Medicine and Health Sciences Commons^™

Opioid Use In Vulnerable Populations, Gyeon Oh

Theses and Dissertations--Epidemiology and Biostatistics

Opioid-related negative health outcomes, such as substance use disorder, misuse, and overdose deaths, have risen as long-term opioid use has increased. The benefit of using long-term opioids for pain is yet to be established. The Centers for Disease Control and Prevention provides guidelines for opioid prescribing in chronic pain, but detailed recommendations on opioid prescribing for vulnerable populations are missing due to lack of evidence-based studies. The purpose of this dissertation is to describe patterns and predictors of opioid use and assess outcomes related to prescribing opioid medications in vulnerable populations, specifically older adults with various levels of cognitive function, …

National Guard Members With Suicide Ideation: The Impact Of Stigma, Mental Health, And Trauma History On Treatment-Seeking Outcomes, Amy Brown

Theses and Dissertations--Social Work

Background. Veterans are overrepresented among suicide deaths in the United States, representing 20% of annual suicide deaths but only about 1% of the U.S. population (Department of Veteran Affairs, 2010). Of all military suicide deaths in 2016, one-third (33.4%) were in the National Guard or Reserves (Department of Defense, 2018). Previous suicidal ideation or behavior (SIB) has been shown to increase risk of subsequent ideation or behavior in both active duty and veteran samples (Bryan, Rudd, & Wertenberger, 2016; Hazlett et al., 2016) but studies of SIB specific to National Guard service members were not found.

Access and Barriers to …

Breast Implant-Associated Anaplastic Large Cell Lymphoma: Molecular Features, Epidemiological Risk Factors, And Evidence-Based Clinical Recommendations, Ryan Decoster

Theses and Dissertations--Clinical and Translational Science

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an emerging cancer of the immune system that can form around textured-surface breast implants. In this dissertation, the cellular and molecular mechanisms of BIA-ALCL are reviewed with a focus on the role of oncogenic JAK-STAT3 signaling in BIA-ALCL tumorigenesis and progression. Herein, the epidemiology of BIA-ALCL is systematically studied to better define the risk of BIA-ALCL and to determine the oncologic safety of smooth surface devices relative to BIA-ALCL formation. Next, a systematic review is conducted which critically appraises current clinical guidelines in order to establish an evidence base to better inform …

The Effect Of Haptoglobin Phenotypes On Markers Of Neuroinflammation In Patients With Aneurysmal Subarachnoid Hemorrhage, Kevin Hatton

Theses and Dissertations--Clinical and Translational Science

Aneurysmal subarachnoid hemorrhage (aSAH) is a severe form of hemorrhagic stroke resulting from the spontaneous rupture of an intracranial aneurysm and release of oxygenated blood into the subarachnoid space. In the United States alone, aSAH occurs in approximately 30,000 patients each year and occurs, primarily, in otherwise healthy adults, frequently without warning. Sadly, approximately 40% of patients with aSAH will die in the first 30 days. Of those who survive, only about 75% will be able to live semi-independently again and only about 60% will be able to return to work.

Delayed brain injuries (DBI), which may affect up to …

Impact Of Nicu Design On Feeding-Related Outcomes In Preterm Infants, Emma Kate Calvert

Theses and Dissertations--Communication Sciences and Disorders

Many NICUs around the country are moving away from traditional open-bay designs in favor of single-family rooms (SFRs) as more is understood about the impact of the sensory environment on neurodevelopment in preterm infants. SFRs house one infant and their family for the length of the infant’s stay and are associated with improvements in numerous outcomes, including increased milk intake and weight gain and earlier transition to enteral feeding. Oral feeding remains a critical requirement for NICU discharge; however, the impact of NICU design on feeding outcomes remains unknown.

The purpose of this study was to compare feeding outcomes between …

Legibility Of Communicative Writing And Drawing In Aphasia: Does The Orthographic Medium Matter?, Nicole Waugaman

Theses and Dissertations--Communication Sciences and Disorders

Expressive language difficulties are commonplace in aphasia and are often further complicated by co-occurring motor speech disoders. Therefore, many people with aphasia (PWA) are unable to meet all their communication needs by speaking, and they may compensate with the use of communicative writing and drawing. Communicative writing and drawing can be defined as preserved, but imperfect, orthographic skills that PWA use to compensate for expressive language deficits resulting from aphasic and/or motor speech difficulties. The purpose of this study was to determine if the orthographic medium used by a PWA to write and draw influenced the legibility of their writing …

An Evaluation Of Postural Control And Balance After Anterior Cruciate Ligament Reconstruction, Kathryn Lucas

Theses and Dissertations--Rehabilitation Sciences

Over 100,000 anterior cruciate ligament reconstructions (ACLR) occur annually in the United States, with one in four individuals sustaining a second injury within the first two years after reconstruction. Due to the proprioceptive nature of the anterior cruciate ligament, the lack of regaining postural control and balance are likely large contributors to the rate of secondary injuries after ACLR. Recent literature has identified cerebral changes after anterior cruciate ligament injury and surgery, likely due to altered sensation and feedback loops. However, no study thus far has investigated the neurological feedback loops that may place this group at higher risk of …

Transcriptomic And Cellular Response To Mechanical Overload And The Underlying Role Of Macrophages In Extracellular Matrix Remodeling, Bailey D. Peck

Theses and Dissertations--Rehabilitation Sciences

The extracellular matrix (ECM) in skeletal muscle plays an integral role in tissue development, structural support, and force transmission. Upon mechanical loading, including resistance exercise, which alter muscle fiber contractile activity, size, orientation and connectivity, remodeling processes must occur that involve both ECM deposition and degradation. ECM remodeling involves many cell types in muscle, but the focus of our research was directed towards macrophages, which participate in the early immune response to damage and loading. We have consistently demonstrated a significant increase in skeletal muscle macrophage abundance using pan macrophage markers (CD11b/CD68) and anti-inflammatory markers (CD206/CD163) following exercise training in …

The Effects Of Dietary Nitrate And Vitamin C On Endothelial Function And Oxidative Stress Biomarkers, Reem Basaqr

Theses and Dissertations--Pharmacology and Nutritional Sciences

Background: Endothelial dysfunction is associated with a decline in the vasodilator nitric oxide (NO) and presents alongside other cardiovascular risk factors in the early stages of atherosclerosis. Independently, inorganic nitrate and vitamin C supplementation have shown promise in providing some restoration of NO bioavailability, reduced oxidative stress, and improvements in endothelial function. Some preliminary evidence has suggested that vitamin C may augment the reduction of nitrite to further liberate NO and improve cardiovascular health. However, co-supplementation has not been adequately studied. Our objective was to compare the effect of inorganic nitrate in the form of concentrated beetroot juice (CBJ) with …

Functional Impact Of Angiotensinogen Specific Domains On Angiotensin Ii-Mediated Functions, Chia-Hua Wu

Theses and Dissertations--Pharmacology and Nutritional Sciences

Angiotensinogen (AGT) is the only substrate for all angiotensin peptides in the renin angiotensin system (RAS). Cleavage of AGT by renin is a rate-limiting step of angiotensin peptides productions in the RAS and regulates angiotensin peptides-associated pathophysiological functions. Only ten N-terminal residues are cleaved by renin and the functions of remaining part of AGT protein, which is called des(angiotensin I)AGT, remain unclear. Despite of pivotal roles of AGT in the RAS, studies related to how AGT is metabolized and how des(angiotensin I)AGT regulates AGT functions or AngII-mediated functions are limited.

Renin cleavage of AGT shows species specificity. It has been …

Role Of Pancreatic Amylin In Alzheimer’S And Brain Microvascular Pathologies, Han Gia Ly

Theses and Dissertations--Pharmacology and Nutritional Sciences

Alzheimer disease (AD) and cerebral vascular disease (CVD) are common causes of impaired cognition and behavior in humans. Epidemiological studies have shown that AD and CVD development and progression associated with metabolic risk factors including type 2 diabetes (T2D). However, the underlying molecular mechanisms remain elusive, which hampers the development of treatment and prevention strategies. Research results from our laboratory and others have shown that amylin, a hormone secreted by the pancreas and involved in glucose homeostasis, induces small-vessel-type pathologies and modulates amyloid composition in both familial (genetically predisposed) and sporadic forms of AD. The results indicate amylin as a …

Apoe As A Metabolic Regulator In Humans, Mice, And Astrocytes, Brandon C. Farmer

Theses and Dissertations--Physiology

Altered metabolic pathways appear to play central roles in the pathophysiology of late-onset Alzheimer’s disease (AD). Carrier status of the E4 allele of the APOE gene is the strongest genetic risk factor for late-onset AD, and increasing evidence suggests that E4 carriers may be at an increased risk for neurodegeneration based on inherent metabolic impairments. A new appreciation is forming for the role of APOE in cerebral metabolism, and how nutritional factors may impact this role. In chapter 1, the literature on nutritional interventions in E4 carriers aimed at mitigating disease risk is reviewed. Studies investigating the mechanism by which …

Involvement Of The Renin Angiotensin System In Marfan Syndrome Associated Thoracic Aortic Aneurysms, Jeff Zheying Chen

Theses and Dissertations--Physiology

Thoracic aortic aneurysms (TAAs) are clinically-silent dilations of the aorta which greatly increase the risk of aortic rupture, a condition with 50-90% mortality. Marfan syndrome (MFS) is caused by mutations in fibrillin-1 (FBN1) and is associated with TAAs. Due to an absence of validated and effective pharmacologic therapies to prevent or reverse TAA, most MFS patients require surgical aortic repair. Understanding MFS associated TAA pathogenesis would direct development of new pharmacologic therapies. Previous research has implicated the renin angiotensin system in TAA. In both males and females, angiotensinogen (AGT) is cleaved serially to generate the main effector peptide angiotensin II …

Ceramide-Enriched Extracellular Vesicles: A Role In Enhancing Amyloid-Beta Neurotoxicity And Mitochondrial Damage In Alzheimer’S Disease, Ahmed Elsherbini

Theses and Dissertations--Physiology

Alzheimer’s disease (AD) is an age-dependent, progressive, neurodegenerative disorder that is characterized clinically by the impairment of cognitive functions concomitant with behavioral and personality changes. AD is associated with distinct pathological hallmarks, namely, intracellular neurofibrillary tangles comprised of hyperphosphorylated tau protein, extracellular amyloid beta (Aβ) plaques, and marked brain atrophy. Besides their main role as the core component of amyloid plaques, oligomeric Aβ have been shown to be neurotoxic. The exact mechanism of Aβ neurotoxicity is yet to be elucidated.

Recently, a pathogenic function of small extracellular vesicles- also known as exosomes- has been proposed, suggesting that exosomes can transfer …

Evaluation Of Rhodococcus Equi Susceptibility To Silver Nanoparticle Antimicrobials, Elizabeth Boudaher

Theses and Dissertations--Veterinary Science

Rhodococcus equi is a significant cause of pneumonia in foals and immunocompromised humans. Antimicrobial resistance among R. equi isolates has developed as a consequence of inappropriate stewardship and bacterial evolution, leading to an increased rate of treatment failures that typically result in foal fatality. In the current study, we evaluated the efficacy of antimicrobial silver nanoparticle (AgNP) complexes in controlling R. equi growth. Previous studies characterizing AgNP-induced antibacterial effects in other Gram-positive pathogens led us to hypothesize that silver nanoparticle antimicrobials impact R. equi viability and intracellular replication. We therefore investigated the effect of silver nanoparticle complexes on R. equi …

Donor Age Effects On The Proliferative And Chondrogenic/Osteogenic Differentiation Performance Of Equine Bone Marrow- And Adipose Tissue Derived Mesenchymal Stem Cells In Culture, Jasmin Bagge

Theses and Dissertations--Veterinary Science

Orthopedic injuries are a major cause of lameness and morbidity in horses. Bone marrow (BM)- and adipose tissue (AT) derived mesenchymal stem cells (MSCs) have shown potential to facilitate the repair of orthopedic injuries and are being used increasingly in veterinary clinics. Presently, the use of MSCs as a therapy for equine patients is most commonly applied as autologous transplants, using BM- and AT-MSCs harvested from the patient shortly after the time of injury. Cell-based therapies are therefore delayed to enable primary cell numbers to be expanded in culture. Of concern, however, are human and rodent studies that have shown …

Host-Parasite Interaction In Horses: Mucosal Responses To Naturally Acquired Cyathostomin Infections And Anthelmintic Treatment, Ashley Elaine Steuer

Theses and Dissertations--Veterinary Science

Cyathostomins are ubiquitous parasites in equids. In rare cases, cyathostomins lead to a generalized typhlocolitis and death. In healthy horses, local reactions are noted to the mucosal larvae; however, the mechanisms and importance of these reactions have not been elucidated. It has been hypothesized that anthelmintics can alter these reactions. Currently, three drug classes are approved for use in horses against cyathostomins; while all products target the adults, only two products are labeled as larvicidal. Adulticidal therapy is implicated in triggering the typhlocolitis, however, current evidence is contradictory. There is also conjecture that the larvicidal drugs can increase the risk …

Comparative Chondrogenesis Of Interzone And Anlagen Cells In Equine Skeletal Development, Chanhee Mok

Theses and Dissertations--Veterinary Science

At the presumptive sites of future synovial joints during mammalian skeletogenesis, articular cartilage develops from interzone located between the cartilaginous anlagen of bones. Thus, two types of cartilaginous tissues differentiate in close proximity. While anlagen cartilage is transient, progressing through endochondral ossification to form bones, articular cartilage is stable and functions throughout life to facilitate both low friction movement and load distribution. Despite important life-long functional properties, articular cartilage has a very limited intrinsic ability to repair structural defects. On the other hand, structural lesions in bones generally heal well by forming a cartilaginous callus and recapitulating endochondral ossification to …

Stress And Cancer Treatment: How A Family’S Adaptability And Cohesion Affects Financial Stress, Emily Marie Johnson

Theses and Dissertations--Family Sciences

According to the American Cancer Society (2019), it is estimated that 1,762,450 new cancer diagnoses occurred in 2019 in the United States. Currently, cancer remains one of the leading causes of death worldwide (American Cancer Society, 2019). As cancer affects the family, roles within the family will shift (e.g., transitioning to a caregiving relationship), causing each family member to adapt. With the costs of cancer steadily increasing, this potentially leaves a devastating impact on the family. When considering family function in terms of Family Systems, John Rolland created the Family Systems Illness Model to explain how families adapt to an …

An Educational Pilot Intervention To Increase Environmental Health Literacy Among Rural Kentucky Youth Attending Summer Camp, Ashley Rose Mattingly

Theses and Dissertations--Nutrition and Food Systems

Risk factors, including exposure to environmental pollutants, poor dietary and overall health outcomes, and low environmental health literacy (EHL), place the rural Appalachian youth population at increased risk for chronic diseases. Implementation of nutrition and pollution curriculum into two week-long summer day camps for youth ages 5-12 years that focus around healthy lifestyles and environmental stewardship has the potential to increase health protective action in this community. This research utilized qualitative interviews of 30 Kids on the Creek Camp attendees to determine the efficacy of the implementation of an active learning lesson to increase EHL by explaining the link between …

Appetite-Regulating Hormones In Energy Compensation With Exercise, Jack Moreland

Theses and Dissertations--Nutrition and Food Systems

Background: The appetite-regulating hormones may influence compensatory increases in energy intake with exercise, although this causal relationship has been difficult to prove in a longitudinal trial.

Methods: 37 participants (29 female) aged 18 to 40 years performed aerobic exercise 6 days (6d), 2 days (2d), or 0 days per week for 12-weeks. Concentrations of ghrelin, leptin, glucagon-like peptide 1 (GLP-1), and insulin were assessed before (fasting, minute 0) and after a standardized meal at minute 15, 30, 45, 60, 90, 120, 150, and 180. Linear mixed-effects models were used to model the relationships between time point (12 weeks vs. baseline) …

Cardiac Effects Of Obesity During Pregnancy In C57bl/6j Mice, Kayla Lynn Dudick

Theses and Dissertations--Nutrition and Food Systems

Objective: Pregnancy requires profound cardiac and metabolic adaptation. Left ventricular (LV) mass is increased in response to pregnancy, but is not associated with cardiac damage. In contrast, obesity-mediated cardiac hypertrophy is pathological. Data from animal studies indicate dietary fatty acid composition may have a protective effect during states of extreme cardiac physiological adaptation. In contrast, aberrant cardiac metabolism is a hallmark of disease. Over a third of reproductive-age women in the United States are obese, but there is a paucity of data describing the effect of obesity on maternal cardiac adaptation to pregnancy. The objective of this study was to …

Epidemiology Of Colorectal Cancer Comorbidities And Stage At Diagnosis, Survival, And Second Primary Malignancies In Kentucky, 2003-2016, Nikita Leigh Vundi

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

Background: Colorectal cancer (CRC) is the third most common type of cancer and the third most common cause of cancer death among men and women in the United States.^1-3 The American Cancer Society estimates that there will be 147,950 new cases of CRC and 53,200 CRC related deaths in the U.S. for the year 2020.3 Kentucky CRC incidence for 2012-2016 was the highest in the nation, and the mortality rate for years 2013-2017 was ranked 5th in the nation.^4-6 Risk factors for CRC include lifestyle factors, genetics, and disease status (comorbidities and treatment).2, 7 Diabetes has been …

Utilizing A Community-Based Doula Care Intervention To Reduce Race-Based Perinatal Health Inequities In Jefferson County, Kentucky, Brendan Mathews

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

Target Population and Need

The United States is currently the only industrialized nation in the world experiencing increasing rates of

pregnancy-related mortality.

1,2

Black women die at 3-4 times the rate of their white counterparts.

1-5

This disparity

is likely caused by the experience of systemic racism, which increases allostatic load and produces epigenetic

modifications linked to higher likelihood for poor birth outcomes. Biases perpetuated by health care providers

result in black women being less likely to receive quality healthcare and more likely to experience poor perinatal

1-7 to all pregnant women.

health outcomes.

The provision of doula-based care can …

The Impact Of Covid-19 On Worksite Wellness Programs, Marilyn S. Campbell

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

Introduction: Worksite wellness programs are popular employer offerings as of the last few decades. The COVID-19 pandemic has caused major shifts in behavior since these programs have been implemented. The purpose of this study was to see how the pandemic has affected various offerings within a university worksite wellness program.

Methods: This study is a secondary analysis of a university worksite wellness program, and it compares participation in the various offerings in response to the COVID-19 pandemic by evaluating 2019 participation (pre-pandemic) to 2020 participation (including onset of the pandemic and after). This worksite wellness program, which is available to …

Utilizing A Formative Program Evaluation Approach And An Application Of Grounded Theory To Assess A Novel Harm Reduction Program, Dia Obonyo

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

Formative program evaluation is conducted during development and early implementation to ensure a program is feasible, appropriate, and acceptable. The Harm Reduction Initiative (HRI), a program of KIRP, the Kentucky AIDS Drug Assistance (KADAP) Income Reinvestment Program, seeks to address some of the underlying causes of infectious disease vulnerability resulting from drug use by focusing on infectious disease testing and linkage to care among high risk individuals. The primary objective of the evaluation was to achieve the following aims: 1) characterize the need for the program, 2) clarify the theory and logic of the program, 3) inform implementation, and 4) …

Safety, Feasibility, And Efficacy Of Early Rehabilitation In Patients Requiring Continuous Renal Replacement: A Quality Improvement Study, Kirby P. Mayer, Amanda R. Hornsby, Victor Ortiz Soriano, Timothy C. Lin, Jennifer T. Cunningham, Hanwen Yuan, Caroline E. Hauschild, Peter E. Morris, Javier A. Neyra

Physical Therapy Faculty Publications

Introduction: Early rehabilitation in critically ill patients is associated with improved outcomes. Recent research demonstrates that patients requiring continuous renal replacement therapy (CRRT) can safely engage in mobility. The purpose of this study was to assess safety and feasibility of early rehabilitation with focus on mobility in patients requiring CRRT.

Methods: Study design was a mixed methods analysis of a quality improvement protocol. The setting was an intensive care unit (ICU) at a tertiary medical center. Safety was prospectively recorded by incidence of major adverse events including dislodgement of CRRT catheter, accidental extubation, bleeding, and hemodynamic emergency; and minor adverse …

Gynecologic Large Cell Neuroendocrine Carcinoma: A Review, Grant Burkeen, Aman Chauhan, Rohitashva Agrawal, Riva Raiker, Jill M. Kolesar, Lowell B. Anthony, B. Mark Evers, Susanne Arnold

Internal Medicine Faculty Publications

Large cell neuroendocrine carcinomas (LCNEC) are rare, aggressive high-grade neuroendocrine neoplasms within the neuroendocrine cell lineage spectrum. This manuscript provides a detailed review of published literature on LCNEC of gynecological origin. We performed a PubMed search for material available on gynecologic LCNEC. We analyzed 104 unique cases of gynecologic LCNECs, of which 45 were cervical primary, 45 were ovarian, 13 were uterine, and 1 was vaginal. A total of 45 cases of cervical LCNEC were identified with a median age of 36 years. Median overall survival was 16 months. We identified 45 ovarian LCNEC cases in the published literature with …

Cancer Patients’ Tobacco Use And Tobacco Treatment Referral Response: Implementation Outcomes At A National Cancer Institute- Designated Cancer Center, Tia Borger

Theses and Dissertations--Psychology

Smoking after cancer diagnosis is linked to cancer-specific and all-cause mortality among other adverse outcomes. Yet, 10-20% of U.S. cancer survivors are current smokers. Implementation of evidence-based tobacco treatment in cancer care facilities is widely recommended, yet rarely accomplished. This study focuses on the early outcomes of a tobacco treatment program integrated within an NCI-designated cancer center. Participants consist of 26,365 patients seen at the cancer center during the first 18 months of implementation. The study is a retrospective chart review of patients’ tobacco use, and among current users, patients’ treatment referral response. Over 99% of patients were screened for …

Modulation Of Epileptogenesis: A Paradigm For The Integration Of Enzyme-Based Microelectrode Arrays And Optogenetics, Corwin R. Butler, Jeffery A. Boychuk, Francois Pomerleau, Ramona Alcala, Peter Huettl, Yi Ai, Johan Jakobsson, Sidney W. Whiteheart, Greg A. Gerhardt, Bret N. Smith, John T. Slevin

Physiology Faculty Publications

BACKGROUND: Genesis of acquired epilepsy includes transformations spanning genetic-to- network-level modifications, disrupting the regional excitatory/inhibitory balance. Methodology concurrently tracking changes at multiple levels is lacking. Here, viral vectors are used to differentially express two opsin proteins in neuronal populations within dentate gyrus (DG) of hippocampus. When activated, these opsins induced excitatory or inhibitory neural output that differentially affected neural networks and epileptogenesis. In vivo measures included behavioral observation coupled to real-time measures of regional glutamate flux using ceramic-based amperometric microelectrode arrays (MEAs).

RESULTS: Using MEA technology, phasic increases of extracellular glutamate were recorded immediately upon application of blue light/488 nm …