Medicine and Health Sciences Commons^™

Role Of Sarm1 In Chronic Immune-Mediated Central Nervous System Inflammation, Kenneth E. Viar Ii

Theses and Dissertations

SARM1 is an injury-induced nicotinamide adenine dinucleotide nucleosidase (NADase) that was previously shown to promote axonal degeneration in response to traumatic, toxic, and excitotoxic stressors. This raises the question of whether a SARM1-dependent program of axonal degeneration is central to a common pathway contributing to disease burden in neurological disorders. The degree to and mechanism by which SARM1 inactivation decreases the pathophysiology of such disorders is of interest to establish the rationale to pursue SARM1 as a therapeutic target. In this study, we compare the course and pathology of experimental autoimmune encephalomyelitis (EAE) in Sarm1-knockout (KO) mice and wild-type …

The Role Of Sphingosine Kinase 2 In Alcoholic Liver Disease, Eric K. Kwong

Theses and Dissertations

Alcoholic liver disease (ALD) is one of the most common liver diseases worldwide characterized by the accumulation of lipids within the liver, inflammation and the possibility of progressing to cirrhosis and liver failure. More importantly, there are currently no effective treatments for ALD and liver transplantation remains the only therapeutic option for end-stage liver disease. Previous studies have shown that ALD is a result of a combination of endoplasmic reticulum (ER) stress, lipid metabolism dysregulation and inflammation. It has been previously reported that alcohol disrupts gut microbiota homeostasis and causes increased endotoxins that contribute to the pathology of ALD. However, …

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 …

Connecting The Dots: Investigating The Effects Of Trans-Synaptic Tau Transmission In The Hippocampus, Michael Bamisile

Theses and Dissertations

Tauopathy, which results from the oligomerization of misfolded tau protein in neurons, is a feature present in a number of neurodegenerative diseases and a hallmark of Alzheimer’s Disease (AD). Tau is an important phosphoprotein that regulates the assembly of microtubules, but tauopathy can occur when tau becomes hyperphosphorylated. Phosphorylation prevents tau from binding to tubulin, which results in cytosolic accumulation of tau and eventual oligomerization. This abnormal accumulation of tau leads to the spreading of hyperphosphorylated tau to downstream synaptically connected neurons through an unknown mechanism. In AD, the hippocampus is one of the first brain structures to be affected …

Regenerative Potential Of Mesenchymal Stem Cell Derived Exosomes, Andrew P. Wong

Theses and Dissertations

Bone defects are a pervasive complication arising from many clinical conditions, both mechanical and pathological. Current treatments for large bony defects focus on applying bone grafts or synthetic materials to the defect area. Cell-based—and especially stem-cell—therapies have advanced greatly thanks to increasing attention focused on their ability to generate new tissues in situ with biomechanical properties approaching that of native tissue, but they suffer from their own shortcomings as well. Exosomes have been shown to play critical roles in cell-signaling and tissue regeneration and are therefore potentially ideal therapeutic vehicles for treating bone defects. Exosomes are small microvesicles counted amongst …

Examining Relationships Among Body Image, Sexuality, And Sexual Functioning In Women With Cervical And Endometrial Cancer, Christina Wilson

Theses and Dissertations

Introduction: Over 74,000 US women are diagnosed annually with endometrial or cervical cancers and experience significant treatment-related difficulties with body image, sexuality, and sexuality. The aims of the research were to examine relationships among body image, sexuality, and sexual functioning, and understand women’s views of these concepts. A novel theoretical framework encompassing these three concepts and contextual variables guided the research.

Methods: A non-experimental cross-sectional pilot study was conducted with pre-menopausal women in an academic medical center who had stages I-III cervical or endometrial cancer, were 3-36 months post-treatment, and had no mental health diagnoses. Participants completed the …

Spag17 Deficiency Impairs Neuronal Cell Differentiation In Developing Brain, Olivia J. Choi

Theses and Dissertations

The development of the nervous system is a multi-level, time-sensitive process that relies heavily on cell differentiation. However, the molecular mechanisms that control brain development remain poorly understood. We generated a knockout (KO) mouse for the cilia associated gene Spag17. These animals develop hydrocephalus and enlarged ventricles consistent with the role of Spag17 in the motility of ependymal cilia. However, other phenotypes that cannot be explained by this role were also present. Recently, a mutation in Spag17 has been associated with brain malformations and severe intellectual disability in humans. Therefore, we hypothesized that Spag17 plays a crucial role in …

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 …

An Investigation Of Neurological Soft Signs As A Discriminating Factor Between Veterans With Post-Traumatic Stress Disorder, Mild Traumatic Brain Injury, And Co-Occurring Post-Traumatic Stress Disorder And Mild Traumatic Brain Injury, David J. Rothman

Theses and Dissertations

While multiple Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veterans suffer from mild Traumatic Brain Injury (mTBI), Post-traumatic Stress Disorder (PTSD), and co-morbid mTBI and PTSD, there remains difficulty disentangling the specific symptoms associated with each disorder using self-report and neurocognitive assessments. We propose that neurological soft signs (NSS), which are tasks associated with general neurologic compromise, may prove useful in this regard. Based on our review of the literature we hypothesized that individuals with PTSD would present with a greater number of NSS than controls or individuals with mTBI. Further, we hypothesized a synergistic effect, such that individuals with …

Long-Term Effects Of Notch1 Signaling On Neural Stem Cells Following Traumatic Brain Injury, Cruz Sevilla Jr

Theses and Dissertations

Traumatic brain injury (TBI) is a devastating problem which stands as a leading cause of death and disability. The elderly is significantly affected by TBI, typically as the result of falls, and recovery is especially limited. This, in part, is associated with decreased tissue-specific stem cell regeneration and replacement of damaged cells in the aged brain. The diminished ability of the aged brain to recover is especially devastating after TBI, likely leading to permanent loss of sensory, motor, and cognitive functions. Studies have shown that the mature mammalian brain contains Neural Stem Cells (NSCs), found in specific regions of the …

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 …

Targeted Therapies For Ewsr1-Fli1 Translocated Ewing Family Of Tumors, Daniel A.R. Heisey

Theses and Dissertations

The EWSR1-FLI1 t(11;22)(q24;q12) translocation is the pathognomonic genomic alteration in 85% of the Ewing Family of Tumors (EWFT) a malignancy of the bone and the surrounding tissue, predominantly affecting children and adolescents. This translocation results in the formation of a chimeric oncoprotein which acts as an aberrant transcription factor that is currently not pharmaceutically druggable, driving the need for more effective targeted therapies. The EWSR1-FLI1 translocation induces a variety of changes including dysregulation of the epigenome and altered gene expression to drive tumorigenesis, and consequently contributes to the hypersensitivity of EWFT to several classes of chemotherapeutics. We sought to exploit …

Culture Of Dental Pulp Stem Cells On Nanoporous Alumina Substrates Modified By Carbon Nanotubes, Ameneh Alizadeh, Amir Razmjou, Mehrorang Ghaedi, Ramin Jannesar, Fahimeh Tabatabaei, Vahid Pezeshkpour, Lobat Tayebi

School of Dentistry Faculty Research and Publications

Purpose: Alumina substrates are one of the commonly used scaffolds applied in cell culture, but in order to prevent formation of biofilm on the alumina substrate, these substrates are modified with carbon nanotube. Methods: The alumina substrate was made by a two-step anodization method and was then modified with carbon nanotubes by simple chemical reaction. The substrates were characterized with FTIR, SEM, EDX, 3D laser scanning digital microscope, contact angle (CA) and surface free energy (SFE). To determine how this modification influences the reduction of biofilm, biofilm of two various bacteria, Escherichia coli (E.coli) and Staphylococcus aureus ( …

Structure-Activity Relationship Studies Of Synthetic Cathinones And Related Agents, Rachel A. Davies

Theses and Dissertations

Synthetic cathinones and related agents represent an international drug abuse problem, and at the same time an important class of clinically useful compounds. Structure-activity relationship studies are needed to elucidate molecular features underlying the pharmacology of these agents. Illicit methcathinone (i.e., MCAT), the prototype of the synthetic cathinone class, exists as a racemic mixture. Though the differences in potency and target selectivity between the positional and optical isomers of synthetic cathinones and related agents have been demonstrated to have important implications for abuse and therapeutic potential, the two MCAT isomers have never been directly compared at their molecular targets: the …

Hospital Characteristics Associated With Hospital Acquired Condition (Hac) Reduction Program Payment Penalties Across Program Years, Emily D. Cochran

Theses and Dissertations

Objective: The primary objective of this study was to examine the relationship between hospital structural characteristics and penalization status (penalized or not penalized) in any given hospital acquired condition (HAC) Reduction Program year, FY 2015 through 2018. Structural characteristics included hospital type, case mix index, average daily census, bed size, ownership, disproportionate share percentage, location, and American Nurses Credentialing Center Magnet status. The secondary objective of the study was to determine whether a hospital's penalization status across one or more HAC Reduction Program years is related to quality performance (Total HAC Score) in subsequent years. These objectives were achieved through …

Perceived Impact Of Ambient Operating Room Noise By Certified Registered Nurse Anesthetists, Marianne S. Cosgrove

Theses and Dissertations

It is widely acknowledged that elevated levels of noise are commonplace in the healthcare environment, particularly in high acuity areas such as the operating room (OR). Excessive ambient noise may pose a threat to patient safety by adversely impacting provider performance and interfering with communication among perioperative care team members. With respect to the certified registered nurse anesthetist (CRNA), increased ambient OR noise may engender distractibility, diminish situation awareness and cause untoward health effects, thereby increasing the possibility for the occurrence of error and patient injury.

This research project analytically examines the perceived impact of ambient noise in the operating …

From Sunrise To Sunset: A Lifespan Approach To Understanding The Mental Health Of A Subset Of American Farmers, Janna L. Imel

Theses and Dissertations

Prior research has indicated higher risk of suicide for farmers and identified depression and anxiety as mental health concerns, though the majority of research was conducted in the 1980s-1990s. In today’s economic, social, and political climate, farmers are exposed to situations and stressors reminiscent of the 1980s Farm Crisis. An added risk is the aging workforce of farmers, as age-related conditions can make farming even riskier. This study investigated the mental health of a subset of American farmers by exploring farm-related stressors, coping mechanisms, and mental health outcomes. Dispositional mindfulness was explored as a specific coping mechanism. Participants (N …

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 …

A Hybrid Molecule Of Melatonin And Curcumin For Therpeutic Use In Pulmonary Fibrosis, Varsha V. Nair

Theses and Dissertations

Pulmonary fibrosis (PF) is a serious lung disease, as its life expectancy is only 3-5 years upon occurrence and more than 50 % of the cases are idiopathic, i.e., unknown cause. Two drugs, pirfenidone (PIR) and nintedanib, have recently been approved; however, their efficacies are moderate without evidence of prolonged survival. While this is primarily due to our insufficient knowledge about key PF pathogenesis, inductions of oxidative stress and transforming growth factor-b1 (TGF-b1) have been suggested in PF lungs. Hence, anti-oxidative melatonin (MEL) and curcumin (CUR) have been studied yet their efficacies remain moderate without clear understanding about the mechanisms …

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 …

The Effects Of Notch Signaling On Functional Recovery Following Traumatic Brain Injury, Jyoti Lodha

Theses and Dissertations

2.5 million people sustain a traumatic brain injury (TBI) annually in the United States. Although there is potential for functional recovery following TBI, there is no definitive treatment to improve recovery after TBI. Our lab has shown that TBI enhances an endogenous neurogenic response in the subventricular zone and hippocampus. TBI-induced neural stem cells (NSCs) can integrate into regions such as the hippocampus and olfactory bulb. Although the mechanism behind TBI-enhanced neurogenesis remains unknown, the Notch signaling pathway has been implicated as a regulator in the maintenance and survival of NSCs.

This thesis explores the effects of Notch pathway manipulation …

Illumination Of The Golgi Apparatus Of Pathogenic And Nonpathogenic Naegleria Species, Tyler M. Poe

Theses and Dissertations

In this study, Naegleria fowleri, a pathogenic amoeba and the causative agent of Primary Amebic Meningoencephalitis (PAM), was utilized to determine the presence or absence of classically conserved Golgi molecules featured in the expression of a Golgi apparatus. Previous studies concluded no Golgi expression via light microscopy and transmission electron microscopy, but a recent report on Naegleria gruberi indicated the presence of dispersed Golgi tubules. Non-pathogenic species of the Naegleria genus such as Naegleria gruberi 30540 and Naegleria lovaniensis 30569 were utilized in Western immunoblot analysis compared to reduced whole-cell lysate proteins of two strains of N. fowleri and …

Construction And Validation Of A Non-Medical Use Of Prescription Opioids Outcome Expectancies Scale Among College Students In China, Cheuk Chi Tam

Theses and Dissertations

Background:Non-medical use of prescription opioids (NMUPO) has become a clear threat to public health. Young adults (aged 18 to 25) have a high risk of NMUPO. My prior work on Chinese undergraduates indicates a high prevalence of lifetime NMUPO (49.2%). Health behavior theories propose that outcome expectancies are robust psychosocial determinants of substance use. Literature has identified the influence of outcome expectancies on alcohol and drug use. However, the role of outcome expectancies in NMUPO in China is unknown, and a scarcity of a valid measures for NMUPO outcome expectancies may be a barrier. Our previous research also found …

Eralpha Isoforms Modulate The Tumorigenicity Of 24r,25(Oh)2d3 In Estrogen-Responsive Cancer, Anjali Verma

Theses and Dissertations

Over 200,000 cases of breast cancer are diagnosed every year. Nearly 20% of these patients supplement their diets with some form of vitamin D. This high frequency of vitamin D supplement use may be due in part to research suggesting that cancer patients with higher serum vitamin D₃ levels have better prognoses than patients with low serum vitamin D_3. However, double-blind clinical trials on the efficacy of vitamin D₃ supplementation in breast cancer have been inconclusive. A recent meta-analysis showed evidence of reduced cancer recurrence in patients taking vitamin D₃ supplements who had ‘estrogen receptor positive’ …

Preconditioning Of The Tumor Microenvironment By Means Of Low Dose Chemotherapies For An Effective Immunotherapy Of Breast Cancer, Hussein F. Aqbi

Theses and Dissertations

Breast cancer mortality is mainly due to distant recurrence of the disease arising from dormant tumor cells established by cancer therapies. Patients who initially respond to cancer therapies often succumb to distant recurrence of the disease. It is not clear why people with the same type of breast cancer respond to treatments differently; some escape from dormancy and relapse earlier than others. In addition, some tumor clones respond to immunotherapy while others do not. We investigated how autophagy plays a role in accelerating or delaying recurrence of neu overexpressing mouse mammary carcinoma (MMC) following adriamycin (ADR) treatment, and in affecting …

Understanding The Impact The Hospital Readmission Rate Program And Value Based Purchasing Has Had On The Financial Viability Of Academic Health Centers, 2011 To 2015., David Allen

Theses and Dissertations

Academic Health Centers (AHCs) hold a unique place in today’s health care environment. They service their communities through a tripartite mission of education, research, and provision of complex care to disadvantaged populations. To achieve this mission, AHCs face challenges in funding and cost containment compared to non-AHCs. Additionally, the implementation of government programs like the Hospital Readmission Rate Program (HRRP) and Value Based Purchasing (VBP) have the potential to affect AHCs differently from non-AHCs. While AHC’s unique features are known and there has been research to date on HRRP and VBP, literature has yet to statistically explore the financial differences …

Getting To Zero Preventable Falls: An Exploratory Study, Kate Lim

Theses and Dissertations

Objective: The objective of this study is to examine relations between patient safety culture and processes of care, specifically, how patient safety culture influences the prevention of patient falls. The purpose of this inquiry is to identify the barriers and facilitators that can advance an inpatient rehabilitation facility to become a high reliability organization and advance interdisciplinary teamwork.

Method: A qualitative phenomenological approach was conducted and an interpretive phenomenological analysis explored the experiences of frontline staff with regard to patient safety culture and fall prevention. The study utilized semi-structured interviews with 24 frontline staff from three inpatient rehabilitation hospitals. Participants …

The Effect Of Change In Medi-Cal Dental Coverage On Dental Care Utilization Among Medi-Cal Beneficiaries, Min H. Zhang

Theses and Dissertations

One of the most important factors in accessing dental care is having dental insurance. For people with low incomes, Medicaid is the main source of health insurance. Medi-Cal is California’s Medicaid program. Adult dental services were mostly eliminated in Medi-Cal in 2009 due to the economic downturn and partially restored in 2014. The objective of this study is to evaluate the effect of change in Medi-Cal dental coverage, specifically the partial restoration of adult dental coverage in 2014, on dental care utilization among Medi-Cal beneficiaries. The partial restoration significantly increased the utilization rates in dental clinics from 2014 to 2017 …

Genome-Wide Systems Genetics Of Alcohol Consumption And Dependence, Kristin Mignogna

Theses and Dissertations

Widely effective treatment for alcohol use disorder is not yet available, because the exact biological mechanisms that underlie this disorder are not completely understood. One way to gain a better understanding of these mechanisms is to examine the genetic frameworks that contribute to the risk for developing this disorder. This dissertation examines genetic association data in combination with gene expression networks in the brain to identify functional groups of genes associated with alcohol consumption and dependence.

The first study took advantage of the behavioral complexity of human samples, and experimental capabilities provided by mouse models, by co-analyzing gene expression networks …

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 …