In Vivo Examination Of Peripheral Drivers Of Alzheimer’S Disease, Celso Catumbela

Dissertations & Theses (Open Access)

Alzheimer’s disease (AD) is the leading cause of dementia worldwide, and predominantly affects elderly populations. This disease is well known for its effects on the brain, but a wealth of clinical reports show that dementia can also modify, or be modified by, various peripheral and systemic processes. Yet, the pathological contribution of peripheral comorbidities to AD remains to be fully understood. In an attempt to address some knowledge gaps, we characterized the cerebral and peripheral pathology in mice with history of either liver injury or sepsis. In the former subjects, we found that even in the absence of genetic risk …

Comprehensive Investigation Into The Molecular Mechanisms Driving The Emergence Of Emm4 Group A Streptococcus, Chioma Odo, Samuel A Shelburne, Anthony R. Flores, Steven J Norris, Anna Konovalova, Blake Hanson

Dissertations & Theses (Open Access)

Abstract

Comprehensive Investigation into the Molecular Mechanisms Driving the Emergence of emm4 Group A Streptococcus

Chioma Modeline Odo, M.S.

Advisory Professor: Samuel A. Shelburne, MD, Ph.D.

The major gram-positive bacterium group A Streptococcus (GAS) is a model organism for studying microbial epidemics as it is well known to cause infections that occur in waves. GAS strains are grouped based on the composition of the N-terminal sequence of the M protein which is encoded by the emm gene. With the advent of large-scale whole genome sequencing, GAS clonal emergence events in emm1, emm3, and emm89 types have been identified …

Prevalence And Predictors Of Secondary Traumatic Stress In A National Sample Of Emergency Nurses: A Cross-Sectional Study, Christian Paige Owen

Dissertations & Theses (Open Access)

Background: Emergency nurses experience traumatic situations as part of their professional role, leaving them vulnerable to secondary traumatic stress (STS). The distressing behaviors and symptoms of STS negatively impacts their well-being and ability to provide high quality care. Studies report that emergency nurses experience high levels of STS but less is known about how STS is influenced by their coping strategies and work-related factors. Further evidence is needed to better understand predictors of STS in order to support strategic efforts to improve the well-being and retention of nurses working in trauma-prone environments.

Aims: The specific aims of this study sought …

Exploring The Role Of Il-1Β/Il-1r In The Pathogenesis Of K-Ras Mutant Lung Cancer, Avantika Krishna

Dissertations & Theses (Open Access)

As the leading cause of cancer-related deaths worldwide, the development of targeted therapeutics to treat lung cancer remains crucial. Non-small cell lung cancer (NSCLC), the most common histological subtype predominantly comprises lung adenocarcinoma with driver mutations in the K-ras oncogene (KM-LUAD). KM-LUAD progression partly occurs through activation of the NF-κB pathway initiating an inflammatory response and creating a pro-tumor microenvironment. Notably, the pro-inflammatory cytokine IL-1β a potent activator and product of the NF-κB pathway is elevated in the lungs and sera of KM-LUAD patients. We have shown that IL-1β blockade promotes an anti-tumor immune phenotype in a mouse model of …

Role Of The Immune System In The Modulation Of The Mmr-Deficient Intestinal Stem Cell Niche, Shepard Conner

Dissertations & Theses (Open Access)

Mismatch Repair (MMR) is a crucial DNA repair system to maintain genomic integrity in cells that is integrated by specific genes including MLH1, MSH2, MSH6, and PMS2. These genes play a critical role in repairing errors that occur in base pairing by stabilizing the genetic material. When the MMR system fails to correct those errors, MMR deficiency occurs where monoallelic mutations in the MMR genes result in a condition known as Lynch Syndrome (LS). LS makes up approximately 3% of all colorectal cancer (CRC) and is regarded as a hereditary form of CRC, which progresses from MMR-deficient …

Translational Research Targeting Biliary Tract Cancer, Yan Zhu

Dissertations & Theses (Open Access)

Biliary tract cancer (BTC) is malignant tumor that originates from the biliary tract, including cholangiocarcinoma (CCA) and gallbladder cancer (GBC). In this translational research program targeting BTC, we focus on three aspects: the development of a combination treatment against CCA, the exploration of the immune background of GBC, and the establishment of a CCA mouse model mimicking mutation profiles of CCA patients.

Patients with cholangiocarcinoma have poor clinical outcomes due to late diagnoses, poor prognoses, and limited treatment strategies. To identify novel drug combinations for this disease, we have conducted a genome wide CRISPR screen anchored on the bromodomain and …

Oncogenic Kras And Telomere Biology In Crc Progression, Ronald Depinho

Dissertations & Theses (Open Access)

While colorectal cancer (CRC) patients diagnosed with localized stage disease (as defined by SEER) have a 5-year survival rate of 90%, this rate plunges to 14% for patients diagnosed with metastatic CRC. Consequently, there is an immediate imperative to elucidate the mechanisms that drive the transition to advanced CRC.

Human CRCs carrying oncogenic mutations in the KRAS oncogene, henceforth referred to as KRAS*, exhibit a 25% higher propensity for developing liver metastases. Similarly, in our CRC mouse model, engineered with an inducible Kras* transgene and conditional null alleles of Apc and Tp53 (referred to as iKAP), KRAS* has been …

Spanish-Speaking Limited English-Proficient Patient Satisfaction And Comfort When Comparing Spanish-Speaking Provider To An Interpreter, Cindy Hernandez

Dissertations & Theses (Open Access)

A large population of Americans have limited or no English proficiency (LEP) with about 64% of those being Spanish-speaking. This creates challenges in navigating the American healthcare system, where the majority of providers are solely English-speaking. Studies have demonstrated that when patients have language discordant appointments without interpreters, they are more likely to feel less understood, have questions and comments ignored, and are less likely to receive patient-centered care in communication. It is expected that interpreters improve access to healthcare, especially for Spanish-speaking patients. However, the patient comfort and satisfaction in language discordant genetic counseling appointments has not yet been …

Statistical Modeling Approaches For The Inference Of Cancer Mechanisms, Licai Huang

Dissertations & Theses (Open Access)

The aim of this study was to explore the potential of integrating multi-platform genomic datasets to improve our understanding of the biological mechanisms behind cancer. By merging clinical outcomes with the data obtained from multi-platform genomic studies, we can gain insight into the biological mechanisms behind a patient’s response to treatment. Additionally, the evaluation of the correlations between genetic variations and gene expression provides a better understanding of the functional significance of these variations. Such knowledge has the potential to revolutionize cancer diagnosis and treatment. This thesis describes methods developed to address two related aims. Aim 1: We have developed …

Symptom Experience Of Patients With Advanced Melanoma Undergoing Immune Checkpoint Inhibitor Therapy, Natalie Jackson-Carroll

Dissertations & Theses (Open Access)

Background: Immune checkpoint inhibitors (ICIs) are novel therapeutic agents utilized in the management of advanced melanoma. Though generally well-tolerated, patients receiving ICIs experience treatment-related toxicities at varying onset and intensity. Assessment and evaluation of these toxicities and their impact on a quality of life is essential to comprehensive cancer care. Patient-reported outcomes (PRO) contribute vital data to a clinical assessment, supporting clinicians in their ability to improve outcomes. To date, there is no melanoma-specific or ICI-specific PRO measure of symptom burden available.

Purpose: The purpose of this study was to describe the symptom experience from the patient's perspective and how …

Baby Boomer Gay Men’S Lived Experiences With Primary Healthcare: A Qualitative Study, Aaron J. Loeb

Dissertations & Theses (Open Access)

Background: Baby boomer gay men have experiences discrimination in healthcare settings. Members of the LGBTQIA+ population are often studied as a single entity, which fails to account for the distinct cultural and social generational differences within this population that may affect their experiences of health care. A paucity of research is available on baby boomer gay men’s perspectives about primary healthcare experiences. Such knowledge is necessary to improve inclusiveness in healthcare settings and health outcomes.

Purpose: The purpose of this study was to describe baby boomer gay men’s lived experiences with primary healthcare. The specific aims are to describe: (1) …

Mental Health And Parenting Among Young Adults Experiencing Homelessness With And Without Their Children, Rebecca Bergh

Dissertations & Theses (Open Access)

Background: Parent-child separation and custody loss are common among parenting young adults experiencing homelessness (YAEH). These experiences may be traumatic for YAEH, a population already vulnerable to mental health disorders and high levels of trauma. Little is known about how YAEH who have their children with them compare to YAEH separated from their children in terms of mental health and risk and resilience factors. Further evidence is needed to better understand the parenting and mental health support needs among YAEH, particularly surrounding parent-child separation.

Aims: This study aimed to examine the characteristics of (1) parenting YAEH living with their children …

Diet By Genomic Interactions In Determining Metabolic Traits And Profiles On Glucose Metabolism Among Mexican Americans In Starr County, Texas, Shinhye Chung

Dissertations & Theses (Open Access)

Worsening glycemia, prediabetes and diabetes, is one of the essential diseases in public health, considering their high prevalence, the enormous impact on multiple organs, and the economic burden on the community. Various factors can affect the pathogenesis of worsening glycemia, and this study focused on macronutrient intake, genes, and their interactions with metabolome data. 616 self-reported Mexican American participants in Starr County were recruited with informed consent. 308 identified and 2,471 unidentified metabolites were used for the analysis, and all the metabolites were inverse normalized with less than half of the missing rate. Each of the five glycemic and lipid …

Shared Decision Making In Self-Care Management And Health Outcomes Of Adolescents And Young Adults With Sickle Cell Disease, Judith M. Odityo

Dissertations & Theses (Open Access)

Background: Shared decision making (SDM) is a model of care with a potential to guide disease self-care management and promote optimal health outcomes in adolescents and young adults (AYA) with sickle cell disease (SCD).

Aims: To identify the perceived involvement of AYA with SCD in the SDM process and examine its association with self-care management and health outcomes.

Methods: Data were collected from a major sickle cell center. Using a cross-sectional design, participants completed surveys and data were analyzed with descriptive statistics, analysis of variance, multiple linear regression, and correlational statistics.

Results: Participants (N=25) were on average age 22.72 (SD …

Noninvasive Screening Of Nonalcoholic Fatty Liver Disease Among People Living With Hiv, Essi M. Havor

Dissertations & Theses (Open Access)

Background: Nonalcoholic fatty liver disease (NAFLD) disproportionately affects up to 75% of people living with HIV (PLWH). Given the high HIV prevalence in Houston and Harris County, knowledge of the prevalence of NAFLD in PLWH is needed to inform prevention efforts. In addition, such knowledge is required to raise awareness among at-risk individuals and healthcare professionals.

Specific Aims: This cross-sectional study aimed (1) to examine the demographic, behavioral, clinical, and psychosocial characteristics of PLWH in Houston/Harris County, Texas, and to estimate the prevalence of NAFLD, (2) to determine factors associated with the severity of NAFLD, and (3) to identify specific …

Impact Of Personal, Familial, And Socioeconomic Factors On The Return Of Remotely Collected Samples For Genetic Testing, Jordan Zeiger

Dissertations & Theses (Open Access)

There are a multitude of barriers known to impact access to medical care in the United States. COVID-19 has changed and compounded these barriers and led to a shift in the setting of the genetic counseling (GC) appointment, and in sample types used for genetic testing, specifically with use of telemedicine and remotely collected saliva kits. Previous studies have described lack of patient follow-through in returning these kits. Though the understanding of barriers to medical care, including access to genetics services, is well described, there is little in the literature for how these barriers impact the return of remotely collected …

Impact Of Recent Abortion Legislation On Patient Trust In Healthcare Providers, Jasmine Tyson Ms

Dissertations & Theses (Open Access)

Trust is a key aspect of any patient-provider relationship as patients must rely on their healthcare providers (HCPs) to provide appropriate care and guidance, maintain confidentiality, and act in their best interests. Studies suggest that recent changes to abortion legislation have resulted in a loss of the patient-physician relationship, with individuals describing feelings of isolation and fear regarding safety and confidentiality, and many seeking information outside of the medical community. An anonymous survey was distributed among members of abortion support groups and advocacy organizations in the United States to assess how recent changes to abortion legislation may impact patient trust …

The Need For Racial And Ethnic Health Disparity Curriculum In Genetic Counseling Programs, Yusra Aziz

Dissertations & Theses (Open Access)

Racial and ethnic health disparities (REHD) exist across all organized medicine, including the spectrum of genetic counseling, particularly in genomic testing and access to care. While cultural competency and health disparities have been included as a part of the Standards of Accreditation for Genetic Counseling, there have not been previous efforts to define what topics related to REHD are most important to include in graduate program curriculum. Therefore, this study aimed to determine what topics related to REHD should be taught in genetic counseling program curriculum by assessing what topics genetic counselors (GCs) learned about and in what settings, …

Leveraging Digital Technologies For Management Of Peripartum Depression To Mitigate Health Disparities, Alexandra Zingg

Dissertations & Theses (Open Access)

Health disparities are adverse, preventable differences in health outcomes that affect disadvantaged populations. Examples of health disparities can be seen in the condition of peripartum depression (PPD), a mood disorder affecting approximately 10-15% of peripartum women. For example, Hispanic and African-American women are less likely to start or continue PPD treatment. Digital health technologies have emerged as practical solutions for PPD care and self-management. However, existing digital solutions lack an incorporation of behavior theory and distinctive information needs based on women’s personal, social, and clinical profiles. Bridging this gap, I adapt Digilego, an integrative digital health development framework consisting of: …

Good Faith: Surveillance And Evaluation Of 911 Good Samaritan Laws In The United States, Shane W. Reader

Dissertations & Theses (Open Access)

To fight soaring overdose mortality rates in the United States, lawmakers adopted a variety of harm reduction tools. Among these, 911 Good Samaritan Laws (GSLs) derive their name from the biblical parable of the Good Samaritan, a bystander who broke cultural convention to come to the aid of a man beset by thieves. These laws provide limited criminal immunity for bystanders in possession of controlled substances to encourage them to report drug overdoses. While previous studies associate GSLs with a modest reduction in opioid mortality, analyses often model them as equivocal or divide them coarsely across individual provisions. Evaluating these …

What Is Contributing To Covid-19 Mortality In Harris County, Texas?, Rachel Roy

Dissertations & Theses (Open Access)

The COVID-19 pandemic exposed long-standing inequities that have been present in the United States since its origin. While the entire country has been devastated by this pandemic, low-income and minority communities were hardest hit. Race alone does not predict poor health outcomes. Rather, the historic strategies implemented in the United States, such as redlining, placed racial and ethnic minorities in neighborhoods where cycles of disinvestment in education, transportation infrastructure, flooding infrastructure, healthy food, and clean air and water have created low socioeconomic status and poor health outcomes. This public health research aims to understand how historical processes have created and …

Perceptions And Roles Of Genetic Counselors In Perinatal Palliative Care: Where Are We Now?, Amanda Chamberlain

Dissertations & Theses (Open Access)

After the identification of a life-limiting fetal diagnosis, a perinatal palliative care (PPC) team can provide specialized medical care and emotional support for the family throughout the pregnancy and after delivery. Although the growth of the field of PPC over the last ten years is well-documented, there is only one study to date that explores the experiences of genetic counselors with regards to PPC. This study seeks to further the understanding of genetic counselors’ current perceptions of, experiences with, and roles in the delivery of PPC.

An edited version of the Perinatal Palliative Care Perceptions and Barriers Scale was used …

Listening To Remotely Monitored Home-Based Preferred Music For Pain In Older Adults With Low Back Pain: A Pilot Study Of Feasibility And Acceptability, Setor Kofi Sorkpor

Dissertations & Theses (Open Access)

Background: Low back pain (LBP) is a complex, multifaceted, and widespread condition that impairs the quality of life of older adults aged 65 years or older. Although nonpharmacologic interventions informed by the biopsychosocial model are recommended as first-line therapy for LBP, pharmacologic therapies, including opioids, are commonly used as first-line interventions in practice. This could be attributed to a lack of understanding of the analgesic properties of most nonpharmacologic interventions. Nonetheless, some nonpharmacologic therapies, such as passive music listening, have been shown to modulate pain via pathways that target the neurophysiological mechanisms associated with pain.

Specific Aims: The specific aims …

Body Temperature And Diet As Drivers Of Obesity Development, Jessie Morrill

Dissertations & Theses (Open Access)

Metabolic disease and obesity affect millions of individuals worldwide and the prevalence of obesity is expected to continue to rise. Mechanisms underlying diet-induced metabolic disease and obesity are complex and are largely unknown. In this dissertation research, we aimed to make advances toward understanding how body temperature and high-fat diet consumption contribute to the development of obesity. Herein, we describe the progress that was made toward three research projects. In the first project, we develop novel animal models to determine the impact of reduced body temperature on obesity development and also demonstrate that severe obesity can be reversed through increased …

Lipid Composition And Configuration Drive Biophysical Properties Of The Mammalian Plasma Membrane, Jessica L. Symons

Dissertations & Theses (Open Access)

In the 1970s, it was established that phospholipid (PL) classes are asymmetrically distributed across the (PM) leaflets. Recapitulating strategies coupled with newly developed, high-resolution shotgun lipidomics, our lab confirmed PL class asymmetry and surprisingly measured the endoplasmic leaflet to contain double the number of PLs vs. the exoplasmic leaflet. My re-analysis of classical studies show that PM PL abundance imbalance has been a consistent finding across decades of literature. This is surprising, because bilayers do not tolerate interleaflet area imbalances to the degree that this imbalance would suggest, which prompted us to consider the existence of an elusive membrane resident …

Perceptions Of Integrating Immersive Virtual Reality Simulation As A Teaching Methodology In A Hospital Setting, Ladonna Christy

Dissertations & Theses (Open Access)

Introduction As newly licensed nurses enter the workforce with limited experience and limited clinical reasoning skills, nursing educators must employ innovative strategies to teach graduate nurses how to identify and manage clinical deterioration – skills which are vital to saving lives and improving outcomes. Fully immersive Virtual Reality (VR), (also defined as Immersive VR) is one effective educational strategy available for hospital educators to use for preparing newly licensed nurses to recognize and manage clinical deterioration.

Objective The purpose of this study was to explore perceptions of hospital-based nurse educators, simulation specialists, and nursing leaders with respect to integrating immersive …

Factors Associated With Advance Care Planning Engagement In Healthy Young Adults, Pablo J. Vasquez

Dissertations & Theses (Open Access)

Background: Advance care planning (ACP) is a process that supports individuals at any stage of health in understanding and sharing their personal values and goals pertaining current or future medical needs with their families and healthcare providers. Although ACP is applicable to adults of any age and any stage of the health continuum, it is widely associated with older or terminally ill populations, and the need for end-of-life (EOL) planning in healthy young adults is generally found unnecessary. The National Institutes of Health supports the expansion of ACP research in understudied populations. Investigating ACP in healthy young adults support such …

Investigating The Attitudes Of The D/Deaf Community Towards Genetic Counseling And The Utilization Of Genetic Services, Katie Baudoin, Jennifer Czerwinski, Laura Farach, Malorie Jones, Rebecca Lunstroth, Caitlin Mauer, Chelsea Wagner

Dissertations & Theses (Open Access)

The Deaf community has previously expressed concerns about the process of genetic counseling/testing and the potential implications it can have for Deaf individuals. Prior studies have explored the motivations of Deaf individuals for pursuing genetic testing related to deafness; however, information regarding the interest and motivations for indications other than deafness is limited. Our study aims to characterize attitudes of individuals within the d/Deaf community towards genetic counseling and testing and to assess interest and motivations to seek genetic counseling for indications other than deafness.

Individuals were recruited through local and national d/Deaf organizations to participate in an anonymous, online …

Parental Stress In Tuberous Sclerosis Complex, Jenny Do

Dissertations & Theses (Open Access)

Tuberous Sclerosis Complex (TSC) is a multi-systemic genetic disorder with great clinical variability. As the needs of one child with TSC may vastly differ from another, parenting demands may similarly differ. Characterizing parental stress, or emotional maladaptation arising from parenting duties, can enable healthcare providers to assist parents of children most efficiently with TSC-related symptoms and improve both parent and child health outcomes. This study surveyed 269 parents of children (aged 0-12 years) with TSC and received the following information: children’s TSC clinical features, parent demographics, and a Parent Stress Index (PSI) score. Parents reported higher stress levels for children …

Atr-Mediated Cd47 And Pd-L1 Upregulation Restricts Radiotherapy-Induced Immune Priming And Abscopal Responses In Colorectal Cancer, Cheng-En Hsieh, Cheng-En Hsieh

Dissertations & Theses (Open Access)

Radiotherapy of colorectal cancer (CRC) can prime adaptive immunity against tumor-associated antigen (TAA)-expressing CRC cells systemically. However, incidences of abscopal tumor remission are extremely rare, and the post-irradiation immune escape mechanisms in CRC remain elusive. We report that CRC cells utilize a common DNA repair signaling pathway — ATR/Chk1/STAT3 — to upregulate both CD47 and PD-L1 in response to radiotherapy, which through engagement of SIRPα and PD-1 suppresses the capacity of antigen-presenting cells to phagocytose them thereby preventing TAA cross-presentation and innate immune activation. This post-irradiation CD47 and PD-L1 upregulation can be observed across various human solid tumor cells. Concordantly, …