Medicine and Health Sciences Commons^™

Comparison Of The Times To Exhaustion, Physiological, Perceptual, And Neuromusuclar Responses During Constant Heart Rate, Constant Vo2, And Constant Power Exercise, Pasquale Jiovanni Succi

Theses and Dissertations--Kinesiology and Health Promotion

The purposes of this study were to: 1) Determine if there are differences in the sustainability of exercise when anchored at critical heart rate (CHR), the VO₂ associated with CHR (VO₂CHR), or the power output associated with CHR (PCHR); 2) examine the patterns of responses in power output, metabolic (heart rate [HR], VO₂, respiration rate [RR]), neuromuscular (electromyographic [EMG] amplitude [AMP], mean power frequency [MPF], mechanomyographic [MMG] AMP and MPF, perceptual (rating of perceived exertion [RPE]), and muscle oxygenation responses (%SmO₂) during exercise anchored by HR, VO₂, and power output; and …

Examination Of Sex- And Limb-Specific Fatigue During Unilateral, Isometric Forearm Exercise, Caleb Christian Voskuil

Theses and Dissertations--Kinesiology and Health Promotion

The purpose of this study was to examine the effects of unilateral, isometric handgrip holds to failure for the dominant (Dm) and non-dominant (NDm) limb on ipsilateral ([IPS] exercised side) and contralateral ([CON] non-exercised side) performance fatigability. Twenty individuals participated in this study (Men [n =10]; Women [n = 10; Composite Demographics: Age: 22.2 years; Height: 174.4 cm; Body Mass: 75.0 kg) and completed three visits. Two, 6 s maximal voluntary isometric contractions (MVICs) for the Dm and NDm limb were performed during visit 1, followed by a familiarization of the fatigue test. Visits 2 and 3 included an isometric, …

Mechanical Deviations And Verbal-Cue Altered Gait In The Femoroacetabular Impingement Syndrome Population, Walter Menke

Theses and Dissertations--Kinesiology and Health Promotion

Femoroacetabular impingement syndrome (FAIS) is an abnormal physical hip morphology that causes functional changes and pain during gait. Mechanical gait differences in this population require further biomechanical investigation to elucidate characteristics unique to this group. Fixed speed gait trials were performed on force plates and analyzed in addition to isokinetic strength testing to find a multitude of biomechanical variables including joint moment, joint power, joint work, and peak joint angle. This work has discovered evidence of muscular deficits at the hip, specifically hip extension, as well as knee joint power contributions to gait when compared to controls. These findings suggest …

High Performance: Exploratory Study Into The High Performance Model And Qualitative Secondary Analysis Of Elite Sport Management In The United States, Jon Gregory Hill

Theses and Dissertations--Education Sciences

This dissertation examines the area of high performance in elite sport through high performance professionals’ perspectives in the United States Olympic and Paralympic National Governing Bodies. The study’s purpose was to establish a shared meaning of the high performance sport management model by its elements in the athletic arena. Interviews with 16 high performance directors and managers were conducted to establish definitions, backgrounds, and anatomy of high performance in sport: high performance, high performance sport, high performance management, high performance model.

A qualitative secondary analysis was conducted to examine the high performance model in the U.S. and explore the job …

Stress, Burnout, And Well-Being In New Veterinary Graduates: Evaluating A Pilot Online Professional Development Program, Addie Rose Reinhard

Theses and Dissertations--Community & Leadership Development

Suicide, stress, and burnout are occurring at high rates among veterinary professionals, and the transition from student to practicing veterinarian has been shown to be a particularly stressful time. The aim of this study was to evaluate an online professional development program for new veterinary graduates incorporating peer social support and training in professional skills important for success in the transition to practice. In this mixed methods study, the program was evaluated qualitatively with focus group data and quantitatively by assessing knowledge gained and levels of stress, burnout, social support, and well-being. Seven new veterinary graduates participated in the program, …

Understanding Perspectives Of Clinical And Non-Clinical Healthcare Administrators On Culture And Diversity In The Healthcare Workplace, Katherine Counts

Theses and Dissertations--Community & Leadership Development

The racial and ethnic composition of the U.S. population is becoming increasingly more diverse. The 2010 U.S. Census reported a 29% increase in minority groups other than non-Hispanic Whites. In response to these changing demographics, healthcare organizations have struggled to keep pace with these trends in their hiring of a diverse staff. Healthcare leaders appear to be lagging in their efforts to make adequate changes to increase diversity in their organizations. What factors may be contributing to this inequity? One possible explanation is a limited knowledge of healthcare leaders regarding culture and diversity within the workplace. To this end, this …

Acl Injury, A Time Course Study Of Transcriptional Changes, Thomas Carter

Theses and Dissertations--Medical Sciences

ACL tear is a common injury in the United States with a significant cost and time burden during recovery; reconstructive surgery often results in weakened quadricep muscle and higher risk of posttraumatic osteoarthritis. Prior research has highlighted cellular derangements within the quadriceps after ACL injury and reconstruction, but the early molecular effectors of cellular dysfunction remain to be identified. To further understand the molecular effectors of quadriceps dysfunction following ACL injury, this study aims to quantify the timing and magnitude of transcriptional differences between the quadriceps muscle of injured and contralateral non-injured limbs. These data will provide insight into the …

The Role Of Vascular Endothelial Growth Factor In Leukemia Trafficking, Shaw Powell

Theses and Dissertations--Medical Sciences

Vascular endothelial growth factor (VEGF) is a signaling protein involved in inducing and regulating endothelial cell proliferation and function (Duffy et al 2000). VEGF is also involved in cancer progression, as it induces vascular permeability and promotes angiogenesis to tumor laden areas, giving cancer cells critical oxygen and nutrients (Hoeppner et al.,2012. Studies indicate VEGF prevents lymphoblast apoptosis, which may contribute to leukemia formation and enable the proliferation of leukemic cells (Duffy et al 2000). Ongoing research seeks to further examine VEGF in leukemia, using a rag2:GFP-Myc expressing transgenic zebrafish as the animal model of T-cell Acute Lymphoblastic Leukemia (T-ALL). …

S. Gordonii-Produced Hydrogen Peroxide Modulates Mir-663a And Ccl20 Expression In Oral Epithelial Cells, Marshall Houston Maynard

Theses and Dissertations--Medical Sciences

The mechanisms through which a persistent recognition of commensal bacteria by oral epithelial cells (OECs) mitigates an uncontrolled inflammatory response of the oral mucosa remain unknown. CCL20 secretion by OECs in response to pathogenic bacteria is regulated by S. gordonii (Sg)-induced miR-663a; nevertheless, the mechanisms involved in these Sg-modulated responses remain to be elucidated. Since Sg is a hydrogen peroxide (H₂O₂) producer, and H₂O₂ has been shown to stimulate miRNA expression, we hypothesized that H₂O₂ could be involved in Sg-induced miR663a and CCL20 responses. Expression of miR663a …

Carnosic Acid Differentially Modulates The Nrf2- Antioxidant Response In Male And Female Mice Following Experimental Traumatic Brain Injury, Jacob A. Dunkerson

Theses and Dissertations--Neuroscience

Traumatic brain injury (TBI) is a leading cause of death and disability in the United States. Each year, an estimated 2.8 million Americans are diagnosed with a TBI due to falling, motor vehicle collisions, gun violence, and sports related concussions. Although inflicted by a single event, the post-traumatic effects of TBI often develop into a life-long disease. Survivors often experience cognitive decline, memory loss, emotional instability, changes in personality, and physical disabilities. A single TBI, and more-so repetitive TBI's, place an individual at a greater risk of developing chronic neurological disorders, such as dementia or Alzheimer’s disease, earlier in life. …

Characterizing The Physiology And Genetics Of Contact Dependent Growth Inhibiton Systems In Burkholderia Species, Alice Elizabeth Oates

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Contact-dependent growth inhibition (CDI) systems mediate interbacterial competition. The genes encoding these systems are widespread among Gram-negative bacteria, including Burkholderia pathogens. CDI systems of Burkholderia species are composed of two-partner secretion pathway proteins and function to deliver the toxic C-terminus of a polymorphic surface-exposed exoprotein BcpA (Burkholderia CDI protein A) to the cytoplasm of neighboring recipient bacteria upon cell-cell contact. Specific outer and inner membrane proteins facilitate BcpA translocation both out of the donor bacterium and into the recipient cell cytoplasm. Most Burkholderia species-specific CDI translocation factors in recipient cells are unknown. BcpA intoxication functions as a mechanism by …

Understanding The Impact Of Solvents In Oral Solid Dosage Formulation And Process Development, Matthew Kyle Defrese

Theses and Dissertations--Pharmacy

The successful delivery of chemical compounds for the purpose of therapeutic treatments and prophylactics is a substantial undertaking in modern drug development. Notably, the adoption of high throughput screening techniques has led to the proliferation of poorly water soluble and/or highly potent molecules which further complicate development activities. Spray dried amorphous solid dispersions are an increasingly important formulation strategy to overcome solubility issues while wet granulation approaches are the method of choice for the preparation of highly potent APIs in oral solid dosage forms.

A common connection between these critical techniques is their reliance on solvent-based processing that can often …

Human Regulatory T Cells Control Inflammation From Effector T Cells In Prediabetes, Rui Liu

Theses and Dissertations--Pharmacy

Type 2 diabetes (T2D) is a chronic low-grade inflammatory disease. A T cell cytokine profile (Th17) from PBMCs can distinguish obese T2D from obese non-diabetes subjects. Individual T cell subsets interact with each other and the diverse subsets jointly determine overall inflammation. Cellular metabolism drives cytokine production of CD4⁺ T cells, and therefore contributes to inflammation in T2D. However, specific changes in metabolism and function of CD4⁺ T cells during the progression from lean healthy to obese and diabetic stages in people have not been clarified.

We hypothesize that human regulatory T cells (Treg) impact metabolism of effector …

Abc Transporters In Glioblastoma: Anticancer Drug Transport And Transporter Regulation At The Blood-Brain Barrier, Julia A. Schulz

Theses and Dissertations--Pharmacy

Glioblastoma is one of the deadliest cancers, with a median survival of only one year. Even after aggressive treatment consisting of surgical resection, radiation, and chemotherapy, most glioblastoma patients suffer from tumor recurrence within 6-9 months. One reason for treatment failure of anticancer drugs is the blood-brain barrier that protects the brain by impeding xenobiotic uptake from the blood. To this end, efflux transporters at the human blood-brain barrier, such as P-glycoprotein (ABCB1) and Breast Cancer Resistance Protein (ABCG2), prevent many compounds, including anticancer drugs, from entering the brain. Thus far, approaches to deliver anticancer drugs across the blood-brain barrier …

Investigation Of The Biosynthesis Of The Nucleoside Antibiotic Sphaerimicin, Jonathan Overbay

Theses and Dissertations--Pharmacy

Antibiotic-resistance has become a widespread problem in the United States and across the globe. Meanwhile, new antibiotics are entering the clinic at an alarmingly low rate. Highly-modified nucleosides, a class of natural products often produced by actinobacteria, target MraY bacterial translocase I. MraY is a clinically unexploited enzyme target that is ubiquitous and essential to peptidoglycan cell wall biosynthesis. The nucleoside antibiotics known vary in efficacy and the functionalities contributing to improved activity is poorly understood. Sphaerimicin, a newly discovered modified nucleoside, has potent inhibitory activity with an IC50 of 13.65 nM against MraY. In general, sphaerimicin is primarily effective …

Pharmacist Provision Of Contraception Services In Kentucky: Opinions And Policy Interventions, Dustin K. Miracle

Theses and Dissertations--Pharmacy

Unintended pregnancy continues to be a prevalent issue across the United States, impacting millions of women annually. While several states have enacted policies expanding pharmacist services to allow for provision of hormonal contraception, Kentucky has yet to do so. Likewise, although provision of nonprescription hormonal contraception could be authorized under Kentucky regulation, prior to this study, this had yet to be done. The objectives of this study were to 1) understand the opinions of Kentucky pharmacists and student pharmacists regarding provision of hormonal contraception services through a board-authorized protocol, 2) understand the opinions of Kentucky pharmacists and student pharmacists regarding …

Identification And Characterization Of Epitope Specific Immune Responses In Humans And Mice, David Henson

Theses and Dissertations--Pharmacy

Cardiovascular disease (CVD) is a major cause of morbidity and mortality around the world causing approximately 14% of total disease burden. A major factor in the progression to major CVD within patients is immune activation, which led to the study of various immune products as potential biomarkers for the prediction of cardiovascular events, including antigen-specific antibodies and immune complexes. One focus of this biomarker research is IgG autoantibodies targeting apolipoprotein A-I (ApoA-I), and several studies of these antibodies have found an association with increased CVD events. Based on the encouraging results from these studies and previous research which has identified …

Examining Childhood Outcomes In Neonatal Abstinence Syndrome, Kailyn Conner

Theses and Dissertations--Pharmacy

Rates of neonatal abstinence syndrome have been rising over the past several years, alongside rising rates of opioid use disorder, propelled by the continuing Opioid Epidemic ravaging the country. Children born withdrawing from opioids they were exposed to in utero have known health complications through the first year of life that have been studied in the current literature. Less is known, however, about the outcomes these children face in childhood. As many of these children are progressing to childhood, there is an urgent need for healthcare system to prepare to handle the health needs of these children; outcomes related to …

Elucidating The Role Of The Tyrosine Phosphatase, Shp-2, In Regulation Of Pd-L1 Expression In Non-Small Lung Cancer Using Both Biochemical Analyses And Real-World Genomic Information, Keller Toral

Theses and Dissertations--Pharmacy

Immune checkpoint inhibitors (ICIs), especially those that target programmed cell death protein 1 (PD-1) and programmed cell death ligand-1 (PD-L1), have been shown to provide substantial clinical benefit in many patients with non-small cell lung cancer (NSCLC). While these therapeutic agents can be highly effective in the correct context, the biological systems that malignant cells draft from normal activities of the cell are poorly characterized. Tumor cell-specific expression of PD-L1 is likely important for clinical benefit from PD-1 and PD-L1 inhibitors. It is known that PD-L1 is inappropriately expressed in many cancers harboring mutations in the RAS family of genes. …

Towards A Holistic Risk Model For Safeguarding The Pharmaceutical Supply Chain: Capturing The Human-Induced Risk To Drug Quality, Heather R. Campbell

Theses and Dissertations--Pharmacy

Counterfeit, adulterated, and misbranded medicines in the pharmaceutical supply chain (PSC) are a critical problem. Regulators charged with safeguarding the supply chain are facing shrinking resources for inspections while concurrently facing increasing demands posed by new drug products being manufactured at more sites in the US and abroad. To mitigate risk, the University of Kentucky (UK) Central Pharmacy Drug Quality Study (DQS) tests injectable drugs dispensed within the UK hospital. Using FT-NIR spectrometry coupled with machine learning techniques the team identifies and flags potentially contaminated drugs for further testing and possible removal from the pharmacy. Teams like the DQS are …

Delineating The Biosynthesis Of Capuramycin-Type Antibiotics, Ashley L. Biecker

Theses and Dissertations--Pharmacy

New antibiotic scaffolds with novel drug targets are needed to combat the rise of drug-resistant, infectious microorganisms. The bacterial translocase I is a ubiquitous enzyme in the peptidoglycan biosynthetic pathway that has yet to be targeted by clinically used antibiotics. It catalyzes the transfer of N-acetylmuramoyl-pentapeptide to undecaprenylphosphate in order to generate lipid I during cell wall biosynthesis. A screening of bacterial translocase I inhibitors led to the discovery of the novel compound capuramycin and its analogues: A-500359s, A-503083s, and A-102395, produced by various species of actinomycetes. The capuramycins show potent activity against the bacterial translocase I with IC50s …

Multiple Proteinopathies And Their Role In Cognitive Impairment And Neurodegenerative Diseases, Shama D. Karanth

Theses and Dissertations--Epidemiology and Biostatistics

Most age-related neurodegenerative disorders are associated with the aggregation of misfolded and aberrant proteins. Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders and is highly prevalent in older adults. Neuropathologically, AD is characterized by the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs). Other misfolded proteins, including α-synuclein and transactive response DNA-binding protein 43 (TDP-43), are also commonly observed in aged brains. Aberrant α-synuclein has been associated with Parkinson's disease, Dementia with Lewy bodies, and multiple system atrophy, whereas TDP-43 has been associated with multiple neurological diseases, the most common of which was designated as limbic-predominant, …

Enhancing Drug Overdose Mortality Surveillance Through Natural Language Processing And Machine Learning, Patrick J. Ward

Theses and Dissertations--Epidemiology and Biostatistics

Epidemiological surveillance is key to monitoring and assessing the health of populations. Drug overdose surveillance has become an increasingly important part of public health practice as overdose morbidity and mortality has increased due in large part to the opioid crisis. Monitoring drug overdose mortality relies on death certificate data, which has several limitations including timeliness and the coding structure used to identify specific substances that caused death. These limitations stem from the need to analyze the free-text cause-of-death sections of the death certificate that are completed by the medical certifier during death investigation. Other fields, including clinical sciences, have utilized …

Environmental Respiratory Exposures And Pulmonary Function Among Residents Of Rural Appalachia, Kentucky, John C. Flunker

Theses and Dissertations--Epidemiology and Biostatistics

Introduction

Resource extraction exposures are hypothesized to promote adverse respiratory health outcomes among residents of rural Appalachia, yet no studies to date have simultaneously quantified small-scale geographic variation in residential exposure, individual level health factors, and respiratory health outcomes.

Methods

The Mountain Air Project (MAP) is a community engaged cross-sectional study based in Harlan and Letcher counties of Southeastern Kentucky. MAP utilized a novel small-scale method to define residential exposure boundaries: hydrologic unit code (HUC), which represents distinct drainages (AKA “hollows”) where residents cluster. We assigned the HUC level density of active and abandoned surface and underground mining, oil/gas wells, …

Hospital Nurses' Moral Distress And Coping During Covid-19: A Pilot Study, Abigail Latimer

Theses and Dissertations--Social Work

The COVID-19 pandemic caused a wave of critically ill patients, overwhelming hospitals, and creating unprecedented conditions for hospital employees, particularly bedside nurses. Concerns about the emotional and mental well-being of nurses have already been raised prior to the pandemic and depression, anxiety, and PTSD symptoms among nurses during the pandemic have been observed. Given the increased infection and safety risks, staffing shortages, inadequate personal protective equipment and resources, and hospital restrictions causing many nurses to be patients’ only support, there is also a growing concern about how these institutional and personal restrictions to providing best care and practicing ethically have …

Additive Manufacturing In Personalized Medicine: Patient-Customized Solid Dose Medicines, And Patient-Customized Wound Care Device, Amir Najarzadeh

Theses and Dissertations--Mechanical and Aerospace Engineering

Personalized Medicine - from a one-size fits all to a tailored approach is the future in pharmaceutical therapeutics and medical applications. The aim of this study is demonstrate additive manufacturing in two personalized medicine applications: 1. Patient- customized solid dose medicines, and 2. Patient-customized wound care device. The aim of the first application is to develop an inexpensive and accurate method to design and fabricate patient-customized tablets. Particularly this paper focuses on fabricating and dose controlling of patient-customized extended release prednisolone-poly(vinyle alcohole) PVA. Dry-Blending, Wet Granulation, Extrusion, Spherionization, Hot melt extrusion (HME) was adopted to produce drug loaded prednisolone-PVA filaments …

Precision Drug Delivery For Vancomycin Efficacy And Safety In Critically Ill Patients, Alexander Flannery

Theses and Dissertations--Clinical and Translational Science

Vancomycin is the most commonly prescribed antibiotic for hospitalized patients. Despite this fact and decades of clinical use, clinicians remain challenged to meet dosing targets of this narrow therapeutic index drug as well as minimize the risks of therapy, primarily nephrotoxicity. These concerns are magnified in critically ill patients given their severity. Accordingly, in a series of five clinical studies, we sought to identify optimal methods of vancomycin administration in critically ill patients to maximize efficacy and minimize nephrotoxicity via three techniques: use of continuous versus intermittent infusion, use of first-dose pharmacokinetic calculations to guide dosing, and use of loading …

Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids To Predict Carboplatin Resistance, Justin W. Gorski

Theses and Dissertations--Clinical and Translational Science

The development of patient-derived tumor organoids (TOs) from epithelial ovarian cancer tumor obtained at the time of primary or interval debulking surgery has the potential to play an important role in precision medicine.

Here, we utilize TOs to test front-line chemotherapy sensitivity and to investigate genomic drivers of carboplatin resistance. We developed six high grade serous epithelial ovarian cancer tumor organoids from tissue obtained during debulking surgery (2 neoadjuvant carboplatin exposed, 4 chemo-naïve). Each organoid line was screened for sensitivity to carboplatin at four different doses (100, 10, 1 and 0.1µM). Cell viability curves and resultant EC50 values were determined …

Comparison Of Implant-Retained Overdenture And Conventional Complete Denture In The Edentulous Mandible: A Survey Study To Measure Patients' Satisfaction And Quality Of Life In Dental School Clinical Environment, Ahmad Kutkut

Theses and Dissertations--Clinical and Translational Science

Patient satisfaction and quality of life are integral parts of assessing the quality of oral health care. Current aging population trends suggest a growing need to understand the effects of edentulism on oral health and quality of life. As the proportion of aged Americans expands, there will be an increased need to understand treatment options and patient communication strategies. In addition, as new treatment options and innovative technologies emerge, it will be essential to understand patients' concerns and identify best practices associated with denture treatments' individual fit and function. Advanced denture treatments can now be fabricated using CAD/CAM digital denture …

Therapeutic Drug Monitoring Of Beta-Lactam Antibiotics In Critically Ill Patients With Sepsis, Melissa Thompson Bastin

Theses and Dissertations--Clinical and Translational Science

Sepsis is a devastating diagnosis affecting over 750,000 patients a year, accounting for approximately 10% of all hospital admissions, costs more than $50,000 per patient, and exceeds $17 billion annual spending. The mortality rate for sepsis remains unacceptably high: one out of every three patients diagnosed with sepsis dies. Sepsis physiology induces physiologic changes to drug pharmacokinetic (PK) parameters that alter the ability to achieve the goal pharmacodynamic (PD) target for beta-lactams of >4-fold unbound concentration above the minimum inhibitory concentration for 100% of the dosing interval (100% fT >4x MIC). Sepsis treatment such as volume resuscitation and vasopressor …