Medicine and Health Sciences Commons^™

Modulating The Mtor Pathway Using Inducible Retrogradely Transported Aavs As A Novel Approach To Improve Motor Recovery In Spinal Cord Injury, Christopher Bosse-Joseph

Theses and Dissertations--Medical Sciences

Spinal cord injury poses multiple regeneration barriers, including neuronal-intrinsic and extrinsic factors. Overcoming these barriers has stood as a longstanding challenge in neuroscience. A well-studied mechanism to promote spinal cord regeneration and locomotor recovery is activating the PI3K/mTOR pathway by knocking out phosphatase and tensin homolog protein (PTEN). PTEN knockout (PTEN-KO) studies have traditionally used adeno-associated virus (AAV) viral vectors to improve functional recovery. The use of traditional AAV serotypes to induce PTEN-KO has shown promise to improve functional recovery in rodent models; however, these approaches show significant limitations for translational utility. Firstly, the use of traditional AAV serotypes to …

Understanding The Effects Of Hormone Treatments On The Transgender Singer: A Pedagogical Study And Voice Studio Guide, Erin M. Hannon

Theses and Dissertations--Music

Transitioning from one gender to another can be an arduous and emotionally charged experience, accompanied by many physical and mental transformations. The journey of self-discovery and vocal explorations is both unique and deeply personal. Modifications that emerge in an individual's vocal characteristics have a profound influence on their capacity to communicate and express themselves.

Transgender vocal students and professional singers must navigate the delicate balance between their vocal and gender identities while considering the possible risks of Gender Affirming Hormone Therapy. Though these therapies may significantly alter one's appearance and overall well-being, they are also capable of causing notable declines …

Ideal Body Weight And Body Fat Percentage Predict Relative Energy Deficiency In Sport (Red-S) Scores In Collegiate Athletes, Emily Norman

Theses and Dissertations--Nutrition and Food Systems

Background: Low energy availability (LEA) is the underlying cause of Relative Energy Deficiency in Sport (RED-S) which negatively affects athletes' physiological function, health, and performance. RED-S results from inadequate dietary intake to support energy expenditure for daily living, growth, and optimal performance. It occurs in both male and female athletes, with or without disordered eating. However, screening and diagnosis in athletes can be difficult. Objective: This study aims to identify strong predictors of RED-S and assess its prevalence in collegiate male and female athletes. Methods: A total of 270 NCAA athlete test points from mixed sports were evaluated for RED-S …

Mitochondria As Causes Of And Therapeutic Targets In Chronic Post-Sepsis Skeletal Muscle Weakness, Meagan Scott Kingren

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis, or the organ damage that ensues after the body fails to properly contain a local infection, is the leading cause of in-patient hospitalization in the United States. Advances in critical care medicine over the last 20 years have enabled most sepsis patients to survive the life-threatening dysregulated immune response. However, a majority of survivors report chronic weakness and fatigue years after sepsis, and the cause of this weakness remains largely unknown. This dissertation work focused first on elucidating the major causes of post-sepsis muscle weakness (Aim 1). This aim involved a time-course study to determine when muscle weakness was …

Protein S In Coagulation And Inflammation, Martha Mega Silvia Sim

Theses and Dissertations--Molecular and Cellular Biochemistry

Protein S (PS) is a key regulator, which links inflammation and coagulation and performs multiple proposed functions in both processes. PS exists in the blood as a free soluble form (~40%), bound to complement component 4b-binding protein/ C4BP (~60%), and packaged in platelet α-granules (~2.5%). Subendothelial tissue factor (TF), upon exposure to blood, initiates coagulation, a proteolytic cascade which results in the activation of thrombin, the enzyme responsible for formation of a fibrin clot. PS is a critical anticoagulant that inhibits multiple steps of this process. Only the free fraction of PS has full anticoagulant properties, as C4BP blocks this …

Prenatal Ethanol Exposure Impairs Performance On Spatial And Tactile Sequential Discrimination Task In Juvenile Rats, Caleb S. Bailey

Theses and Dissertations--Psychology

Fetal alcohol spectrum disorders (FASDs) are a set of cognitive and behavioral abnormalities that arise in ~5% of children who have been prenatally-exposed to alcohol. Prenatal alcohol exposure (PAE) can cause impairments in learning acquisition, working memory, response inhibition, and attentional-set shifting that result in exaggerated deficits in executive function and impairments in goal-seeking behavior. There are standard procedures used in rodent research to address some components of these deficits, but few procedures are sensitive enough to comprehensively assess such deficits. To address this issue in FASDs research techniques, we developed a procedure that requires prolonged executive function in a …

The Effect Of An Educational Handout On Knowledge, Awareness And Attitudes Of Pre-Exposure Prophylaxis (Prep) Among Participants At A Needle And Syringe Exchange Site, Mckenzie Buckel

DNP Projects

Background: In 2018, the total number of HIV cases in the United States was 1.2 million. Almost 186,500 of these cases were attributed to intravenous drug use. With the adherence to pre-exposure prophylaxis (PrEP) there is approximately a 49% decrease in the rates of HIV among people who inject drugs and the most significant barrier to PrEP among this population is a lack of awareness and knowledge.

Objective: The purpose of this study was to determine participants’ of a needle and syringe exchange site knowledge, awareness and attitudes of PrEP after reviewing an educational handout about PrEP.

Methods: A quasi …

Examining A Blood Biomarker Approach To Blood-Brain Barrier Disruption, Samantha Ford

Theses and Dissertations--Medical Sciences

Blood-brain barrier disruption has been identified to associate with the pathogenesis several neurological diseases such as dementia [1, 2], multiple sclerosis[3, 4], acute or chronic cerebral ischemia[5], brain trauma[5], meningitis[5], encephalitis[5], stroke[6], and seizures[7]. Being able to effectively identify blood-brain barrier disruption is limited in methodology. The current standard is using a cerebrospinal fluid (CSF) albumin to serum albumin index, which requires the use of a lumbar puncture. A novel method of identifying blood-brain barrier disruption utilizing blood biomarkers is proposed in this study. Participants in this study had previously collected blood and CSF samples, which were analyzed to compare …

Examining The Effects Of Hyperglycemia On Retinal Regeneration, Emmanuella Ec Kyllians

Theses and Dissertations--Biology

Diabetes is a disease that affects how the body processes glucose, leading to a cascade of other complications, one of which is diabetic retinopathy (DR). DR is a neurovascular disease that affects the retina and research has revealed the role of retinal neurodegeneration in its development. Animal models like zebrafish have emerged as important tools for studying the molecular and cellular mechanisms underlying DR. On the other hand, retinitis pigmentosa (RP) is a degenerative disease that involves the progressive degeneration of rods and cones, and hyperglycemia has been found to impair regeneration. Therefore, this study aims to examine the effects …

Exploring The Efficacy Of Mir-33 Antagonism In Promoting Regression Of Intracranial Atherosclerosis In A Nonhuman Primate Model, Peter Hecker

Theses and Dissertations--Pharmacology and Nutritional Sciences

Atherosclerosis, characterized by lipid accumulation and arterial inflammation, is a major contributor to global morbidity and mortality. Despite significant progress in understanding atherosclerosis in extracranial arteries, the study of intracranial atherosclerosis (ICAS) has been relatively neglected, despite its crucial role in stroke and vascular cognitive impairment. Challenges related to ICAS, including its location within the cranium and limited availability of suitable animal models, have hindered research progress in this area. Although nonhuman primates (NHPs) are commonly used for studying extracranial atherosclerosis, a comprehensive understanding of ICAS pathophysiology in these animals is lacking. By subjecting NHPs to a high-fat/cholesterol diet, we …

Assessment Of The Interplay Between Regional Β-Amyloid Burden And White Matter Hyperintensities On Cognition And Default Mode Network In Clinically Normal Older Participants, Doaa G. Ali

Theses and Dissertations--Clinical and Translational Science

Objective: Alzheimer’s disease (AD) and subcortical vascular dementia are considered the most common pathologic contributors to dementia in the aging population. Both frequently coexist in over 80% of community dwelling adults with dementia. The neuropathological development of AD arguably begins with β-amyloid (Aβ) deposition in the brain. This series of studies aims to test the hypothesis that early focal regional amyloid deposition in the brain is associated with cognitive performance in specific cognitive domain scores in preclinical AD (pAD) (study1). Since mixed dementia is widely recognized as the norm rather than the exception, the second study aimed to explore the …

Ethanol Decreases Expression Of Developing Neurons, But Not Neuronal Viability, In A Cultured Rat Hippocampus, Cassidy Count

Theses and Dissertations--Psychology

As of 2019, alcohol use disorders (AUDs) affect roughly 14.1 million individuals over the age of 18 and cost up to $249 billion in economic burden in the United States. In addition to central nervous system (CNS), those affected by AUDs can present with cognitive and behavioral abnormalities. Specifically, those affected by AUDs experience deficits in memory consolidation and retrieval as well as executive functioning, which may be due to cellular changes within the hippocampus. There are at least two prominent and contended theories which explain the mechanism of functional impairment caused by alcohol: 1) alcohol induces excitotoxic neuronal death …

Art Education In Medical Education: Benefits And Challenges, Sara K. Brown

Theses and Dissertations--Art and Visual Studies

Humanity is synergistic with art and medicine. Likewise, art education can be impactful throughout medical education. Art as a tool to develop the next generation of healthcare differs from the clinical goals of creative art therapies. Over the prior decade, many medical schools now provide curricular offerings in the arts and humanities. Less is known about the application in postgraduate medical settings. The focus of this thesis is to review the pairing of artist-educators with postgraduate medical training programs.

One such program is ArtsCAFE (Arts Connect Around Food and Enrichment), an intercollegiate project fusing experienced arts educators with medical educators …

Nutritional Status In Critical Care Of Covid-19 Patients, Dolph Lewis Davis Iii

Theses and Dissertations--Nutrition and Food Systems

Critical care nutrition is a poorly researched, and such a sudden pandemic event requiring manipulation of nutritional status via propofol-induced sedation for mechanical ventilation is potentially impactful on patient outcomes. This paper seeks to provide context to the impact of critical care protocols on the nutritional status of obese patients suffering from COVID-19.

Defining Patient Cohorts For Guiding Clinical Trials And Treatment In Lafora Disease: A Model For The Rare Disease Community, Katherine Janae Donohue

Theses and Dissertations--Molecular and Cellular Biochemistry

In the US, approximately 8000 rare diseases have been identified. Combined, rare diseases impact more than 30 million people in the U.S. alone, with 75% of those being children. However, research, funding, and therapeutic development for the rare disease community remains challenging because of the incredible diversity – not only between diseases, but often even within a single disease.

LD is an ultra-rare childhood dementia and epilepsy caused by mutations in one of two driver genes: EPM2A, which encodes for the glycogen phosphatase laforin, and EPM2B/NHLRC1, which encodes the E3 ubiquitin ligase malin. Children with LD …

Classification And Effect Of Correctors On Sitosterolemia-Associated Mutants In Abcg8, Brittney Poole

Theses and Dissertations--Medical Sciences

Objective: To classify mutants of ABCG8 identified in subjects with clinically confirmed Sitosterolemia, a rare form of Familial Hypercholesterolemia distinguished by the accumulation of phytosterols in plasma and tissues and determine the effects of correctors and/or regulators of proteostasis on maturation of the ABCG5/ABCG8 sterol transporter.

Methods: Disease-causing missense mutants within the cytosolic domain of ABCG8 were generated through site-directed mutagenesis. Normal and mutant proteins were expressed in human hepatocytes. Cellular proteins were prepared, and maturation was assessed by SDS-PAGE and immunoblotting. Formation of the higher molecular weight, mature form of glycoproteins was used as a bioassay for trafficking the …

Establishment And Verification Of A Sars Cov2 Antibody Detection Assay Comparing Venous And Mitra Samples, Stephen C. Mayer

Theses and Dissertations--Medical Sciences

During the COVID-19 pandemic in 2020, the need for highly-specific, wide-spread, and rapid serological testing surged. In this study, we showed very strong positive correlation between venous blood collection and Mitra home sampling kits for the detection of anti- spike IgGs using an in-house ELISA protocol (based on a protocol from Mt. Sinai). This study demonstrates the utility of using at-home, patient-centric testing to enhance the sero-surveillance methods currently in place for viral tracking and monitoring.

Investigating The Effects Of In-Vivo Therapeutics Hypoxia Treatment Paradigms In Neurite Outgrowth Patterns, Jae Hyun Yoo

Theses and Dissertations--Medical Sciences

Spinal cord injury, specifically in the cervical C3-C4 region of the cervical spine, contributes to impaired breathing and a diminished quality of life. Therefore it is important to find effective and safe therapeutics to restore breathing function. Indeed, there are a myriad of research being performed in addition to valuable collaboration amongst different institutions. As such, inspired by a previous experiment, we decided to test our hypothesis that an enriching environment consisting of different hypoxic environments - sustained and intermittent hypoxia alongside normoxia - would result in neurite outgrowth. Moreover, we hypothesized that sustained hypoxia would result in the greatest …

Mammalian Target Of Rapamycin Cell Signaling Pathway In Phosphatase And Tensin Homolog Induced Kinase 1 Knockout Rat Model Of Familial Parkinson's Disease, Martha Helena Mortell

Theses and Dissertations--Medical Sciences

More than 10 million people are living with Parkinson’s disease (PD), one million of which are people in the United States. PD is the second most common age-related neurodegenerative disorder, after Alzheimer’s disease, and is characterized by the accumulation of a-synuclein aggregates and the degeneration of dopaminergic neurons. The loss of endogenous dopamine in PD brain accounts for the motor decline presented clinically in PD patients. Etiological factors of PD include oxidative damage and inflammation, although the detailed mechanisms remain unknown. Risk factors for PD include gender, age, environmental factors, and gene mutations.

The current thesis research employed phosphatase and …

Apoe Genotype And Sex Modulate Ketogenic Diet Enhancements To Metabolism And Gut Microbiome In Young Mice, Andrew T. Yackzan

Theses and Dissertations--Medical Sciences

The apolipoprotein ε (APOE) allele in humans has been associated with risk for development of Alzheimer’s disease (AD). There are predominately three variations of the allele – ε2 (E2), ε3 (E3), and ε4 (E4) – with E4 contributing the greatest risk of AD development. Recent research has unveiled evidence of neurometabolic and neurovascular deficits in E4 carriers present decades before the onset of dementia; it is believed these chronic defects play a major role in the development of AD, thus making them a potential target for preventative intervention. The purpose of this study was to examine the effect of a …

Evaluating The Role Of Mmp9 In Hyperhomocysteinemia Induced Cerebrovascular Pathology, Alexandria Linton

Theses and Dissertations--Neuroscience

Vascular contributions to cognitive impairment and dementia (VCID) is one of the leading causes of dementia, along with Alzheimer’s disease (AD), and often manifests as a comorbidity of AD. Elevated plasma homocysteine, known as hyperhomocysteinemia (HHcy), is a risk factor for VCID; however, the mechanism underlying the connection between HHcy and development of VCID pathology remains elusive. Understanding this mechanism would reveal novel therapeutic targets with the potential to be disease modifying, which are a critical need for a disease that lacks any approved treatment. Previous studies from our lab have strongly associated neuroinflammation and blood brain barrier (BBB) dysregulation …

Promotion Of Early Recognition Of Depression To Improve Health Related Quality Of Life In Pediatric Oncology Patients, Jennifer Blankenship

DNP Projects

Background: Depression and anxiety are serious complications of cancer and deemed a challenging diagnosis due to the symptoms of depression mimicking common side effects of chemotherapy and radiation. Signs/symptoms frequently are underrecognized thus appropriate treatment is delayed, compromising the health-related quality of life (HRQOL) for pediatric oncology patients.

Purpose: Analyze existing physician and Advanced Practice Provider (APP) clinical practice regarding depression, via a pre- and post-survey and educational PowerPoint on the use of the Center for Epidemiological Studies Depression Scale for Children (CES-DC) to promote early recognition of depression.

Methods: A prospective, single-arm, study was completed in the Kentucky Children’s …

Evaluating The Microbiome To Boost Recovery From Stroke: The Embrs Study, Tyler Hammond

Theses and Dissertations--Neuroscience

Accumulating evidence suggests that gut microbes modulate brain plasticity via the bidirectional gut-brain axis and may play a role in stroke rehabilitation. A severely imbalanced microbial community has been shown to occur following stroke, causing a systemic flood of neuro- and immunomodulatory substances due to increased gut permeability and decreased gut motility. Here we measure post-stroke increased gut dysbiosis and how it correlates with gut permeability and subsequent cognitive impairment.

We recruited 12 participants with acute stroke, 12 healthy control participants, and 18 participants who had risk factors for stroke, but had not had a stroke. We measured the gut …

Uncovering The Role Of Apoe4 On Alzheimer’S Disease-Related Neuroinflammation, Courtney Marie Kloske

Theses and Dissertations--Physiology

Alzheimer’s disease (AD) is the most common neurodegenerative disease and is characterized by two hallmark pathologies: amyloid-beta plaques (Ab plaques) and hyperphosphorylated, aggregated tau tangles. These pathologies are typically accompanied by the presence of neuroinflammation which is primarily mediated by microglia. Interestingly, several genetic risk factors that increase the risk of AD also have direct impacts on neuroinflammation. Of interest, Apolipoprotein E (ApoE) is the largest genetic risk factor for AD. ApoE has three isoforms- E4 confers an increased risk for AD, E3 is considered the “control” phenotype, and E2 is protective against AD. E4 plays a role in virtually …

Evaluating The Relationship Between Plasma Biomarkers And Dementia Using Hierarchical Clustering Analysis And Linear Modeling, Zachary Winder

Theses and Dissertations--Physiology

Dementia is a disorder characterized by a significant decline from baseline in one or more cognitive domains that interferes with independence. Prevalence of dementia worldwide is estimated at 50 million people, with that number expected to triple by 2030, coming with a cost of roughly $2 trillion. Clinically, dementia is diagnosed using cognitive evaluations, with varying domains affected and to different degrees depending on the underlying pathology and stage of disease. Alzheimer’s disease (AD) and vascular contributions to cognitive impairment and dementia (VCID) are the two leading causes of dementia, and both have pathologies which can be visualized using MRI. …

A Study Of The Analysis Of Hemp-Derived Oil Products: Development Of A Method For The Analysis Of Phytocannabinoids In Medicinal Products, Erin Johnson

Theses and Dissertations--Pharmacology and Nutritional Sciences

Human interactions with cannabis have a history spanning millennia as a source of fiber, food, and medicine. The plant came across Asia, Europe, and Africa with the movements of people and travelers eventually coming to the Americas with European explorers. In colonizing North America, cannabis fiber was key to the production of canvas and ropes for ships. Although fiber was the driver for cannabis production in the United States, medicinal uses were prevalent and propelled the eventual regulations. The Pure Food and Drug Act of 1906 mandated accurate labeling on drugs such as cannabis followed by the Marihuana Tax Act …

Efficacy Of Prebiotic Dietary Intervention To Mitigate Risks For Dementia Via The Gut-Brain Axis, Lucille M. Yanckello

Theses and Dissertations--Pharmacology and Nutritional Sciences

Alzheimer’s disease (AD) is the most common form of dementia with various risk factors including age, environmental factors such as brain injury and genetic factors, such as the E4 allele of the Apolipoprotein gene. Presence of the APOE4 allele increases AD risk by two- to four- fold. Recent studies have shown that mild traumatic brain injury (mTBI), even without loss of consciousness, increases risk of dementia diagnosis by more than two-fold in military personnel and is also a significant environmental risk factor for developing dementia in the general population. The gut-brain axis (GBA) or bi-directional communication between the brain and …

Modeling The Effects Of Adverse Childhood Experiences Using A Mouse Model Of Neglect: Mechanisms Of Adiposity Expansion In Females, Jacqueline Leachman

Theses and Dissertations--Pharmacology and Nutritional Sciences

Adverse childhood experiences (ACEs) are an independent risk factor for chronic disease, including obesity and metabolic syndrome. We have previously shown that a mouse model of early life stress, maternal separation and early weaning (MSEW), exacerbates high-fat diet (HF)-induced obesity only in adult female mice. In agreement, the analysis of several cohorts of participants exposed to ACEs have shown that women are more susceptible to develop obesity than men. Therefore, the aim of this study was to investigate the link between early life stress and obesity in pre-clinical and clinical settings. Male and female MSEW mice fed 1 week a …

Deletion Of Period Genes Exacerbates Diet-Induced Obesity In Female, But Not Male, Mice, Elizabeth Kantra

Theses and Dissertations--Biology

Sex differences in obesity in mice are mediated by differential responses of circadian rhythms to high-fat feeding in males and females. Other studies also showed circadian Period genes regulate diet-induced obesity in mice. In this study, we investigated the role of the Period genes in regulating sex differences in obesity. Male and female C57BL/6J wild type, Per1/2 KO, and Per1/2/3 KO mice were housed in 12L:12D and fed high-fat diet for 12 weeks. We found a striking sex difference in obesity such that disabling the Period genes exacerbated adiposity in female, but not male, mice. Increased adiposity in female Period …

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 …