Digital Commons Network^™

Psychometric Performance Of The Arabic Versions Of The Cancer Behavior Inventory‐Brief And The Functional Assessment Of Cancer Therapy‐Breast In Saudi Arabia, Maaidah M. Algamdi Msn

Dissertations and Theses (Open Access)

Background: Arabic is the mother tongue of 26 countries, including Saudi Arabia where cancer is the fourth leading cause of death. Cancer is a sensitive issue in the Arabic population and a clear understanding of patients’ perceptions of self-efficacy for coping with cancer and quality of life helps assess interventions designed to facilitate optimal patient outcomes. In preliminary studies, the Cancer Behavior Inventory-Brief (CBI-B) was translated and back translated between English and Arabic, and reviewed for translational validity by an expert panel. The Arabic version of the CBI-B (CBI-BA) had acceptable evidence of translational validity with an overall translational validity …

Regulation Of The Escrt Function Of Alix, Sheng Sun

Dissertations and Theses (Open Access)

The ESCRT (endosomal sorting complex required for transport) is an evolutionary conserved membrane remodeling machinery that performs membrane invagination and abscission. ALIX is a widely expressed adaptor protein that is critically involved in three classical ESCRT-mediated processes, including MVB (multivesicular body) sorting, cytokinetic abscission and retroviral budding. Previous studies have demonstrated that ALIX involvement in these ESCRT-mediated processes requires ALIX interaction with the ESCRT-III component CHMP4 as well as a cargo protein. However, the native form of ALIX contains a default intramolecular interaction between N-terminal Bro1 domain and C-terminal PRD (proline-rich domain), leading to a closed conformation of ALIX that …

Lipocalin 2 Promotes The Establishment Of A Pro-Tumorigenic Microenvironment In Pancreatic Cancer, Sobeyda B. Gomez-Chou

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a disease characterized by a dismal prognosis with a 5-year survival rate of 7%. A unique hallmark of this disease is an abundant desmoplastic reaction that can account for up to 90% of the solid tumor volume. Key components of the PDAC stroma include the extracellular matrix (ECM) rich in collagen type I and III, activated pancreatic stellate cells (PSCs) and inflammatory cells such as neutrophils and macrophages. The main line of evidence has suggested a pro-tumorigenic role for the PDAC stroma as it has been shown to help enhance tumor growth, invasive potential and …

Ethnic Identity And Teratogenic Risk Perceptions, Katie M. Chan

Dissertations and Theses (Open Access)

Elevated perceptions of teratogenic risk can cause anxiety and confusion among pregnant women. To assess whether ethnic identity and demographic factors can influence teratogenic risk perceptions, 194 pregnant women in Houston were surveyed using the Multigroup Ethnic Identity Measure (MEIM) and visual analog scales to quantify perceptions of teratogenic risk for common exposures during pregnancy. Overall, participants estimated an elevated baseline risk of 25% for birth defects among the general population. In addition, participants overestimated birth defect risks for specific exposures, such as alcohol and marijuana. Based on the MEIM scores, ethnic identity was not significantly associated with teratogenic risk …

Insights Into Determinants That Contribute To Colonization, Virulence And Antibiotic Resistance In Enterococci, Maria Camila Montealegre

Dissertations and Theses (Open Access)

Enterococcus faecalis and Enterococcus faecium are increasingly common as causative agents of human infections, many of which are very difficult to treat due to multi-drug resistance. The work presented in the first part of this dissertation elucidates a mechanism for the regulation of pilus expression. I showed that ATT is the initiation codon of ebpA, the first gene of an operon that codes for the endocarditis and biofilm-associated pili (Ebp), a recognized virulence factor in E. faecalis. The presence of this rare start codon downregulates EbpA translation and protein levels, diminishing biofilm and binding abilities of …

Developing And Using Methyl-Specific Antibodies To Study The Biological Roles Of Arginine Methylation, Vidyasiri Vemulapalli

Dissertations and Theses (Open Access)

Arginine residues can be modified in three different ways to produce asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and monomethylarginine (MMA). These modifications are catalyzed by a family of nine protein arginine methyltransferases (PRMT1-9), which are of three types (I, II, and III). The majority of Type I enzymes asymmetrically dimethylate Glycine- and Arginine-rich (GAR) motifs, except for PRMT4, which methylates Proline-, Glycine-, and Methionine-rich (PGM) motifs. The same substrates (GAR or PGM motifs) can also be dimethylated by PRMT5 in a symmetric fashion. However, it is not clear whether there are dedicated residues within these motifs for ADMA and SDMA, …

Network Dynamics Of Visual Object Recognition, Mehmet C. Kadipasaoglu

Dissertations and Theses (Open Access)

Visual object recognition is the principal mechanism by which humans and many animals interpret their surroundings. Despite the complexity of neural computation required, object recognition is achieved with such rapidity and accuracy that it appears to us almost effortless. Extensive human and non-human primate research has identified putative category-selective regions within higher-level visual cortex, which are thought to mediate object recognition. Despite decades of study, however, the functional organization and network dynamics within these regions remain poorly understood, due to a lack of appropriate animal models as well as the spatiotemporal limitations of current non-invasive human neuroimaging techniques (e.g. fMRI, …

Poly (Adp) Ribose Polymerase Inhibitors For The Treatment Of Malignant Peripheral Nerve Sheath Tumor, Christine M. Kivlin

Dissertations and Theses (Open Access)

Malignant peripheral nerve sheath tumor (MPNST) is a rare subtype of soft tissue sarcoma. Surgical excision has remained the standard of care for this highly aggressive malignancy for over a decade. Conventional chemotherapy and radiotherapy have shown limited efficacy in MPNST; therefore, it is imperative that targeted treatment be identified to improve the outcome for MPNST patients. Poly (ADP) ribose polymerase (PARP) inhibitors were first reported over a decade ago to have substantial anti-tumorigenic effects in malignancies with defective DNA repair, specifically those with BRCA1/2 (breast cancer, early onset 1/2) mutations. Further evaluation of these inhibitors has shown multiple mechanisms …

Mechanisms Of Regulation Of Tau Ires Mediated Translation, Niza Nemkul

Dissertations and Theses (Open Access)

The translation of most eukaryotic mRNAs occurs in a cap-dependent manner. However, a subset of mRNAs are capable of initiating translation in a cap-independent manner by utilizing sequences in their 5’ UTR called IRES. It was previously shown that the 5’ UTR of the tau mRNA contains an IRES. In this study I show that IRES dependent translation of tau IRES is regulated at multiple levels in order to regulate the expression of the tau protein.

Tau protein is ubiquitously expressed but is concentrated in the brain. In this study, I utilized neural and non-neural cell lines to show that …

Characterization Of Stem Cell Turnover In A Living Epithelial Bilayer, Elizabeth Sumner

Dissertations and Theses (Open Access)

Homeostatic maintenance of epithelia requires the renewal and replacement of old or dying cells while sustaining a functional barrier. Imbalance between cell production and elimination are hypothesized to underlie many pathological conditions. However, our knowledge of cell turnover within living tissues remains largely restricted to static images due to the limited ability to study epithelia in their native context. Here we report that clearance of damaged basal stem cells promotes compensatory proliferation of neighboring stem cells to maintain overall population numbers in a bilayered epithelium. Time-lapse imaging and electron microscopy experiments reveal that dying cells are rapidly cleared as nearby …

No Difference In Health Related Quality Of Life Between Therapeutic Options For Type 1 Gaucher Disease, Victoria Wagner

Dissertations and Theses (Open Access)

Type 1 Gaucher disease (GD) is the most common lysosomal storage disorder. Previously, treatment for GD was limited to intravenous enzyme replacement therapy (ERT). ERT reduces symptoms and increases health­related quality of life (HRQoL) in people with this condition. In 2014, oral substrate reduction therapy (SRT) was approved for type 1 GD treatment. Although both therapies alleviate disease symptoms, effects of SRT on HRQoL and preferences for therapy are not well established. Electronic surveys were administered to adults with type 1 GD. HRQoL was scored with the Short Form­36 Version 2 ® Health Survey and descriptive statistics were used to …

The Thioredoxin Trx-1 Regulates The Major Oxidative Stress Response Transcription Factor, Skn-1, In Caenorhabditis Elegans, Katie C. Mccallum

Dissertations and Theses (Open Access)

The ability to respond to hostile environmental conditions is critical for the survival of an organism. Oxidative stress is an adverse state in which reactive oxygen species (ROS) accumulate to a harmful level and, if left unresolved, can lead to cellular dysfunction and organismal disease. Sophisticated detoxification systems, characterized by a battery of enzymatic antioxidants, are utilized to neutralize ROS thereby reducing stress. However, ROS are also purposefully produced by designated cellular enzymes to facilitate the signaling and regulation of critical physiological processes. Therefore, both the production and neutralization of ROS must be tightly controlled. Indeed, the expression of detoxification …

Factors Influencing Uptake Of Risk-Reducing Salpingo-Oophorectomy By Brca1 And Brca2 Mutation Carriers, Victoria E. Breen

Dissertations and Theses (Open Access)

Germline mutations in the BRCA1 and BRCA2 genes are associated with significantly increased risks for ovarian cancer. The National Comprehensive Cancer Network (NCCN) currently recommends that female BRCA mutation carriers undergo risk-reducing salpingo-oophorectomy (RRSO) after age 35; however, not all women elect this option. The purpose of this study was to prospectively survey women with BRCA mutations currently undergoing ovarian cancer screening about their intention to have an RRSO and the various factors influencing their decision. Of the 26 women who completed our survey, 26 (100%, CI: 86.8-100) plan to undergo an RRSO in their lifetime. The average woman reported …

The Role Of 5-Alpha Reductase 3 In Steroid Metabolism, Zahi Mitri

Dissertations and Theses (Open Access)

Background

The growth and development of prostate cancer is largely driven by androgen mediated signaling. The 5-alpha reductase family of enzymes plays an essential role in the conversion of testosterone to the more potent androgen, 5-alpha dihydrotestosterone (DHT), which is capable of binding the androgen receptor to activate gene targets and downstream signaling. This study aimed to evaluate the role of 5-alpha reductase 3 (SRD5A3), a novel member of the 5-alpha reductase family, in steroid metabolism and prostate carcinogenesis.

Materials and Methods

HEK293 cells were transfected with the SRD5A3 human cDNA ORF Clone from OriGene. Steroid substrates (testosterone, progesterone, androstenedione, …

The Psychosocial Effects Of The Li-Fraumeni Education And Early Detection (Lead) Program On Indivdiuals With Li-Fraumeni Syndrome, Jessica L. Ross

Dissertations and Theses (Open Access)

Li-Fraumeni syndrome (LFS) is a hereditary cancer syndrome that leads to an increased risk of multiple cancers. In the past five years new screening protocols have been developed that provide improved screening options for individuals with LFS. However, very little has been published on the psychosocial impact of these screening protocols. The goals of this study were to determine how participation in screening impacts individuals psychosocially, to examine the benefits and drawbacks of screening, and to evaluate possible barriers to continued screening. This qualitative study consisted of phone interviews with 20 individuals that took part in an LFS screening program …

Trim24 Orchestrates Metabolic Reprogramming And Emt In Breast Cancer, Kaushik Thakkar

Dissertations and Theses (Open Access)

In this dissertation, I report the oncogenic functions of an epigenetic regulator Tripartite Motif Protein 24 (TRIM24) coupled with metabolic reprogramming and epithelial mesenchymal transition (EMT) in breast cancer. TRIM24 was first established by our laboratory as a previously unknown negative regulator of p53 via its RING domain, as a co-regulator of nuclear receptors and a PHD/Bromodomain reader of specific histone modifications. TRIM24 expression correlates with poor prognosis of breast cancer, but the mechanisms of TRIM24-mediated oncogenesis are unknown. In the first part of my thesis, I found that TRIM24 is aberrantly expressed in early stages of breast cancer progression. …

Investigating Metastatic Lineage In Colorectal Cancer By Single Cell Dna Sequencing, Marco Leung

Dissertations and Theses (Open Access)

Metastasis is the primary cause of human cancer deaths. Patients with metastatic colorectal cancer (mCRC) show only an 11% 5-year survival rate, compared to those without local or distant metastases (92% 5-year survival rate). Understanding the CRC tumor evolution may provide valuable insights on how to improve treatment in patients with mCRC. However, the genomic basis of metastasis has been difficult to study, in part due to the extensive intratumor heterogeneity at both the primary and metastatic tumor sites, and the low frequency of subclones with metastatic potential. Previous studies have applied conventional bulk next-generation sequencing (NGS) methods, which have …

Patient Perception Of Negative Non-Invasive Prenatal Testing Results, Ann Theresa Wittman

Dissertations and Theses (Open Access)

Non-invasive prenatal testing (NIPT) uses cell-free fetal DNA to assess for fetal aneuploidy during pregnancy. NIPT has higher detection rates and positive predictive values than previous methods; however, NIPT is not diagnostic. Studies suggest patients may underestimate the limitations of prenatal screening. Therefore, we conducted a prospective cross-sectional study of ninety-four women from genetic counseling clinics in Houston, Texas to assess patient understanding of the residual risk for aneuploidy after receiving a negative NIPT. The majority of participants (66%) understood the residual risk for Down syndrome following negative NIPT; however, 34% of participants indicated that negative NIPT completely eliminated the …

Rerouting Pre-Existing Host Vaccine-Induced Immunity To Wards Breast Cancer, Bharat Kumar Reddy Chaganty

Dissertations and Theses (Open Access)

For decades, investigators have attempted to activate the immune system to prevent cancer metastasis or recurrence; however, owing to host immune tolerance to cancer antigens and the immunosuppressive environment at tumor sites, many such attempts have failed. The recent success of anti-CTLA4, PD-L1 and PD-1 antibodies targeting immune checkpoint pathways and HPV vaccines has renewed hope that patient survival can be increased through enhancing T-cell responses. We propose to test a novel approach that may bypass host immune tolerance to cancer cells. We hypothesize that host T-cell immunity acquired through vaccination against or natural infection with infectious diseases—e.g., influenza—can be …

Accurate Mutation Annotation And Functional Prediction Enhance The Applicability Of -Omics Data In Precision Medicine, Tenghui Chen

Dissertations and Theses (Open Access)

Clinical sequencing has been recognized as an effective approach for enhancing the accuracy and efficiency of cancer patient management and therefore achieve the goals of personalized therapy. However, the accuracy of large scale sequencing data in clinics has been constrained by many different aspects, such as clinical detection, annotation and interpretation of the variants that are observed in clinical sequencing data. In my Ph.D thesis work, I mainly investigated how to comprehensively and efficiently apply high dimensional -omics data to enhance the capability of precision cancer medicine. Following this motivation, my dissertation has been focused on two important topics in …

Nipt Results Indicative Of Maternal Neoplasms: Genetic Counselors' Preferences And Attitudes, Meagan E. Giles

Dissertations and Theses (Open Access)

Performing non-invasive prenatal testing (NIPT) on a pregnant woman with a chromosomally abnormal neoplasm may incidentally lead to the diagnosis of cancer due to the coexistence of circulating tumor and placental DNA. Published information regarding NIPT’s accuracy for neoplasm screening is limited, and guidance for patient management is currently lacking. This challenges clinicians’ ability to counsel patients regarding the implications of these results, which often is the responsibility of a genetic counselor. Over three hundred board-eligible/certified genetic counselors were surveyed regarding their awareness, preferences, and attitudes towards NIPT’s ability to indicate maternal neoplasms. Despite 95% of this cohort being aware …

Organization And Regulation Of Proteins Required For Initiation Of Cell Division In Escherichia Coli, Veronica W. Rowlett

Dissertations and Theses (Open Access)

The process of bacterial cell division relies on the assembly of multiple proteins to form the cell division machine, or “divisome.” FtsZ, a bacterial homolog of eukaryotic tubulin, forms a ring-like structure, the “Z ring,” at midcell and serves as a scaffold for divisome assembly and potential force generator during synthesis of the division septum. Both FtsA, a bacterial homolog of eukaryotic actin, and ZipA, a single-pass transmembrane protein, anchor the Z ring to the inner membrane, are required for the localization of other divisome proteins to midcell, and likely influence the assembly state of FtsZ. Positioning of the Z …

Characterization Of The Ato Gene Family In Alternative Carbon Metabolism, Heather A. Danhof

Dissertations and Theses (Open Access)

As a commensal colonizer and opportunistic pathogen, Candida albicans is the most clinically important human associated fungus. Systemic infection carries an unacceptably high mortality rate of ~40% in the growing population of immunocompromised individuals. Macrophages are important innate immune cells that limit the niches in the human body in which C. albicans can persist through phagocytic removal. However, following phagocytosis C. albicans readily escapes from the immune cell by differentiating into filamentous hyphae, a process that should be inhibited in the normally acidic phagolysosome. We have shown that C. albicans induces germination by neutralizing the phagolysosome. To better understand this …

In Vivo Kinome Screen Reveals Non-Canonical Cdk-Driven Metabolic Adaptation In Brain Metastasis, Frank J. Lowery Iii

Dissertations and Theses (Open Access)

Brain metastasis, which frequently arises from breast cancer, lung cancer, melanoma, and colorectal cancer, remains a severely unmet medical need and its incidence continues to rise while treatment options remain palliative. To better understand the biology underlying its aggressive, incurable nature, I performed an unbiased in vivo kinome screen to identify potential driver kinases of experimental brain metastasis in a nude xenograft model using the human breast cancer cell line MDA-MB-231. Several of the kinase pools led to decreased brain metastasis-specific survival in nude mice, shortening survival time by up to 50% relative to controls. Targeted next-generation sequencing (NGS) was …

Clinical And Demographic Variables Associated With Cognitive Deficits, Symptom Severity, And Duration After Concussive Injury In Adolescents: A Retrospective Study, Seema S. Aggarwal

Dissertations and Theses (Open Access)

Background: Concussions in adolescents are a public health concern with the growing popularity of high school sports. Recent legislation mandates that athletes who are suspected of a concussion be cleared to return-to-play by a clinician. More research is needed to develop a concussion predictive model to identify populations at risk for more severe and prolonged symptoms and long-term neurologic deficits.

Aims: The aims of this study were to (1) examine the effect of race and gender on neurocognitive and symptom scores and (2) determine which clinical (e.g., number of concussions, migraine history, learning disabilities/ attention deficit disorders) and demographic factors …

Cardiac Papillary Fibroelastoma: Single-Institution Experience With 14 Surgical Patients, Walid K Abu Saleh, Odeaa Al Jabbari, Basel Ramlawi, Michael J Reardon

The Texas Heart Institute Journal

In general, treatment for symptomatic and asymptomatic cardiac papillary fibroelastoma is surgical resection-particularly of left-sided lesions, because of the risk of systemic embolization. However, few institutions have enough experience with these tumors to validate this approach. We present our institutional experience with papillary fibroelastoma and discuss our current approach. We searched our institution's cardiac tumor database, identified all patients diagnosed with cardiac papillary fibroelastoma from 1992 through 2014, and recorded the clinical and pathologic characteristics of each case. We found 14 patients (mean age, 60.5 ± 12.3 yr) who had 18 lesions. Eleven patients (79%) were symptomatic; however, we could …

Biventricular Myocardial Performance Is Impaired In Proportion To Severity Of Obstructive Sleep Apnea, Selahattin Akyol, Mustafa Cortuk, Ahmet Oytun Baykan, Kemal Kiraz, Abdurrezzak Borekci, Taner Seker, Mustafa Gur, Murat Cayli

The Texas Heart Institute Journal

Obstructive sleep apnea (OSA) is an independent risk factor for cardiovascular morbidity and death. Little information is available regarding the relationship between the severity of OSA and myocardial performance in OSA patients who have normal ejection fractions. We prospectively investigated this relationship, using the tissue-Doppler myocardial performance index (TD-MPI).

We conducted overnight, full-laboratory polysomnographic examinations of 116 patients, and calculated the left and right ventricular TD-MPIs. Patients were classified into 3 groups in accordance with their apnea-hypopnea index (AHI) levels: AHImild (≥5 to <15), AHImoderate (≥15 to <30), and AHIsevere (≥30).

Left and right ventricular TD-MPI values were higher in the AHIsevere group than in the AHImild and …

Comparison Of Interactive Voice Response (Ivr) With Paper Administration Of Instruments To Assess Functional Status, Sexual Function, And Quality Of Life In Elderly Men, D Cifelli, D Cella, Jt Farrar, E Barrett-Connor, Ce Lewis, M Pahor, X Hou, Pj Snyder

Faculty, Staff and Students Publications

PURPOSE: Patient-reported outcome (PRO) measures are essential for assessing subjective patient experiences. Interactive voice response (IVR) data collection provides advantages for clinical trial design by standardizing and centralizing the assessment. Prior to adoption of IVR as a mode of PRO administration in the Testosterone Trials (TTrials), we compared IVR to paper versions of the instruments to be used. METHODS: IVR versions of the FACIT-Fatigue scale and Psychosexual Daily Questionnaire, Question 4, were developed. In one pilot study, IVR versions of these scales were compared to paper versions in 25 men = 65 years at each of two clinical sites. In …

Longitudinal Changes In Vascular Risk Markers And Mortality Rates Among A Latino Population With Hypertension, Matthew C Pflederer, Carlin S Long, Brenda Beaty, Edward P Havranek, Philip S Mehler, Angela Keniston, Mori J Krantz

The Texas Heart Institute Journal

Vascular markers such as pulse-wave velocity and carotid intima-media thickness (CIMT) might improve the prediction of incident cardiovascular disease beyond traditional risk factors. These vascular markers have not been well characterized in minority populations and might be more useful than inflammatory biomarkers. We conducted a prospective, longitudinal cohort study among hypertensive patients in an urban safety-net hospital. We evaluated inflammatory biomarkers, arterial pulse-wave velocity, and carotid intima-media thickness at baseline, 1 year, and 2 years. The primary outcome variable was CIMT. Generalized linear mixed-effects models were used to evaluate associations between CIMT and predictive variables accounting for the correlation of …

Advancing A Guiding Catheter Across A Mechanical Aortic Valve, Wassim Shatila, Guilherme V Silva

The Texas Heart Institute Journal

No abstract provided.