Medicine and Health Sciences Commons^™

Toward Personalized Medicine: The Potential Role Of Rna Interference In Plasma Cell Dyscrasia, Jonathan E Phipps

Doctoral Dissertations

A major contributor to mortality in patients with plasma cell dyscrasias (PCDs); i.e., multiple myeloma, light chain deposition disease and AL amyloidosis is the deposition as insoluble aggregates of monoclonal immunoglobulin light chain proteins (LC) in the kidneys and other organs. Currently anti-plasma cell chemotherapies are used to reduce LC synthesis, and slow deposition. While effective, these treatments are toxic, non-specific, expensive, and might not be appropriate in all cases, making the identification of an alternate means of reducing toxic LC species desirable. To this end, we have investigated whether RNA interference (RNAi) could achieve these goals.

Human (RPMI 8226, …

Prenatal Care Choices In Appalachia: A Qualitative, Critical Realist Description & Content Analysis, Julia Cain Phillippi

Doctoral Dissertations

Introduction: Appalachian women have high rates of preterm birth and low birth weight infants. A new format of group prenatal care, known as CenteringPregnancy, decreases the rate of preterm birth and low birth weight when compared with individual care. However, clinics in Appalachia often struggle to recruit women into group care. Theory & Methods: Using critical realism and the middle-range theory of motivation-ease as frameworks, this qualitative study had two research questions: ‘What influences Appalachian women’s choice of traditional prenatal care instead of CenteringPregnancy care?’ and ‘What are Appalachian women’s perceptions of prenatal care and their access to prenatal care?’. …

Characterization Of A Small Animal Spect Platform For Use In Preclinical Translational Research, Dustin Ryan Osborne

Doctoral Dissertations

Imaging Iodine-125 requires an increased focus on developing an understanding of how fundamental processes used by imaging systems work to provide quantitative output for the imaging system. Isotopes like I-125 pose specific imaging problems that are a result of low energy emissions as well as how closely spaced those emissions are in the spectrum. This work seeks to characterize the performance of a small animal SPECT-CT imaging system with respect to imaging I-125 for use in a preclinical translational research environment and to understand how the performance of this system relates to critical applications such as attenuation and scatter correction. …

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 …

“This Is Me. I Like Who I Am”: A Qualitative Descriptive Study Using Photo Elicitation To Examine The World Of The School-­Age Child With Cystic Fibrosis, Renee Carol Burk

Doctoral Dissertations

School-age children with Cystic Fibrosis (CF) possess valuable knowledge about themselves. They have experience and ability to offer insight about living with CF. Previous studies, exploring the perceptions of CF children, give little attention to eliciting and listening to their voices. Also, traditional data collection methods limit children from participating in research. The purpose of this study was to explore and describe how school-age children with CF see themselves in the world they live.

The study utilized qualitative description methodology. Symbolic Interactionism served as the researcher’s philosophical lens. It is a perspective that seeks to understand the social world of …

The Role Of Systemic Inflammation In The Development Of Equine Laminitis, Elizabeth Maryrose Tadros

Doctoral Dissertations

Laminitis is a crippling disease of horses that can result in chronic lameness and debilitation, and sometimes warrants euthanasia. It is a complication of inflammatory conditions such as gastrointestinal disease, and also occurs in obese, insulin-resistant horses with Equine Metabolic Syndrome (EMS). Inflammation and insulin resistance are risk factors for laminitis, and these mechanisms might converge to induce laminitis in susceptible animals.

Systemic inflammation is often attributed to endotoxemia, although circulating endotoxin concentrations are not commonly measured in the clinical setting. Although a theoretic basis exists for endotoxemia in the pathogenesis of laminitis, administration of endotoxin alone does …

Identification Of Novel Molecular Targets Of Resveratrol In Colorectal Carcinogenesis, Nichelle Chantil Whitlock

Doctoral Dissertations

Current research suggests resveratrol, a phytoalexin found predominately in grapes, may function as a chemopreventive and/or chemotherapeutic agent for various cancers, including colorectal cancer. However, the underlying mechanism(s) involved in these activities remain elusive. Thus, the objective of the studies discussed here sought to investigate the effect of resveratrol treatment on gene modulation in human colorectal cancer cells in order to identify and characterize novel molecular targets that contribute to the observed anticancer activities of resveratrol. Here, we identify activating transcription factor 3 (ATF3) and early growth response-1 (Egr-1) as novel targets of resveratrol and provide data to elucidate the …

Asymmetric Total Synthesis Of Congeners Of Hydramycin, An Anthraquinone-Type Antitumor Agent, Costyl Ngnouomeuchi Njiojob

Doctoral Dissertations

Hydramycin is an antitumor antibiotic isolated from Streptomyces violaceus. It is a pyranoanthraquinone-type antitumor agent that has shown broad-spectrum activity against a variety of human-derived cancer cell lines. Among tumors evaluated at the National Cancer Institute (lung, colon, melanoma, breast and prostate), GI₅₀s were <10⁻¹⁰ M in the NCI's 60-cell-line panel. We embarked on the synthesis and evaluation of a simplified congener 2-(1-hydroxy-1-(oxiran-2-yl)ethyl)-4H-naphtho[2,3-h]chromene-4,7,12-trione(17), which would facilitate synthesis while retaining the potent activity. Hydramycin has two chiral centers, and our goal is to design and synthesize all the possible enantiomers (four in …

The Effect Of Reflective Writing Interventions On Critical Thinking Skills, Jessica L Naber

Doctoral Dissertations

The importance of critical thinking as an outcome for students graduating from undergraduate nursing programs is well-documented by both the American Association of Colleges of Nursing (AACN) and the National League for Nursing (NLN). Graduating nurses are expected to apply critical thinking in all practice situations to improve patient health outcomes. Reflective writing is one strategy used to increase understanding and ability to reason and analyze. The lack of empirical evidence regarding the effectiveness of reflective writing interventions on increasing critical thinking skills supports the need for examining reflective writing as a critical thinking strategy. The purpose of this study …

Immunologic Risk Prediction Model For Kidney Graft Function, Christina Diane Bishop

Doctoral Dissertations

Clinicians lack appropriate non-invasive methods to be able to predict, diagnose, and reduce the risk of rejection in the years following kidney transplantation. Protocol biopsies and monitoring of serum creatinine levels are the most common methods of monitoring graft function after transplant; however, they have several negative aspects. Use of traditional factors regarding donors and recipients such as Human Leukocyte Antigen (HLA) DNA typing, pre-transplant anti-HLA antibody levels, and basic demographics (age, ethnicity/race, gender), has proved inadequate for post-transplant graft monitoring past the first few years. We propose that by utilizing immunologic factors available to clinicians across the United States, …

Behavioral Activation Of Religious Behaviors: Treating Depressed College Students With A Randomized Controlled Trial, Maria Elizabeth Anne Armento

Doctoral Dissertations

Abstract

Although spiritual or religious behaviors are sometimes targeted within behavioral activation protocols (Hopko & Lejuez, 2007; Hopko, Lejuez, Ruggiero, & Eifert, 2003), the efficacy of a protocol that exclusively develops a religiously-based behavioral repertoire has not been investigated. This randomized controlled study investigated the efficacy of a brief protocol for religious action in behavioral activation (PRA-BA) relative to a no-treatment “support” condition among mild to moderately depressed undergraduate students (n = 50). PRA-BA consisted of an individualized one-session intervention and 2-week activation interval. Clinical outcomes assessed depression, environmental reward, anxiety, and quality of life. Repeated measures ANOVAs indicated …

Disaster Education For Nurses: A Comparison Of Two Instructional Methods For Teaching Basic Disaster Life Support In The Light Of Self-Efficacy Theory, Mary Catherine Nypaver

Doctoral Dissertations

Abstract

Nurses constitute the largest group in the healthcare workforce and are called on to assist in emergencies such as disasters. Research has shown that professionals with higher levels of knowledge are more likely to respond to actual emergencies. Yet most hospital based nurses do not possess the skills needed for disaster response. The Basic Disaster Life Support (BDLS) course, with its comprehensive content, represents the gold standard for disaster education. Since confidence also plays a role in response, a tool to measure this variable could be useful. There were five purposes of this study: determine whether one teaching method …

Role Of Il-17 And Th17 Cells In Hsv Induced Ocular Immunopathology, Amol Sahebrao Suryawanshi

Doctoral Dissertations

Herpes simplex virus (HSV) infection of the cornea leads to a blinding immuno-inflammatory condition of the eye also called stromal keratitis (SK). SK immunopathology is characterized by the infiltration of CD4⁺ T cells of Th1 phenotype as well as the development of new blood vessels into the normally avascular cornea. Studies in mouse models of SK have firmly established the role of CD4⁺ T cells, and particularly of Th1 phenotype, as the principal mediators of SK immunopathology. However, with the recent discovery of IL-17A and Th17 cells, the role of this cytokine as well as Th17 cells remains …

Using Sport To Build Community: Service-Learning With Iraqi Refugees, Ashleigh Morgan Huffman

Doctoral Dissertations

The purpose of this study was to explore the connections between Sport for Development and Peace (SDP), service-learning, and community-university partnerships through the implementation of the Service-Learning: Sport and Community Development (SCD) class. It was my hope that this research would produce a usable model, a framework for other scholars and practitioners interested in developing community-university partnerships. I wanted this project to not only answer the “why” questions for SDP and service-learning, but also the “how” questions – specifically, how to create a reflexive and collaborative partnership that balances the needs of the community and university. I wanted to create …

Physical Activity Assessment In Wheelchair Users, Scott Alexander Conger

Doctoral Dissertations

Purpose: To examine the relationship between hand rim propulsion power and energy expenditure during wheelchair locomotion. Methods: Fourteen individuals who used manual wheelchairs were included in this study. Each participant performed five different locomotion activities in a wheelchair with a PowerTap hub built into the rear wheel. The activities included wheeling on a level surface that elicited a low rolling resistance at three different speeds (4.5, 5.5, and 6.5 km∙hr^-1), wheeling on a rubberized 400m track that elicited a higher rolling resistance at one speed (5.5 km∙hr^-1), and wheeling on a sidewalk course that included uphill …

A Geospatial Based Decision Framework For Extending Marssim Regulatory Principles Into The Subsurface, Robert Nathan Stewart

Doctoral Dissertations

The Multi-Agency Radiological Site Survey Investigation Manual (MARSSIM) is a regulatory guidance document regarding compliance evaluation of radiologically contaminated soils and buildings (USNRC, 2000). Compliance is determined by comparing radiological measurements to established limits using a combination of hypothesis testing and scanning measurements. Scanning allows investigators to identify localized pockets of contamination missed during sampling and allows investigators to assess radiological exposure at different spatial scales. Scale is important in radiological dose assessment as regulatory limits can vary with the size of the contaminated area and sites are often evaluated at more than one scale (USNRC, 2000). Unfortunately, scanning is …

Terminal Sedation, Karen L Smith

Doctoral Dissertations

This dissertation will support full ethical endorsement of terminal sedation for those most urgently in crisis and need of beneficence, those who are dying and in the final hours or days and suffering. To clarify the practice I first detail ethical differences between euthanasia, physician assisted suicide and terminal sedation. Moreover, I identify new areas where harms and benefits need to be evaluated as affecting not only patients, but also families and caregivers. I evaluate the current practice to allow the development of ethical guidelines and greater consensus on deciding the hard cases. This work may also serve to assist …

Mechanism Of Phospholipid Induction Of Cell Migration, Dongwei Wu

Doctoral Dissertations

Lysophosphatidic acid (LPA) is a potent bioactive lipid component of oxidized low density lipoproteins (oxLDL). High concentrations of LPA have been detected in human atherosclerotic plaques. Our data has shown that LPA highly induces smooth muscle cell (SMC) migration. Cyr61, a matricellular protein, which also accumulates in human atherosclerotic plaques, has been implicated in the injury-induced neointimal formation. Smooth muscle cell migration is a key event in the development of atherosclerosis, and it contributes to the progressive growth of atherosclerotic lesions. Data generated by this study demonstrate that LPA markedly induces Cyr61 expression in mouse aortic smooth muscle cells (MASMC). …

The Relationship Between Self-Directedness And Health Promotion In The Elderly, Barbara L Hulsman

Doctoral Dissertations

With the number of people living longer and with more chronic problems, it is important that health educators examine who they are educating as well as the methods and circumstances of the education. The purpose of this study was to identify the relationship between self-directedness and health promotion in the elderly. A convenience sample of 108 elders who use Senior Centers in rural East Tennessee comprised the study group. The sample was asked to complete the Self-Directed Learning Readiness Scale, the Health Promoting Lifestyle Profile II, and a demographic information survey at a regular meeting of a Senior Center. A …

Having An Elective Cesarean Section: Doing What's Best, Cynthia R Acuff Michaluk

Doctoral Dissertations

The purpose of this study was to discover a theory on how women decide to deliver their babies by cesarean section instead of experiencing a trial of labor and expected vaginal delivery when it is appropriate. The specific goals are to answer the research questions: What is the decision-making process by which healthy, low-risk women choose to deliver their babies by cesarean delivery in the absence of medical indications? What antecedents occur to influence a pregant woman's decision to undergo a maternal request cesaren section? Seven women from the surrounding Knoxville area underwent in-depth interviews. To qualify for the study, …

Chemical Tools To Characterize Membrane-Protein Binding Interactions Using Synthetic Lipid Probes, Meng Meng Rowland

Doctoral Dissertations

Signaling lipids such as diacylglycerol (DAG) and the phosphatidylinositol polyphosphates (PIP_ns) play crucial roles in numerous cellular pathways. However, characterization of their activities is hindered by the complexity of associated signaling pathways and of the membrane environment. To address this issue, we have developed lipid probes that are effective for characterizing biological events using different applications, including activity-based probing (PIP_ns and DAG) and microarray analysis (PIP_ns). The activity-based probes have been applied to label receptor targets in multiple cancer cell proteomes through photocrosslinking followed by click reactions. The probes were found to label several …

Development Of An Autonomous Mammalian Lux Reporter System, Daniel Michael Close

Doctoral Dissertations

Since its characterization, the definitive shortcoming of the bacterial luciferase (lux) bioluminescent reporter system has been its inability to express at a functional level in the eukaryotic cellular background. While recent developments have allowed for lux function in the lower eukaryote Saccharomyces cerevisiae, they have not provided for autonomous function in higher eukaryotes capable of serving as human biomedical proxies. Here it is reported for the first time that, through a process of poly-bicistronic expression of human codon-optimized lux genes, it is possible to autonomously produce a bioluminescent signal directly from mammalian cells. The low background of …

“It Can Start From Anything”: An Existential Phenomenological Investigation Of Athletes’ Experiences Of Psychological Momentum, Greg Young

Doctoral Dissertations

Psychological Momentum (PM) is a commonly recognized phenomenon in sport, yet remains one of the least understood (Taylor & Demick, 1994). Previous research examined PM using archival data (Gayton & Very, 1993; Gilovich, Vallone, & Tversky, 1985; Koehler & Conley, 2003; Silva, Hardy, & Crace, 1988), hypothetical and contrived scenarios (Eisler & Spink, 1998; Miller & Weinberg, 1991; Perreault, Vallerand, Montgomery, & Provencher, 1998; Vallerand, Colavecchio, & Pelletier, 1988), and actual performance (Mack, et al., 2008). More recently, Jones and Harwood (2008) used semi-structured interviews to examine participants’ …

Kenshi’S Experiences Of Kendo: A Phenomenological Investigation, Takahiro Sato

Doctoral Dissertations

The aim of this study was to extend existing literature on the martial arts by examining the experience of kendo (Japanese fencing) participants. In-depth, existential phenomenological interviews were conducted with nine (eight males and one female) currently competitive kendo practitioners (i.e., kenshi), ranging in age from 19 to 40 years. All participants were of Japanese descent but resided in the United States at the time of the interviews. Thematic analysis of the transcripts revealed several prominent aspects of the lives and performance experiences of kenshi. The most important finding was the relatively equal emphasis participants placed on the mastery …