Medicine and Health Sciences Commons^™

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 …

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, …

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 …

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 …

Exercise Recommendations For Active Adults At Risk For Sudden Cardiac Death: “Can I Continue To Exercise?”, Kacie Lynn Baker

Theses and Dissertations

Sudden arrhythmic death syndrome (SADS) is due to genetic conditions associated with cardiac ion channelopathies and cardiomyopathies. Many of these conditions have exercise guidelines regarding eligibility and disqualification recommendations for competitive athletes through the American Heart Association and the American College for Cardiology. This study investigates how medical professionals communicate these exercise recommendations to patients, and in turn, how well patients understand these recommendations. The study also explores motivations for either continuing or discontinuing an exercise practice after a diagnosis. A questionnaire was distributed through cardiac disease-focused support groups and organizations. Data from 67 individuals with a SADS condition were …

Mast Cells And Lipid Cross-Talk In Skin Inflammation, Piper Alexandra Wedman

Theses and Dissertations

Atopic dermatitis (AD) is an inflammatory skin disease whose pathogenic mechanisms remain unclear. Using a validated human AD-like mouse model, we observed that skin remodeling started at a pre-symptomatic stage of AD that included cellular infiltration of the hypodermis, accompanied with activated/degranulated mast cells (MC). Local MC activation was quantified using a novel method of computer-assisted image analysis we developed and reported. Using a variation of this method, we defined morphometric parameters allowing for quantitation rather than scoring of cellular infiltration. Cell recruitment correlated with MC activation, chemokine production and increased levels of sphingolipid sphingosine-1-phosphate (S1P), produced by sphingosine kinase-1 …

The Perceived Utility Of Personalized Genomic Medicine In Individuals With A Family History Of Heart Disease: A Pilot Study, Dana Margaret Mittag

Theses and Dissertations

According to the World Health Organization (2005), cardiovascular disease (CVD) is the number one cause of death in most countries. Assessing a patient’s risk for heart disease may include incorporating factors such as their gender, age, weight, tobacco history, cholesterol, blood pressure, family history, and more recently, genetics. Genome-wide association studies (GWAS) have made it possible to identify risk loci for many of the common, complex disorders, including coronary artery disease (CAD). As the medical genetics community undergoes a shift from a genetics focus to a genomics oriented focus, genomic medicine is becoming more accessible. Research has begun to examine …

Radioactive Contamination Of Natural Biological Systems: Oxidative Balance And Genetic Stability, Daniel Einor

Theses and Dissertations

The global demand for nuclear energy grows, and so do the risks of an accidental release of nuclear products into the environment. Therefore, understanding the health and ecological effects of contamination by radionuclides should be of great interest for biomedical specialists and the public. Empirical studies unequivocally show that high doses of ionizing radiation (IR) shift the redox-balance of many biological systems and increase the rates of genetic errors. However, the effects of chronic low doses of radiation vary significantly between tissues and between species. The present dissertation comprises the results of experimental and meta-analytical research of a variety of …

Applications Of Multimedia Resources Developed As Part Of The Virtual Cell Animation Collection In Undergraduate Introductory Biology, Eric Edward Goff

Theses and Dissertations

Calls for reform in undergraduate STEM education have arisen from an increased need for well-trained biology graduates in the future scientific workforce. To address this need, many institutions have focused on a pedagogical restructuring of instructional practices to promote deeper conceptual understanding of core biological concepts. This study investigates the implementation of multimedia resources as a possible reliable supplement to undergraduate introductory biology and aims to provide empirical evidence on the instructional best practices of their use. As a central part of this study, we focus on one specific multimedia package, the Virtual Cell Animation Collection, due to its developmental …

Assessment Of Patient Satisfaction With The Provision Of Fertility Information In Women With Lynch Syndrome, Rachel Elizabeth Hickey

Theses and Dissertations

Lynch Syndrome (LS), one of the most common hereditary cancer syndromes, is primarily known for its substantially increased risks for colorectal cancer. The incidence of gynecologic cancers (endometrial and ovarian cancers) equals or exceeds the incidence of colorectal cancers in female patients with LS. The prevention and treatment methods for these cancers can drastically affect fertility and reproduction. Previous studies with cancer patients have revealed challenges in acquiring information related to these topics; thus far, no research has assessed whether there is an informational gap regarding fertility information for women in the LS population. The purpose of this study was …

Adoptees’ Experiences With Direct-To-Consumer Genetic Testing: Emotions, Satisfaction, And Motivating Factors, Anna Childers

Theses and Dissertations

Public awareness of the role of genetics in disease continues to expand along with the use of direct-to-consumer genetic testing (DTC-GT). One subset of customers taking advantage of the growing DTC-GT market is adoptees. Prior research has shown that adoptees appear to be more motivated than non-adoptees to learn about their genetic disease risk but have similar responses to health-related information acquired through DTC-GT. In this exploratory qualitative study, fourteen adoptees were asked about their motivations for pursuing DTC-GT; satisfaction with results; emotions throughout the process; and interest in meeting with a genetic counselor. Motivations for pursuing DTCGT fell into …

Pediatric Genetic Counselor Perspective On Serving The Foster Care Population And The Integration Of Genetic Information Within The Health Passport, Angela Rose Douglas

Theses and Dissertations

Many states within the foster care system have adopted a document referred to as the health passport, which provides a condensed summary of a child's health history. This passport is intended to remain with the child as he/she moves between placements to improve communication between foster parents, caseworkers, and medical professionals. This exploratory research study examines the foster care system's utility of a child's health passport and opportunities for improvement through an online survey of the pediatric genetic counselor population. First, counselor perspectives on serving foster children were gathered and summarized into themes. Major elements and/or obstacles of counseling the …

Recipients’ Perspectives Regarding Expanded Carrier Screening Of Gamete Donors, Erika Kristy Jackson

Theses and Dissertations

Purpose: This study explored the perspectives of intended parents regarding genetic carrier screening of a gamete donor. The main goal of this study was to determine how much genetic carrier screening information a recipient would prefer to receive about potential donors. The study also aimed to identify factors that potentially influence a recipient’s choice of donor based on genetic screening results. Methods: An online questionnaire was developed to assess intended parents’ preferences regarding expanded carrier screening (ECS) of their donors. Participants were recruited from various online support groups and were eligible if they had previously utilized or were currently utilizing …

Comparison Of Atypical Bacteriophages That Infect Caulobacter Crescentus, Doreen Nguyen

Theses and Dissertations

Several Caulobacter bacterial genomes have been recently sequenced, and all of the genomes contained one or more clusters of genes with phage origins. This observation indicates that bacteriophages contribute to the Caulobacter gene pool, so in order to understand bacteria genomes we will need to understand phage genomes as well. As part of understanding the phage genomes, we want to isolate novel bacteriophages and study their genomics. This study resulted in the isolation of 12 new phages, including four that differ from the well-studied CbKlike phages. Two of these novel phages are Podoviruses with icosahedral heads and small tails, and …

Environmental Relationships And Predator-Prey Interactions Within The Snapper-Grouper Complex In The Southeastern U.S. Atlantic – Implications For Fisheries Management, Dawn M. Glasgow

Theses and Dissertations

Stock assessments indicate many valuable fish species are declining, or are considered overfished and/or are undergoing overfishing. Fisheries scientists and managers in the southeastern U.S. typically have utilized a single-species approach, and relied on catch per unit effort data derived from fishery-independent surveys to determine indices of abundance for economically important reef fish. However, catchability for these surveys vary for many reasons including environmental and predator-prey relationships. This research was developed to elucidate environmental influences on reef fish assemblages and distribution of reef-associated marine predators, and examine predator-prey dynamics that may influence relative abundance of large predators based on chevron …

Modulation Of Pkr Activity During Hiv Infection And Cellular Stress By Pact And Trbp, Evelyn E. Chukwurah

Theses and Dissertations

A crucial component of the cellular response to stress is the attenuation of protein synthesis to allow the cell to dedicate resources for the restoration of homeostasis or towards the induction of apoptotic cell death in case the stressors overwhelm the cell. This process is itself regulated by one of the four eIF2α kinases of which PKR (Protein Kinase R) is responsible for inhibiting general translation during viral infection, oxidative stress, ER stress, heat shock or serum withdrawal.

During viral infection, PKR is transcriptionally induced by interferon but remains latent until it interacts with dsRNA. This interaction induces a conformational …

Differences In Resting-State Functional Connectivity Of Chronic Migraine, With And Without Medication Overuse Headache, And The Effectiveness Of Sphenopalatine Ganglion Block As A Treatment For Repairing Dysfunctional Connectivity., Kaitlin Krebs

Theses and Dissertations

Chronic Migraine (CM) is a debilitating neurological condition that occurs when the migraine frequency progresses to a chronic state of more than 15 headache days per month. The overuse of analgesic medication (MOH) is one of the most prominent risk factor of this chronification and little is known about why it is a cause. The repetitive inhibition of the Sphenopalatine Ganglion is one promising treatment that is used to treat chronic migraine. The purpose of this study is to determine if a specific pattern of disruption is present for chronic migraine, both with and without medication overuse headache, and if …

Factors Influencing The Collagen Fiber Angle Distribution In The Mouse Aorta, Shana Roach Watson

Theses and Dissertations

The aortic extracellular matrix (ECM) consists of microstructural proteins, collagen and elastin, together with proteoglycans and other components. The matrix metalloproteinases (MMPs) are proteolytic enzymes that influence morphological and structural changes in the ECM and can degrade the matrix as it responds to cellular behaviors such as angiogenesis, apoptosis, proliferation, and migration. Collagen is the most important component among the extracellular proteins because it provides strength and stability to the tissue. Changes in collagen content play a major role in the development of atherosclerosis. These changes can be induced by increased or decreased proteinase activity. Therefore, we studied the collagen …

The Role Of Epidermal Stem/Progenitor-Like Cells In Hpv-Mediated Pre-Neoplastic Transformation, Yvon L. Woappi

Theses and Dissertations

The role of epidermal basal stem cells in dysplasia is a matter of great interest in the human papillomavirus (HPV)-driven cancers. To assess the relationship between “stemness” and HPV-mediated transformation, we made use of 3-D suspension culture and fluorescence activated cell sorting (FACS) to purify stem/progenitor-like cells from primary normal human keratinocyte (NHKc) cultures. We found that NHKc cells derived from multicellular keratinocyte spheroids were enriched for a basal subpopulation of epidermal stem-like cells, that could be maintained for prolonged time in culture and used to conduct transfection experiments with full-length HPV16 DNA. Thus, by using these stem cell enrichment …

Linking Obesity & Breast Cancer: Role Of Monocyte Chemoattractant Protein-1 And High Fat Diet-Induced Inflammation On Mammary Tumorigenesis, Taryn L. Cranford

Theses and Dissertations

More than two-thirds of the adult population in the United States is classified as overweight or obese. In order to fully comprehend this rapidly increasing dilemma, further understanding of the complex phenomena that are involved with obesity and its many comorbidities is necessary. Chronic inflammation represents a distinctive, recurrent feature of obesity and has been associated with an increased risk of breast cancer. Monocyte chemoattractant protein 1 is a crucial component of the inflammatory process and represents a potential therapeutic treatment target, not only in obesity but also in breast cancer. Using a monocyte chemoattractant protein deficient model, we examined …

Regulation Of Chronic And Acute Inflammatory Disease By Microrna And Microbiota, Pegah Mehrpouya-Bahrami

Theses and Dissertations

Inflammation is implicated in cancer development, degenerative diseases, allergies as well as artherosecelorsis. Dysregulated immune responses lead to chronic inflammation and tissue damage. Finding the ways to terminate inflammatory responses when no longer needed, demands further investigation. Herein, we investigated the modulation of acute and chronic inflammatory disease models by inducing antiinflammatory state. Acute inflammatory model was induced with SEB, an enterotoxin produced by a ubiquitous Gram-positive coccus, Staphylococcus aureus (S. aureus), which exerts profound toxic effects on the immune system, which leads to the cytokine storm and adverse immune response. SEB is the main cause of nosocomial infections, acute …

The Effect Of Arsenic On Type 2 Diabetes And Inflammation, Kayla Penta

Theses and Dissertations

Arsenic, a ubiquitous environmental contaminant, has been shown to cause a number of health effects. At high concentrations the inorganic form is a well-known toxin, but at lower concentrations the effects range from various cancers, to cardiovascular disease and type 2 diabetes. At higher concentrations of arsenic (500- 1000μg/L) there have been epidemiological studies conducted demonstrating an increased risk in the development of type 2 diabetes with this exposure. At lower levels of arsenic exposure (<500 μg/L) the epidemiological results are inconclusive. Arsenic is also an immunotoxicant, meaning that it will cause changes in the immune response. The changes in the immune response will vary depending on a number of variables, including amount of arsenic exposure, forms of exposure and route of exposure. We wanted to determine if arsenic could modulate the immune system, and if this change could lead to an increase in susceptibility to type 2 diabetes development. We chose to examine this in C57BL/6 and db/+ mice – two non-susceptible strains. After 8 weeks (4 weeks old to 12 weeks old) of low dose inorganic arsenic exposure (50 μg/kg or 500 μg/kg) we evaluated changes in body composition, glucose tolerance and immune response. We saw that there were differences based on sex, genotype and treatment group present after the 8-week treatment period in body composition, while there were minimal changes in glucose tolerance. Finally, the immune response showed great variability depending on sex, genotype and treatment group. This project has demonstrated that while we are trying to compare differences in in vivo and epidemiological studies to find a link between arsenic and type 2 diabetes, there may be deeper levels of complications based on individual variability to arsenic exposure.

Cannabinoid-Mediated Epigenetic Regulation Of Immune Functions, Jessica Margaret Sido

Theses and Dissertations

The cannabinoid system consisting of exogenous and endogenous ligands as well as dedicated receptors has been proposed to play a regulatory role in immune functions. The exogenous cannabinoid Δ9-tetrahydrocannabinol (THC), one of the most widely studied marijuana derivatives, has been associated with multiple anti-inflammatory properties over the years. The majority of THC research has centered on the shift from Th1 to Th2 responses however, the complexity of inflammation has since increased. Recent studies have revealed that epigenome, Th cell subsets, and immunoregulatory cell induction, are all known to impact inflammation. In the current research, we have attempted to look holistically …

Goal Achievement In Young Adults With Asperger Syndrome And High Functioning Autism, Melissa Racobaldo

Theses and Dissertations

Purpose: This study aimed to evaluate perspectives of young adults with Asperger syndrome (AS) and High Functioning Autism (HFA) regarding supports and services, future goals, and confidence in their success. The goal of this study was to identify valuable supports and areas in which this support was lacking. Identifying areas of support for young adults with AS/HFA transitioning into adulthood aids in providing consistent services for successful goal achievement. The study has value among genetic counselors as the discovery of genetic etiologies of autism has led to referral of families with ASD to the genetics clinic. Methods: Young adults with …

Characterization Of Stard4 And Stard6 Proteins In Human Ovarian Tissue And Human Granulosa Cells And Cloning Of Human Stard4 Transcripts, Aisha Shaaban

Theses and Dissertations

Progesterone is essential hormone for pregnancy, which is produced by the human corpus luteum in early pregnancy until the placenta assumes this function. Transport of the cholesterol from the outer to the inner mitochondrial membrane is the rate limiting step for the de novo synthesis of pregnenolone (the precursor to progesterone), a process mediated by STARD1. STARD1 contains a C-terminal lipid binding domain which binds cholesterol and an N-terminal domain targeting STARD1 to the mitochondrial membrane. Unlike STARD1, STARD4 and STARD6 proteins lack a mitochondrial targeting sequence; however, they can bind cholesterol and increase steroidogenesis in model systems. In this …

Mcp-1 In Colorectal Cancer: Benefits Of Exercise, Jamie Lee Mcclellan

Theses and Dissertations

The etiology of colon cancer is a complex phenomenon that involves both genetic and environmental factors. However, only about 20% have a familial basis with the largest fraction being attributed to environmental causes that can lead to chronic inflammation. Tumors associated macrophages drive the pro-inflammatory response in the tumor micro-environment and are associated with poor prognosis in certain cancers. Monocyte chemoattractant protein 1 (MCP-1) is thought to be the most important chemokine for recruitment of macrophages to the tumor microenvironment. In chapter 1, we examined the timing and magnitude of the intestinal inflammatory cytokine response in relation to tumorigenesis in …

Marine Population Connectivity: Range Boundaries And Climate Change, Rhiannon Leigh Rognstad

Theses and Dissertations

Population connectivity, particularly in open systems, is an important metric for understanding population-level processes on both ecological and evolutionary timescales. In coastal marine systems, adults are typically sedentary and dispersal occurs primarily during a larval stage when individuals are transported in ocean currents. Because coastal marine populations exist as networks of interconnected subpopulations, variation in the magnitude and extent of population connectivity can have profound effects on population dynamics and species distribution limits. Connectivity is a complex process, affected by a multitude of factors, including adult inputs and physical dispersal, which operate at multiple scales and may interact. This dissertation …

Status Epilepticus Induced Alterations In Hippocampal Anatomy And Neurotransmission, Denise K. Grosenbaugh

Theses and Dissertations

Status epilepticus (SE) is a life-threatening neurologic emergency occurring when the brain is in an unrelenting state of seizure activity. Approximately 40% of people who encounter a single event of SE go on to develop epilepsy, characterized by spontaneously occurring seizures. While the exact mechanisms underlying seizure origin are not understood, at a fundamental level seizures initiate due to an imbalance between inhibitory and excitatory neurotransmission. We explored the impact of SE and the development of epilepsy on GABAA receptor mediated inhibitory neurotransmission and kainate receptor (KAR) mediated excitatory neurotransmission.

Stiripentol (STP), a positive allosteric modulator of the GABAA receptor, …

"What Happens In Romania..." Comes Back To The United States And Becomes A Quilt, Ashley Ehlers, Kaitlyn Torres

Senior Theses

Our senior thesis project is a quilt that chronicles our experiences on the Maymester trip to Romania through the Honors College, during which we were able to shadow surgeons in the Oncology Hospital and General Surgery III Hospital in Cluj-Napoca. In our quilt, we included some of the most common surgeries we saw while shadowing Romanian doctors: breast removal, gall bladder removal, appendix removal, removal of a section of the large intestine, and removal of the uterus. The final product of this quilt shows every level of the abdominal muscles and organs from the anterior skin to the kidneys.

To …

Synaptic Organization Of Noradrenergic And Opioid Circuitry In The Basolateral Amygdala: Anatomical Correlates Of Memory Consolidation, Jingyi Zhang

Theses and Dissertations

The studies comprising this dissertation were designed to investigate the synaptic organization of norepinephrine and opioid system in the anterior subdivision of the basolateral nucleus of amygdala (BLa) in rat. Light and electron microscopy were combined with immunohistochemistry to determine the synaptic incidence and postsynaptic targets of noradrenergic axon terminals, to localize mu opioid receptor at the ultrastructural level and to determine whether there is convergence of norepinephrine inputs and enkephalin inputs in the BLa. It was determined that about half of the norepinephrine inputs formed synapses in the BLa and the main postsynaptic targets were small caliber CAMK+ dendritic …