Medicine and Health Sciences Commons^™

Prognostic Performance Of Prospective Versus Retrospective Electrocardiographic Gating In Coronary Computed Tomographic Angiography, Pradnya Velankar, Kongkiat Chaikriangkrai, Ninad Dewal, Sayf Khaleel Bala, Belqis Elferjani, Sama Alchalabi, Su Min Chang

The Texas Heart Institute Journal

Coronary computed tomographic angiography (CCTA) with prospective electrocardiographic gating reduces radiation exposure, but its prognostic power for predicting cardiovascular risk in patients with suspected CAD has not been fully validated. To determine whether prospective gating performs as well as retrospective gating in this population, we compared these scan modes in patients undergoing 64-slice CCTA.

From January 2009 through September 2011, 1,407 patients underwent CCTA; of these, 915 (mean age, 57.8 ± 13.5 yr; 54% male) had suspected coronary artery disease at the time of CCTA and were included in the study. Prospective gating was used in 195 (21%) and retrospective …

Genetic Testing In Cardiovascular Medicine, Ali J Marian

The Texas Heart Institute Journal

No abstract provided.

Investigating The Roles Of Tap63 And Tap73 In Cutaneous Squamous Cell Carcinoma And Lung Adenocarcinoma, Andrew J. Davis

Dissertations and Theses (Open Access)

TP63 and TP73 (which encode p63 and p73, respectively) are highly conserved transcription factors with important roles in development and tissue homeostasis. Similar to their homolog, p53, both p63 and p73 have been shown to mediate tumor suppression in multiple tissue types. Interestingly, however, both genes are expressed as multiple isoforms, which appear to have different and, in many cases, antagonistic functions. Through the use of isoform-specific null alleles of p63 and p73 our lab and others have shown that the full-length N-terminal isoforms of p63 and p73 (referred to as TAp63 and TAp73, respectively) exhibit distinct functions in development, …

Trichuris Muris Whey Acidic Protein Induces Type 2 Protective Immunity Against Whipworm, Neima Briggs

Dissertations and Theses (Open Access)

Human whipworm (Trichuris trichiura) infects approximately 1 in 15 people worldwide, representing the leading infectious cause of colitis and subsequent, inflammatory bowel disease (IBD). Current control measures focused on mass deworming have had limited success due to low drug efficacies. Vaccination would be an ideal, cost-effective strategy to induce protective immunity, leading to control of infection and transmission. Here we report the identification of whey acidic protein, a whipworm secretory protein, as a strong immunogen for inducing protective efficacy in a surrogate mouse T. muris infection model. The near full-length recombinant WAP protein (rTm-WAP49), as well …

Ube4b Levels Determine The Efficacy Of Egfr And Stat5 Inhibitors In Treatment Resistant Neuroblastoma, David James Savage

Dissertations and Theses (Open Access)

Neuroblastoma is the most common malignancy in infants. Overexpression of the epidermal growth factor receptor (EGFR) in neuroblastoma tumors can result in enhanced EGFR signaling, uncontrolled proliferation, and may provide a mechanism for chemotherapy resistance. UBE4B, an E3/E4 ubiquitin ligase, ubiquitinates the EGFR and promotes its lysosomal degradation ultimately attenuating EGFR signaling. Interestingly, the UBE4B gene lies in a chromosomal region (1p36) whose loss is correlated with poor patient outcomes due to inefficient EGFR degradation and enhanced cell proliferation. We examined whether depletion of UBE4B in a chemoresistant neuroblastoma cell line would affect tumor responses to drugs that specifically target …

Identification Of Intracranial Lesions With Dual-Energy Computed To Mography And Magnetic Resonance Phase Imaging, Megan C. Jacobsen

Dissertations and Theses (Open Access)

On conventional Single-energy Computed Tomography (SECT), lesions with an attenuation greater than 100 Hounsfield Units (HU) can be definitively diagnosed as calcification. However, low-density calcifications and hemorrhage may have overlapping attenuation ranges between 40 and 100 HU and, therefore, cannot be differentiated with SECT alone. On T2*-weighted Gradient Recalled Echo (GRE) MRI, these lesions appear as “foci of susceptibility” in which their signal is hypointense due to the magnetic susceptibility of the lesions differing from that of the background tissue.

Dual-energy Computed Tomography (DECT) and Phase-Sensitive Magnetic Resonance Imaging (PS-MRI) represent two new imaging paradigms which both have the potential …

Aging Exacerbates Neutrophil Pathogenicity In Ischemic Stroke, Meaghan Roy-O'Reilly

Dissertations and Theses (Open Access)

Ischemic stroke is a major cause of disability and mortality worldwide. As most patients cannot receive the currently approved therapies for ischemic stroke, novel treatments are critically needed. Cerebral ischemia causes irreversible tissue damage, referred to as the “tissue core”, which is surrounded by a salvageable penumbral region. Excitotoxicity, oxidative stress and inflammation can further damage this “tissue-at-risk”, resulting in even greater functional loss and poorer injury outcomes.

Aging represents the single strongest risk factor for high mortality and poor outcome after stroke in patients. This phenotype is also seen in animal models, with aged mice experiencing higher mortality and …

Auto-Delineation Of Oropharyngeal Clinical Target Volumes Using Deep Learning Techniques, Carlos Eduardo Cardenas

Dissertations and Theses (Open Access)

Head and neck intensity modulate radiation therapy allows for the delivery of high-precision radiotherapy by conforming radiation dose to the defined treatment targets achieving more accurate target dose distribution and better sparing of normal tissues. However, producing very precise treatment plans may be ineffective if the target volumes are not defined accurately. Furthermore, there are several reports of significant inter-observer variability when delineating these target volumes for head and neck cancers making this variability one of the largest sources of uncertainty in head and neck radiation therapy.

The purpose of this study was to develop algorithms to automate target delineation …

The Role Of Perivascular Fibrosis In Post-Stroke Glymphatic Impairment And Cerebral Amyloid Angiopathy, Matthew D. Howe

Dissertations and Theses (Open Access)

In healthy brain tissue, toxic amyloid-β (Aβ) proteins are transported by the pulsatile flow of cerebrospinal fluid (CSF) along perivascular drainage pathways. Ischemic stroke may disrupt this process, leading to a perivascular build-up of Aβ, termed cerebral amyloid angiopathy (CAA). I hypothesize that an abnormal pattern of extracellular matrix deposition within the vascular basement membrane, termed fibrosis, impairs Aβ drainage from the aged brain after stroke. I further hypothesize that inhibition of astrocytic transforming growth factor-β (TGF-β) signaling can reverse these phenotypes. Finally, I also hypothesize that serum biomarkers of perivascular fibrosis can be used to diagnose CAA following intracerebral …

Changes In The Testes Following Spinal Cord Injury And The Attenuating Effects Of Licofelone, Ryan Fortune

Dissertations and Theses (Open Access)

Spinal cord injury is a devastating disease that researchers have had very limited success in treating. In addition to interrupted innervation, spinal cord injury causes pathologic changes in a multitude of organ systems. Male infertility is one such complication that is particularly devastating because the patient population is predominantly young men. Our lab has previously shown that the blood testis barrier breaks down after spinal cord injury. This dissertation shows the local metabolomic and mRNA changes that spinal cord injury causes within the testes using a Sprague Dawley rat model, including the elevation in eicosanoids, increased oxidative stress, chronically elevated …

Microrna Functions In Uv-Induced Cutaneous Squamous Cell Carcinoma, Tran Nguyen

Dissertations and Theses (Open Access)

Cutaneous squamous cell carcinoma (cuSCC) is the second most common skin cancer, for which long term UV exposure and chronic wounding are the dominant risk factors. Despite these clinically established connections, little is understood about the early molecular response of human skin to UV exposure and its connection to acute wounding and cuSCC. Thus, our goal is to find common and specific signatures driven by UV-exposure and wounding as a means of developing new approaches for treating and preventing cuSCC.

Here, we perform integrated analyses of RNA-seq and miR-seq on 3 datasets: (1) UV-unexposed and acute UV-exposed human skin, (2) …

Genomic And Transcriptomic Landscape Of Colorectal Premalignancy, Kyle Chang

Dissertations and Theses (Open Access)

Colorectal cancer (CRC) is the third most commonly diagnosed cancer among men and women in the United States, with 3 to 5 percent of the cases diagnosed in the background of a hereditary form of the disease. Biologically, CRC is divided into two groups: microsatellite instable (MSI) and chromosomally unstable (CIN). Genomic and transcriptomic characterization of CRC has emerged from large-scale studies in recent years due to the advancement of next-generation sequencing technologies. These studies have identified key genes and pathways altered in CRC and provided insights to the discovery of therapeutic targets. Despite the wealth of knowledge acquired in …

Enhancing Radiation Sensitivity In Non-Small Cell Lung Cancer, Yifan Wang

Dissertations and Theses (Open Access)

Lung cancer is the leading cause of cancer-related death. While radiation therapy is one of the standard treatments for lung cancer, the disease outcome after radiotherapy is still far from satisfactory despite ongoing advances in radiation techniques. Enhancing the radiosensitivity of lung cancer has the potential to improve the disease outcome of radiation treatments. Using a novel high throughput radiation sensitizing screen, previous work in the lab has identified several potent radiation sensitizers. The focus of my dissertation is on two of the identified pathways, HSP90 and MEK, using the potent and clinically relevant inhibitors ganetespib and trametinib. Using both …

The Cross-Talk Between Neurons And Microglia Through Interleukin-4 After Ischemic Injury, Shun-Ming Ting

Dissertations and Theses (Open Access)

After ischemic stroke, the loss of blood supply to the affected region of the brain leads to a series of pathological events known as ischemic cascades, that include excitotoxicity and microglia/macrophage over-activation resulting in damaging inflammatory responses. Studies from our research group suggest that the viable neurons in the ischemic penumbra (location receiving less profound damage, as compare to ischemic core) produce and release a potent anti-inflammatory cytokine, interleukin(IL) -4. We propose that this neuronal response to sublethal ischemia is designed to guide surrounding microglia/macrophages to a reparative and anti-inflammatory (M2) phenotype.

The research included in this study is designed …

The Protective Effects Of Memantine On The Morphology And Activity Of Irradiated Dendritic Spines, Thanh Lam

Dissertations and Theses (Open Access)

Abstract: The Protective Effects of Memantine on the Morphology And

Activity of Irradiated Dendritic Spines

Thanh T. Lam, M.S.

Advisory Professor: David R. Grosshans, M.D, Ph.D.

Although radiotherapy is an effective treatment for brain tumors, the adverse effects of such treatments may result in a decline in cognitive functioning. To prevent or reverse such radiation-induced cognitive dysfunctions, it is critical to understand the cellular and subcellular effects of radiation. In this study, both Thy-1 YFP mice and cultured cortical neurons were used to investigate changes in dendritic spines after cortical neurons were irradiated. The results indicated that irradiation has long-term …

Improved Target Coverage Of Spinal Metastases Through The Use Of Flattening Filter Free Beams, Laura Bennett

Dissertations and Theses (Open Access)

Of the patients that are diagnosed with metastatic disease, up to 40% will develop vertebral osseous metastases. These metastases tend to be located in close proximity to the spinal cord itself, making it difficult to achieve the recommended minimum dose of 14 Gy for single fraction SBRT or 21 Gy¹ for three fraction SBRT while maintaining acceptable doses to the cord and cauda equina. This proximity of the target to critical structures has the potential to compromise the efficacy of the radiation treatment plan in favor of reducing normal tissue dose, resulting in poor local control and tumor recurrence …

Mir-484 Functions As An Onco-Mir In Triple Negative Breast Cancer, Nashwa Kabil

Dissertations and Theses (Open Access)

Triple negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer (BC), with a poor prognosis with currently used therapies, and thus represents an unmet therapeutic challenge. Lack of molecular targets (i.e. ER, PR, HER2) and significant genetic heterogeneity are the major reasons contributing to early relapse and high mortality rates. Numerous studies have indicated that microRNAs (miRs) have an important role in BC progression, invasion, angiogenesis, and metastasis. We analyzed miRNA expression profiles of BC patient data bases and identified that miR-484 is highly upregulated in all subtypes of BC patients, with the highest expression in TNBC …

Design, Fabrication, And Validation Of 3d Printed, Patient-Specific Compensators For Postmastectomy Radiation Therapy, Daniel Craft

Dissertations and Theses (Open Access)

The purpose of this study was to use 3D printed, patient-specific tissue compensators to overcome the 3D planning limitations for postmastectomy radiation therapy (PMRT). Tissue compensators can be used to reduce dose heterogeneity, hot and cold spots at field junctions, and treatment complexity, but are currently seldom used due to the difficulty in designing, fabricating, and validating them.

To produce compensators using 3D printing technology, suitable materials had to be found and characterized. Several materials were found to be promising, but previously unreported material uncertainties were also discovered that must be carefully controlled for in 3D printing studies. A new …

Omics Approaches To Uncover Germline And Somatic Variation Underlying Inherited Sarcomagenesis, Justin Wong

Dissertations and Theses (Open Access)

Sarcomas are rare mesenchymal tumors, making up 15% of all childhood and 1% of all adult tumors. They account for a disproportionate share of mortality in young adults, and if left untreated, are highly likely to metastasize. However, sarcoma etiology is poorly understood, and having numerous histological subtypes has complicated elucidation. To better understand factors underlying sarcomagenesis, we leveraged two rare inherited cancer predisposition syndromes, Li-Fraumeni Syndrome (LFS), and LFS-like (LFSL), both with a high incidence of sarcomas. LFS is caused by mutations in the tumor suppressor gene TP53 (p53), but has variable and incomplete penetrance, suggesting additional acquired …

Sex-Related Differences In Outcomes Of Thoracic Organ Transplantation And Mechanical Circulatory Support, Daoud Daoud, Faisal H Cheema, Jeffrey A Morgan, Gabriel Loor

The Texas Heart Institute Journal

No abstract provided.

Physician Burnout: Causes, Consequences, And (?) Cures, Herbert L Fred, Mark S Scheid

The Texas Heart Institute Journal

No abstract provided.

High-Risk Cardiovascular Conditions In Sports-Related Sudden Death: Prevalence In 5,169 Schoolchildren Screened Via Cardiac Magnetic Resonance, Paolo Angelini, Benjamin Y Cheong, Veronica V Lenge De Rosen, Alberto Lopez, Carlo Uribe, Anthony H Masso, Syed W Ali, Barry R Davis, Raja Muthupillai, James T Willerson

The Texas Heart Institute Journal

Improving preparticipation screening of candidates for sports necessitates establishing the prevalence of high-risk cardiovascular conditions (hr-CVC) that predispose young people to sudden cardiac death (SCD). Our accurate, novel protocol chiefly involved the use of cardiac magnetic resonance (CMR) to estimate this prevalence.

Middle and high school students from a general United States population were screened by means of questionnaires, resting electrocardiograms, and CMR to determine the prevalence of 3 types of hr-CVC: electrocardiographic abnormalities, cardiomyopathies, and anomalous coronary artery origin from the opposite sinus with intramural coronary course (ACAOS-IM). We examined the range of normal left ventricular size and function …

Characterizing The Recognition Motif And Novel Substrates Of Carm1, Sitaram Gayatri

Dissertations and Theses (Open Access)

A limited pool of proteins attains vast functional repertoire due to posttranslational modifications (PTMs). Arginine methylation is a common posttranslational modification, which is catalyzed by a family of nine protein arginine methyltransferases or PRMTs. These enzymes deposit one or two methyl groups to the nitrogen atoms of arginine side-chains. Elucidating the substrate specificity of each PRMT will promote a better understanding of which signaling networks these enzymes contribute to. Although many PRMT substrates have been identified, and their methylation sites mapped, the optimal target motif for each of the nine PRMTs has not been systematically addressed. Here we describe the …

Body Dissatisfaction And Suicidal Ideation Among Psychiatric Inpatients With Eating Disorders, Katrina A Rufino, Humsini Viswanath, Rebecca Wagner, Michelle A Patriquin

Staff and Researcher Publications

The current study the relationship between eating disorders (EDs) and suicidal ideation and suicide attempt in adult inpatients. In particular, the present study investigated one potential mechanism, body dissatisfaction (BD), which may contribute to increased risk for suicide in adult ED patients. A sample of 432 psychiatric inpatients ranging from 18 to 65 years of age participated in the current study. Findings indicated that patients who have higher levels of BD also had higher levels of passive and active suicidal ideation and previous suicide attempts. Higher levels of BD were also related to increased suicidal ideation after controlling for depression …

Precision Oncology Decision Support: Current Approaches And Strategies For The Future, Katherine C Kurnit, Ecaterina E Ileana Dumbrava, Beate Litzenburger, Yekaterina B Khotskaya, Amber M Johnson, Timothy A Yap, Jordi Rodon, Jia Zeng, Md Abu Shufean, Ann M Bailey, Nora S Sánchez, Vijaykumar Holla, John Mendelsohn, Kenna Mills Shaw, Elmer V Bernstam, Gordon B Mills, Funda Meric-Bernstam

Faculty, Staff and Student Publications

With the increasing availability of genomics, routine analysis of advanced cancers is now feasible. Treatment selection is frequently guided by the molecular characteristics of a patient's tumor, and an increasing number of trials are genomically selected. Furthermore, multiple studies have demonstrated the benefit of therapies that are chosen based upon the molecular profile of a tumor. However, the rapid evolution of genomic testing platforms and emergence of new technologies make interpreting molecular testing reports more challenging. More sophisticated precision oncology decision support services are essential. This review outlines existing tools available for health care providers and precision oncology teams and …

Catheter Ablation Of Ventricular Tachycardia, Nilesh Mathuria

The Texas Heart Institute Journal

No abstract provided.

New Insights Into Predictors Of Cardiac Implantable Electronic Device Infection, Hossein Sadeghi, Abolfath Alizadehdiz, Amirfarjam Fazelifar, Zahra Emkanjoo, Majid Haghjoo

The Texas Heart Institute Journal

Infection is an important complication of cardiac implantable electronic device procedures. To further study the factors associated with infection, we retrospectively reviewed the records of 3,205 consecutive patients who had undergone de novo or revision cardiac electronic device implantation at our institution from March 2011 through March 2015. We recorded all infections and specified whether they were related to the characteristics of the patient, device, or procedure. To identify predictors of infection, we performed multivariate analysis.

Device infections were identified in 85 patients (2.7%), at a mean follow-up time of 27 ± 11 months. The main predictors of device infection …

Dissecting The Molecular Mechanism Of Early Tumor Dissemination In Non-Small Cell Lung Cancer, Xingtong Liu

Dissertations and Theses (Open Access)

Lung cancer is the most common cause of cancer related death in the United States and worldwide. It has been shown that 30%-55% of patients with early stages of non-small cell lung cancer (NSCLC) developed and died of recurrence after curative resection, suggesting that tumor cell dissemination occurred early in those patients before surgery. However, molecular evidence, underline mechanisms and risk factors for the NSCLC relapse remain largely unknown. Addressing these questions will be critical for the development of strategies to stratify the risk of recurrence and approaches to reduce these risks. My thesis focused on dissecting the molecular basis …

Obstructive Sleep Apnea In Heart Failure: Review Of Prevalence, Treatment With Continuous Positive Airway Pressure, And Prognosis, Himad K Khattak, Faisal Hayat, Salpy V Pamboukian, Harvey S Hahn, Brian P Schwartz, Phyllis K Stein

The Texas Heart Institute Journal

Obstructive sleep apnea is a sleep-related breathing disorder that has a major impact on cardiovascular function. It has been associated with hypertension, coronary artery disease, cardiac arrhythmias, sudden cardiac death, and heart failure. This review focuses on the relationship between obstructive sleep apnea and heart failure with either reduced or preserved ejection fraction. We discuss the pathophysiology of obstructive sleep apnea, as well as its prevalence, treatment outcomes with continuous positive airway pressure, and prognosis in these 2 distinct types of heart failure. We also identify areas in which further work is needed to improve our understanding of this association …

Glucose-6-Phosphate Dehydrogenase Deficiency Is Associated With Cardiovascular Disease In Us Military Centers, John E Thomas, Seungho Kang, Charles J Wyatt, Forest S Kim, A David Mangelsdorff, Fred K Weigel

The Texas Heart Institute Journal

Glucose-6-phosphate dehydrogenase (G6PD) protects erythrocytes from oxidative stress and hemolysis; G6PD deficiency is the most prevalent enzymopathy. The United States military routinely performs tests to prevent exposing G6PD-deficient personnel to antimalarial drugs that might cause life-threatening hemolytic reactions. In addition, G6PD is a key determinant of vascular function, and its deficiency can lead to impaired nitric oxide production and greater vascular oxidant stress—precursors to atherosclerosis and cardiovascular disease. Using military medical records, we performed a retrospective, cross-sectional study to investigate whether deficient G6PD levels are associated with a higher prevalence of cardiovascular disease than are normal levels, and, if so, …