorders

The primary purpose of this investigation was to explore the effects of varying degrees of vocal tract semi-occlusion in Vocal Function Exercises (VFEs) on attainment of pre- established maximum phonation time (MPT) goals in individuals between the ages of 18 and 45 with normal voice. Individuals were randomized into three experimental groups: the traditional VFE with a semi-occluded vocal tract (SOVT), modified /o/ with partial occlusion, and modified /a/ without significant occlusion. For six weeks, the participants completed the four exercises two times each, twice daily on corresponding vocal tract postures assigned by group. Results indicated significant change in percent …

Inter-Rater Reliability Of Diagnostic Language Testing Administered Via Telepractice, Sarah E. Adams

Theses and Dissertations--Communication Sciences and Disorders

Federal law mandates children with language disorders receive free and appropriate intervention. Diagnosis is the first step in the intervention continuum; however, children in rural America are underserved due to personnel shortages. Limited studies have demonstrated the reliability of language testing conducted via telepractice. Further research examining the reliability of language tests administered via telepractice is necessary. The purpose of this study was to assess inter-rater reliability of three language tests administered via telepractice.

Longitudinal Adaptations In Muscle Strength, Functional Performance, Gait Biomechanics, And Patient-Reported Function After Unilateral Total Knee Arthroplasty, Paul W. Kline

Theses and Dissertations--Rehabilitation Sciences

Objective: The aims of this research were to identify gaps in the literature related to impairments after total knee arthroplasty (TKA) (Aim 1) and define recovery between 3 and 6 months after TKA across four domains: 1) hip and knee muscle performance, 2) functional performance, 3) patient-reported function, and 4) biomechanics of walking and stair descent (Aim 2). Additionally, this project sought to explore the relationships between each domain (Aim 3) and establish predictive models to allow clinicians to use clinical measures to predict future gait biomechanics in patients after TKA (Aim 4). Ultimately, the results of this research would …

Effect Of A 12-Week Home-Based Neuromuscular Electrical Stimulation Treatment On Clinical Outcomes Following Articular Cartilage Knee Surgery, Caitlin E. Whale Conley

Theses and Dissertations--Rehabilitation Sciences

Articular cartilage defects in the knee are common, and can result in pain, decreased function and decreased quality of life. Untreated defects are considered to be a risk factor for developing osteoarthritis, a progressive degenerative joint disease with minimal treatment options. To address these issues, various surgical procedures are available to treat articular cartilage defects in the knee. While these procedures overall have positive results, after surgery patients experience large and persistent deficits in quadriceps strength. A contributing factor to this post-surgical weakness is believed to be the extended post-operative non-weight bearing period, with full weight bearing not initiated until …

A Grounded Theory Study Of Maternal Engagement Of Low Income, Young Rural Mothers In Home-Based, Early Intervention Services, Elaine K. Fehringer

Theses and Dissertations--Rehabilitation Sciences

Home-based, early intervention programs as a preferred delivery model are widely endorsed, heavily funded and highly utilized as prevention and remediation initiatives for families with young children (Eckenrode, et al., 2010; Karoly, Killion, & Cannon, 2005). Of concern, is that while an estimated 40 billion dollars are spent annually between federally funded programs and private foundations, a significant number of families disengage from services before the end of a child’s eligibility period (Stevens, Ammerman, Putnam, Gannon, & van Ginkel, 2005). Several meta-analyses indicate only modest effectiveness of home-based services (Tandon, et al., 2008). It is estimated that well over 500,000 …

The Relationship Between Selective Attention And Global Coherence In Narrative Discourse Following Right Hemisphere Stroke, Katherine Mccomas Maddy

Theses and Dissertations--Rehabilitation Sciences

Stroke is the leading cause of serious, long-term disability and nearly half of older stroke survivors experience moderate to severe disability. A common impairment following stroke is impaired discourse production. Functional outcome studies have proposed that the recovery of discourse abilities is critical to achieving a good quality of life. Communication impairments often persist into the chronic stages of recovery and can cause individuals to withdraw from social situations. Discourse production deficits may not be apparent in basic communication interactions, but become more obvious during complex conversations following non-aphasic brain injury (NABI) or right hemisphere stroke (RHD). The purpose of …

Telomerase Reverse Transcriptase In Atherosclerosis, Hua Qing

Theses and Dissertations--Pharmacology and Nutritional Sciences

Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase and the limiting factor for the enzyme activity. The expression of TERT and telomerase activity is increased in atherosclerotic plaques. However, the role of TERT dysregulation during atherosclerosis formation remains unknown.

The work herein first identified a multi-tiered regulation of TERT expression in smooth muscle cells (SMC) through histone deacetylase (HDAC) inhibition. HDAC inhibition induces TERT transcription and promoter activation. At the protein level in contrast, HDAC inhibition decreases TERT protein abundance through enhanced degradation, which decreases telomerase activity and induces senescence. Furthermore, during vascular remodeling in vivo, TERT protein …

The Role Of Progesterone Receptor Membrane Component 1 In Receptor Trafficking And Disease, Kaia K. Hampton

Theses and Dissertations--Pharmacology and Nutritional Sciences

The progesterone receptor membrane component 1 (PGRMC1) is a multifunctional protein with a heme-binding domain that promotes cellular signaling via receptor trafficking, and is essential for some elements of tumor growth and metastasis. PGRMC1 is upregulated in breast, colon, lung and thyroid tumors. We expanded the analysis of PGRMC1 in the clinical setting, and report the first analysis of PGRMC1 in human oral cavity and ovarian tumors and found PGRMC1 to correlate with lung and ovarian cancer patient survival. Furthermore, we discovered a specific role for PGRMC1 in cancer stem cell viability. PGRMC1 directly associates with the epidermal growth factor …

Insulin Actions On Hippocampal Neurons, Shaniya Maimaiti

Theses and Dissertations--Pharmacology and Nutritional Sciences

Aging is the main risk factor for cognitive decline. The hippocampus, a brain region critical for learning and memory formation, is especially vulnerable to normal and pathological age-related cognitive decline. Dysregulation of both insulin and intracellular Ca2+ signaling appear to coexist and their compromised actions may synergistically contribute to neuronal dysfunction with aging. This dissertation focused on the interaction between insulin, Ca2+ dysregulation, and cognition in hippocampal neurons by examining the contributions of insulin to Ca2+ signaling events that influence memory formation. I tested the hypothesis that insulin would increase cognition in aged animals by altering Ca2+-dependent physiological mechanisms involved …

Protection From Aortic Aneurysm By Bmal1 Deletion From Smooth Muscle Cells, Jenny Lutshumba

Theses and Dissertations--Physiology

Abdominal aortic aneurysm (AAA) is a devastating condition that occurs primarily among older people with high mortality when a rupture occurs. Currently there is no proven pharmacological therapy for AAA due to poor understanding of the underlying pathogenesis. The brain and muscle transcription factor ARNT-like (Bmal1), which is known to regulate circadian rhythm, has been implicated in vascular pathologies including atherosclerosis and vascular remodeling, but its role in AAA has not been explored.

Vascular smooth muscle is a central player in aneurysm formation and development because it is critical in all three aortic aneurysm hallmark processes including (a) degradation of …

Neuroinflammation In Alzheimer's Disease And Vascular Cognitive Impairment, Erica M. Weekman

Theses and Dissertations--Physiology

It was once believed that the brain was immunologically privileged with no resident or infiltrating immune cells; however, now it is understood that the cells of the brain are capable of a wide range of inflammatory processes and phenotypes. Inflammation in the brain has been implicated in several disease processes such as Alzheimer’s disease (AD) and vascular cognitive impairment and dementia (VCID); however, the role of inflammation in these two dementias is poorly understood.

When we stimulated a pro-inflammatory phenotype with an adeno-associated viral vector in a transgenic mouse model of AD that develops Aβ plaques, we saw a pro-inflammatory …

New Insights Into Post-Sepsis Muscle Weakness Elucidated Using A Novel Animal Model, Allison M. Steele

Theses and Dissertations--Physiology

Sepsis is a severe life-threatening critical illness that damages multiple physiological systems. After hospital discharge, more than 70% of severe sepsis survivors report profound weakness which significantly impacts quality of life. Such weakness gives rise to new limitations of daily living, which ultimately leads to loss of independence in many patients. Despite wide recognition of this serious issue by clinicians and researchers alike, the mechanisms contributing to chronic skeletal muscle dysfunction after sepsis are not well understood. Lack of progress in this field is largely due to the absence of an appropriate animal model; current models are either too mild …

Role Of Skeletal Paracrine Signals In The Proliferation And Chondrogenic Differentiation Of Interzone Cells, Parvathy Thampi

Theses and Dissertations--Veterinary Science

Articular cartilage in mammals has a limited intrinsic capacity to repair structural injuries and defects, a fact that contributes to the chronic and progressive nature of osteoarthritis. Current treatment modalities do not enable articular cartilage to achieve a complete and permanent restoration of normal structure and function with large or partial thickness lesions. In contrast to mammals, Mexican axolotl salamanders (Ambystoma mexicanum) have demonstrated the remarkable ability to spontaneously and completely repair even large joint cartilage lesions, an intrinsic healing process that involves interzone cells in the intraarticular space. Further, when interzone tissue is transplanted into critical sized …

Biology And Detection Of Pregnanes During Late Gestation In The Mare, Michelle Arelia Ann Wynn

Theses and Dissertations--Veterinary Science

Progesterone in the mare declines to almost undetectable concentrations in late gestation. It’s metabolized into several pregnanes, some circulating at very high concentrations. Although the function of many pregnanes remains unclear, 5α-dihydroprogesterone and allopregnanolone are bioactive. Measurements of pregnanes in late gestation are typically by immunoassay, although results are confounded by cross-reactivity with related pregnanes. Conversely, liquid chromatography tandem mass spectrometry (LC-MS/MS) allows differentiation of individual pregnanes. The purposes of these studies were: 1) to evaluate the ability of a 5α-reductase inhibitor, dutasteride, to alter pregnane metabolism and pregnancy outcome, 2) to evaluate changes in target pregnanes in late gestation …

An Investigation Into Specific Seminal Plasma Proteins And Their Effect On The Innate Immune Response To Breeding In The Mare, Carleigh Elizabeth Fedorka

Theses and Dissertations--Veterinary Science

The mare experiences a transient innate immune response to breeding, the resolution of which is crucial for optimal fertility. The majority of mares are able to modulate this inflammation in a timely fashion, but a subpopulation exists which fail to do so and are considered susceptible to persistent breeding-induced endometritis (PBIE). Seminal plasma has been shown to modulate aspects of this inflammation. Recently, two seminal plasma proteins have garnered interest for their immune modulating properties: cysteine-rich secretory protein-3 (CRISP-3) and lactoferrin. These proteins have been found to alter the binding between sperm and neutrophils based on sperm viability in vitro …