Medicine and Health Sciences Commons^™

Cortical Stimulation Mapping Of Heschl’S Gyrus In The Auditory Cortex For Tinnitus Treatment, Austin Huang

CMC Senior Theses

Tinnitus is the perception of sound in the absence of an actual sound stimulus. Recent developments have shifted the focus to the central nervous system and the neural correlate of tinnitus. Broadly, tinnitus involves cortical map rearrangement, pathological neural synchrony, and increased spontaneous firing rates. Various cortical regions, such as Heschl’s gyrus in the auditory cortex, have been found to be associated with different aspects of tinnitus, such as perception and loudness. I propose a cortical stimulation mapping study of Heschl’s gyrus using a depth and subdural electrode montage to conduct electrocorticography. This study would provide high-resolution data on abnormal …

Functionalized Carbon Nanotubes In Hydrophobic Drug Delivery, Kun Chen

Dissertations

The direct incorporation of carboxylated carbon nanotubes (f-CNTs) into hydrophobic drug particles during their formation via anti-solvent precipitation is presented. The approach is tested using two drugs namely antifungal agent Griseofulvin (GF) and antibiotic Sulfamethoxazole (SMZ) that have very different aqueous solubility. It is observed that the f-CNTs dispersed in the water serve as nucleating sites for crystallization and are readily incorporated into the drug particles without altering crystal structure or other properties. The results show that the hydrophilic f-CNTs dramatically enhance dissolution rate for both drugs. The increased degree of functionalization leads to higher hydrophilicity and therefore faster dissolution …

Characterization And Functional Rescue Of Congenital Muscular Dystrophy With Megaconial Myopathy In A Mouse Model Of The Disease, Ambreen A. Sayed

Electronic Theses and Dissertations

Congenital muscular dystrophy with megaconial myopathy (MDCMC) is an autosomal recessive disorder characterized by progressive muscle weakness and wasting. Megamitochondria in skeletal muscle biopsies and cognitive impairments in MDCMC patients are observations exclusive to this type of muscular dystrophy. The disease is caused by loss of function mutations in the choline kinase beta (CHKB) gene which results in dysfunction of the Kennedy pathway for the synthesis of phosphatidylcholine (PC). A rostro-caudal muscular dystrophy (rmd) mouse with a deletion in the Chkb gene resulting in MDCMC-like symptoms has been reported by our lab. In order to test if the rmd mice …

Modeling Human Cancer Therapy Response In Patient Derived Xenografts, Joan Malcolm

Electronic Theses and Dissertations

Patient‐derived xenografts (PDXs) generated by implanting human tumor tissue into a transplant compliant mouse host have been of increasingly importance to preclinical development and have been demonstrated to have advantages compared to cancer cell lines and cell‐line xenografts (CLX) for modeling therapeutic responses in cancer. Nevertheless, many open questions remain regarding the relationship between study design factors and classification of treatment response and the molecular fidelity of tumors passaged in PDXs relative to the original patient tumor(s). The research described in this dissertation addresses both of these significant issues related to the use of PDXs as a tool for modeling …

Characterization Of G-Protein Coupled Receptors In Pain, Depression And Anxiety, Neil Lax

Electronic Theses and Dissertations

Chronic pain and major depressive disorder are widespread conditions in the world. Interestingly, these conditions often occur comorbidly, with each individual disease amplifying the symptoms of the other. A significant amount of preclinical research in pain and depression focuses on G-protein coupled receptors (GPCRs), implying that GPCRs may be useful in treating this comorbidity. Our efforts have sought to characterize several poorly understood GPCRs, including the serotonin receptor subtypes 2C and 7 (5-HT2CR and 5-HT7R) and metabotropic glutamate receptor 5 (mGluR5), along with more well-known GPCRs such as the mu opioid receptor (MOR), and the role that they play in …

The Invisible Brain Injury Crisis, Michael E. Rosenthal

Capstones

According to the Center for Disease Control and Prevention’s 2013 data, over 282,000 hospitalizations and 2.5 million emergency department visits were at least in part attributable to TBI. In the same year, about 56,000 people died.

Emergency departments in 2012 treated about 329,290 kids under 20 for TBI following an injury taking place during physical activity.

This project explores the rise in traumatic brain injuries and examines the difficult path that some of the survivors have to go through during recovery. By telling the story through my own personal experiences, I guide the reader through what the initial trauma and …

Examining Environmental Hazards In Rental Homes And Habitability Laws In Clark County, Nevada, Jorge Luis Bertran

UNLV Theses, Dissertations, Professional Papers, and Capstones

It is well established that home conditions are linked to the health outcomes of occupants. There are over 880,000 housing units in Clark County, Nevada; nearly half of those are renter-occupied units (ROUs). Currently, there is limited research on the characteristics of environmental hazards found in Clark County ROUs and the strength of habitability statutes created to protect tenants from substandard housing. Understanding how renters in Clark County are affected by environmental hazards in ROUs and the processes by which landlords and tenants resolve grievances related to those hazards would benefit public health. It would enhance the ability to quickly …

Cocoa, Postprandial Lipoproteins, And Inflammation In Type 2 Diabetes: A Secondary Data Analysis, Rickelle Tallent

UNLV Theses, Dissertations, Professional Papers, and Capstones

Background: Type 2 Diabetes (T2D) is associated with dyslipidemia and chronic low-grade inflammation, which greatly increases the risk of cardiovascular disease (CVD) in this population. Hyperlipidemia and inflammation in the postprandial state substantially contribute to atherosclerosis development and CVD risk, and have shown to be exacerbated by high-fat meals. Dietary cocoa is a rich source of flavanols that is associated with favorable effects on cardiovascular health, such as improvements in the lipid profile and chronic inflammation, in non-diabetic adults.

Objective: To conduct a secondary data analysis using unpublished data from a previously conducted clinical study to determine whether acute cocoa …

A Recombinant Virus And Reporter Mouse System To Study Chronic Chikungunya Virus Pathogenesis, Alissa Roxanne Young

Arts & Sciences Electronic Theses and Dissertations

Chikungunya virus (CHIKV) is an arthritogenic alphavirus that during acute disease causes fever as well as severe joint and muscle pain. Chronic joint and muscle pain persists in a significant subset of patients, yet we still have a poor understanding of what drives this chronic disease. While replicating virus has not been detected in the joints of patients with chronic arthritis or in various animal models at chronic time points, persistent viral RNA can be detected for months after acute infection.

To identify the cells that could be contributing to chronic CHIKV pathogenesis, we developed recombinant viruses that express Cre …

Singing As A Therapeutic Technique To Improve Gait For People With Parkinson Disease, Elinor Harrison

Arts & Sciences Electronic Theses and Dissertations

Abstract of the Dissertation

Singing as a Therapeutic Technique to

Improve Gait for People with Parkinson Disease

by

Elinor Clare Harrison

Doctor of Philosophy in Movement Science

Neurosciences

Washington University in St. Louis, 2018

Professor Gammon Earhart, Chair

Gait impairment is common in older adults and even more prevalent for people with Parkinson disease (PD). Gait dysfunction is often characterized by reductions in speed, step frequency, and step length. In addition, decreased ability to regulate step length and step frequency may contribute to increased gait variability, making walking less stable and increasing risk for falls. As gait deficits are often …

The Role Of Apolipoprotein E In Regulating Tau Pathogenesis And Neurodegeneration In A Tauopathy Mouse Model, Yang Shi

Arts & Sciences Electronic Theses and Dissertations

APOE4 is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). APOE4 increases brain amyloid-β (Aβ) pathology relative to other APOE isoforms. However, whether APOE independently influences tau pathology, the other pathological hallmark of AD and other tauopathies, or tau-mediated neurodegeneration, is not clear. By generating P301S tau transgenic mice on either a human APOE knock in (KI) or APOE knockout (KO) background, we show that the presence of human APOE, regardless of APOE isoforms, leads to various degrees of brain atrophy in 9-month old P301S mice, whereas APOE ablation strongly protects against neurodegeneration. In particular, P301S/E4 mice develop …

Freezing Of Gait: Mechanisms, Mechanics, And Management, Peter S. Myers

Arts & Sciences Electronic Theses and Dissertations

Parkinson disease (PD) is a neurodegenerative disease with multiple motor and non-motor symptoms, including postural instability, gait impairments, and cognitive deficits. More than 50% of individuals with PD experience a symptom called freezing of gait (FOG), described as a transient inability to take another step forward. Individuals with PD who experience FOG (freezers) have further postural, gait, and cognitive impairments compared to individuals with PD without FOG (non-freezers). While degeneration of the dopaminergic neurons in the substantia nigra is accepted as the primary etiology of the disease, research shows that the disease has a global impact on the brain, accounting …

A Tail Of Two Pancancer Projects: Somatic Variant Identification And Driver Gene Discovery Using Tcga, Matthew Hawkins Bailey

Arts & Sciences Electronic Theses and Dissertations

The implementation of next-generation genomic sequencing has exploded over the past dozen years. Large consortia, such as The Cancer Genome Atlas (TCGA); the International Cancer Genetics Consortium (ICGC); and the Pediatric Cancer Genome Projects (PCGP), made great strides in democratizing big data for the scientific community. These data sets provide a rich resource to build tools for somatic variant discovery and exploratory analysis. Public repositories hold the answer to many novel biological and clinical revelations i.e., the discovery of complex indels, splice creating mutations, alternative super enhancer binding sites, machine learning models to predict mutation impact, and cancer subtype classification …

Sequence Analysis Methods For The Design Of Cancer Vaccines That Target Tumor-Specific Mutant Antigens (Neoantigens), Jasreet Hundal

Arts & Sciences Electronic Theses and Dissertations

The human adaptive immune system is programmed to distinguish between self and non-self proteins and if trained to recognize markers unique to a cancer, it may be possible to stimulate the selective destruction of cancer cells. Therapeutic cancer vaccines aim to boost the immune system by selectively increasing the population of T cells specifically targeted to the tumor-unique antigens, thereby initiating cancer cell death.. In the past, this approach has primarily focused on targeted selection of ‘shared’ tumor antigens, found across many patients. The advent of massively parallel sequencing and specialized analytical approaches has enabled more efficient characterization of tumor-specific …

The Role Of Fibrillin-1 In Eye Development And Disease, Wendell Brooks Jones

Arts & Sciences Electronic Theses and Dissertations

The ciliary zonule of the human eye consists of a circumferential array of fibers that connect the ocular lens to the nonpigmented ciliary epithelium (NPCE) located at the inner wall of the eye. Zonular fibers consist of bundles of beaded filaments called microfibrils. Microfibrils are major structural elements of the extracellular matrix and are present in pure form in the ciliary zonule. Microfibrils are composed principally of fibrillin-1 (FBN-1); a large extracellular matrix glycoprotein. In humans, mutations in FBN1 underlie Marfan syndrome; a pleiotropic connective tissue disorder that profoundly affects the eye. Ocular manifestations include ectopia lentis (dislocated lenses), cataracts, …

The Mitochondrial Calcium Uniporter Regulator 1 (Mcur1) Matrix Domain Is A Self-Associated Multimer Sensitive To Divalent Cations, Naveed Siddiqui

Electronic Thesis and Dissertation Repository

Mitochondria are primarily appreciated for the generation of adenosine triphosphate (ATP), a chemical store of energy required by all cells. These organelles, however, also play key roles in apoptosis, autophagy and shaping cytosolic calcium (Ca²⁺) signaling via Ca²⁺ uptake into the mitochondrial matrix. This Ca²⁺ uptake is mediated chiefly via the mitochondrial Ca²⁺ uniporter (MCU), an inner mitochondrial membrane protein that oligomerizes to form a Ca²⁺ selective pore. MCU is regulated by several protein binding partners, including the recently identified MCU regulator-1 (MCUR1). MCUR1 stabilizes a higher order MCU heterocomplex through interactions with MCU …

The New World Of Pet Prosthetics, Anna Brooks

Capstones

When an abandoned dog was found in Brooklyn with his paw gnawed off, the animal shelter had two options: amputate the leg, or put the dog down. But neither seemed like a solution. So they decided to do something different, and fit the dog for a prosthetic leg. Prosthetics for people have been around for millennia, and now these devices are moving into the animal kingdom. This story explores the new world of animal prosthetics, and how these devices have changed the lives of animals like Mr. Stubbs — the first alligator with a prosthetic tail — and saved the …

A Modern-Day Affliction: Did Wifi Make Joel Dean Sick?, Dominic Mckenzie

Capstones

Electromagnetic Hypersensitivity is one of many disorders that exist in a strange border zone between recognized syndromes and discredited ones. One young man, a computer engineer by trade, had his life turned upside down by the disorder that has doctors and scientists across the world confused on how to treat it. Here's his story:

https://medium.com/@dominic.mckenzie/capstone-1dd7ff866a29

Towards An In Vitro Model Of Testing Osteoblast Cellular Function In Contact With Various Surfaces, Raheleh Miralami

Theses & Dissertations

Past studies have shown that the success of total joint replacements depends on the biocompatibility of orthopaedic materials, which can be improved by modifying the implant surface. However, the exact roles of these modifications and their effective mechanisms are poorly understood. The objective of this study was to develop and evaluate a model system to investigate the impact of nano-structured surfaces, produced by the ion beam-assisted deposition (IBAD) technique, on biomarkers of osteointegration using an in vitro model. The IBAD technique was employed to deposit zirconium oxide (ZrO₂), Titanium oxide (TiO₂), and Titanium (Ti) nano-films on …

Functional And Mechanical Role Of Splice Variant Of Mucin4 (Muc4/X) And Trefoil Factors In Pancreatic Cancer Pathogenesis, Rahat Jahan

Theses & Dissertations

Pancreatic Cancer (PC) is one of the vicious cancers as it ranks third in the race of leading cause of cancer-related death. Lack of early diagnostic marker, poor understanding of molecular mechanism of the disease and failure to conventional chemotherapy makes this disease dreadful.

Mucin 4 (MUC4), a high molecular weight glycoprotein is one of the top differentially expressed molecules in PC while not expressed in normal pancreas. Accumulating evidence from our lab suggested its tumorigenic role in PC by increasing cell proliferation, invasion, chemotherapy resistance, tumor growth, and metastasis. Previously, our lab and other has identified 24 different splice …

Phr: Patient Health Record, Quinn Nelson

Theses/Capstones/Creative Projects

The rapid development of information technology systems has expanded into multiple disciplines and results in systems that are limited by initial design and implementation: the Healthcare Information Technology (HIT) space is no different. The introduction of the Electronic Health Record (EHR) system has changed the way healthcare operates. Initial designs of these systems were focused on serving the needs of insurance companies and healthcare billing departments. Research shows that the design of EHR systems negatively impact provider-patient interactions and the care they receive. This capstone project capitalizes on the collaboration efforts between UNO and UNMC – by joining a research …

Epidemiological Studies Of Soybean Vein Necrosis Virus And Potential Resistance Mechanisms To Its Vector Neohydatothrips Variabilis (Beach), Jing Zhou

Graduate Theses and Dissertations

Soybean (Glycine max (L.) Merrill) is one the most important crops in global agriculture with annual production of over 260 million metric tons. As the dependence of a growing global population to soybean has increased, so does the importance of soybean diseases and pests. Over 200 pathogens attack soybean; among them, viruses pose a major threat to the soybean industries accounting for approximately 10% of the annual yield reduction caused by diseases in the past two decades. Soybean vein necrosis virus (SVNV) is a relatively newly discovered virus causing the homonymous disease. The widespread occurrence of the disease in major …

Early Oral Feeding After Bowel Resection, Jennifer Strang

Theses & Dissertations

Research Focus: The primary purpose of this project was to determine if there was an association of factors with time to first solid meal in gastrointestinal (GI) surgery patients and the impact solid diet has on length of stay (LOS) in the hospital, GI symptoms, and incidence of post-operative ileus (POI). A secondary purpose was to observe and describe when an oral diet was started and the progression of diet after GI surgery.

Research Methods: This study was a cross-sectional, retrospective chart review of a convenience sample in a multi-centered hospital system conducted in 84 GI resection patients …

The Role Of Cyp2a5 In Cadmium-Induced Liver Injury, Julia Salamat

Electronic Theses and Dissertations

Cadmium is present in food and groundwater. Tobacco smoking and occupational exposure are also major sources for cadmium. Cadmium is primarily accumulated in liver, a major organ metabolizing exogenous chemicals. Chemical metabolism may cause detoxification, but it can also cause bio-activation resulting in liver damage. Cytochrome P450s (CYP) are major liver metabolism enzymes, and cadmium chloride (CdCl2) can induce CYP2A5 in mice. We examined the effect of CYP2A5 on CdCl2-induced liver injury using CYP2A5-knockout (cyp2a5-/-) mice. The cyp2a5-/- mice and their control WT mice were injected CdCl2 intraperitoneally at 5 mg/kg body weight, respectively, to induce liver injury. …

The Study Of Alcoholic Liver Diseases, Seun Emmanuel Owoseni

Electronic Theses and Dissertations

Excessive alcohol consumption is the primary contributing factor in the development of alcoholic liver diseases (ALD). Nicotine contained in tobacco is a major addictive alkaloid, which enhances the effects of ALDs. The major enzyme involved in nicotine metabolism is cytochrome P450 2A5 (CYP2A5) which is produced in the liver. Alcohol can stimulate the CYP2A5 enzyme. We utilized cyp2a5-/- knockout mice in this research to examine the effects of CYP2A5.

The cyp2a5-/- mice and wild-type (WT) mice were fed liquid ethanol diet with or without nicotine to induce ALD. Nicotine enhancing effects on ALD were observed in WT mice but not …

Genetic Evolution And Prognostic Determinants Of Pancreatic Cancer On Longitudinal Liquid Biopsies, Vincent Bernard

Dissertations & Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest 5-year survival rates amongst solid tumors. As early detection of PDAC is unusual and typically incidental, most patients present with locally advanced and metastatic disease where effective therapeutic strategies remain a significant unmet need. Specifically, surrogate biomarkers for tumor monitoring of PDAC may lead to improved elucidation of clinical actionability and prognostic potential. On the other hand, tumor tissue is rarely sampled in patients presenting with de novo or recurrent metastatic PDAC, apart from a fine needle aspiration or a core needle biopsy performed for diagnosis. This precludes the opportunity for …

Hypothalamic Circuits In The Control Of Feeding And Emotional Behaviors, Leandra Mangieri

Dissertations & Theses (Open Access)

Feeding results from the integration of both nutritional and affective states, and is guided by complex neural circuitry in the brain. The hypothalamus is a critical center controlling feeding and motivated behaviors. We found that targeted photostimulation of projections from the lateral hypothalamus (LH) to the paraventricular hypothalamus (PVH) in mice elicited voracious feeding and repetitive self-grooming behavior. GABA neurotransmission in the LH->PVH circuit mediated the evoked feeding behavior, and elicited behavioral approach, whereas glutamate release promoted repetitive self-grooming, which was stress-related in nature. Optogenetic inhibition of LH^GABA ->PVH circuit reduced feeding after fasting, whereas photostimulation abruptly …

Insights Into The Reactivation, Regulation And Essentiality Of Oxidative Protein Folding Pathways In Actinobacteria, Belkys Sanchez

Dissertations & Theses (Open Access)

Accurate disulfide bond formation is important for proper folding, stability and function of exported proteins. The process of disulfide bond formation, termed oxidative protein folding, is catalyzed by thiol-disulfide oxidoreductase enzymes. Oxidative protein folding pathways influence processes essential for bacterial physiology and pathogenicity. In the Gram-positive actinobacterial pathogens Actinomyces oris and Corynebacterium diphtheriae oxidative protein folding is catalyzed by the primary thiol-disulfide oxidoreductase MdbA. MdbA is required for assembly of adhesive pilus, which mediate receptor-dependent bacterial interactions, or coaggregation, in A. oris. In the first part of this dissertation, I identify components of the electron transport chain (ETC) required for …

Synthesis And Characterization Of Targeted Bar Encapsulated Polylactic-Co-Glycolic Acid Nanoparticles To Inhibit Porphyromonas Gingivalis Biofilm Formation., Ranjith Radha Krishnan

Electronic Theses and Dissertations

Periodontal disease is one of the most prevalent infectious diseases worldwide. Between 30-50% of the global adult population suffers from periodontal disease. Some form of periodontitis is present in 46% of American adults, corresponding to annual expenditures in excess of 14 billion dollars for treatment and prevention. Current treatments for periodontal diseases involve mechanical removal of plaque, correction of risk factors, gingival surgery and/or antibiotic therapy. To our knowledge there is no effective therapeutic approach that aims to limit pathogen colonization of the oral biofilm or re-colonization after treatment. Interaction of the pathogen Porphyromonas gingivalis with oral streptococci is critical …

Quantitative Microbial Risk Assessment For Parts, Ground, And Msc Poultry Product Including Intervention Analysis And Exploration Of Enterobacteriaceae As An Indicator Organism In Poultry Processing, Leigh Ann Parette

Graduate Theses and Dissertations

Samples collected at five different large bird poultry processing facilities over a period of 7 months from prescald to post debone locations were enumerated for Enterobacteriaceae, Salmonella spp., and Campylobacter spp. and the results were used to create Quantitative Microbial Risk Analyses (QMRA) models for parts, ground, and mechanically separated chicken (MSC) products. Sensitivity analyses indicated the points in the process at which reductions would be most advantageous to the endpoint and simulation models were run to test reductions required to meet the current USDA performance standards.

These data were analyzed to determine the reductions from one node (location) to …