Medicine and Health Sciences Commons^™

Hours Of Gaming Or Non-Academic Computer Use, Substance Use, Mental Health Status And School Performance Among Texas Adolescence: Findings From The 2017 Yrbs In Texas, Shanxiazi Gao

Dissertations and Theses (Open Access)

Online gaming activities among adolescents and adults has increased exponentially in the last decade, and mental health issues associated with excessive gaming have drawn attention from health care professionals worldwide (Griffith, 2016). Recognizing this trend, American Psychiatric Association (APA) categorized gaming disorder/addiction as a mental health condition in 2013 in an effort to prevent the expansion of relevant mental health issues (American Psychiatric Association, 2013). Additionally, the World Health Organization (WHO) declared gaming disorder/addiction as a mental health disease, (World Health Organization, 2018). As a result of this declaration, Diagnostic and Statistical Manual of Mental Disorders (DSM-5) has established nine …

How Participatory Are We? A Systematic Review Comparing Women’S Participation In Participatory Action Research, Community Based Participatory Research And Participatory Learning In Action, Magdalene Hakala-Hartman

Dissertations and Theses (Open Access)

Objective. This systematic review compares the extent of participation of women in maternal and child health and healthy living-type research projects based on three participatory research frameworks, Participatory Action Research (PAR), Community Based Participatory Research (CBPR), and Participatory Learning in Action (PLA), by examining roles, tasks, engagement, and the duration and complexity of their participation- as guided by the Community Engagement in Research Index (CERI). The review analyzed differences in underlying structure of the studies connected to their theoretical underpinnings. Methods. Ovid Medline, PubMed, EBSCO, CINAHL, Embase, Scopus, and Academic Search Complete were searched for studies published 2009 – 2018. …

Quantifying The Impact Of Laboratory And Care Systems On Relinkage To Hiv Care In A Southern, Urban Environment, Kellie L. Watkins

Dissertations and Theses (Open Access)

Background: HIV viral suppression reduces the likelihood of transmission to just 5%,1 demonstrating the critical link between care and prevention, yet only 51% of people living with HIV (PLWH) were retained in care and 46% achieved viral suppression in the Houston area (2012), with the out-of-care (OOC) population increasing between 2008-2011.2,3

Methods: Record-search investigations across HIV surveillance and care data systems determined if potentially OOC persons referred to the Houston Health Department (HHD) from 2013-2015 (N=1287) qualified for public health follow up. A portion were randomized to a non-intervention group (n=200) to assess the program effectiveness. Participants without a disposition …

Sociodemographic Determinants Of Mental Health Outcomes Among Unhealthy Weight Youth In The United States, Chenchita Malolan

Dissertations and Theses (Open Access)

Background

The prevalence of unhealthy weight (defined as a body mass index ≥ 85th %ile for age and sex) among children and adolescents in the United States remains unacceptably high. In parallel, the prevalence of mental health issues in youth is rising as well. Current research shows a strong association between overweight/obesity and poor mental health outcomes. Specifically, youth of unhealthy weight have higher rates of anxiety and depression. The objective of this study is to evaluate the specific the current (2016-17) population-level prevalence of unhealthy weight, mental health issues and the sociodemographic (e.g. sex, age, race, ethnicity, household income) …

A Secondary Data Analysis For The Refinement Of Empirical Modelling For The Estimation Of Environmental Health & Safety Program Resourcing For Colleges And Universities, Seth Michael Parker

Dissertations and Theses (Open Access)

The use of potentially hazardous physical, chemical, biological, and radiological agents is inherent to the teaching, research, and services missions of any university. To manage the risks associated with these agents, it is common for universities to host environmental health & safety (EH&S) programs to protect the safety of the institution’s students, faculty, staff, and visitors. However, since EH&S programs in universities are primarily focused on prevention, it is difficult to estimate the appropriate “industry average” in terms of budget and staffing resources a particular university needs for such programs. Historically, the Campus Safety, Health, and Environmental Management Association (CSHEMA) …

Evaluation Of Presage® As A 3d Dose Verification To Ol In Proton Beams, Mitchell Carroll

Dissertations and Theses (Open Access)

Radiotherapy techniques have advanced and radiation dose plans have become much more complex over the last decade. This is especially true in proton therapy, which involves extremely steep dose gradients as a result of positioning the Bragg peak to cover the volumes to be treated. The Bragg peak can be shifted significantly in the patient as a result of nonuniformities in the tissue composition in its path, which can result in treatment complications. Some traditional dose verification tools used in proton beam commissioning and treatment plan verification are film, TLD, and ionization chambers. Such 0D and 2D dosimeters are incapable …

Intratumoral Sting Activation Sensitizes Poorly Immunogenic Cancers To Checkpoint Blockade Immunotherapy, Casey Ager

Dissertations and Theses (Open Access)

Unprecedented durable tumor regression can be achieved in patients with checkpoint blockade immunotherapy, yet these responses are rare and are not observed in all tumor types. Castration resistant prostate cancer (CRPC) and pancreatic adenocarcinoma (PDAC) are two common lethal cancers that remain refractory to checkpoint blockade, requiring development of new therapeutic approaches to promote responsivity in patients with these diseases. Both CRPC and PDAC are characterized by an immunosuppressive tumor milieu rich in cells of the myeloid lineage, which regulate T cell activity in many ways independent of the coinhibitory receptor axis. We investigated whether activation of acute inflammatory signaling …

Bayesian Integrative Analysis Of Omics Data, Youyi Zhang

Dissertations and Theses (Open Access)

Technological innovations have produced large multi-modal datasets that range in multiplatform genomic data, pathway data, proteomic data, imaging data and clinical data. Integrative analysis of such data sets have potentiality in revealing important biological and clinical insights into complex diseases like cancer. This dissertation focuses on Bayesian methodology establishment in integrative analysis of radiogenomics and pathway driver detection applied in cancer applications. We initially present Radio-iBAG that utilizes Bayesian approaches in analyzing radiological imaging and multi-platform genomic data, which we establish a multi-scale Bayesian hierarchical model that simultaneously identifies genomic and radiomic, i.e., radiology-based imaging markers, along with the latent …

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

Dissertations and 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 …

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

Dissertations and 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 …

Assembly And Display Of Surface Proteins In Actinomyces Oris, Sara Siegel

Dissertations and Theses (Open Access)

Bacteria are an integral part of human health and disease. In the human host, dental plaques form as a result of up to 700 individual bacterial species colonizing oral surfaces and forming a multispecies biofilm. These biofilms are the cause of prevalent human diseases such as dental caries, gingivitis, and periodontitis. The microbes present in the oral biofilm are highly spatially and temporally structured and require a primary colonizing species to adhere to host tissue. As an important primary colonizer of the oral biofilm, the actinobacterium Actinomyces oris utilizes cell wall anchored proteins and glycoconjugates to initiate adherence to host …

Investigating The Single Cell Heterogeneity And Physiological Impact Of Mistranslation, Christopher Evans

Dissertations and Theses (Open Access)

Bacterial populations grow clonal populations; however, individual cells have a variety of phenotypes. The physiological heterogeneity observed in populations has been attributed to variations in the processes of gene expression. For example, promoter expression has been shown to be heterogeneous within a population and contribute to increased stress tolerance in a subpopulation of cells. In comparison to transcription, the influence of translation on single cells is unclear. In this study, my collaborators and I have developed a dual-fluorescence reporter that allows us to measure the mistranslation rate in single cells in vivo. Using this reporter, we found that mistranslation …

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

Dissertations and 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 …

The Role Of Tumor Suppressor Dear1 In The Acquisition Of Mammary Stem/Progenitor Cell Properties, Uyen Le

Dissertations and Theses (Open Access)

Breast cancer is the most commonly diagnosed cancer in women in America. Ductal carcinoma in situ (DCIS), one of the earliest pre-invasive forms of invasive ductal carcinoma (IDC), has a 30-50% risk of progressing to IDC. Understanding the mechanisms regulating progression from DCIS to IDC would help identify biomarkers to stratify patients at higher risk of progression or metastasis. Cumulative literature suggests the earliest phase of dissemination from the primary tumor is driven by the epithelial-mesenchymal transition (EMT) program. DEAR1 is a tumor suppressor gene which is mutated, undergoes loss of heterozygosity in breast cancer, and is downregulated in DCIS …

Involvement Of Gdap1 In The Regulation Of Mtorc1 Activity In A Drosophila Mliv Model, Kristen Clemons

Dissertations and Theses (Open Access)

The master regulator of metabolism and growth, mechanistic target of rapamycin complex 1 (mTORC1), is responsible for maintaining metabolic homeostasis by sensing nutrient and energy levels within the cell to promote or inhibit translation and autophagy accordingly. In the childhood neurodevelopmental disorder Mucolipidosis type IV (MLIV), mTORC1 activity is decreased. The underlying mechanism for reduced mTORC1 signaling in MLIV is poorly understood. The gene encoding ganglioside-induced differentiation associated protein 1 (GDAP1) is transcriptionally upregulated in MLIV. This project investigated the involvement of GDAP1 in MLIV disease pathology. Using the UAS/GAL4 system in an established MLIV Drosophila model, we …

A Compressed Sensing Approach To Detect Immobilized Nanoparticles Using Superparamagnetic Relaxometry, Sara Thrower

Dissertations and Theses (Open Access)

Superparamagnetic relaxometry (SPMR) is an emerging technology that leverages the unique properties of biologically targeted superparamagnetic iron oxide nanoparticles to detect cancer. The use of ultra-sensitive sensors enables SPMR to detect tumors ten times smaller than current imaging methods. Reconstructing the distribution of cancer-bound nanoparticles from SPMR measurements is challenging because the inverse problem is ill posed. Current methods of source reconstruction rely on prior knowledge of the number of clusters of bound nanoparticles and their approximate locations, which is not known in clinical applications. In this work, we present a novel reconstruction algorithm based on compressed sensing methods that …

Behavioral Insights Into Nociceptor Function: A Systematic Approach To Understanding Postsurgical And Neuropathic Pain Mechanisms In Rats, Max Odem

Dissertations and Theses (Open Access)

Postsurgical and neuropathic pain are each clinically common, and often associated with ongoing pain. Ongoing pain has been linked to ongoing activity (OA) in human C-fiber nociceptors. Preclinical studies using rodent neuropathic models have concentrated on allodynia driven by OA generated in non-nociceptive Aβ fibers, but little attention has been paid to postsurgical pain in sham controls or to C-fiber nociceptor OA promoting ongoing pain.

Operant assays that reveal negative motivational and cognitive aspects of voluntary pain-related behavior may be particularly sensitive to pain-related alterations. In the mechanical conflict (MC) test, rodents can freely choose to escape from a brightly …

Targeting Ph Domain Proteins For Cancer Therapy, Zhi Tan

Dissertations and Theses (Open Access)

Targeted therapy has been one of the most promising treatment options for cancer during the past decade. Discoveries of potent and selective small molecule inhibitors are critical to new and promising targeted therapy. Pleckstrin Homology (PH) domain proteins are one of the biggest protein families in the human proteome. However, no drugs have been achieved to the late development stages, let alone getting to the market. Thus, a deeper understanding of this protein family is required and there is an urgent need to develop novel small molecule compounds targeting these proteins.

Studies of PH domains began around two decades ago …

A Role For Epac1 And Epac2 In Nociceptor Hyperexcitability And Chronic Pain After Spinal Cord Injury, Samantha Berkey

Dissertations and Theses (Open Access)

Chronic pain is a major complaint of those living with spinal cord injury (SCI), affecting 65-80% of the SCI population, but the treatment options remain limited or non-existent. The cAMP sensor EPAC has previously been shown to play a key role in chronic inflammatory and neuropathic pain, though the contribution from each of its two main isoforms, EPAC1 and EPAC2, is unclear. Here I test the hypothesis that both EPAC1 and EPAC2 play a key role in the maintenance of persistent nociceptor hyperexcitability and chronic pain after SCI.

Using both a T9 SCI mouse model and a T10 SCI rat …

Adenylyl Cyclase Type 9: Regulation And Cardiac Function, Tanya A. Baldwin, Tanya A. Baldwin

Dissertations and Theses (Open Access)

Abnormalities in cardiac stress signaling underlie a number of cardiovascular diseases (e.g. arrhythmias and heart failure). Cardiac stress signaling pathways normally integrate signals from the sympathetic nervous system to promote efficient contraction and relaxation under stress. Sympathetic control through β-adrenergic stimulation is propagated by adenylyl cyclase (AC). AC synthesizes cyclic AMP (cAMP), an important second messenger that initiates signaling pathways to modulate physiological and pathophysiological functions of the heart, including the activation of PKA and subsequent phosphorylation of ion channels, contractile machinery, and stress response proteins that enhance cardiac function. Alterations of cAMP signaling occur in the failing heart and …

3d Scintillator Detector Quenching Characterization For Scanning Proton Beams, Fahed Alsanea

Dissertations and Theses (Open Access)

Proton pencil beam scanning is becoming the standard treatment delivery technique for proton therapy centers. Scanned proton pencil beams provide a highly conformal dose distribution. The complex dose distribution poses challenges for quality assurance measurements leading to sophisticated detector setups and time consuming measurements. Fast 3D measurements are therefore desirable to verify the complex dose distribution and to enable the utilization of the full potential of proton therapy. The overall objective of this project is to improve volumetric scintillators detectors to provide 3D measurements for applications for beam commissioning, quality assurance program, and patient-specific treatment delivery verification.

Detectors based on …

Integrative Bioinformatics Approaches To Elucidating Prostate Cancer Cell Heterogeneity, Plasticity, And Treatment Response, Hsueh-Ping Chao

Dissertations and Theses (Open Access)

Prostate cancer (PCa) is the most common non-cutaneous tumor in American men, and the second leading cause of cancer-related deaths. PCa-related deaths can be attributed to heterogeneous tumors containing metastatic and therapy-resistant cancer cells. Cancer stem cells (CSC) are an important contributor to this tumor heterogeneity, which are present in primary tumors and become enriched in castration resistant PCa (CRPC). Our lab has demonstrated that the prostate cancer stem cells (PCSCs) are enriched in the phenotypically undifferentiated PCa cell population that lacks the expression of differentiation marker prostate-specific antigen (PSA). Our work has also demonstrated that PCa cells manifest significant …

Investigation Of Novel Virulence Mechanisms In Candida Albicans, Elisa Marie Tafoya Vesely

Dissertations and Theses (Open Access)

Candida albicans is the most important fungal species associated with humans. Normally present in the human microbiome as a commensal colonizer, C. albicans is also the fourth most prevalent organism isolated from bloodstream infections in hospitals. Disseminated infections have an associated mortality rate of around 40%. The results of the work described in this dissertation cover the broad subject of C. albicans adaptation to the host and the mechanisms by which this organism is able to survive and cause infection through a variety of means. A key determinant in disease progression is interaction with innate immune cells, specifically macrophages and …

Il-1Α Blockade Reduces Immune Suppression In The Early Tumor Micro-Environment, Brenda Melendez

Dissertations and Theses (Open Access)

IL-1α Blockade Reduces Immune Suppression in the Early Tumor Micro-Environment

Brenda Melendez, B.S.

Advisory Professor: Gregory Lizee, PhD.

Immunotherapy against melanoma has shown great promise in the clinic for treating advanced-stage patients. However, a major barrier against effective T cell mediated cytotoxicity is immunosuppression in the tumor micro-environment. It has been described that tumors secrete pro-inflammatory cytokines capable of modulating immune responses that favors the growth of tumor cells. Specifically, IL-1 plays a critical role in myeloid cell recruitment and activation, which can in turn inhibit T cell activity in vivo. Moreover, IL-1 is also known to up-regulate immune inhibitory …

Heme Peroxidase Hpx-2 Protects Caenorhabditis Elegans From Pathogens, Yi Liu

Dissertations and Theses (Open Access)

Heme-containing peroxidases are important components of innate immunity. Many of them functionally associate with NADPH oxidase (NOX)/dual oxidase (DUOX) enzymes by using the hydrogen peroxide they generate in downstream reactions. In Caenorhabditis elegans, a ShkT-containing peroxidase, SKPO-1, and the dual oxidase, BLI-3, contribute to resistance against the human pathogen Enterococcus faecalis, likely functioning in conjunction with each other. However, the exact mechanism(s) by which peroxidases and NOX/DUOXs contribute to pathogen resistance remain unclear. Here, we demonstrated that another peroxidase, HPX-2 (Heme-PeroXidase 2), is required for resistance against some, but not all pathogens. Tissue specific …

Comparing Attributional And Relational Similarity As A Means To Identify Clinically Relevant Drug-Gene Relationships, Safa Fathiamini

Dissertations and Theses (Open Access)

In emerging domains, such as precision oncology, knowledge extracted from explicit assertions may be insufficient to identify relationships of interest. One solution to this problem involves drawing inference on the basis of similarity. Computational methods have been developed to estimate the semantic similarity and relatedness between terms and relationships that are distributed across corpora of literature such as Medline abstracts and other forms of human readable text. Most research on distributional similarity has focused on the notion of attributional similarity, which estimates the similarity between entities based on the contexts in which they occur across a large corpus. A relatively …

Ontology-Based Clinical Information Extraction Using Snomed Ct, Jun Li

Dissertations and Theses (Open Access)

Extracting and encoding clinical information captured in unstructured clinical documents with standard medical terminologies is vital to enable secondary use of clinical data from practice. SNOMED CT is the most comprehensive medical ontology with broad types of concepts and detailed relationships and it has been widely used for many clinical applications. However, few studies have investigated the use of SNOMED CT in clinical information extraction.

In this dissertation research, we developed a fine-grained information model based on the SNOMED CT and built novel information extraction systems to recognize clinical entities and identify their relations, as well as to encode them …

Development And Implementation Of A Homogeneous And A Heterogeneous Anthropomorphic End To End Quality Assurance Audit System Phantom For Magnetic Resonance Guided Radiotherapy Modalities Ranging From 0.35 T To 1.50 T, Angela Steinmann

Dissertations and Theses (Open Access)

Introduction: Magnetic resonance (MR) guided radiation therapy (MRgRT) is an emerging field that integrates an MR imager with either a linear accelerator or three radioactive cobalt-60 sources. Before institutions participate in multi-institutional NCI-sponsored clinical trials, they are required to perform a credentialing test provided by IROC-Houston. During the credentialing test, end-to-end phantoms are used to evaluate the institution’s ability to perform consistent and accurate radiation treatments. IROC-Houston’s conventional anthropomorphic phantoms are not visible in MR, thus they are insufficient for MRgRT systems. The purpose of this work was to create an anthropomorphic thorax and a head and neck (H&N) phantom …

Simvastatin Does Not Sensitize Ibc3 Her2+ Inflammatory Breast Cancer Brain Metastases To Whole Brain Irradiation In An Immunocompromised Mouse Model, Swaminathan Kumar

Dissertations and Theses (Open Access)

Retrospective data analysis suggests that inflammatory breast cancer (IBC) patients who take statins have better locoregional control after radiotherapy than those who do not [23]. Our lab has previously demonstrated that simvastatin radiosensitizes IBC cells in vitro [23], and brain metastases have strong expression of cholesterol-regulation genes compared to lung metastases in vivo [unpublished]. Delaying whole-brain irradiation (WBI) beyond 21 days is insufficient to reduce the incidence of brain metastases (developed by injecting IBC3 cells through the tail vein) in our mouse model because even high rates of cell killing leave substantial cell volume in established metastases [unpublished].

With the …

Development And Commissioning Of An Independent Peer Review System For A Small Animal Irradiator, Mary Peters

Dissertations and Theses (Open Access)

Dosimetry for small animal irradiators lacks the standardization of clinical radiotherapy practice, yet plays a central translational role in human trial design. The purpose of this work was to improve the dosimetric accuracy and consistency of animal studies by developing an independent peer review system to verify dose delivery from animal irradiators. This study focused on the development of a mouse phantom and characterization of the thermoluminescent dosimetry system for a commonly used small animal irradiator.

First, a mouse model and irradiation stand were designed with the purpose of being used in a mailable audit. Two mouse phantoms were machined …