Medicine and Health Sciences Commons^™

The Use Of Gesture In Self-Initiated Self-Repair Sequences By Persons With Non-Fluent Aphasia, Eleanor M. Feltner

Theses and Dissertations--Linguistics

This study examines the relationship between types of gestures and instances of self-initiated self-repair (SISR) used by persons with non-fluent aphasia (NFA), which is a type of aphasia characterized by stilted speech or signing (Papathanasiou et al., 2013), in interactions with clinicians. Conversation repairs in this study are assessed using the framework of Conversation Analysis (CA), which is an approach for describing, analyzing, and understanding social interaction (Sidnell, 2010). Previous linguistic studies have demonstrated a distinct preference for the use of gesture during a repair by persons with aphasia (Goodwin, 1995; Klippi, 2015; Wilkinson, 2013). This study draws more conclusive …

The Role Of Sox4 In Regulating Choroid Fissure Closure And Retinal Neurogenesis, Wen Wen

Theses and Dissertations--Biology

The development of the vertebrate eye is tightly controlled by precise genetic regulations. From a single ocular primordium to bilateral eyes with complex structures and cell types, it requires intensive proliferation and migration for cells in both the ectoderm and mesoderm to accomplish ocular morphogenesis, and during this process cell differentiation and interaction takes place to establish the complex composition of ocular cell types and cellular connections. Genetic defects can lead to severe abnormalities in eye morphogenesis and cell differentiation during ocular development. A tremendous amount of work has been done to identify both intrinsic and extrinsic factors that regulate …

Comprehensive Sexuality Education In Kentucky, Luciana D. Hockersmith

Theses and Dissertations--Community & Leadership Development

Discussions of sex education of any kind can be controversial in a given setting. Traditional approaches to sex education prompt debate regarding effectiveness. Key indicators central to the effectiveness of sex education continue to be rates of teen pregnancy and transmission of sexually transmitted diseases (STDs). With discontentment surrounding the effectiveness of “traditional approaches,” a more wide-ranging method is worthy of being explored. The curriculum approach of Comprehensive Sexuality Education (CSE) includes six key concepts, and subsequent sub-concepts, intended to provide a broad and even all-inclusive range of topics for a similarly broad and even all-inclusive range of ages of …

Cerebrovascular Risk Factors, Arteriolar Sclerosis, And Cognitive Decline In The Kentucky Appalachian “Stroke-Belt”, Omar M. Al-Janabi

Theses and Dissertations--Medical Sciences

The relationship between cerebrovascular disease (CVD) risk factors and cognitive impairment or dementia has been widely studied with significant variability in findings between groups. We hypothesized that chronic small vessel injury in the form of arteriolar sclerosis, measured quantitatively using MRI to measure total white matter hyperintensity (WMH) volumes, would identify specific association of CVD risk factors and patterns of cognitive decline, associated with mild cognitive impairment of the cerebrovascular type, that represent the core features of vascular cognitive impairment in our cohort.

A Cross-sectional analysis of clinical and quantitative MRI data on 114 subjects with normal cognitive function (n=52) …

Evaluating The Use Of Second LifeTm For Virtual Team-Based Learning In An Online Undergraduate Anatomy Course, Christena Gazave

Theses and Dissertations--Medical Sciences

Team-based learning (TBL) is one strategy for improving team-work and critical thinking skills. It has proven to be an engaging teaching pedagogy in face-to-face classes, however, to our knowledge, has never been implemented online in a 3-D virtual world. We implemented virtual TBLs in an online undergraduate anatomy course using Second Life^TM, and evaluated whether it engaged students. This study was conducted over 2 semesters with 39 total students. Surveys and content analysis of transcripts were used to evaluate student engagement. Our results indicate virtual TBLs were engaging for most students. The average engagement score was 7.8 out …

Looking To The Future Of Stroke Treatment: Combining Recanalization And Neuroprotection In Acute Ischemic Stroke, Michael E. Maniskas

Theses and Dissertations--Neuroscience

Stroke is the 5^th leading cause of death in the U.S. with 130,000 deaths and around 800,000 affected annually. Currently, there is a significant disconnect between basic stroke research and clinical stroke therapeutic needs. Few animal models of stroke target the large vessels that produce cortical deficits seen in the clinical setting. Also, current routes of drug administration, intraperitoneal and intravenous, do not mimic the clinical route of intra-arterial drug administration. To bridge this divide, we have retro-engineered a mouse model of stroke from the current standard of care for emergent large vessel occlusion (ELVO) stroke, endovascular thrombectomy, to …

Novel Targets For Mitochondrial Dysfunction Following Traumatic Brain Injury, Heather M. Yonutas

Theses and Dissertations--Neuroscience

Mitochondrial dysfunction is a phenomenon observed in models of Traumatic Brain Injury (TBI). Loss of mitochondrial bioenergetics can result in diminished cellular homeostasis leading to cellular dysfunction and possible cellular death. Consequently, the resultant tissue damage can manifest as functional deficits and/or disease states. Therapeutic strategies to target this mitochondrial dysfunction have been investigated for models TBI and have shown promising effects.

For this project, we tested the hypothesis that mitoNEET, a novel mitochondrial membrane protein, is a target for pioglitazone mediated neuroprotection. To test this, we used a severe Controlled Cortical Impact (CCI) injury model in mitoNEET null and …

Biobehavioral Influences Of Anxiety, Depression, And Hostility Symptoms On Health-Related Outcomes In Patients With Heart Failure, Lynn P. Roser

Theses and Dissertations--Nursing

The incidence of heart failure (HF) has increased each year as more people are living longer with heart disease and other chronic conditions. Recently, there has been much interest in the psychological dimensions of HF and the influence psychological symptoms have on the health outcomes (e.g., self-care, rehospitalization, mortality and quality of life) of patients living with HF. Patients with HF frequently experience symptoms of anxiety, depression, and hostility that may be associated with poor health outcomes. The purpose of this dissertation was to examine how psychological variables influence health outcomes of patients with HF, how psychological variables change over …

Effects Of Obesity On United States Farmers: A Pilot Study, Sharon C. Hunsucker

Theses and Dissertations--Nursing

Previous research described the value farmers place on their ability to work. The impact of obesity on workers is an increasing concern in occupational health research; yet, knowledge regarding the impact of obesity on the performance of farm work is limited. Identifying the impact of obesity on farmer’s work ability can guide healthcare workers in promoting and motivating farmers to implement lifestyle changes to improve health and sustain longevity in their ability to work.

The purpose of this dissertation was to examine the impact of obesity on the work ability of U.S. farmers. Specific aims were to 1) examine the …

Identification Of Early Markers Of Occult Tissue Hypoperfusion In Patients With Multiple Trauma Injuries, Kathryn M. Moore

Theses and Dissertations--Nursing

Injury is a global health problem and in the United States is the leading cause of death for persons aged 1 – 44 years. The primary causes of trauma related death are head injury and hemorrhage; hemorrhagic shock is difficult to recognize in the first hours after trauma. Identification of specific and optimal criteria upon which to base effective triage decisions for trauma patients has been an elusive goal for decades.

The purpose of this dissertation was to identify measures available in the prehospital phase of care and in the Emergency Department that should be included for a more comprehensive …

Hearts In The Balance: The Impact Of Desired Versus Received Social Support Needs On Persons With Heart Failure, Melanie P. Schrader

Theses and Dissertations--Nursing

Social support is the collection of tangible and intangible experiences that surround people as they cope with daily stressors. High quality social support is important among patients with cardiovascular disease (CVD) because it has positive effects on social, psychological and physical well-being, and those with good social support cope better with the travails of CVD. Although there are many studies of social support in CVD, little work has been done on the topic of discrepancies between desired and received social support in the context of gender.

The purpose of this dissertation was to determine if there are gender differences in …

Psychological Distress And Cardiac Disease, Tracey Vitori

Theses and Dissertations--Nursing

The purpose of this dissertation was to evaluate the association of psychological distress with cardiac disease, events, and mortality. Specific aims were to: 1) to evaluate the association between hostility level and recurrence of acute coronary syndrome (ACS) and all-cause mortality in patients with coronary heart disease (CHD); 2) to evaluate the psychometric properties of the Brief Symptom Inventory (BSI) hostility and anxiety subscales in a group of incarcerated participants at high risk of cardiovascular disease; and 3) to evaluate the association of patient and caregiver psychological state with quality of life in both patient and caregiver, and postoperative complications …

A Randomized Controlled Trial Of Anesthesia Guided By Bis Vs. Standard Care And Effects On Cognition, Zohn Centimole

Theses and Dissertations--Nursing

Postoperative cognitive dysfunction (POCD) occurs frequently in individuals undergoing major surgery with general anesthesia. POCD adversely affects morbidity and health-related quality of life. Derived electroencephalographic (EEG) monitoring is utilized to guide the anesthesia provider in titration of volatile anesthetics. POCD has been associated volatile anesthetic neurotoxicity. EEG monitors are known to reduce a patient’s total cumulative dose exposure to volatile anesthetics. There is currently little evidence to support utilization of EEG monitors as a guide to reduce the incidence of POCD.

The purpose of this dissertation was to develop and test a technique of general anesthesia, delivered by anesthesia providers …

Analysis Of Kentucky Medicaid Managed Care Versus Fee-For-Service Systems: Medication Adherence In Patients With Prevalent Chronic Diseases, Catherine K. Herren

Theses and Dissertations--Pharmacy

Objectives: Managed care organizations reduce healthcare costs and may improve patient health outcomes by encouraging better control of prevalent chronic diseases. The purpose of this study was to determine whether changing from a fee-for-service program to a capitated managed care program improved medication adherence for Medicaid patients in Kentucky with hypertension, hypercholesterolemia, or type 2 diabetes.

Methods: We conducted a quasi-experimental study of patients enrolled in Kentucky Medicaid to evaluate the impact of transitioning to capitated managed care in November 2011. Medication adherence was measured using the proportion of days covered (PDC) method. Multivariable analyses measured the adjusted …

The Effect Of Nicotine Co-Administration On Alcohol-Induced Reactive Hippocampal Cell Proliferation During Abstinence In An Adolescent Model Of An Alcohol Use Disorder, Megan Heath

Theses and Dissertations--Pharmacy

A significant consequence of alcohol use disorders (AUDs) is hippocampal neurodegeneration. The hippocampus is responsible for learning and memory, and neurodegeneration in this brain region has been shown to result in cognitive deficits. Interestingly, some alcoholics demonstrate improvements in hippocampus-dependent functions, potentially due the phenomenon termed adult neurogenesis. Adult neurogenesis, the process by which neural stem cells (NSCs) proliferate, differentiate into neurons, migrate into the granule cell layer, and survive, occurs in two brain regions; however, this study examines only neurogenesis occurring in the subgranular zone of the hippocampal dentate gyrus. Four-day binge ethanol exposure in an animal model causes …

Elucidating Proteasome Catalytic Subunit Composition And Its Role In Proteasome Inhibitor Resistance, Kimberly C. Carmony

Theses and Dissertations--Pharmacy

Proteasome inhibitors bortezomib and carfilzomib are FDA-approved anticancer agents that have contributed to significant improvements in treatment outcomes. However, the eventual onset of acquired resistance continues to limit their clinical utility, yet a clear consensus regarding the underlying mechanisms has not been reached.

Bortezomib and carfilzomib are known to target both the constitutive proteasome and the immunoproteasome, two conventional proteasome subtypes comprising distinctive sets of catalytic subunits. While it has become increasingly evident that additional, ‘intermediate’ proteasome subtypes, which harbor non-standard mixtures of constitutive proteasome and immunoproteasome catalytic subunits, represent a considerable proportion of the proteasome population in many cell …

In Vitro Activity Of Polymyxin B And Meropenem Alone And In Combination Against Carbapenem-Resistant Enterobacteriaceae, Brandon T. Kulengowski

Theses and Dissertations--Pharmacy

Background: Infections caused by carbapenem-resistant Enterobacteriaceae such as Escherichia coli and Klebsiella pneumoniae are among the most urgent threats of the infectious disease realm. The incidence of these infections has only been increasing over the years and due to very limited treatment options, mortality is estimated at about 50%.

Methods: To evaluate the in vitro activity of meropenem and polymyxin B against carbapenem-resistant Enterobacteriaceae, antimicrobial susceptibility testing and time-kill studies were performed on K. pneumoniae clinical isolates representing a wide range of meropenem resistance (MICs 4 – 128 mg/L).

Results: Regrowth was observed at clinically relevant concentrations of meropenem alone …

Development Of Cocaine Hydrolase For Therapeutic Treatment Of Cocaine Abuse, Xiabin Chen

Theses and Dissertations--Pharmacy

Cocaine abuse is a world-wide public health and social problem without a U.S. Food and Drug Administration (FDA)-approved medication. An ideal anti-cocaine medication would accelerate cocaine metabolism producing biologically inactive metabolites by administration of an efficient cocaine-specific exogenous enzyme. Recent studies in our lab have led to discovery of the desirable, highly efficient human cocaine hydrolases (hCocHs) that can efficiently detoxify and inactivate cocaine without affecting normal functions of central nervous system (CNS). Preclinical and clinical data have demonstrated that these hCocHs are safe for use in humans and effective for accelerating cocaine metabolism. However, the actual therapeutic use of …

Acute Kidney Injury In Patients Treated With Vancomycin And Piperacillin-Tazobactam: A Retrospective Cohort Analysis, Wilbur Cliff Rutter

Theses and Dissertations--Pharmacy

Empiric antimicrobial therapy often consists of the combination of Gram-positive coverage with vancomycin (VAN) and Gram-negative coverage, specifically an anti-pseudomonal beta-lactam, such as piperacillin-tazobactam (PTZ). Nephrotoxicity is commonly associated with VAN therapy; however, recent reports demonstrate increasing nephrotoxicity rates among patients treated with the combination of VAN and PTZ. This study evaluated the effect of the VAN/PTZ combination on acute kidney injury (AKI), as defined by the RIFLE criteria, compared to VAN and PTZ monotherapies.

Overall, 11,650 patients were analyzed, with 1,647 (14.1%) AKI cases occurring. AKI was significantly more frequent in the VAN/PTZ group (21%) compared to either monotherapy …

Clinical Outcomes Associated With Time To Antimicrobial Therapy Change From Vancomycin To Daptomycin In Staphylococcal Bacteremia, Sarah J. Tennant

Theses and Dissertations--Pharmacy

Background: Staphylococcus aureus is an aerobic, Gram positive commensal organism that is capable of causing a wide spectrum of disease. This study contributes to previously published literature regarding daptomycin versus vancomycin use in S. aureus bacteremia (SAB).

Methods: Adult patients admitted between 2010 and 2014, billed for ICD-9 code V09.0, 038.11, 038.12, 041.11, or 041.12, and received vancomycin and daptomycin were included in this retrospective analysis. Patients were stratified by time to change in antibiotics from vancomycin to daptomycin to the early switch (1-3 days), intermediate switch (4-7 days), or late switch (8 days or later) group. The primary outcome …

Towards Elucidation Of The Mechanism Of Biological Nanomotors, Zhengyi Zhao

Theses and Dissertations--Pharmacy

Biological functions such as cell mitosis, bacterial binary fission, DNA replication or repair, homologous recombination, Holliday junction resolution, viral genome packaging, and cell entry all involve biomotor-driven DNA translocation. In the past, the ubiquitous biological nanomotors were classified into two categories: linear and rotation motors. In 2013, we discovered a third type of biomotor, revolving motor without rotation. The revolving motion is further found to be widespread among many biological systems. In addition, the detailed sequential action mechanism of the ATPase ring in the phi29 dsDNA packaging motor has been elucidated: ATP binding induces a conformational entropy alternation of ATPase …

Development Of New Biological Nanopores And Their Application For Biosensing And Disease Detection, Shaoying Wang

Theses and Dissertations--Pharmacy

Nanopore technology has recently emerged as a new real-time single molecule sensing method. The current dominant technologies, such as mass spectrometry and immunoassay, for protein analysis is still slow and complex, which can’t meet the urgent need and fields of use. Development of a highly simple, portable and sensitive detection system for pathogen detection, disease diagnosis, and environmental monitoring is in great need. Membrane embedded Phi29 connector nanopore, the first protein nanopore coming from bacteriophage, was mainly focusing on DNA and RNA translocation in previous studies. Here, Phi29 connector nanopore was first time established for antibody detection by engineering Epithelial …

Rna Nanotechnology For Next Generation Targeted Drug Delivery, Fengmei Pi

Theses and Dissertations--Pharmacy

The emerging field of RNA nanotechnology is developing into a promising platform for therapeutically application. Utilizing the state-of-art RNA nanotechnology, RNA nanoparticles can be designed and constructed with controllable shape, size for both RNA therapeutics and chemical drug delivery. The high homogeneity in particle size and ease for RNA therapeutic module conjugation, made it feasible to explore versatile RNA nanoparticle designs for preclinical studies.

One vital module for therapeutic RNA nanoparticle design is RNA aptamer, which can enable the RNA nanoparticles find its specific target for targeted drug delivery. A system of screening divalent RNA aptamers for cancer cell targeting …

Vena Cava Filter Utilization And Retrieval: A Quality Of Care Issue, Joshua Brown

Theses and Dissertations--Pharmacy

Vena cava filters (VCFs) are mechanical devices implanted in the inferior vena cava to trap thrombi from travelling to the pulmonary circulation, resulting in pulmonary embolism. VCFs are available as permanent or non-permanent, retrievable devices and are generally indicated for use in patients unable to receive systemic anticoagulation or at exceedingly high risk for pulmonary embolism (PE). Retrievable devices allow for removal of the VCF once the contraindication to anticoagulation or high risk of PE has abated. Since the introduction of retrievable VCFs in the early 2000’s, use of VCFs has increased three-fold, with >85% of all VCFs placed being …

Investigating Mechanisms Determining Cancer Cell Sensitivity To Carfilzomib And Novel Strategies To Overcome Resistance, Lin Ao

Theses and Dissertations--Pharmacy

Proteasome inhibitors (PIs) are a class of FDA-approved anti-cancer agents which includes the first-generation PI bortezomib (BTZ) and second-generation carfilzomib (CFZ). Drug resistance is a major challenge in PI therapy with no solution currently available. While a few resistance mechanisms had been proposed for BTZ, little was known about CFZ resistance before the start of our studies. In this dissertation work, we investigated multiple mechanisms contributing to CFZ resistance—alterations in the drug transporter activity, metabolic stability, and proteasome activity profiles—and evaluated potential strategies to overcome CFZ resistance.

We observed marked upregulation of the drug efflux transporter P-glycoprotein (P-gp) in our …

Rna As A Unique Polymer To Build Controllable Nanostructures For Nanomedicine And Nanotechnology, Hui Li

Theses and Dissertations--Pharmacy

RNA nanotechnology is an emerging field that involves the design, construction and functionalization of nanostructures composed mainly of RNA for applications in biomedical and material sciences. RNA is a unique polymer with structural simplicity like DNA and functional diversity like proteins. A variety of RNA nanostructures have been reported with different geometrical structures and functionalities. This dissertation describes the design and construction of novel two-dimensional and three-dimensional self-assembled RNA nanostructures with applications in therapeutics delivery, cancer targeting and immunomodulation. Firstly, by using the ultra-stable pRNA three-way junction motif with controllable angles and arm lengths, tetrahedral architectures composed purely of RNA …

Evaluating A Bystander Intervention Program On Reproductive Coercion: Using Quasi-Experimental Design Strategies To Address Methodologic Issues In Randomized Community Prevention Trials, Catherine P. Starnes

Theses and Dissertations--Epidemiology and Biostatistics

Community (or cluster) randomized trials are trials in which communities or groups of individuals (clusters) are randomized to receive the intervention of interest. Community randomized trials frequently more closely resemble a natural experiment than a randomized controlled trial (RCT) following intervention allocation. In particular, the effects of non-compliance can pose methodologic challenges in estimating the intervention effect which may require a quasiexperimental approach in order to minimize bias.

The motivating example to illustrate these issues is the Green Dot High School (GDHS) study. The GDHS study was a longitudinal, cluster-randomized controlled trial designed to assess the effectiveness of a bystander …

Exploration Of The Misuse, Abuse, And Diversion Of Gabapentin, Rachel Vickers Smith

Theses and Dissertations--Epidemiology and Biostatistics

Gabapentin is currently approved by the Food and Drug Administration (FDA) as an adjunctive anti-convulsant and an analgesic for post-herpetic neuralgia. Though gabapentin was initially presumed to have limited or no abuse potential, which may have contributed to its widespread off-label prescribing, there have been increasing anecdotal and published reports of its misuse by substance abusers in the community and penal system. However, to date, there has been limited systematic evaluation of the scope and risk of gabapentin misuse and its associated effects. This dissertation assesses the etiology and prevalence of gabapentin misuse, abuse, and diversion in a multi-faceted approach, …

Biventricular Finite Element Modeling And Quantification Of 3d Langragian Strains And Torsion Using Dense Mri, Zhanqiu Liu

Theses and Dissertations--Mechanical and Aerospace Engineering

Statistical data suggests that increased use of evidence-based medical therapies has largely contributed to the decrease in American death rate caused by heart disease. And my studies are about two applications of magnetic resonance imaging (MRI) as a non-invasive approach in evidence-based health care research. In my first study, the achievement of a pulmonary valve replacement surgery was assessed on a patient with tetralogy of Fallot (TOF). In order to evaluate the remodeling of right ventricle, two biventricular finite element models were built up for pre-surgical images and post-surgical images. In my second study, 3D Lagrangian strains and torsion in …

The Role Of Fat Grafting And Adipose-Derived Stem Cells In Breast Reconstruction, Krishna S. Vyas

Theses and Dissertations--Clinical and Translational Science

Fat grafting is a common surgical procedure that involves the transfer of fat from one area of the body to another in order to improve contour deformities, such as in breast reconstruction. Advantages of the technique include using autologous tissue rather than a foreign body and the added benefit of having liposuction to remove fat from an undesirable location. Although adipose tissue could be the ideal soft tissue filler, fat grafting is plagued by tremendous variability in long-term retention, with volume survival rates of 20-80%, resulting in suboptimal outcomes and repetitive procedures.

The mechanisms contributing to long-term fat graft survival …