Medicine and Health Sciences Commons^™

Molecular Mechanisms Of Opioid Use Disorder In Human Brain Models, Emily Mendez

Dissertations & Theses (Open Access)

Opioid use disorder (OUD) is a national and global public health crisis with no end in sight. While studies from animal models hint at widespread epigenetic and transcriptomic alterations of opioid drugs, the molecular consequences of long-term exposure to opioid drugs in human brain is still unclear, and human-centered translational models are necessary to discern the human cell type-specific effects of OUD.

Using postmortem brain Brodmann area 9 (BA9) from the UTHealth Brain Collection for Research on Psychiatric Disorders, I identified angiogenic gene networks perturbed in the RNA and protein of OUD subjects, as well as downregulation of many neuron-correlated …

Proof-Of-Concept For Converging Beam Small Animal Irradiator, Benjamin Insley

Dissertations & Theses (Open Access)

The Monte Carlo particle simulator TOPAS, the multiphysics solver COMSOL., and

several analytical radiation transport methods were employed to perform an in-depth proof-ofconcept

for a high dose rate, high precision converging beam small animal irradiation platform.

In the first aim of this work, a novel carbon nanotube-based compact X-ray tube optimized for

high output and high directionality was designed and characterized. In the second aim, an

optimization algorithm was developed to customize a collimator geometry for this unique Xray

source to simultaneously maximize the irradiator’s intensity and precision. Then, a full

converging beam irradiator apparatus was fit with a multitude …

Feasibility And Measurement Of Bedside Pumping In The Nicu: A Mixed Methods Study, Jessica Gomez

Dissertations & Theses (Open Access)

Abstract

Background: Supporting preterm infants with mother’s own milk (MOM) can improve health outcomes and decrease mortality.¹ Freshly pumped MOM, within four hours of expression, has the highest availability of bioactive components versus stored MOM. However, fresh milk is often not readily available due to the disconnected process of breastfeeding that occurs with preterm infants in the NICU. One convenient solution to improve access to fresh MOM is for the mother to pump at the infant's bedside. This intervention could improve the mother's pumping experience and provide the infant access to fresh MOM.

Purpose: This study aimed to evaluate …

Development Of A Remote Dosimetric Audit Framework For Carbon Therapy, Paige Taylor

Dissertations & Theses (Open Access)

Carbon ion therapy is available at over a dozen institutions around the world and is being employed for treatment of cancer. The increased biological effect of carbon compared to conventional photon-based radiotherapy holds promise for the therapeutic benefit in historically radioresistant tumors. While ion chamber dosimetry has been used for day-to-day clinical measurements of absorbed dose, there are few options for remote dosimetry. The availability of such tools would support the development of a robust remote audit program for carbon ion therapy.

The Imaging and Radiation Oncology Core (IROC) conducts remote audits of photon and proton therapy. These audits are …

Advancing Precision Medicine: Unveiling Disease Trajectories, Decoding Biomarkers, And Tailoring Individual Treatments, Yanfei Wang

Dissertations & Theses (Open Access)

Chronic diseases are not only prevalent but also exert a considerable strain on the healthcare system, individuals, and communities. Nearly half of all Americans suffer from at least one chronic disease, which is still growing. The development of machine learning has brought new directions to chronic disease analysis. Many data scientists have devoted themselves to understanding how a disease progresses over time, which can lead to better patient management, identification of disease stages, and targeted interventions. However, due to the slow progression of chronic disease, symptoms are barely noticed until the disease is advanced, challenging early detection. Meanwhile, chronic diseases …

Operationalizing The Datagauge Framework In A Health Information Exchange Utilizing Hepatitis C Data, Edward Yao

Translational Projects (Open Access)

This project aims to implement the DataGauge framework in a health information exchange (HIE) setting as a proof of concept. The modified DataGauge framework, described by Diaz-Garelli et al. (2019), is utilized to test its functionality and applicability with any dataset. The specific objective of the project is to determine the number of hepatitis C-positive tests within the HIE. The implementation involved multiple iterations following the DataGauge framework's steps for data extraction and analysis. Five iterations were conducted, resulting in both successful and failed queries based on the validity of the data standards. The findings revealed that the HIE, in …

Investigating The Role Of Il-10 Producing Nkt Cells In Prevention Of Graft Versus Host Disease, Drew Boagni

Dissertations & Theses (Open Access)

The standard curative treatment for hematologic malignancies is allogeneic stem cell transplantation (ASCT), in which the patient’s immune system is replaced with that of a healthy donor. This can lead to cure through the graft versus leukemia (GVL) effect but can also cause graft versus host disease (GVHD), which is characterized by systemic inflammation and organ damage mediated by dysregulated donor T cells. Preclinical studies have shown invariant natural killer T cells (iNKT) cells can prevent GVHD while preserving GVL. iNKT cells are unconventional T cells which recognize glycolipid antigens presented in the context of CD1d. Upon activation, they secrete …

Economic And Policy Determinants Of National Abortion Rates: A Cross-National Study, Olufunke Akiyode

Dissertations & Theses (Open Access)

Abortion is as old as humanity and exists in all cultures. The number and rate of abortions differ among countries and regions of the world. Some determinants of abortion may include economic indicators and policy restrictiveness. This study analyzes the economic and policy determinants of abortion by evaluating the association of income and policy on abortion rates. It uses a panel data regression to examine the association between income, Gini Coefficient and abortion rates. Gini Coefficient measures income inequality, and GNI represents a country’s income. Publicly available longitudinal data obtained from the World Bank, United Nations, United Nations Population Development …

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) …

Exploring The Novice Nurses’ Perceptions Of Communication Dynamics In The Operating Room, Lasandra Brown

Dissertations & Theses (Open Access)

Background: Communication among the multidisciplinary team members in an operating room setting is essential for effective and safe patient care. Studies have previously addressed communication breakdowns among team members, and miscommunications have been demonstrated to significantly challenge efficiency in the operating room. Novice nurses play an integral role in the success of operating room procedures and must possess strong communication skills that facilitate optimal patient outcomes.

Purpose: The aim of this study was to explore novice nurses’ perceptions of factors that influence the dynamics of team communication in the operating room setting.

Methods: An inductive thematic, qualitative analysis of 11 …

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 …

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 …

A Larval Zebrafish (Danio Rerio) Model Of Adherent-Invasive Escherichia Coli Infections, Erika Flores, Erika Flores

Dissertations & Theses (Open Access)

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is a broad term for chronic intestinal disorders that severely impact patient morbidity and quality of life. The global prevalence of IBD is rising, with over one million patients affected in the US alone. Adherent-invasive E. coli (AIEC) is a pathobiont frequently found in IBD biopsies. AIEC adhere to and invade epithelial cells, and can survive inside macrophages in vitro. However, how AIEC contributes to IBD in vivo remains unclear. Here a larval zebrafish (Danio rerio) model of AIEC was established, which facilitates the study of the …

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 …

Endothelial To Mesenchymal Transition In Human And Murine Congenital Diaphragmatic Hernia Pulmonary Hypertension, Jamie L. Gilley

Dissertations & Theses (Open Access)

Background: Congenital diaphragmatic hernia (CDH) is one of the most complex congenital disorders, characterized by pulmonary hypertension and hypoplasia. CDH-associated pulmonary hypertension (CDH-PH) features devastating morbidity and mortality (25-30%) among neonates. An unmet need is determining the mechanisms triggering CDH-PH to save infants and improve their quality of life. Prior data suggest abnormal remodeling of the pulmonary vascular extracellular matrix, presumed to be driven by endothelial-to-mesenchymal transition (EndoMT), hinders postnatal vasodilation and limits efficacy of anti-PH therapy in CDH. Although abnormal vascular development and remodeling are known CDH traits, there is limited data on the role of EndoMT in CDH-PH. …

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 …

Difference In Smoking Patterns And Quitting Status Between Premium And Non-Premium Cigar Users After Two Years Of Follow Up In Us Adults: Findings From The Population Assessment Of Tobacco And Health (Path) Study, 2016-2019, Sarah Valencia

Dissertations & Theses (Open Access)

Previous studies have described the demographics, purchasing behaviors, trends in frequencies of cigar use, and quitting status among cigar poly users, however, there has not been a study that evaluates differences in demographic characteristics and quitting status for premium and non-premium U.S. adult cigar users. This study used secondary data analyses of the Population Assessment of Tobacco and Health (PATH) Study public-use files dataset for adult traditional cigar users in wave 4 (2016-2018) and wave 5 (2018-2019). Traditional cigars were classified as premium or non-premium at wave 4 (2016-2018) using the brand and price per stick of cigar that was …

Multiparametric Magnetic Resonance Imaging Artificial Intelligence Pipeline For Oropharyngeal Cancer Radiotherapy Treatment Guidance, Kareem Wahid

Dissertations & Theses (Open Access)

Oropharyngeal cancer (OPC) is a widespread disease and one of the few domestic cancers that is rising in incidence. Radiographic images are crucial for assessment of OPC and aid in radiotherapy (RT) treatment. However, RT planning with conventional imaging approaches requires operator-dependent tumor segmentation, which is the primary source of treatment error. Further, OPC expresses differential tumor/node mid-RT response (rapid response) rates, resulting in significant differences between planned and delivered RT dose. Finally, clinical outcomes for OPC patients can also be variable, which warrants the investigation of prognostic models. Multiparametric MRI (mpMRI) techniques that incorporate simultaneous anatomical and functional information …

Lymphatic Dysfunction And Associated Systemic Inflammation In Lymphedema, Assessed By Nirf-Li Imaging And Plasma Cytokine/Chemokine Analysis, Anna Vang

Dissertations & Theses (Open Access)

Breast cancer-related lymphedema (BCRL) manifests as swelling of the upper extremities and trunk as a result of lymphatic fluid buildup due to radiation therapy (RT), surgical lymph node removal, or chemotherapy. As there is currently no cure, BCRL treatment aims to improve quality of life (QOL). First-line treatment involves specialized massage therapy and the use of compression garments. Second-line treatments include reparative lymphatic microsurgeries such as lymphovenous bypass (LVB) and/or vascularized lymph node transplant (VLNT). There is a need for better understanding of the etiology of BCRL and lymphatic microsurgery outcomes. Blood specimens and near-infrared fluorescent lymphatic imaging (NIRF- LI)data …

Kir-Based Inhibitory Cars Overcome Car-Nk Cell Trogocytosis-Mediated Fratricide And Tumor Escape, Ye Nmn Li

Dissertations & Theses (Open Access)

Trogocytosis is an active process that transfers surface material from targeted to effector cells. Using multiple in vivo tumor models and clinical data, we report that chimeric antigen receptor (CAR) activation in natural killer (NK) cells promoted the transfer of the CAR-cognate-antigen from tumor to NK cells, resulting in (1) lower tumor antigen density, thus impairing the ability of CAR-NK cells to engage with their targets, (2) induced self-recognition and continuous CAR-mediated engagement, resulting in fratricide of trogocytic antigen expressing NK cells (NK^TROG+) and NK cell hyporesponsiveness. This phenomenon could be offset by a dual-CAR system incorporating both …

Gene Expression–Based Algorithms For The Identification Of Drug Combinations In Personalized Medicine, Lon Fong

Dissertations & Theses (Open Access)

Three of the major problems facing cancer therapeutics are 1) drug resistance, the intrinsic or acquired ability of cancer cells to evade the effect of the therapies used to treat them; 2) heterogeneity among individual patients’ disease at the molecular level and the resulting variability in therapeutic response; and 3) the limitations of genomics biomarkers in matching patients to the most effective therapy. One possible solution to drug resistance is the use of combination therapies rather than monotherapies. Use of multiple drugs, each with a different mechanism of action, lowers the chances that the cancer cells will develop or have …

Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing

Dissertations & Theses (Open Access)

Systemic sclerosis (SSc; scleroderma) is a chronic systemic autoimmune and connective tissue disorder characterized by vasculopathy, autoimmune phenomena, and widespread fibrosis. Skin thickening and tightening is the cardinal feature of SSc and is responsible, in part, for the considerable morbidity of this disease. There are currently no targeted treatments for skin manifestations in SSc, primarily due to our fragmented understanding of its pathophysiologic mechanisms. In PART I, we report a previously unappreciated link between aberrant expression of the developmental gene sine oculis homeobox homolog 1 (SIX1) in skin-associated adipocytes in SSc skin and the early loss of dermal white adipose …

The Cx3cl1-Cx3cr1 Chemokine Axis Contributes To Tumor Immune Evasion And Its Blockade Enhances Responses To Anti-Pd-1 Immunotherapy, Apoorvi Chaudhri

Dissertations & Theses (Open Access)

CX3CL1 secreted in the tumor microenvironment serves as a chemoattractant playing a critical role in metastasis of CX3CR1 expressing cancer cells. While CX3CR1 can be expressed in both cancer and immune-inhibitory myeloid cells to facilitate their migration, the mechanisms employed by this axis on these cells to mediate immune suppression remain poorly understood. Here, we explore the immune evasion strategies implemented by this axis and find that it initiates a resistance program in cancer cells that results in 1) facilitation of tumor cell migration, 2) secretion of soluble mediators to generate a pro-metastatic niche, 3) secretion of mediators to attract …

Uncovering Novel Mechanism Of Immune Modulation Of Invariant Natural Killer T Cells By Liposomal Α-Galactosylceramide, Alexandra S. Flegle

Dissertations & Theses (Open Access)

Invariant Natural Killer T cells (iNK-T cells) are a powerful regulatory immune cell that can recruit both innate and adaptive immune cells. Unlike conventional T cells (CD4⁺ and CD8α⁺), they recognize glycolipid antigens via the MHC-class-I like molecule, CD1d. A synthetically derived glycolipid from the marine sponge, Agelas mauritianus, alpha-Galactosylceramide (α-GalCer) potently activates iNK-T cells. Within a few hours after activation, iNK-T cells produce high quantities of T_H1 and T_H2 type cytokines, thus shape subsequent adaptive immunity towards inflammation (T_H1) or immune-suppression (T_H2). Structural modification of α-GalCer’s phytosphingosine …

The Safe And Effective Clinical Deployment Of Artificial Intelligence Tools, Kelly Nealon

Dissertations & Theses (Open Access)

18 million new cancer cases are diagnosed each year. Roughly half of these patients will be treated with radiation therapy, a complex technique that requires an interdisciplinary team of clinical staff and expensive equipment to be delivered safely. Cancer centers in Low- and Middle-Income Countries (LMIC) have an especially difficult time meeting the demands of radiation therapy as the complexity of treatment techniques increase, with only 37% of patients in these regions having access to the care they need. Artificial Intelligence (AI) based tools are being developed to simplify the treatment planning and quality assurance processes to increase the number …

Improving Dose-Response Correlations For Locally Advanced Nsclc Patients Treated With Imrt Or Pspt, Yulun He

Dissertations & Theses (Open Access)

The standard of care for locally advanced non-small cell lung cancer (NSCLC) is concurrent chemo-radiotherapy. Despite recent advancements in radiation delivery methods, the median survival time of NSCLC patients remains below 28 months. Higher tumor dose has been found to increase survival but also a higher rate of radiation pneumonitis (RP) that affects breathing capability. In fear of such toxicity, less-aggressive treatment plans are often clinically preferred, leading to metastasis and recurrence. Therefore, accurate RP prediction is crucial to ensure tumor coverage to improve treatment outcome. Current models have associated RP with increased dose but with limited accuracy as they …

Targeting Metabolic Alterations Associated With Smooth Muscle Α-Actin Pathogenic Variant Attenuates Moyamoya-Like Cerebrovascular Disease, Anita Kaw

Dissertations & Theses (Open Access)

Heterozygous pathogenic variants in ACTA2, encoding smooth muscle α-actin (α-SMA), predispose to thoracic aortic aneurysms and dissections. De novo missense variants disrupting ACTA2 arginine 179 (p.Arg179) cause a multisystemic disease termed smooth muscle dysfunction syndrome (SMDS), which is characterized by early onset thoracic aortic disease and moyamoya disease-like (MMD) cerebrovascular disease. The MMD-like cerebrovascular disease in SMDS patients is marked by bilateral steno-occlusive lesions in the distal internal carotid arteries (ICAs) and their branches. To study the molecular mechanisms that underlie the ACTA2 p.Arg179 variants, a smooth muscle-specific Cre-lox knock-in mouse model of the heterozygous Acta2 R179C variant, termed …

Treatment Planning Automation For Rectal Cancer Radiotherapy, Kai Huang

Dissertations & Theses (Open Access)

Background

Rectal cancer is a common type of cancer. There is an acute health disparity across the globe where a significant population of the world lack adequate access to radiotherapy treatments which is a part of the standard of care for rectal cancers. Safe radiotherapy treatments require specialized planning expertise and are time-consuming and labor-intensive to produce.

Purpose:

To alleviate the health disparity and promote the safe and quality use of radiotherapy in treating rectal cancers, the entire treatment planning process needs to be automated. The purpose of this project is to develop automated solutions for the treatment planning process …

Uncovering Molecular Targets To Overcome Immunosuppression In Non-Small Cell Lung Cancer With Acquired Tki Resistance, Sonia A. Patel

Dissertations & Theses (Open Access)

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. Targeted therapeutic agents, such as epidermal-like growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) or monoclonal antibodies targeting vascular endothelial growth factor (VEGF/R), can effectively inhibit upregulated signaling pathways driving tumorigenesis in NSCLC and many other cancers. Unfortunately, however, resistance to such targeted therapies inevitably arise in most patients and can occur through a variety of resistance mechanisms including genomic alterations and upregulation of bypass pathways. Additionally, patients who have acquired resistance to these targeted agents typically have tumors characterized by an immunosuppressive tumor microenvironment and thus …

The Substance Use Disorder Peer Workforce In Texas And The United States: Assessing And Addressing The Workforce Development And Economic Evaluation Gaps, Sierra Castedo De Martell

Dissertations & Theses (Open Access)

The infrastructure for addressing problematic substance use and substance use disorder (SUD) across the US has shortages in many areas, and suffered additional challenges during the COVID-19 pandemic. One method to address shortages in SUD care infrastructure relatively quickly is to expand the peer workforce delivering peer recovery support services (PRSS). This workforce has expanded to cover most US states over the past two decades, but gaps in the evidence base for peer workforce development and economic evaluations of PRSS have persisted. To address these gaps, three studies were undertaken with the following aims: (1) Conducted a systematic review of …