Medicine and Health Sciences Commons^™

“He’S Not Too Young”: Empowering Parents In Child Language Development Through Upwords, A Parenting Education Program, Lynda Chima Aririguzo

Dissertations and Theses (Open Access)

Community-based early literacy intervention programs show promise in improving the home language environment, particularly for children at increased risk of language delays and poor school readiness. However, the literature on parents’ perspective of these programs is limited. This study investigated the perspectives and language scores of participants in upWORDS, a community-based literacy intervention program in Houston, TX. Through mixed-methods, this study aimed to describe the program’s impact on parents’ views on child development, changes in child behaviors, and continued application of information from the program. It also aimed to identify patterns in parent-reported measurements of children’s language skills over time. …

Uses Of Continuous-Time Markov Chain To Describe Longitudinal Patient-Reported Outcomes For Survival Prediction And Dimension Reduction, Ting-Yu Chen

Dissertations and Theses (Open Access)

A patient-reported outcome (PRO) is a type of outcome reported directly from patients, and it has been widely used in medical research and clinical trials to measure a patient’s symptoms, health-related quality of life, physical functioning, and health status. Previous studies have linked PROs to survival outcomes, but most of them only used the PRO information at baseline or at a specific clinical time point [1, 2]. Even though some of these studies collected longitudinal PROs, only few of them evaluated the association between the longitudinal PROs and a survival outcome. One of the major challenges in longitudinal PRO studies …

Hepatitis C Infection In Men Who Have Sex With Men, Jing Zhao

Dissertations and Theses (Open Access)

Hepatitis C virus (HCV) infection is the leading cause of cirrhosis, hepatocellular carcinoma, and liver transplantation. Current treatment rates and efficacy are inadequate to manage the disease burden caused by HCV; thus, efforts are needed to control HCV transmission. Besides the well-known transmission routes, which are health-care-associated transmission and transmission through injecting drugs, HCV could also be transmitted by sexual contact, especially among men having sex with men (MSM). MSM also have higher drug use prevalence than the general population, which may contribute to HCV infection by sexual disinhibition and other risky behavior. Since 2000, there have been emerging reports …

Utilization Of Mind-Body Practices For Adults With Fibromyalgia: 2017 National Health Interview Survey, Jennifer Contreras

Dissertations and Theses (Open Access)

Fibromyalgia (FM) is a medical condition characterized by chronic pain and tenderness. Individuals with FM may experience burdensome symptoms, which impact their health-related quality of life. Treatment for FM includes pharmacological and non pharmacological practices. Non-pharmacological treatments for FM include dietary management, routine exercise, and physical and mind-body therapies. There is growing evidence that the utilization of mind-body practices is increasing in the United States, but there have been limited investigations done to observe the use of mind-body practices in the FM population. The purpose of this study is to identify predictors of the use of meditation and/or meditative movement …

The Impact Of Food Security Status On The Food Shopping Behavior And Patterns Of 2018 Brighter Bites Participants At Baseline, Sarah A. Crulcich

Dissertations and Theses (Open Access)

Households with children continue to have a greater prevalence of food insecurity compared to the national average. While the national food security rates have improved in recent years, it remains stagnant among children. The purpose of this study was to conduct a cross-sectional regression analysis on food shopping patterns and behavior among Brighter Bites participants stratified by food security status to offer more insight into how these households obtain fresh produce. We used baseline survey data from Brighter Bites participants completed during fall 2018. The results indicate that food insecure Brighter Bites households shop more frequently for produce at locations …

Novel Propensity Score Methods For Multiple And Continuous Treatments: Applications To Ehr Data, Derek W. Brown

Dissertations and Theses (Open Access)

Propensity scoring is often utilized to overcome the challenges posed by covariate imbalance to make causal inferences within observational studies. While methods for utilizing propensity scoring in a binary treatment case are well studied and established, generalizations to multiple unordered (multinomial) and continuous treatments are more complicated. In Aim 1, we developed and tested a novel multinomial treatment propensity score method, the GPS-CDF method, which derives a single scalar balancing score that can match and stratify subjects. Simulation results showed superior performance of the new methodology compared to standard multinomial propensity score methods. The proposed GPS-CDF method was also applied …

Tuberculosis Among Dairy Workers In Bailey County, Texas, Anabel Rodriguez

Dissertations and Theses (Open Access)

On January 2016, Texas State Department of Health Services (DSHS) Public Health Region 1 (PHR 1) conducted T-SPOT.TB tests in response to two requests to screen dairy workers potentially exposed to cattle infected with Mycobacterium bovis or bovine tuberculosis (bTB) in Bailey County, Texas. Out of 140 workers tested, 14 had confirmed latent tuberculosis infection (LTBI)—prevalence of 10.0%. This first study gave rise to questions concerning tuberculosis (TB) knowledge and exposure history among dairy workers in this same county. The second study focused on determining TB knowledge among dairy workers through a series of questions administered by research personnel on …

Assessing The Readiness Of Relatives To Undergo Cascade Genetic Testing For Inherited Predispositions To Cancer Using The Transtheoretical Model Stages Of Change, Erica M. Bednar

Dissertations and Theses (Open Access)

National guidelines recommend cascade genetic testing (CGT) for blood relatives after a cancer predisposition gene mutation is identified in an individual. Despite recommendations for CGT, only 30-60% of first-degree relatives (FDRs) complete CGT. The proportion of untested relatives who are planning to have CGT is unknown. We used the Transtheoretical Model to assess the readiness (stage of change) for CGT among living, untested FDRs at-risk for a hereditary predisposition to cancer. An anonymous, online survey was open to U.S. adults with an autosomal dominant, adult-onset, hereditary predisposition to cancer. Participants reported demographic information, their genetic testing information, and information on …

The Effect Of Hospital Engagement Network Participation On Central Line-Associated Bloodstream Infections And Readmission Rates, Tyler Wallace

Dissertations and Theses (Open Access)

In 2012, the Centers for Medicare and Medicaid Services (CMS) launched the Hospital Engagement Network (HEN) program to decrease patient harm events in United States’ (US) hospitals. The HEN program became the nation’s largest quality improvement collaborative (QIC) focusing on improving patient care. Results from the program’s formal evaluation were inconclusive on whether the HEN program was effective. There have been no other known studies on this program’s effectiveness. Even with the evidence lacking, the CMS continues to fund programs similar to the HEN program. This study’s research aim was to compare patient outcomes for HEN participants to nonparticipants to …

Evaluation Of Food Journal Application Validity In Comparison With Dhq Iii, Michael Roa

Dissertations and Theses (Open Access)

As chronic conditions associated with the high prevalence of obesity/overweight in the United States continue to rise, research focusing on nutrition has grown in recent years. The gold standard for collecting detailed nutritional information on individuals is food journals, mostly via pen and paper. Alternatively, smartphone food journal applications have become more popular and widely accessible in recent years. These applications allow the user to quickly make meal entries, often taking advantage of the application’s food and servings database.

This study compared the results of the third iteration of the Diet History Questionnaire (DHQ III) with a dietary journal data …

Commissioning Of Micro-Cube Thermoluminescent Dosimeters For Small Field Dosimetry Quality Assurance In Radiotherapy, Brandon Luckett

Dissertations and Theses (Open Access)

Small field dosimetry presents complications and uncertainties that could be circumvented by using detectors which are smaller than the radiation field. This study evaluates the reproducibility and accuracy of TLD micro-cubes for use in stereotactic radiosurgery (SRS) remote auditing quality assurance (QA) for treatment centers participating in clinical trials. This study tested the hypothesis that TLD micro-cubes could be commissioned to evaluate small field dosimetry, and provide reproducibility within 3%, as well as assure agreement between measured dose and calculated doses to within 5%.

The aims of this thesis were to characterize and commission TLD micro-cubes as well as to …

Inhibition Of Urothelial Carcinoma By Type I Interferon Activation Of The Innate And Adaptive Immune Response, Devin Plote

Dissertations and Theses (Open Access)

Bacillus Calmette-Guerin (BCG) is the first line therapy for bladder cancer patients with non-invasive disease. However, roughly 40% of patients exhibit no response, tumor recurrence or tumor progression following BCG treatment. Type I interferon (IFN-I) has potent anti-tumor effects against urothelial carcinoma (UC) and may be an alternative treatment option for patients who do not respond to BCG standard of care. However, the mechanisms that mediate the IFN-I-stimulated immune responses against UC are not fully elucidated. Herein, we evaluated the anti-tumor mechanisms of IFN-I in UC by use of adenoviral interferon-α (Ad-IFNα/Syn3) in human patients, and poly(I:C) or lentiviral IFNa …

The Gsk-3Β-Fbxl21 Axis Regulates Tcap Via Ubiquitin-Mediated Proteasomal Pathway In The Cytoplasm, Jiah Yang

Dissertations and Theses (Open Access)

Protein turnover is one of the most essential mechanisms controlling circadian rhythms. F-Box and Leucine Rich Repeat Protein21 (FBXL21) is a circadian E3 ligase which shows oscillatory mRNA transcripts and protein levels. It was previously found to perform subcellular compartment-specific E3 ligase activities targeting the core clock proteins CRYPTOCHROME(CRY)1/2. Here we identified a new sarcomeric target substrate, Telethonin(TCAP), which also shows circadian oscillation in its mRNA transcript and protein expression and, importantly, interaction with FBXL21 in an anti-phasic manner. Via computational and pharmacological tests, we identified Glycogen Synthase Kinase-3β(GSK-3β) as a regulator of FBXL21. Biochemical and molecular characterizations demonstrated that …

Evaluating The Therapeutic Efficacy Of Grb2 Inhibition In Ovarian Malignancies, Olivia Lara

Dissertations and Theses (Open Access)

Purpose: Adaptor proteins such as growth factor receptor-bound protein-2 (Grb2) play important roles in cancer cell signaling. In the present study, we examined the biological effects of liposomal antisense oligodeoxynucleotide that blocks Grb2 expression (L-Grb2) in ovarian cancer models.

Experimental Design: Murine orthotopic models of ovarian cancer (OVCAR5 and SKOV3ip1) were used to study the biological effects of L-Grb2 on tumor growth. In vitro experiments (cell viability assay, Western blot analysis, siRNA transfection, and reverse phase protein array) were carried out to elucidate the mechanism and potential predictors of tumor response to L-Grb2.

Results: Treatment with L-Grb2 decreased tumor growth …

Identifying And Targeting Adaptive Changes To Bet Inhibition In Ovarian Cancer, Christopher Lafargue

Dissertations and Theses (Open Access)

Purpose: To identify combination strategies using Bromodomain and Extra-Terminal Domain (BET) inhibitors in a mechanism driven fashion to maximize anti-tumor activity, and to determine the efficacy of BET inhibitor combinations in pre-clinical ovarian cancer mouse models.

Experimental Design: We used a novel, previously uncharacterized pan-BET inhibitor, CN210, for all in vitro (MTT, apoptosis, protein expression, reverse phase protein array (RPPA) analysis and in vivo (orthotopic mouse model)) experiments. The poly (ADP-ribose) polymerase (PARP) inhibitor olaparib, as well as the mechanistic target of rapamycin (mTOR) inhibitors rapamycin and INK-128 were also used. Statistical analyses of in vitro and in vivo experiments …

An Information Theory Model For Optimizing Quantitative Magnetic Resonance Imaging Acquisitions, Drew Mitchell

Dissertations and Theses (Open Access)

Quantitative magnetic resonance imaging (qMRI) is a powerful group of imaging techniques with a growing number of clinical applications, including synthetic image generation in post-processing, automatic segmentation, and diagnosis of disease from quantitative parameter values. Currently, acquisition parameter selection is performed empirically for quantitative MRI. Tuning parameters for different scan times, tissues, and resolutions requires some measure of trial and error. There is an opportunity to quantitatively optimize these acquisition parameters in order to maximize image quality and the reliability of the previously mentioned methods which follow image acquisition.

The objective of this work is to introduce and evaluate a …

Modeling Proton Relative Biological Effectiveness Using Monte Carlo Simulations Of Microdosimetry, Mark A. Newpower

Dissertations and Theses (Open Access)

Proton therapy is a radiotherapy modality that can offer a better physical dose distribution when compared to photon radiotherapy by taking advantage of the Bragg peak, a narrow region of rapid energy loss. Proton therapy is also known to offer an enhanced relative biological effectiveness (RBE) compared to photons. In the current clinical standard, RBE is fixed at 1.1 at all points along the proton beam, meaning protons are assumed to require 10% less dose than photons to achieve target coverage and organ at risk (OAR) sparing. However, there is mounting clinical evidence, and a significant number of in vitro …

Role Of C-Met And Egfr In Acquired Resistance To Parp Inhibitors In Triple-Negative Breast Cancer, Clinton Yam

Dissertations and Theses (Open Access)

Triple-negative breast cancer is associated with a poor prognosis and treatment options are limited. The Poly (ADP-ribose) polymerase (PARP) inhibitors, olaparib and talazoparib, were recently approved for metastatic breast cancer (including triple-negative breast cancer) in patients with a germline BRCA1/2 mutation. Despite impressive response rates of ~60%, the prolongation in median progression-free survival with PARP inhibitors is modest, suggesting the emergence of resistance. We previously demonstrated that c-MET contributes to intrinsic resistance to PARP inhibitors in triple-negative breast cancer. However, whether c-MET plays a role in acquired resistance to PARP inhibitors in triple-negative breast cancer remains unclear. Here, we show …

Oxidative Phosphorylation: A Critical Feature And Novel Therapeutic Target In Melanoma Brain Metastases, Grant Fischer

Dissertations and Theses (Open Access)

We recently showed via RNA-sequencing (RNA-seq) analysis of clinical samples that melanoma brain metastases (MBMs) have higher expression of oxidative phosphorylation (OXPHOS) genes (including PPARGC1A or PGC1α) than patient-matched extracranial metastases (ECMs). Thus, the central hypothesis of this dissertation is that OXPHOS plays a critical role in the pathogenesis of MBMs.

RNA-seq analysis identified increased expression of OXPHOS genes in intracranial (ICr) vs. subcutaneous (SQ) xenografts of 4 different human melanoma cell lines. Increased OXPHOS in the ICr xenografts was confirmed by direct metabolite analysis and [U-¹³C]-glucose tracing analysis. Together, these studies indicate that the brain TME …

The Influence Of The Pep-Pts And Other Metabolic Systems On The Master Virulence Regulator Atxa And To Xin Gene Expression In Bacillus Anthracis, Naomi Bier-Reizes

Dissertations and Theses (Open Access)

AtxA, the master virulence gene regulator in Bacillus anthracis, is a PRD-containing virulence regulator (PCVR) as indicated by the crystal structure, post-translational modifications, and activity of the protein. PCVRs are transcriptional regulators, named for the regulatory domains subject to phosphorylation by the phosphoenolpyruvate phosphotransferase system (PEP-PTS), termed PTS Regulatory Domains (PRD), and for their impact on virulence gene expression. Generally, the phosphorylation of a PCVR regulates protein activity and multimerization. AtxA is phosphorylated at two histidine residues - one in each of its two PRDs. Phosphorylation at position 199 allows for AtxA to positively affect expression of virulence genes, whereas …

Dhhc5 Regulates Beta-Adrenergic Signaling In The Heart Through Palmitoylation Of G Alpha Proteins, Jie Chen

Dissertations and Theses (Open Access)

S-palmitoylation is a reversible posttranslational modification that plays an important role in regulating protein localization, trafficking, and stability. Recent studies have shown that some proteins undergo extremely rapid palmitoylation/depalmitoylation cycles after cellular stimulation supporting a direct signaling role for this posttranslational modification. The work in this dissertation investigated whether β-adrenergic stimulation led to stimulus-dependent palmitoylation of downstream signaling proteins in immortalized and primary cell models. I found that β-adrenergic stimulation led to rapidly increased Gαs and Gαi palmitoylation only in primary cardiomyocytes. The kinetics of palmitoylation was temporally consistent with the downstream production of cAMP and contractile responses. I identified …

Tracking Treatment Response And Resistance To Parp Inhibition (Talazoparib) In Hereditary Pancreatic Cancer., Jennifer Goldstein

Dissertations and Theses (Open Access)

polyADP ribose polymerase (PARP) inhibitors are a class of drugs that block the PARP enzymes, involved in the repair of singe-stranded DNA breaks through the base excision repair pathway. PARP inhibition leads to replication-associated double stranded DNA breaks, which are repaired by homologous recombination (HR). In tumors with HR defects (i.e. BRCA mutants), there is a shift to error-prone DNA repair and subsequent genomic instability and cell death.

In 2014, Olaparib became the first FDA-approved PARP inhibitor for the treatment of BRCA-mutant ovarian cancer. In the phase III POLO (Pancreas cancer OLaparib Ongoing) trial presented at the American Society …

Bilirubin Nanoparticle As An Anti-Inflammatory Therapy For Graft Versus Host Disease, Sumedha Pareek

Dissertations and Theses (Open Access)

Graft versus host disease (GvHD) caused by alloreactive donor lymphocytes is a fatal complication of hematopoietic stem cell transplant (HSCT). Myeloablative conditioning regimen, consisting of chemotherapy and/or radiation, given prior to HSCT can cause tissue damage. This non-specific tissue damage triggers cross-presentation of alloantigens to the donor immune cells, causing recruitment of leukocytes and production of inflammatory cytokines. Targeting this inflammation without affecting the anti-leukemia effects of HSCT, continues to be one of the biggest challenge in finding a therapy for GvHD. Bilirubin is a tetrapyrrole pigment, found in the blood, with natural anti-oxidative and anti-inflammatory properties. Using mouse models …

Role Of Nudt21 Mediated Alternative Polyadenylation And Hyaluronan In The Development Of Pulmonary Hypertension, Scott Dale Collum

Dissertations and Theses (Open Access)

Pulmonary hypertension (PH) is a progressive disease with serious effects on quality of life and life expectancy of patients. PH is a complex disease that likely develops due to multiple influences, and no curative treatments exist for this disease. It has been shown that alternative polyadenylation (APA) due to depletion of Nudix Hydrolase 21(NUDT21) is involved in several disease states including the chronic lung disease idiopathic pulmonary fibrosis (IPF). Additionally, hyaluronan, an extracellular matrix glycosaminoglycan has been associated with PH. The role and mechanism of NUDT21 and hyaluronan have not yet been described in this disease. My results reveal that …

Investigations Of The Structure-Function Relationship In Kainate Receptors Using FöRster Resonance Energy Transfer, Douglas Litwin

Dissertations and Theses (Open Access)

Kainate receptors belong to the family of ion channels known as the ionotropic glutamate receptors. Ionotropic glutamate receptors mediate the majority of excitatory synaptic transmission, modulate the release of presynaptic glutamate, and facilitate dendrite formation. Kainate receptors are unique among the ionotropic glutamate receptors in being modulated by sodium ions. They have also been implicated in the development of higher learning and epilepsy. In recent years a wealth of structural data has become available for the AMPA and NMDA classes; however, the structural characterization of kainate receptors has been limited. The work in this dissertation utilizes luminescence resonance energy transfer …

Modeling Cancer Using Li-Fraumeni Syndrome Patient-Derived Induced Pluripotent Stem Cells, Ruoji Zhou

Dissertations and Theses (Open Access)

Li-Fraumeni syndrome (LFS) is an autosomal dominant disease caused by germline mutations in the gene TP53, which predispose individuals to a wide range of malignancies, including osteosarcoma and breast cancer. In the previous study, our group developed a novel disease model platform by reprograming LFS patients' fibroblasts to induced pluripotent stem cells (iPSCs), and further differentiate these iPSCs into mesenchymal stem cells (MSCs) then to osteoblasts (OBs), the cells from which osteosarcomas originate. Interestingly, LFS iPSC-derived osteoblasts recapitulated the osteosarcoma phenotype, creating “a bone tumor in a dish”. This “tumor in a dish” platform proved that LFS is an …

Quantifying Uncertainty In A Measurement-Based Assessment Of Relative Biological Effectiveness In Carbon Ion Radiotherapy, Shannon Hartzell

Dissertations and Theses (Open Access)

One of the largest inconsistencies in dose delivered during carbon ion therapy is due to uncertainties in relative biological effectiveness (RBE), a value that is calculated via one of several clinically implemented algorithms. This study investigates the uncertainty in measured microdosimetric parameters for RBE calculation by the Microdosimetric Kinetic Model (MKM), Repair Misrepair Fixation model (RMF), and Local Effect Model I (LEM) using a Tissue Equivalent Proportional Counter (TEPC).

Microdosimetric spectra, kinetic energy spectra, and dose fragment contributions were calculated using Monte Carlo (GEANT IV) for monoenergetic and SOBP carbon beams of clinical energy. From microdosimetric spectra, lineal energy values …

Dissecting The Roles Of Human Smc Complexes In Transcription Regulation And Chromatin Organization, Ruoyu Wang

Dissertations and Theses (Open Access)

Metazoans utilize a constellation of distal regulatory elements to control gene transcription, and therefore they have to forge highly complex chromatin loops to spatially bridge these regulatory elements and genes in the three-dimensional (3D) genome. However, the hierarchy of chromatin contacts and their underlying mechanisms are not well-understood. SMC complexes including Cohesin complex and Condensin complex has been widely proposed to organize 3D genome structure, and further regulate metazoans’ gene transcription. Here, we aim to dissect the direct functions of SMC complexes (both Cohesin and Condensin) in transcriptional regulation and 3D genome organization, by utilizing an inducible protein degradation system. …

P53r245w Mutation Elicits Metastatic Phenotype In Pten Deficient Prostate Cancer, Ky Pham

Dissertations and Theses (Open Access)

Trp53 mutations are the most frequent genetic alterations in prostate cancer and are associated with more aggressive disease and worse overall survival. The majority of Trp53 mutations in prostate cancer are missense mutations, resulting in amino acid substitutions with profound effect. In addition to the loss of wild type function, missense mutations in Trp53 result in a gain-of-function (GOF) phenotype. This GOF phenotype confers biologic advantages to the tumor cells, enabling them to metastasize and invade distant organs. In this study, we generated mice carrying a conditional prostate-specific p53R245W mutant and Pten deletion to access the role of this common …

Fasting Reduces Intestinal Radiotoxicity Enabling Dose-Escalated Radiotherapy For Pancreatic Cancer, Marimar De La Cruz Bonilla

Dissertations and Theses (Open Access)

Surgical resection is the only potentially curative treatment for pancreatic cancer, but only 15-20% of patients have resectable tumors. In unresectable cases, stereotactic body radiotherapy (SBRT) may be used to give tumor-directed radiotherapy (RT). Unfortunately, this can cause severe gastrointestinal (GI) toxicity due to proximity of the pancreatic head to the duodenum. Protecting the intestine from the toxic side-effects of radiation may enable dose-escalation that could achieve more effective local control of disease. We and others have previously shown that a fast of 24 hours protects mice from lethal doses of the DNA-damaging agent etoposide. In this study, we demonstrate …