Medical Sciences Commons^™

Therapeutic Targeting Of Relaxin Signaling In Ischemic Heart Disease, Siva Teja Vk Devarakonda

Theses and Dissertations

Ischemic heart disease is characterized by reduced perfusion of oxygenated blood to the myocardium, potentially resulting in infarction upon occlusion of coronary arteries. While prompt reperfusion and advances in in-hospital care have led to a decline in short term mortality, sustained damage to the ventricle, along with reperfusion injury, can lead to progressive deterioration in cardiac function. Limiting the extent of this initial ischemia-reperfusion injury and combating the course of adverse remodeling remains the scope of several preclinical studies geared towards improving cardiac health after MI. To this, relaxin-2 – the peptide hormone that regulates maternal hemodynamic function during pregnancy …

Modulation Of Autophagy And Senescence To Enhance The Response To Therapy In Triple Negative Breast Cancer, Liliya Tyutyunyk-Massey

Theses and Dissertations

Abstract

Although great strides have been made over the decades in development and optimization of anti-cancer therapies, even highly effective drugs often fail to completely eliminate tumors. Residual tumor cells can enter into a state of dormancy for prolonged periods of time but eventually are able to regain proliferative capacity and reemerge as chemotherapy-resistant disease. Because recurrent disease is a leading contributor to patient’s mortality, it is paramount to identify strategies for effectively destroying residual tumor cells.

Cytotoxic drugs and ionizing radiation are used as standard therapies in a variety of cancers. These modalities induce apoptosis, autophagy and senescence. Senescence …

Axon Initial Segment Integrity In Aging And Traumatic Brain Injury, Mazen M. Gouda

Theses and Dissertations

According to the Center for Disease Control’s (CDC) report to the Congress, there are 2.2 million emergency department visits; 80,000 hospitalizations; and 50,000 deaths each year due to traumatic brain injury. Adults 65 years and older account substantially for the majority of the hospitalization and deaths. Over 70% of the traumatic brain injuries of the older adults are classified as mild to moderate; however, even with these milder injuries, older adults present with a significantly higher morbidity and mortality compared to all other age groups (LeBlanc et al., 2006). With that in mind, it seems essential to develop a deeper …

Characterization Of The Novel Interaction Between Neisseria Gonorrhoeae Tdfj And Its Human Ligand S100a7, Stavros Maurakis

Theses and Dissertations

Neisseria gonorrhoeae is an obligate human pathogen that causes the common STI gonorrhea, which presents a growing threat to global health. The WHO estimated 78 million new cases of gonorrhea worldwide in 2017, with estimates of 820,000 new cases in the United States alone according to the CDC. High-frequency phase and antigenic variation inherent in N. gonorrhoeae, coupled with its natural ability to rapidly acquire and stably integrate antimicrobial resistance factors into its genome, have culminated in an infection against which there is no effective vaccine, and for which the list of viable therapeutic options is quickly shrinking. Moreover, no …

Diuretic, Natriuretic, And Vasodepressor Activity Of A Lipid Fraction Enhanced In Medium Of Cultured Mouse Medullary Interstitial Cells By A Selective Faah Inhibitor, Zdravka P. Daneva

Theses and Dissertations

The relationship between the endocannabinoid system in the renal medulla and the long-term regulation of blood pressure is not well understood. To investigate the possible role of the endocannabinoid system in renomedullary interstitial cells, mouse medullary interstitial cells (MMICs) were obtained, cultured and characterized for their responses to treatment with a selective inhibitor of fatty acid amide hydrolase (FAAH), PF-3845. Treatment of MMICs with PF-3845 increased cytoplasmic lipid granules detected by Sudan Black B staining and multilamellar bodies identified by transmission electron microscopy. HPLC analyses of lipid extracts of MMIC culture medium revealed a 205nm-absorbing peak that showed responsiveness to …

Conjugated Bile Acid And Sphingosine 1-Phosophate Prompt Cholangiocarcinoma Cell Growth Via Releasing Exosomes, Waad A. Alruwaili

Theses and Dissertations

Cholangiocarcinoma (CCA) is a fatal primary malignancy that is formed in the bile ducts. Cancer-associated myofibroblasts play a crucial role in CCA proliferation and invasion. Furthermore, there is a growing interest in the role of the exosome in the interaction between the cancer-associated myofibroblasts and cholangiocarcinoma which lead to CCA growth. However how cholangiocarcinoma-derived exosome affect the cancer-associated myofibroblasts in the tumor microenvironment remain unknown. In this study, we examined whether exosome produced by cholangiocarcinoma could involve in the prompt of CCA cells growth by regulation of myofibroblast. We found that cholangiocarcinoma-derived exosome could prompt elevated α-smooth muscle actin and …

A High Fructose Diet Alters Affective-Like Behavior And Metrics Of Synaptic Mitochondrial Function Differentially In Male And Female Rats, Alix H. Kloster

Theses and Dissertations

Fructose consumption has become a normalized part of the standard American diet over the past 40 years. While fructose consumption is a known risk factor of metabolic syndrome, there is increasing evidence that fructose consumption influences brain and behavior. Recently, more interest has been focused on mitochondrial dysfunction as a potential link between metabolic stress and modifications of the central nervous system. Mitochondria are in the unique position of both regulating and being vulnerable to alterations in energy homeostasis. Sex-differences are well categorized in the presentation of metabolic symptoms associated with excessive fructose consumption. Thus, it is important to characterize …

Pharmacodynamics Of Monoamine Transporter Releasing Agents And Reuptake Inhibitors, Alexa Holloway

Theses and Dissertations

Ligands of the human monoamine transporters encompass a wide range of both illicit and therapeutic drugs that act upon neural circuitry related to reward, motivation, and the processing of salient stimuli. The present study utilizes two methods for analyzing transporter substrates and inhibitors in order to characterize activity and assess potency. The first measures transient changes in intracellular calcium as a surrogate for transporter activity by harnessing the electrical coupling of monoamine transporters and L-type calcium channels. This is used to analyze novel chimera of the strong hDAT inhibitors methylphenidate and ��-PPP in order to assess the contribution of specific …

The Role Of Tumor And Tumor Microenvironment On Breast Cancer-Associated Adipocyte Plasticity, Janina V. Pearce

Theses and Dissertations

Cancer-associated cachexia is a condition defined by a sustained net-negative energy imbalance. Although the different types of adipose tissue – white, beige, and brown – have been implicated in contributing to cancer-associated cachexia, the mechanisms of these maladaptive changes and their impact on whole-body energy expenditure have not been fully elucidated. Using breast cancer as our model, we demonstrate white adipose tissue browning in murine and human breast cancer; furthermore, we demonstrate that this effect is extremely localized and takes place early in tumor progression. We utilized in vitro cell culture techniques and demonstrate that cancer secreted factors and cross-talk …

Embryonic Stem Cell-Derived Exosomes Increase The Antiproliferative Activity Of Doxorubicin In Breast Cancer, Alexander M. Hirsch

Theses and Dissertations

The field of cancer research has grown immensely in recent decades and has led to a better understanding of the causes of the disease, as well as greatly improved treatment for various types of cancers, especially breast cancer. One of the most effective treatments involves the chemotherapeutic drug doxorubicin (DOX). DOX is an effective tool against all types of breast cancer, especially against triple negative breast cancer. However, DOX causes adverse side effects that include damage to the heart and skeletal muscle, particularly above specific cumulative doses. Recent evidence suggests that embryonic stem cell-derived (ES) exosomes, nanoscale extracellular vesicles that …

The Cardiovascular Demands Of Division I Sideline Cheerleaders During Training And Football Games, Mckenna Cornett

Theses and Dissertations

The purpose of this study was to evaluate the autonomic balance and cardiovascular demands of collegiate sideline cheerleaders between practice and game settings, and throughout four quarters of a football game; and to evaluate the physical fitness of collegiate Division I cheerleaders. Eleven cheerleaders volunteered to participate (age; 18.9+0.8y, height; 163.2+4.3cm, and body mass; 64.9+8.7kg). Basic physical fitness was assessed by evaluating blood pressure, resting heart rate, grip strength, and body composition. Physiological data (maximal heart rate [HR], average HR, physiological intensity, physiological load, maximal activity, and average activity) were collected at four practices and four games using a Zephyr …

Out Of The Shell: Exploring The Phagocytic Capabilities Of The B Cell And Isolated Lymphoid Follicle-Lie Structures In The Red-Eared Slider, Trachemys Scripta, Marc A. Ashford Jr.

Theses and Dissertations

Management of immunity is crucial for survival in all living organisms. While there is a large amount of research for established model organisms, such as the mouse model, much less is known about reptiles. When compared to immunity in mammals, we discover many differences such as susceptibility to certain pathogens, alteration of immune processes due to environmental temperature, the total absence of certain lymphoid organs contained in mammals, among many others. Despite this, the reptile has shown in many studies that they are worthy systems to study immunity in an evolutionary perspective and recent studies may show that they may …

Usefulness Of The Captia Syphilis Igg Eia Test Method And Reverse Algorithm For Detection Of Syphilis Infection In A Public Health Setting, Patricia Armour

Theses and Dissertations

Syphilis, a systemic sexually transmitted disease, is on the rise in the US, with infection rates the highest recorded since 1994 according to the CDC. Useful laboratory testing is an important diagnostic tool for determining individual syphilis infection and preventing community-wide disease spread.

The purpose of this study was to determine the usefulness of a specific automated treponemal test method, the Captia^TM Syphilis IgG EIA, and the syphilis reverse algorithm interpretation for detecting syphilis infection among patients seeking care in a public health clinic. The study employed a retrospective, nonexperimental descriptive correlational design with data collected between 2012-2013 from …

Investigating The Role Of Nicotinic Acetylcholine Receptors (Nachrs) In The Development And Maintenance Of Chemotherpy-Induced Peripheral Neuropathy In Mice, Wisam B. Toma

Theses and Dissertations

Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a major dose-limiting side effect of several anticancer drugs. The prevalence of CIPN ranges from one-third to two-thirds of cancer patients. CIPN can persist for months to years after completion of chemotherapy. Despite the efficacious use of paclitaxel in the treatment of tumors, it can induce many sensory symptoms, such as paresthesia, numbness, tingling and burning pain, and mechanical and cold allodynia, which typically are present in the hands and feet. Similar to other types of chronic pain, paclitaxel-induced CIPN is comorbid with depression and anxiety in cancer survivors, and paclitaxel induces changes in affect-like …

Effects Of Chemotherapy On Motivated Behavior And Opioid Reward In Rats, Luke P. Legakis

Theses and Dissertations

Paclitaxel, vincristine, oxaliplatin, and bortezomib are cancer chemotherapy drugs with adverse effects that include chemotherapy-induced neuropathic pain (CINP) as well as depression of behavior and mood. In the clinical setting, opioids are often used concurrently with or following chemotherapy to treat pain related to the cancer or CINP, but repeated opioid exposure can also increase the risk of opioid abuse. This dissertation evaluated the effect of chemotherapy treatment on motivated behaviors and opioid reward in rats. The main findings of this evaluation are as follows: (1) Chemotherapy, at doses that produce robust and sustained mechanical hypersensitivity produce only weak or …

Impaired Cardiorespiratory Fitness Following Thoracic Radiotherapy, Justin M. Canada

Theses and Dissertations

Cancer (CA) is the second leading cause of death in the United States preceded only by cardiovascular disease (CVD). Over the past 30 years, the 5-year survival rate for all cancers combined has increased by more than 20%. This improved survival rate is due to early diagnosis and advances in treatment involving a multimodality treatment approach that includes radiotherapy [RT] with about half of all CA patients receiving some type of RT sometime during the course of their treatment. Cardiotoxicity is one of the most important adverse reactions of RT and leads to a meaningful risk of CVD-related morbidity and …

Penalized Mixed-Effects Ordinal Response Models For High-Dimensional Genomic Data In Twins And Families, Amanda E. Gentry

Theses and Dissertations

The Brisbane Longitudinal Twin Study (BLTS) was being conducted in Australia and was funded by the US National Institute on Drug Abuse (NIDA). Adolescent twins were sampled as a part of this study and surveyed about their substance use as part of the Pathways to Cannabis Use, Abuse and Dependence project. The methods developed in this dissertation were designed for the purpose of analyzing a subset of the Pathways data that includes demographics, cannabis use metrics, personality measures, and imputed genotypes (SNPs) for 493 complete twin pairs (986 subjects.) The primary goal was to determine what combination of SNPs and …

Metabotropic Glutamate Receptor 2 Activation: Computational Predictions And Experimental Validation, Amr Ellaithy

Theses and Dissertations

G protein-coupled receptors (GPCRs) are the largest family of signaling proteins in animals and represent the largest family of druggable targets in the human genome. Therefore, it is of no surprise that the molecular mechanisms of GPCR activation and signal transduction have attracted close attention for the past few decades. Several stabilizing interactions within the GPCR transmembrane (TM) domain helices regulate receptor activation. An example is a salt bridge between 2 highly conserved amino acids at the bottom of TM3 and TM6 that has been characterized for a large number of GPCRs. Through structural modeling and molecular dynamics (MD) simulations, …

Regulation Of Prostaglandin D2 And Angiogenesis-Related Factors From Human Skin Mast Cells By Interleukin-6 And Resveratrol, Cody Cody Mchale

Theses and Dissertations

Mast cells are classically recognized as the effector cells of Immunoglobulin E (IgE)-mediated hypersensitivity reactions (i.e. allergic reactions). Mast cells also play an important role in the innate immune response to parasitic helminth infection. Allergic disease including allergic rhinitis, asthma, atopic dermatitis, and anaphylaxis, is a major health concern in the United States with greater than 60 million Americans suffering from allergy and asthma. In addition, mast cells have more recently been implicated in non-allergic disease including various human cancers, which will affect approximately 39.6% of U.S. men and women. Therefore, understanding the immunological and molecular mechanisms that regulate mast …

Family Planning Decisions After A Child’S Diagnosis Of Rett Syndrome: A Pilot Study, Erin E. Huggins

Theses and Dissertations

Rett syndrome (RTT) is a rare neurodevelopmental disorder that primarily affects females. In 99% of cases, RTT is believed to occur sporadically, or de novo. However, in rare cases, RTT can be passed down from parent to child through gonadal mosaicism or asymptomatic carrier mothers. It is known that having a child with an inherited genetic condition can lead to changes in family planning; however, little research has investigated this phenomenon in sporadic genetic conditions, such as RTT. This present study used a questionnaire to assess family planning decisions of parents of children with RTT. Forty-three percent of respondents reported …

Parental Experience With Whole Exome Sequencing Reanalysis And Its Impact On The Diagnostic Odyssey, Nicole D. Lucas

Theses and Dissertations

Advances in genomic technology and an increase in the number of gene-disease associations have helped reduce the number of individuals living without a diagnosis. Whole exome sequencing (WES) analyzes the entire human exome in an attempt to determine if there is a molecular etiology for individuals who remain undiagnosed after other clinical or molecular investigations. Still, WES leaves most individuals undiagnosed, resulting in feelings of disappointment and uncertainty. Individuals who remain undiagnosed after WES can subsequently undergo WES reanalysis later due to improvements in bioinformatics, software updates, and an increase in known genedisease associations. This is the first study, to …

The Nervous System And Cancers Of The Head And Neck, Christian A. Graves

Theses and Dissertations

The anatomy of the head and neck is closely associated with the nervous system which plays an important role in the prognosis of head and neck cancer (HNC). However, the molecular interactions between these compartments and HNC remain poorly understood. We present a novel big data approach utilizing clinical data, sequencing, and machine learning to identify and validate potential molecular pathways by which the nervous system affects the development and progression of HNC. Our studies demonstrate across multiple datasets that perineural invasion (PNI) frequently occurs in HPV+ HNC. Furthermore, we show novel activating and missense mutations and pathways that may …

Understanding Barriers To Genetic Testing For Sickle Cell Trait: The African-American Male Perspective, Shandrea Foster

Theses and Dissertations

Research has shown a reluctance in African-American males to pursue testing for sickle cell trait. Few studies have tried to discern what barriers are contributing to this issue within the African-American male community. Research suggests a lack of knowledge may be the biggest contributing factor. This study hypothesized there would be a significant difference in knowledge of sickle cell trait based on educational level, age, and health beliefs. African-America male participants (N=116), ages 18 and over, completed a questionnaire assessing knowledge, risk perception, health beliefs, barriers, and motivating factors within the context of sickle cell trait. One-way and two-way analysis …

Assessing The Barriers To Cardiac Care In Carriers Of Duchenne And Becker Muscular Dystrophy, Lauren Renae Eekhoff

Theses and Dissertations

Duchenne and Becker muscular dystrophy (DBMD) are X-linked conditions due to mutations within the dystrophin gene that cause progressive muscle weakness, respiratory insufficiency, and cardiomyopathy in affected males. Approximately twothirds of women who have a son with DBMD are carriers of the condition. Carriers typically do not manifest muscular symptoms but are at risk for cardiac abnormalities such as dilated cardiomyopathies. The American Academy of Pediatrics (AAP) recommends that carriers of DBMD receive a complete cardiac evaluation by a cardiologist that includes an echocardiogram and electrocardiogram (EKG) with reevaluation every five years. According to a recent study33, as many as …

The Impact Of Communication Deficits On Puberty And Sexual Development In Adolescents On The Autism Spectrum, Ashton Wolfe

Theses and Dissertations

Transitioning into a sexually mature adult is a challenging time for both an adolescent with autism spectrum disorder (ASD) and his or her family. Sexual development begets challenges due to the demands it places on the social and communication skills needed to explore developmental changes that are occurring physically, emotionally and hormonally. A diagnosis of ASD is largely established by quantifying impediments in social and communication skills through observation. With deficits in these skills, one can assume that social and communication difficulties can create obstacles in the sexual development of affected individuals. Our study used quantitative and qualitative measures to …

Is Current Fragile X Syndrome Counseling Enough? Expanding The Clinical Phenotype Of Fragile X In Premutation And Intermediate Allele Carriers, Zahra Saadat Girnary

Theses and Dissertations

Fragile X syndrome (FXS) is caused by a triplet repeat expansion on the FMR1 gene. Individuals with >200 repeats have FXS, while individuals between 45-54 and 55- 200 repeats have the FMR1 intermediate allele and premutation, respectively. FXS is characterized by autism and intellectual disability while the premutation is associated with fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI). However, recent research shows that the premutation may be associated with psychiatric manifestations. Currently, there are no established clinical features associated with the intermediate allele. This study sought to 1) study knowledge regarding FXTAS, FXPOI, as well …

Discussing History Of Mental Illness During Prenatal Genetic Counseling: Patient Interest And Comfort, Sarah Nimrichter

Theses and Dissertations

Purpose: This study aimed to explore patient interest in and comfort with discussing a personal and/or family history of mental illness with a genetic counselor during a prenatal genetic counseling session. Methods: Participants included pregnant women who met with a genetic counselor for routine prenatal screening/testing counseling at Palmetto Health USC Medical Group Department of OB/GYN. Following their appointment, they were given a copy of the invitation to participate, questionnaire, and mental health resource page by the genetic counselor who performed their genetic counseling. Results: Forty participants completed questionnaires. 70% of participants indicated some level of interest in discussing mental …

Role Of Mir-489 In Her2 Positive Breast Cancer, Yogin Patel

Theses and Dissertations

Human epidermal growth factor receptor 2 (HER2 or ErBb2) is a receptor tyrosine kinase overexpressed in 20-30% of breast cancers and associated with poor prognosis and outcome. Dysregulation of several micro RNAs (miRs) plays a key role in breast cancer progression and metastasis. In this study, we screened and identified miRs dysregulated in HER2-positive breast cancer cells. Molecular study demonstrated that miR-489 was specifically downregulated by the HER2-downstream signaling, especially the MAPK pathway. Restoration or overexpression of miR-489 in HER2-positive breast cancer cells significantly inhibited cell growth in vitro and decreased the tumorigenicity and tumor growth in xenograft mice. Mechanistically, …

Advanced Clearing Methods And Imaging Techniques For Optimized Three- Dimensional Reconstruction Of Dense Tissues, Caleb A. Padgett

Theses and Dissertations

Advances in tissue clearing have allowed biological and biomedical researchers to image entire segments of tissue and generate three-dimensional reconstructions, allowing for a better understanding of the structural and morphological characteristics of large tissues. This study compared three commonly utilized clearing methods and analyzed their effectiveness in increasing imaging depth for three-dimensional reconstruction of large tissue segments. Mouse heart, mouse brain, mouse colon, and embryonic chick tissues were cut into thick sections, cleared and immunolabeled with an antibody specific to each tissue type, and imaged using a confocal microscope. The results of this study concluded that most tissues cleared by …

Effect Of Resveratrol On The Development Of Eczema, Christopher Carlucci

Theses and Dissertations

Atopic dermatitis is a type of eczema characterized by chronic inflammation of the skin, affecting millions of people worldwide. Resveratrol, a naturally occurring stilbenoid, is widely believed to exhibit beneficial effects on a host of chronic diseases. Although some previous studies have aimed to evaluate the effects of resveratrol on the pathogenesis of atopic dermatitis, this relationship remains ill-defined. We have previously established that mast cell activation, remodeling, and cellular infiltration in the hypodermis all begin prior to the IgE-mediated immune response in an atopic dermatitis mouse model, and that this early pathogenesis is directly related to an increase in …