Medicine and Health Sciences Commons^™

Patterns Of Pneumoconiosis Mortality In Kentucky: Analysis Of Death Certificate Data, Jake Beggs

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

ABSTRACT

Background: Despite ongoing surveillance efforts, mortality rates associated with total pneumoconiosis, and particularly coal worker’s pneumoconiosis, have remained elevated. Methods: Kentucky death certificate data from 2003-2011 was statistically compared to other coal mining states and descriptively analyzed from 2011-2013 to determine the mortality burden and public health implications of pneumoconiosis and coal worker pneumoconiosis (CWP) on Kentucky residents from 2003-2013. Results: Kentucky’s total pneumoconiosis and coal workers’ pneumoconiosis mortality rates decreased from 2003-2009, then increased in following years, showing a significant quadratic trend from 2003-2013 (p<.05) compared to West Virginia, Pennsylvania, and the overall United States rates that had significant negative linear trends from 2003-2011(p<.05). Deaths from pneumoconiosis primarily occurred in white males from CWP in the Appalachian region. Individuals diagnosed with pneumoconiosis died from respiratory illness 50% of the time, heart-related problems (23%) and cancer (12%). Autopsies were only performed on 12% of decedents over the three year study period and the primary locations of death were in hospital (47%) and at home (36%). Conclusions: Increased coal mining industry worker environmental exposure protection should be enhanced in Kentucky. Additionally, healthcare efforts should focus on increasing patient education to ensure early detection and treatment for individuals suffering from pneumoconiosis as well as for comorbid conditions such as Chronic Obstructive Pulmonary Disease. To further target healthcare and treatment of pneumoconiosis patients, increased autopsies of individuals with pneumoconiosis should be performed to identify involvement of other conditions such as silicosis and optimize pneumoconiosis fatality surveillance.

Post-Laminectomy Back Pain: Understanding The Progress From Acute To Chronic Pain State, James Derek Calhoun

DNP Projects

In the United States, 74.6% of patients who have lumbar laminectomy surgery have residual low back pain (Hussain & Erdek, 2014) and overall costs of low back pain may reach up to $200 billion per year (Carey & Frebuger 2013). To further address this problem, a study was conducted to determine if treatment in a chronic pain clinic could result in a reduction in the development of a chronic pain state for adult patients who have had lumbar laminectomy surgeries. A convenience sample of 50 patients was selected from the Interventional Pain Associates clinic at the University of Kentucky. Records …

Dating Violence On Small Rural College Campuses: Are Administrator And Student Perceptions Similar?, Jean Allen Oldham

Theses and Dissertations--Kinesiology and Health Promotion

In recent years dating violence has become more and more prevalent on college campuses. Reports of the range of dating violence vary widely, with studies reporting from 20% to 85% of college women experiencing dating violence. However, almost all research has been conducted among urban and/or large colleges and universities, with virtually no attention to what is happening on small and/or rural college and university campuses.

When a possible 20% of college women have experienced dating violence on college campuses, there becomes a crucial need for administration at a college to have an accurate assessment of the college’s liability, and …

Is There A Relationship Between Hip Structure, Hip Muscle Strength, And Lower Extremity Frontal Plane Kinematics During Treadmill Running?, Michael William Robinson Baggaley

Theses and Dissertations--Kinesiology and Health Promotion

INTRODUCTION: Excessive hip adduction (HADD) has been associated with a number of lower extremity overuse injuries, and it has been suggested that it may be the result of reduced strength of the hip abduction musculature. Hip structure has been postulated to influence both hip abduction (HABD) strength and HADD. The purpose of this study was to investigate the relationship between hip structure, HABD strength, and frontal plane kinematics during running. METHODS: Peak isometric HABD strength, lower extremity kinematics, femoral neck-shaft angle (NSA), and pelvis width-femur length (pw-fl) ratio were recorded for 25 female subjects. Pearson correlations (P < .05) were performed between variables. RESULTS: A fair relationship was observed between femoral NSA and HABD strength (r = …

Factors Influencing Peripheral Skin Temperature Circadian Rhythm In Young Adult Males, Hannah Tranel

Theses and Dissertations--Kinesiology and Health Promotion

Periodic cues, including scheduled exercise, social interactions, sleep habits, and feeding time, have been shown to alter the circadian system. A disruption in circadian rhythms has been shown to have negative effects on health. Frequent skin temperature measures have been shown to be a valid method of assessing circadian rhythm parameters. The purpose of this study was to determine group mean differences in temperature amplitude, stability and lag measures among groups of young men of varying (optimal, fair and poor) adiposities. The strength of the association among the temperatures parameters and measures of body composition, physical fitness and activity, nutritional …

Behind The Mirrors: Examining The Role Of African American Cosmetologists And Salons In Domestic Violence Advocacy And Education, Pangela H. Dawson

Theses and Dissertations--Educational Policy Studies and Evaluation

African American beauty salons across the country have historically served as settings for social interaction, political activism, and community organizing in the African American community. These settings often offer opportunities for intimacy between cosmetologists and their clients. Research findings suggest that the unique bonds between women in salons can be a viable option when providing health intervention and education to large numbers of women. Data indicates that salon campaigns and promotions which focused on health issues such as stroke and diabetes education, breast and cervical cancer awareness, healthy living, and smoking cessation, have been efficacious in changing unhealthy habits or …

The Effect Of Tactical Tasks And Gear On Muscle Activation Of Swat Officers, Jason M. Keeler

Theses and Dissertations--Kinesiology and Health Promotion

Special Weapons and Tactics (SWAT) officers constitute a subgroup of specialized law enforcement officers that perform a variety of tactical operations while wearing approximately 40 kg of tactical gear. Lower back pain is a prevalent musculoskeletal injury suffered by SWAT officers. Tactical gear places significant stress on the lower back. Thus, it is important to quantify the effect that tactical gear has on muscle activation levels of torso musculature while performing occupational tasks. Electromyography was evaluated on 20 male subjects (age: 34.7±4.5 yr.; height: 1.79±.10 m; body mass: 91.53±17.32 kg; mass of gear: 13.82±1.90 kg) while performing four tactical tasks …

Bioerodible Calcium Sulfate Bone Grafting Substitutes With Tailored Drug Delivery Capabilities, Bryan R. Orellana

Theses and Dissertations--Biomedical Engineering

Bone regeneration or augmentation is often required prior to or concomitant with implant placement. With the limitations of many existing technologies, a biologically compatible synthetic bone grafting substitute that is osteogenic, bioerodible, and provides spacing-making functionality while acting as a drug delivery vehicle for bioactive molecules could provide an alternative to ‘gold standard’ techniques.

In the first part of this work, calcium sulfate (CS) space-making synthetic bone grafts with uniformly embedded poly(β-amino ester) (PBAE) biodegradable hydrogel particles was developed to allow controlled release of bioactive agents. The embedded gel particles’ influence on the physical and chemical characteristics of CS was …

Listeria Monocytogenes Can Utilize Both M Cell Transcytosis And Inla-Mediated Uptake To Cross The Epithelial Barrier Of The Intestine During An Oral Infection Model Of Listeriosis, Hilary Denney

Theses and Dissertations--Medical Sciences

The invasive pathways, InlA- and InB-mediated uptake and M cell transcytosis, that Listeria monocytogenes uses to invade the intestine have mainly been studied using infection models that do not truly replicate what occurs during a natural infection. Recently, our lab has developed an oral infection model that is more physiolocally relevant to what occurs during food borne listeriosis. We have sought to evaluate the relative roles of the previously defined invasive pathways, in our oral model of infection. We have done this by utilizing an InlAmCG Lm strain that is able to bind murine E-cadherin, knockout Lm strains, ΔinlA Lm …

Dopamine And Glutamate Dysfunction In A Rodent Model Of Attention-Deficit/Hyperactivity Disorder: Implications For Future Neuropharmacology, Erin M. Miller

Theses and Dissertations--Neuroscience

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common disorders of childhood. It is theorized to be caused by catecholamine dysfunction in the striatum (Str) and frontal cortex (FC). The spontaneously hypertensive rat (SHR) has been used as a model for ADHD because of its attention deficits, impulsiveness, and hyperactivity. Prior studies of dopamine (DA) in the Str and FC have revealed conflicting results in the SHR compared to control, indicative of a need for a better understanding of DA dynamics in this model. In addition to the DA hypothesis, studies have begun implicating glutamate in the etiology of ADHD. …

Immunotherapy In Combination With Behavioral Enrichment In A Canine Model Of Aging, Paulina R. Davis

Theses and Dissertations--Pharmacology and Nutritional Sciences

Alzheimer’s disease (AD) is characterized by cognitive decline and hallmark neuropathology, including β-amyloid (Aβ). Therapeutic strategies for AD are focusing on reducing Aβ. Canines develop Aβ neuropathology and cognitive decline with age similar to AD patients. In previous studies, immunization with Aβ1-42 (VAC) in aged canines decreased brain Aβ but did not improve cognition. Behavioral enrichment (ENR) improved cognition without reducing brain Aβ. We hypothesized that VAC combined with ENR would provide cognitive benefits and reduce Aβ neuropathology, as compared individual VAC and ENR treatments. Aged beagles were placed into groups: control, VAC with fibrillar Aβ1-42, ENR, and combination treatment …

Immobilizing Mutation In An Unconventional Myosin15a Affects Not Only The Structure Of Mechanosensory Stereocilia In The Inner Ear Hair Cells But Also Their Ionic Conductances, Diana Syam

Theses and Dissertations--Medical Sciences

In the inner and outer hair cells (OHCs) of the inner ear, an unconventional myosin 15a localizes at the tips of mechanosensory stereocilia and plays an important role in forming and maintaining their normal structure. A missense mutation makes the motor domain of myosin 15a dysfunctional and is responsible for the congenital deafness DFNB3 in humans and deafness and vestibular defects in Shaker-2 (Sh2) mouse model. All hair cells of homozygous Shaker-2 mice (Myo15^sh2/sh2) have abnormally short stereocilia, but, only stereocilia of Myo15^sh2/sh2OHCs start to degenerate after the first few days of postnatal development …

Beyond Peroxisome: Abcd2 Modifies Pparα Signaling And Identifies A Subclass Of Peroxisomes In Mouse Adipose Tissue, Xiaoxi Liu

Theses and Dissertations--Pharmacy

ABCD2 (D2) has been proposed as a peroxisomal long-chain acyl-CoA transporter that is essential for very long chain fatty acid metabolism. In the livers of mice, D2 is highly induced by fenofibrate, a PPARα ligand that has been widely used as a lipid lowering agent in the treatment of hypertriglyceridemia. To determine if D2 is a modifier of fibrate responses, wild-type and D2 deficient mice were treated with fenofibrate for 14 days. The absence of D2 altered expression of gene clusters associated with lipid metabolism, including PPARα signaling. Using 3T3-L1 adipocytes, which express high levels of D2, we confirmed that …

Quantification Of Factors Governing Drug Release Kinetics From Nanoparticles: A Combined Experimental And Mechanistic Modeling Approach, Kyle Daniel Fugit

Theses and Dissertations--Pharmacy

Advancements in nanoparticle drug delivery of anticancer agents require mathematical models capable of predicting in vivo formulation performance from in vitro characterization studies. Such models must identify and incorporate the physicochemical properties of the therapeutic agent and nanoparticle driving in vivo drug release. This work identifies these factors for two nanoparticle formulations of anticancer agents using an approach which develops mechanistic mathematical models in conjunction with experimental studies.

A non-sink ultrafiltration method was developed to monitor liposomal release kinetics of the anticancer agent topotecan. Mathematical modeling allowed simultaneous determination of drug permeability and interfacial binding to the bilayer from release …

Synthesis And Biological Evaluation Of Novel Resveratrol And Combretastatin A4 Derivatives As Potent Anti-Cancer Agents, Nikhil Reddy Madadi

Theses and Dissertations--Pharmacy

Resveratrol has been reported as a potential anticancer agent but cannot be used as an antitumor drug due to its chemical and metabolic instability. We have designed and synthesized 184 novel compounds related to resveratrol in an attempt to produce more potent and drug-like molecules. We have identified a tetrazole analog of resveratrol, ST-145(a) as a lead anticancer agent from the resveratrol analog series of compounds with a GI₅₀ value of less than 10nM against almost all the human cancer cell lines in the National Cancer Institute’s screening panel.

In a separate study, we tested the hypothesis that the …

Multi-Component Microparticulate/Nanoparticulate Dry Powder Inhalation Aerosols For Targeted Pulmonary Delivery, Xiaojian Li

Theses and Dissertations--Pharmacy

The aim of the work was to design, manufacture, and characterize targeted multi-component dry powder aerosols of (non-destructive) mucolytic agent (mannitol), antimicrobial drug (tobramycin or azithromycin), and lung surfactant mimic phospholipids (DPPC:DPPG=4:1 in molar ratio). The targeted dry powder for inhalation formulation for deep lung delivery with a built-in rationale of specifically interfering several disease factors of chronic infection diseases in deep lungs such as cystic fibrosis, pneumonia, chronic bronchitis, and etc. The dry powder aerosols consisting of selected chemical agents in one single formulation was generated by using spray drying from organic solution.

The physicochemical properties of multi-component dry …

Human Butyrylcholinesterase Mutants For Cocaine Detoxification, Shurong Hou

Theses and Dissertations--Pharmacy

Cocaine is one of the most reinforcing drugs of abuse and has caused serious medical and social problems. There is no FDA-approved medication specific for cocaine. It is of a high priority to develop an effective therapeutic treatment for cocaine abuse. Human butyrylcholinesterase (BChE) has been recognized as a promising candidate of enzyme therapy to metabolize cocaine into biologically inactive metabolites and prevent it from reaching central nervous system (CNS). However, the catalytic activity of wide-type human BChE against cocaine is not sufficiently high for treatment of cocaine abuse. Dr. Zhan’s lab has successfully designed and discovered a series of …

Lobelane Analogs With Various Methylene Linker Lengths And Acyclic Lobelane Analogs As Potential Pharmacotherapies To Treat Methamphetamine Abuse, Zheng Cao

Theses and Dissertations--Pharmacy

Methamphetamine interacts with vesicular monoamine transporter-2 (VMAT2) to inhibit dopamine (DA) uptake and promotes DA release from presynaptic vesicles, increasing cytosolic DA available for methamphetamine-induced reverse transport by DA transporters. By inhibiting VMAT2, lobelane, a defunctionalized, saturated lobeline analog, decreases methamphetamine-evoked DA release and methamphetamine self-administration in rats. In this dissertation structure-activity relationships around the lobelane structure were investigated on racemic lobelane analogs with varying methylene linker lengths at central piperidine ring. Affinity for dihydrotetrabenazine (DTBZ) sites on VMAT2 and for inhibition of VMAT2 function was determined to be 0.88-63 and 0.024-4.6 µM, respectively, and positively correlated. The most potent …

Investigating Structure And Protein-Protein Interactions Of Key Post-Type Ii Pks Tailoring Enzymes, Theresa E. Downey

Theses and Dissertations--Pharmacy

Type II polyketide synthase (PKS) produced natural products have proven to be an excellent source of pharmacologically relevant molecules due to their rich biological activities and chemical scaffolds. Type II-PKS manufactured polyketides share similar polycyclic aromatic backbones leaving their diversity to stem from various chemical additions and alterations facilitated by post-PKS tailoring enzymes. Evidence suggests that post-PKS tailoring enzymes form complexes in order to facilitate the highly orchestrated process of biosynthesis. Thus, protein-protein interactions between these enzymes must play crucial roles in their structures and functions. Despite the importance of these interactions little has been done to study them. In …

The Off-Label Use Of Atypical Antipsychotics And Its Impact On Attention Deficit/Hyperactivity Disorder (Adhd), Minji Sohn

Theses and Dissertations--Pharmacy

Atypical antipsychotics (AAPs) (also known as second-generation antipsychotics) are the US Food and Drug Administration (FDA) approved medications for schizophrenia, bipolar I disorder, depression and autism. Compared to the typical antipsychotics, AAPs were marketed as reducing adverse side effects such as extrapyramidal symptoms. This resulted in extensive use of AAPs for not only the FDA approved indications but also other conditions that are not approved. However, several post-marketing clinical trials evaluated the use of AAPs and reported serious adverse side effects, including metabolic syndrome, cardiovascular events, or death.

The extensive use of AAPs by pediatrics is an important policy problem …

Flavonoids With Novel Nicotinic Activity As Potential Pharmacotherapies To Treat Ethanol-Induced Neurotoxicity, Joseph A. Lutz

Theses and Dissertations--Pharmacy

Ethanol causes neurotoxicity via several mechanisms at different points in the cycle of dependence, including neuroinflammation and oxidative stress during ethanol exposure as well as excitotoxicity during ethanol withdrawal. The primary therapeutic implication is that ethanol-induced neurotoxicity requires multifunctional pharmacotherapies which reduce all mechanisms. Using an innovative pharmacological high throughput screening method on a large plant extract library we discovered flavonoids with alpha7 nicotinic acetylcholine receptor (nAChR) activity. In addition to their well-known anti-inflammatory and antioxidant properties, this novel activity means they can potentially reduce excitotoxicity and therefore makes them ideal for inhibition of ethanol-induced neurotoxicity. Rhamnetin, the candidate compound, …

Phosphatidylinositol 3-Kinase (Pi3k) As A Therapeutic Target In Nsclc, Christopher W. Stamatkin

Theses and Dissertations--Pharmacy

Deregulated activation of phosphatidylinositol 3-kinase (PI3K) pathway is central to many human malignancies. The functions of this pathway are critical for normal cell metabolism, proliferation, and survival. In lung cancers, the PI3K pathway activity is often aberrantly driven by multiple mutations, including EGFR, KRAS, and PIK3CA. Molecules targeting the PI3K pathway are intensely investigated as potential anti-cancer agents. Although inhibitors of the pathway are currently in clinical trials, rational and targeted use of these compounds, alone or in combination, requires an understanding of isoform-specific activity in context. We sought to identify class IA PI3K enzyme (p110a/PIK3CA, p110b/PIK3CB, p110d/PIK3CD) activities using …

Primary And Secondary Prevention Of Hepatitis C Virus Among Rural Appalachian People Who Use Drugs, Dustin B. Stephens

Theses and Dissertations--Clinical and Translational Science

Hepatitis C virus (HCV) remains a major cause of morbidity and mortality worldwide, with 3% of the global population chronically infected. Clinical impacts in the United States are projected to increase for two decades, and mortality attributed to HCV now exceeds HIV. Injection drug use (IDU) is the most common route of transmission in the developed world. Advances in treatment offer hope of mitigating HCV impacts, but substantial barriers obstruct people who inject drugs (PWID) from receiving care, particularly in medically underserved regions including Central Appalachia. This study assessed IDU paraphernalia sharing longitudinally over 24 months in a sample of …

Assessing Candidacy For Intensive Language Therapy: A Preliminary Study, Jessica N. Bellamy

Theses and Dissertations--Communication Sciences and Disorders

The goal of the present study was to examine changes in the speech and language performance of patients with chronic, non-fluent aphasia over the course of a three-hour group speech and language treatment session, a time allotment comparable to intensive therapy practices. Nine participants, (three groups of three), with chronic, non-fluent aphasia were seen for a single group therapy session three hours in length. Therapeutic activities were designed to be as similar as possible for each group of participants. Each participant was individually assessed before (time 1), during (time 2), and after (time 3) the group treatment session. Assessments included …

Social-Emotional Development In Children With Hearing Loss, Lori Gayle Harris

Theses and Dissertations--Communication Sciences and Disorders

Many positive outcomes have been documented for children with hearing loss utilizing current treatment approaches such as early identification and intervention, including appropriately fit sensory devices and communication modes that focus on listening and spoken language. However, challenges related to social-emotional development have been widely observed. The development of communication skills in children with hearing loss is impacted by many factors, including the degree of hearing loss, the child's age at onset and identification, the presence of other disabilities, and when the child receives intervention. While there are a variety of therapeutic options available for children with hearing loss to …

The Relationship Of Somatosensory Perception And Fine-Force Control In The Adult Human Orofacial System, Nicole M. Etter

Theses and Dissertations--Rehabilitation Sciences

The orofacial area stands apart from other body systems in that it possesses a unique performance anatomy whereby oral musculature inserts directly into the underlying cutaneous skin, allowing for the generation of complex three-dimensional deformations of the orofacial system. This anatomical substrate provides for the tight temporal synchrony between self-generated cutaneous somatosensation and oromotor control during functional behaviors in this region and provides the necessary feedback needed to learn and maintain skilled orofacial behaviors.

The Directions into Velocity of Articulators (DIVA) model highlights the importance of the bidirectional relationship between sensation and production in the orofacial region in children learning …

The Relationship Between Patient Expectations, Functional Outcome, Self-Efficacy, And Rehabilitation Adherence Following Cartilage Repair Of The Knee: A Sequential Explanatory Analysis, Jenny L. Toonstra

Theses and Dissertations--Rehabilitation Sciences

Patient expectations have been shown to be a major predictor of outcomes. Furthermore, fulfilled expectations have been linked to increased patient satisfaction and rehabilitation adherence. Expectations may be influenced by a variety of factors, including patient characteristics, pre-operative function, or disease characteristics. However, it is currently unknown what factors and to what degree they may influence patient expectations prior to knee surgery. Furthermore, understanding the importance and values of those expectations for recovery using qualitative methods has not previously been conducted in this patient population.

A mixed methods design was used. Twenty-one participants scheduled to undergo cartilage repair of the …

Occupational Therapists' Experiences With Ethical And Occupation-Based Practice In Hospital Settings, Joanne P. Estes

Theses and Dissertations--Rehabilitation Sciences

Changes in health care delivery practices are impacting the provision of care in all venues. Occupational therapists working in hospital settings strive to meet professional mandates for occupation-based practice within a medical-model system. Ethical practice is another aspect of service provision vulnerable to contextual influences. The aims of the two studies reported here were to explore occupational therapists’ experiences with occupation-based practice, and with ethical issues, in hospital settings. Grounded theory methods were employed for both studies. Data were collected via individual, semi-structured interviews with 22 participants for the first study. For the second study, nine participants participated in individual, …

Expression And Splicing Of Alzheimer’S Disease Risk Gene Phosphatidylinositol-Binding Clathrin Assembly Protein, Ishita Parikh

Theses and Dissertations--Physiology

Recent Genome Wide Association Studies (GWAS) have identified a series of single nucleotide polymorphism (SNP)s that are associated with Alzheimer’s disease (AD). One of the SNPs, rs3851179 (G/A), is near the gene phosphatidylinositol-binding clathrin assembly protein (PICALM). To evaluate whether this SNP is associated with PICALM expression, we quantified PICALM mRNA in 56 brain cDNA samples. Using linear regression analysis, we analyzed PICALM expression relative to rs3851179, AD status, and cell type specific markers. An association was detected between rs3851179 and PICALM, microvessel mRNA, glial fibrillary acidic protein (GFAP) mRNA, and synaptophysin (SYN) mRNA. To gain clarity …

Nucleoside Reverse Transcriptase Inhibitors Are Anti-Inflammatory And Target Dry Age-Related Macular Degeneration, Benjamin J. Fowler

Theses and Dissertations--Physiology

Age-related macular degeneration (AMD) is a principal cause of blindness in the United States and other industrialized nations. An estimated 10 million Americans are afflicted with AMD, which is comparable in scope to the 12 million living with cancer, or the 5 million with Alzheimer’s disease. The prevalence of AMD steadily increases with age, affecting 2% of the population at age 40, and one in four people by age 80. For reasons that are not fully understood, AMD is more common in lightly-pigmented and female populations. Treatment of AMD is largely an unmet need: There are no FDA approved therapies …