Medicine and Health Sciences Commons^™

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 …

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 …

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 …

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 …

Rad Modulation Of The L-Type Calcium Channel Confers Systolic Advantage In The Heart, Brooke Mildred Ahern

Theses and Dissertations--Physiology

Heart failure is a major public health problem and a leading cause of mortality. This clinical condition affects populations of all ages, and is the result of various cardiomyopathies. Almost half of these patients suffer specifically from heart failure with reduced ejection fraction; these hearts have decreased performance due to a failure of the heart to contract with sufficient force to meet demand. While there are therapies available to increase contractility, none of these enhance contraction without also further promoting pathological signaling and remodeling.

Under normal physiological conditions, the body elevates cardiac output through the fight-or-flight response. This response activates …

The Role Of Microtubule-Associated Protein Tau In Neuronal Excitability And Epileptogenesis, Ryan A. Cloyd

Theses and Dissertations--Physiology

Tauopathies, including Alzheimer’s disease (AD), are devastating diseases with an immense burden on society which is predicted to increase in coming decades. In addition to progressive loss of memory and cognitive function, patients with tauopathies have a 6-10 fold increase in lifetime risk for seizures, and many are diagnosed with epilepsy. The presence of epileptiform activity on electroencephalogram (EEG) recordings from patients with AD predicts faster cognitive decline compared to patients without abnormal EEG readings. Electrophysiological measurements in murine models of AD have identified neuronal hyperexcitability. Furthermore, reducing tau phosphorylation or expression confers seizure resistance in animal epilepsy models. Although …

A Novel Role For Neurotensin In Regulation Of Stem Cell Function In The Small Intestine, Stephanie Rock

Theses and Dissertations--Toxicology and Cancer Biology

Neurotensin (NT) is a nutrient-regulated gut hormone that plays important roles in lipid absorption, obesity, metabolic disorders, and normal and neoplastic growth in the intestine. In this study, we 1) elucidate the mechanisms regulating NT release from endocrine cells, 2) examine the role of NT on proliferation and stem cell function in the small intestine and 3) define the effects of NT on colorectal cancer stem cells. We report that NT release from endocrine cells is enhanced by the MAPK scaffold protein Kinase Suppressor of Ras 1 (KSR1) and the exocyst complex component 70 (Exo70). Moreover, free fatty acid stimulated …

Anterior Cruciate Ligament Injury-Induced Alterations In Inflammation And Muscle Physiology, Emily R. Hunt

Theses and Dissertations--Rehabilitation Sciences

Long term weakness and atrophy of the quadriceps muscle are a direct result of anterior cruciate ligament (ACL) injuries and persist for up to 10 years post injury. Muscle atrophy ensues regardless of ligamentous reconstruction surgery, indicating that muscle atrophy following injury is a function of the ligament rupture and not reconstruction surgery. Elucidating the mechanisms underlying quadriceps atrophy following ACL rupture is crucial for developing interventions to restore proper quadriceps size and mitigate weakness thereby allowing for improved patient function. In addition to understanding the specific mechanisms that contribute to quadriceps atrophy following ACL rupture, the timing of atrophic …

Determining The Role Of Satellite Cells During Skeletal Muscle Adaptation, Davis A. Englund

Theses and Dissertations--Rehabilitation Sciences

Physical inactivity, advancing age, limb immobilization, degenerative diseases and various systemic diseases (many cancers, sepsis, HIV, COPD, kidney disease) all lead to skeletal muscle wasting. The loss of muscle mass is of major clinical importance because it leads to an increased risk for morbidity, disability, and the loss of independence; collectively contributing to a substantive increase in healthcare utilization and cost. The prevalence of cachexia (disease-induced muscle wasting) can reach as high as 80% in certain patient populations and the average cost per hospital stay is $4,641 more than in non-cachectic patients. Direct healthcare costs attributable to sarcopenia were estimated …

Targeting Maladaptive Plasticity After Spinal Cord Injury To Prevent The Development Of Autonomic Dysreflexia, Khalid C. Eldahan

Theses and Dissertations--Physiology

Vital autonomic and cardiovascular functions are susceptible to dysfunction after spinal cord injury (SCI), with cardiovascular dysregulation contributing to morbidity and mortality in the SCI population. Autonomic dysreflexia (AD) is a condition that develops after injury to the sixth thoracic spinal segment or higher and is characterized by potentially dangerous and volatile surges in arterial pressure often accompanied with irregular heart rate, headache, sweating, flushing of the skin, and nasal congestion. These symptoms occur in response to abnormal outflow of sympathetic activity from the decentralized spinal cord typically triggered by noxious, yet unperceived nociceptive stimulation beneath the level of lesion. …

Inhibition Of Cholesterol Biosynthesis Through Rnf145-Dependent Ubiquitination Of Scap, Li Zhang, Prashant Rajbhandari, Christina Priest, Jaspreet Sandhu, Xiaohui Wu, Ryan E. Temel, Antonio Castrillo, Thomas Q. De Aguiar Vallim, Tamer Sallam, Peter Tontonoz

Saha Cardiovascular Research Center Faculty Publications

Cholesterol homeostasis is maintained through concerted action of the SREBPs and LXRs. Here, we report that RNF145, a previously uncharacterized ER membrane ubiquitin ligase, participates in crosstalk between these critical signaling pathways. RNF145 expression is induced in response to LXR activation and high-cholesterol diet feeding. Transduction of RNF145 into mouse liver inhibits the expression of genes involved in cholesterol biosynthesis and reduces plasma cholesterol levels. Conversely, acute suppression of RNF145 via shRNA-mediated knockdown, or chronic inactivation of RNF145 by genetic deletion, potentiates the expression of cholesterol biosynthetic genes and increases cholesterol levels both in liver and plasma. Mechanistic studies show …

The Effects Of Exercise Preconditioning On Focal Ischemic Stroke, Gillian Grohs

Theses and Dissertations--Medical Sciences

Cleaved fragments of the extracellular matrix protein perlecan have been shown to promote neuroprotection and repair after ischemic stroke. The cysteine proteases cathepsin B and L as well as the metalloprotease bone morphogenic protein 1 (BMP-1) are capable of releasing the biologically active C-terminal laminin-like globular domain (LG3) of perlecan. Exercise, a known method of reducing stroke risk and severity, has been shown to increase the expression of some proteases associated with perlecan processing. Using a transient distal middle cerebral artery occlusion (MCAo) model for focal ischemic stroke we show that while 7 days of running only slightly decreased infarct …

Neuroinflammation In Alzheimer's Disease And Vascular Cognitive Impairment, Erica M. Weekman

Theses and Dissertations--Physiology

It was once believed that the brain was immunologically privileged with no resident or infiltrating immune cells; however, now it is understood that the cells of the brain are capable of a wide range of inflammatory processes and phenotypes. Inflammation in the brain has been implicated in several disease processes such as Alzheimer’s disease (AD) and vascular cognitive impairment and dementia (VCID); however, the role of inflammation in these two dementias is poorly understood.

When we stimulated a pro-inflammatory phenotype with an adeno-associated viral vector in a transgenic mouse model of AD that develops Aβ plaques, we saw a pro-inflammatory …

Regulation Of Uv-Protective Pathways Downstream Of The Melanocortin 1 Receptor In Melanocytes, Erin M. Wolf Horrell

Theses and Dissertations--Physiology

Malignant cutaneous melanoma is the deadliest form of skin cancer, and a majority of melanoma diagnoses are a result of exposure to ultraviolet (UV) radiation. UV radiation causes DNA damage, which if not repaired correctly via nucleotide excision repair (NER) can result in mutations and melanomagenesis. The melanocortin 1 receptor (MC1R) is a G_s protein coupled receptor located on melanocyte plasma membranes and is involved in protecting the skin from UV induced damage. MC1R signaling results in the activation of two protective pathways: 1) induction of eumelanin synthesis downstream of micropthalmia-associated transcription factor (MITF) and 2) acceleration of NER …

Global-Scale Analysis Of The Dynamic Transcriptional Adaptations Within Skeletal Muscle During Hypertrophic Growth, Tyler Kirby

Theses and Dissertations--Physiology

Skeletal muscle possesses remarkable plasticity in responses to altered mechanical load. An established murine model used to increase mechanical load on a muscle is the surgical removal of the gastrocnemius and soleus muscles, thereby placing a functional overload on the plantaris muscle. As a consequence, there is hypertrophic growth of the plantaris muscle. We used this model to study the molecular mechanisms regulating skeletal muscle hypertrophy.

Aged skeletal muscle demonstrates blunted hypertrophic growth in response to functional overload. We hypothesized that an alteration in gene expression would contribute to the blunted hypertrophic response observed with aging. However, the difference in …

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

Theses and Dissertations--Physiology

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

Physiological And Toxicological Roles Of Abc Transporters In Cellular Efflux Of Substrates, Donna J. Coy

Theses and Dissertations--Toxicology and Cancer Biology

ATP-binding cassette (ABC) transporters are transmembrane proteins that transport a wide variety of substrates across intra and extra-cellular membranes. A few examples of endo and xenobiotic substrates are metabolic products, lipids, sterols, and drugs. An important function of ABC transporters involved in export is to prevent intracellular the buildup of toxic products. Several ABC transporters have also been associated with drug resistance upon treatment with chemotherapeutic agents. P-glycoprotein (P-GP) and the multidrug resistant (MRP) transporters of the ABC C family are examples of transporters that confer chemo-resistance.

We have studied two unique roles of ABC transporters in the liver and …