Medicine and Health Sciences Commons^™

Effects Of Cellular Heterogeneity And Immune Cells In Angiotensin Ii-Infused Hemorrhaged Ascending Aortas, Kyung Sik Jung

Theses and Dissertations--Toxicology and Cancer Biology

A previous thoracic aortic aneurysm time course study from our laboratory determined that ascending aortic dilation was significantly increased by day 5, and reached a plateau by day 28 of angiotensin II (AngII) infusion. We also found that mice had hemorrhage localized to the ascending aortas by day 5 of AngII infusion. The purpose of these studies was to provide mechanistic insight into the development of AngII-induced ascending aortic hemorrhage.

Male C57BL/6 mice fed normal diet were subcutaneously infused with either AngII (1000 ng/kg/min) or saline for 5 days. To examine cellular heterogeneity, hemorrhaged ascending aortas were collected and sectioned …

Cofilin Navigates Cellular Cytoskeleton And Invasion Responses To Tgf-Β Towards Prostate Cancer Metastasis, Joanne Collazo Santiago

Theses and Dissertations--Toxicology and Cancer Biology

Cofilin’s activity to nucleate actin filament assembly, is regulated by phosphorylation at a single site on the amino terminus, Serine 3. Phosphorylation at this site abolishes the ability of ADF/cofilin to bind to F-actin and inhibits its severing function. This work characterizes the ability of dephosphorylated cofilin (mutation at Serine 3 site) to navigate prostate cancer actin cytoskeleton and metastatic properties in response to TGF-β. TGF-β increased Lim Domain Kinase 2 (LIMK-2) activity leading to cofilin phosphorylation and decrease actin filament severing in wild type cofilin (WTCFL) PC-3 cells. Constitutively active cofilin in Serine 3 cofilin mutants (S3ACFL) promoted prostate …

Using Geospatial Technologies To Characterize Relationships Between Travel Behavior, Food Availability, And Health, Warren J. Christian

Theses and Dissertations--Geography

Epidemic obesity in the U.S. has prompted exploration of causal factors related to the built environment. Recent research has noted statistical associations between the spatial accessibility of retail food sources, such as supermarkets, convenience stores, and restaurants, and individual characteristics such as weight, socioeconomic status, and race/ethnicity. These studies typically use residential proximity or neighborhood density to food sources as the measure of accessibility. Assessing food environments in this manner, however, is very limiting. Since most people travel outside of their neighborhood on a daily basis, the retail food sources available to individuals residing in the same area could vary …

Data Mining And Pattern Discovery Using Exploratory And Visualization Methods For Large Multidimensional Datasets, Hsin-Fang Li

Theses and Dissertations--Epidemiology and Biostatistics

Oral health problems have been a major public health concern profoundly affecting people’s general health and quality of life. Given that oral health data is composed of several measurable dimensions including clinical measurements, socio-behavioral factors, genetic predispositions, self-reported assessments, and quality of life measures, strategies for analyzing multidimensional data are neither computationally straightforward nor efficient. Researchers face major challenges to identify tools that circumvent the processes of manually probing the data.

The purpose of this dissertation is to provide applications of the proposed methodology on oral health-related data that go beyond identifying risk factors from a single dimension, and to …

Description And Service Innovation In Adolescent Transition Within Kentucky State Agency Education Programs, Amy C. Marshall

Theses and Dissertations--Rehabilitation Sciences

Of all Kentucky youth, state agency children are at the highest risk of making unsuccessful post-secondary transitions to adulthood. The intent of both studies comprising this dissertation was to understand and guide transition planning to make future improvements to transitions of adolescents in state agency programs.

The Kentucky Youth at Risk in Transition Study was a mixed methods study that identified and described the understandings of student transitions in state agency education programs from the perspectives of youth and administrators. The study included 105 nontraditional education programs funded and supervised by the Kentucky Educational Collaborative for State Agency Children (KECSAC). …

Developing The Rehabilitation Education For Caregivers And Patients (Recap) Model: Application To Physical Therapy In Stroke Rehabilitation, Megan M. Danzl

Theses and Dissertations--Rehabilitation Sciences

Patient and caregiver education is recognized as a critical component of stroke rehabilitation and physical therapy practice yet the informational needs of stroke survivors and caregivers are largely unmet and optimal educational interventions need to be established. The objective of this dissertation was to develop a theory and model of “Rehabilitation Education for Caregivers and Patients” (RECAP) in the context of physical therapy and stroke rehabilitation, grounded in the experiences and perceptions of stroke survivors, their caregivers, and physical therapists.

Qualitative research methods with a novel grounded theory approach were used. Potential constructs of RECAP were identified from existing research. …

A Comparison Of Upper Extremity Function Between Female Breast Cancer Survivors And Healthy Controls: Typical Self- Report Of Function, Motion, Strength And Muscular Endurance, Mary Insana Fisher

Theses and Dissertations--Rehabilitation Sciences

Many women who have experienced breast cancer (BC) report continued impairments in upper extremity (UE) function beyond the time required for normal healing after surgical treatment. Most research supporting this has not made comparisons between survivors of breast cancer (BCS) to a sample of healthy women. This lack of comparison to a healthy cohort prevents an understanding of whether continued deficits in UE function are due to normal aging or the BC treatment.

The purpose of this research was to compare quality of life (QOL) and UE function among long term breast cancer survivors and similar aged women without cancer. …

Predictors Of Outcome Following Standardized Rehabilitation For Patients With Shoulder Pain, Stephanie D. Moore

Theses and Dissertations--Rehabilitation Sciences

Shoulder dysfunction is frequently treated and persistent symptoms are common. Differential diagnosis of shoulder injuries can be challenging and knowledge of a diagnosis alone does not appear to be enough information to predict outcomes. Determination of a set of factors that predict outcome would assist clinicians in making the most effective treatment decision for patients with shoulder pain. The purposes of this dissertation were to investigate patient-clinician agreement in an orthopedic population of patients with shoulder pain and to determine what combination of factors best predicts positive patient-reported outcome following standardized rehabilitation in patients with shoulder pain.

In the first …

Anterior Cruciate Ligament Prevention: Effect Of Neuromuscular Training Compliance On Muscular Strength Development, Daisuke Sugimoto

Theses and Dissertations--Rehabilitation Sciences

The anterior cruciate ligament (ACL) originates from posterior part of the medial side of the lateral condyle of femur to anterior intercondylar notch between a transverse meniscal ligament and medial side of medial meniscus of tibia. Once ACL is disrupted, pain, effusion and atrophy are commonly observable and cause functional disability. Because of the functional limitations, athletic participation is severely restricted. ACL injury is more prevalent in physically active females compared to their male counterparts in the sports of basketball and soccer in high school and collegiate levels.

Several attributes of females are considered risk factors for the higher ACL …

Relationship Between Nonmedical Benzodiazepine Use And Psychiatric Disorders Among Rural Appalachian Drug Abusers, Derek Szesny

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Abstract

Background: Inhabitants of Appalachian Kentucky are encumbered by tremendous health disparities, exhibit high rates of prescription drug abuse, and often co-present with psychiatric disorders. Compared to opioids, little research has focused on the nonmedical use of benzodiazepines.

Objective: To examine the association between nonmedical benzodiazepine use and major depressive disorder (MDD), generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), and anti-social personality disorder (ASPD) in a population of opioid drug abusers.

Methods: Data for this cross-sectional study was obtained from the Social Networks among Appalachian People (SNAP) study. Contingency tables analysis and the

X2statistic were used to …

The Effect Of State Expansion Of Medicaid Eligibility On Uninsurance Rates And Health Outcomes Of Nonelderly Adulst, Lazarus Ude Eze

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Abstract

Background:

Arizona, New York, and Maine expanded Medicaid eligibility to include nonelderly non-disabled childless adults between 2001 and 2002. This study examines whether this policy affects the percentage of uninsured nonelderly adult population and years of potential life lost in the state.

Methods

I compared the three states with Medicaid expansion with three other states with similar demographic characteristics but without expansions. The study population consists of uninsured adults between ages of 19 and 64 years of income equals or below 138% federal poverty level. I carried out a paired-samples t-test on the data and also plotted a line …

Experiences Of Speech-Language Pathology Graduate Students: An Exploratory Phenomenological Study, Anysia J. Ensslen

Theses and Dissertations--Educational Leadership Studies

Within the past decade little research has been conducted in the United States to examine the preparedness of beginning speech-language pathologists; the seminal article used for this research study comes from the United Kingdom (Horton, Byng, Bunning, & Pring, 2004). Literature from the past few decades indicates that there may be deficiencies in the way that beginning speech-language pathologists are being trained clinically.

The review of the literature suggests that the field may lack a clear and broadly supported learning theory or framework for the clinical supervision and training of speech-language pathology graduate students. The literature further supports the importance …

Behavioral Intentions And Nonmedical Anabolic Steroid Use Among Non Intercollegiate Athlete Males Ages 18-30, Vitesh Enaker

Theses and Dissertations--Kinesiology and Health Promotion

The purpose of this study was to increase understanding of factors associated with nonmedical anabolic steroid use among males ages 18-30 who do not participate in intercollegiate athletics. The Behavioral Intentions and Ergogenic Aid/Performance Enhancer use among non-intercollegiate athlete males survey instrument was developed, reviewed for content validity by a jury of experts, and pilot tested. The pilot testing results (n=25) demonstrated acceptable reliability (Cronbach’s alpha= 0.74). The final version of the Behavioral Intentions and Ergogenic Aid/Performance Enhancer use among non-intercollegiate athlete males survey instrument was administered at two distribution sites which included Ford’s Fitness Center in Lexington, Kentucky and …

Development Of An Eeg Brain-Machine Interface To Aid In Recovery Of Motor Function After Neurological Injury, Elizabeth Salmon

Theses and Dissertations--Biomedical Engineering

Impaired motor function following neurological injury may be overcome through therapies that induce neuroplastic changes in the brain. Therapeutic methods include repetitive exercises that promote use-dependent plasticity (UDP), the benefit of which may be increased by first administering peripheral nerve stimulation (PNS) to activate afferent fibers, resulting in increased cortical excitability. We speculate that PNS delivered only in response to attempted movement would induce timing-dependent plasticity (TDP), a mechanism essential to normal motor learning. Here we develop a brain-machine interface (BMI) to detect movement intent and effort in healthy volunteers (n=5) from their electroencephalogram (EEG). This could be used in …

Noninvasive Near-Infrared Diffuse Optical Monitoring Of Cerebral Hemodynamics And Autoregulation, Ran Cheng

Theses and Dissertations--Biomedical Engineering

Many cerebral diseases are associated with abnormal cerebral hemodynamics and impaired cerebral autoregulation (CA). CA is a mechanism to maintain cerebral blood flow (CBF) stable when mean arterial pressure (MAP) fluctuates. Evaluating these abnormalities requires direct measurements of cerebral hemodynamics and MAP. Several near-infrared diffuse optical instruments have been developed in our laboratory for hemodynamic measurements including near-infrared spectroscopy (NIRS), diffuse correlation spectroscopy (DCS), hybrid NIRS/DCS, and dual-wavelength DCS flow-oximeter. We utilized these noninvasive technologies to quantify CBF and cerebral oxygenation in different populations under different physiological conditions/manipulations. A commercial finger plethysmograph was used to continuously monitor MAP. For investigating …

Effects Of Intranasally Administered Dnsp-11 On The Central Dopamine System Of Normal And Parkinsonian Fischer 344 Rats, James H. Sonne

Theses and Dissertations--Neuroscience

Due to the blood-brain barrier, delivery of many drugs to the brain has required intracranial surgery which is prone to complication. Here we show that Dopamine Neuron Stimulating Peptide 11 (DNSP-11), following non-invasive intranasal administration, protects dopaminergic neurons from a lesion model of Parkinson’s disease in the rat. A significant and dose-dependent increase in an index of dopamine turnover (the ratio of DOPAC to dopamine) was observed in the striatum of normal young adult Fischer 344 rats by whole-tissue neurochemistry compared to vehicle administered controls.

Among animals challenged with a moderate, unilateral 6-hydroxy-dopamine (6-OHDA) lesion of the substantia nigra, those …

Molecular And Cellular Characterization Of Dopamine Neuron Stimulating Peptides, Kristen Kelps

Theses and Dissertations--Neuroscience

Parkinson’s disease, the second most common neurodegenerative disease, is characterized by the loss of dopaminergic neurons within the substantia nigra. Currently, the treatments available for PD are symptomatic treatments that do not stop the progression of the disease. Trophic molecules, such as glial cell-line derived neurotrophic factor (GDNF), have been evaluated as potential therapeutic molecules that could stop the loss of neurons and potentially restore some of the neurons that have already been lost. However, these trophic molecules are large making them difficult to produce and delivery. Here we characterize three peptides (DNSP-5, DNSP-11, and DNSP-17) to determine it they …

Changes In Sleep Architecture And Cognition With Age And Psychosocial Stress: A Study In Fischer 344 Rats, Heather M. Buechel

Theses and Dissertations--Pharmacology and Nutritional Sciences

Changes in both sleep architecture and cognition are common with age. Typically these changes have a negative connotation: sleep fragmentation, insomnia, and deep sleep loss as well as forgetfulness, lack of focus, and even dementia and Alzheimer’s disease. Research has shown that psychosocial stressors, such as isolation from family and friends or loss of a loved one can also have significant negative effects on sleep architecture and cognitive capabilities. This leaves the elderly in a particularly vulnerable situation: suffering from cognitive decline and sleep dysregulation already, and more likely to respond negatively to psychosocial stressors. Taking all of these factors …

Inhibition Of Calpains By Calpastatin: Implications For Cellular And Functional Damage Following Traumatic Brain Injury, Kathleen M. Schoch

Theses and Dissertations--Physiology

Traumatic brain injury (TBI) is a devastating health problem based on its high incidence, economic burden, and lack of effective pharmacological treatment. Individuals who suffer an injury often experience lifelong disability. TBI results in abrupt, initial cell damage leading to delayed neuronal death. The calcium-activated proteases, calpains, are known to contribute to this secondary neurodegenerative cascade. Prolonged activation of calpains results in proteolysis of numerous cellular substrates including cytoskeletal components, membrane receptors, and cytosolic proteins, contributing to cell demise despite coincident expression of calpastatin, the specific inhibitor of calpains.

A comprehensive analysis using two separate calpastatin transgenic mouse lines was …

Sex Differences In Cell Death And Steroid Hormone Receptors In Cortical Explants, Amanda L. Trout

Theses and Dissertations--Physiology

Estrogens, such as the biologically active 17-b estradiol (E2) have many actions in the male and female brain. Not only does E2 regulate reproductive behavior in adults, it organizes and activates the brains of younger animals in a sex-specific manner. In addition, many human studies have shown E2 to provide protection against a variety of neurological disorders, including stoke. These studies have been controversial and depend largely on the type and timing of hormone replacement. Animal studies are much less controversial and clearly demonstrate a neuroprotective role for E2 following ischemic brain injury. Because much of E2 neuroprotection requires sex …

Mechanistic Basis For Atrial And Ventricular Arrhythmias Caused By Kcnq1 Mutations, Daniel C. Bartos

Theses and Dissertations--Physiology

Cardiac arrhythmias are caused by a disruption of the normal initiation or propagation of electrical impulses in the heart. Hundreds of mutations in genes encoding ion channels or ion channel regulatory proteins are linked to congenital arrhythmia syndromes that increase the risk for sudden cardiac death. This dissertation focuses on how mutations in a gene (KCNQ1) that encodes a voltage-gated K⁺ ion channel (Kv7.1) can disrupt proper channel function and lead to abnormal repolarization of atrial and ventricular cardiomyocytes.

In the heart, Kv7.1 coassembles with a regulatory protein to conduct the slowly activating delayed rectifier K^{+ …}

Evaluation Of Insulin-Like Growth Factor-1 As A Therapeutic Approach For The Treatment Of Traumatic Brain Injury, Shaun W. Carlson

Theses and Dissertations--Physiology

Traumatic brain injury (TBI) is a prevalent CNS neurodegenerative condition that results in lasting neurological dysfunction, including potentially debilitating cognitive impairments. Despite the advancements in understanding the complex damage that can culminate in cellular dysfunction and loss, no therapeutic treatment has been effective in clinical trials, highlighting that new approaches are desperately needed. A therapy that limits cell death while simultaneously promoting reparative mechanisms, including post-traumatic neurogenesis, in the injured brain may have maximum effectiveness in improving recovery of function after TBI. Insulin-like growth factor-1 (IGF-1) is a potent growth factor that has previously been shown to promote recovery of …

Glutamate Dysregulation And Hippocampal Dysfunction In Epileptogenesis, Seth R. Batten

Theses and Dissertations--Medical Sciences

Epileptogenesis is the complex process of the brain developing epileptic acitivity. Due to the role of glutamate and the hippocampus in synaptic plasticity a dysregulation in glutamate neurotransmission and hippocampal dysfunction are implicated in the process of epileptogenesis. However, the exact causal factors that promote epileptogenesis are unknown.

We study presynaptic proteins that regulate glutamate neurotransmission and their role in epileptogenesis. The presynaptic protein, tomosyn, is believed to be a negative regulator of glutamate neurotransmission; however, no one has studied the effects of this protein on glutamate transmission in vivo. Furthermore, evidence suggests that mice lacking tomosyn have a …

Conviction Celerity, Punishment Severity, And Treatment Compliance As Predictors Of Dui Recidivism: Mediation And Moderation Models Of Deterrence, Megan F. Dickson

Theses and Dissertations--Sociology

Driving under the influence (DUI) is one of the most frequently committed offenses in the United States and approximately one-third of DUI offenders are recidivists. Researchers have evaluated multiple DUI prevention approaches, most of which have been rooted in deterrence theory. Recently, the criminal justice system has moved away from deterrence-based approaches and begun employing various forms of rehabilitation to reduce DUI recidivism. This shift in the criminal justice system has lead researchers to begin exploring the effects of rehabilitation on DUI offenders, including an examination of offender compliance with rehabilitation programs. Although each of these areas has been investigated …

High-Activity Mutants Of Human Butyrylcholinesterase For Cocaine Abuse Treatment, Liu Xue

Theses and Dissertations--Pharmacy

Cocaine is a widely abused drug without an FDA-approved medication. It has been recognized as an ideal anti-cocaine medication to accelerate cocaine metabolism producing biologically inactive metabolites via a route similar to the primary cocaine-metabolizing pathway, i.e. butyrylcholinesterase (BChE)-catalyzed hydrolysis. However, the native BChE has a low catalytic activity against cocaine. We recently designed and discovered a set of BChE mutants with a high catalytic activity specifically for cocaine. An ideal, therapeutically valuable mutant of human BChE should have not only a significantly improved catalytic activity against cocaine, but also certain selectivity for cocaine over neurotransmitter acetylcholine (ACh) such …

Computational Modeling, Design, And Characterization Of Cocaine-Metabolizing Enzymes For Anti-Cocaine Medication, Lei Fang

Theses and Dissertations--Pharmacy

Cocaine is a widely abused and addictive drug, resulting in serious medical and social problems in modern society. Currently, there is no FDA-approved medication specific for cocaine abuse treatment. The disastrous medical and social consequences of cocaine abuse have made the development of an anti-cocaine medication a high priority. However, despite decades of efforts, traditional pharmacodynamic approach has failed to yield a truly useful small-molecule drug due to the difficulties inherent in blocking a blocker like cocaine without affecting the normal functions of the transporters or receptors. An alternative approach, i.e. pharmacokinetic approach, is to interfere with the delivery of …

Multistate Markov Chains And Their Application To The Biologically Resilient Adults In Neurological Studies Cohort, Erin L. Abner

Theses and Dissertations--Epidemiology and Biostatistics

Dementia is increasingly recognized as a major and growing threat to public health worldwide, and there is a critical need for prevention and treatment strategies. However, it is necessary that appropriate methodologies are used in the identification of risk factors. The purpose of this dissertation research was to develop further the body of literature featuring Markov chains as an analytic tool for data derived from longitudinal studies of aging and dementia.

Data drawn from 649 participants in the University of Kentucky’s Alzheimer’s Disease Center’s (UK ADC) Biologically Resilient Adults in Neurological Studies (BRAiNS) cohort, which was established in 1989 and …

Alterations In Visual Processing And Its Impact On Upright Postural Stability In Athletes Following Sport-Related Concussion, Andrea E. Cripps

Theses and Dissertations--Rehabilitation Sciences

Athletes are at risk of sustaining a concussion in all sports and at all competitive levels which may lead to balance impairments. Balance results from the integration of visual, vestibular, and somatosensory information. The underlying pathophysiology for balance impairments is not well understood and visuo-motor processing impairments and how these impairments contribute to balance in concussed athletes has not been reported. Objectives: (1) to investigate the influence of visual perturbation on upright postural stability and balance in athletes who have recently suffered a sports-related concussion, (2) to establish the test-retest reliability of a simple visuo-motor processing task. Design: A longitudinal, …

Scapular Muscle Assessment In Patients With Lateral Epicondylalgia, Joseph M. Day

Theses and Dissertations--Rehabilitation Sciences

The role rehabilitation plays in the management of patients with lateral epicondylalgia (LE) remains elusive secondary to high recurrence rates. Addressing scapular muscle deficits may be important in the rehabilitation of patients with LE. However, it is unknown if scapular muscle impairments exist in a working population of patients with LE. The purpose of this dissertation was to assess scapular muscle strength and endurance in a working population of patients with LE.

Clinical scapular muscle assessment tools are limited in their ability to isolate specific muscles. Rehabilitative ultrasound imaging (RUSI) is a potentially useful tool but few studies have investigated …

Nmda Receptors In The Dorsal Vagal Complex Of Normal And Diabetic Mice, Eva C. Bach

Theses and Dissertations--Physiology

The dorsal vagal complex (DVC), containing the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus nerve (DMV), plays a pivotal role in autonomic regulation. Afferent fibers from peripheral organs and higher brain centers synapse in the NTS, which integrates these synaptic connections as well as information from systemically circulating hormones and metabolites. The integrated information is relayed to the dorsal motor nucleus of the vagus nerve (DMV), which in turn, projects motor fibers to elicit parasympathetic control of digestive and other viscera. Physiological functions mediated by the DVC are disrupted in diabetic patients and …