Pharmacologic And Genetic Manipulations Of Angiotensin Signaling In Thoracic Aortic Disease Models, Andrew M. Peters

Dissertations and Theses (Open Access)

Thoracic aortic aneurysms and dissections (TAAD) are a major cause of morbidity and mortality in patients. Many different risk factors have been associated TAAD, but hypertension is the largest risk factor. Subsets of TAAD patients have identifiable syndromic genetic diseases, yet a number of genetic non-syndromic patients have been identified. Infusion of angiotensin II into mouse models causes aortic disease through inflammation and fibrosis. An angiotensin type I receptor (AT1R) blocker (ARB) or an angiotensin converting enzyme (ACE) inhibitor (ACEi) can reverse aortic pathology in some mouse models. I set out to better understand the relationship between angiotensin and TAAD …

Skin Necrosis Induced By Coumarin Congeners, Herbert L Fred

The Texas Heart Institute Journal

No abstract provided.

Optimizing Emergency Department Throughput Using Best Practices To Improve Patient Flow, Puneet Freibott Dnp, Rn, Nea-Bc, Ccrn-K'S

Journal of Nursing & Interprofessional Leadership in Quality & Safety

Emergency Department (ED) crowding and bottle necks are the reality of hospitals across the country. Patients seeking care and needing inpatient beds via the emergency rooms are facing delays with attaining the right level of care. Orchestrating a patient through an ED admission requires a multidisciplinary effort to provide safe, effective and efficient care. This quality improvement project conducted in a tertiary acute care hospital focused on Centers for Medicare and Medicaid metrics to measure Emergency Department (ED) throughput. This multidisciplinary initiative focused on reducing time stamps for patient arrival to the ED through departure to hospital or home. Outcomes …

Insula And Amygdala Resting-State Functional Connectivity Differentiate Bipolar From Unipolar Depression, E Ambrosi, D B Arciniegas, A Madan, K N Curtis, M A Patriquin, R E Jorge, G Spalletta, J C Fowler, B C Frueh, R Salas

Staff and Researcher Publications

Objective: Distinguishing depressive episodes due to bipolar disorder (BD) or major depressive disorder (MDD) solely on clinical grounds is challenging. We aimed at comparing resting-state functional connectivity (rsFC) of regions subserving emotional regulation in similarly depressed BD and MDD.

Method: We enrolled 76 in-patients (BD, n = 36; MDD, n = 40) and 40 healthy controls (HC). A seed-based approach was used to identify regions showing different rsFC with the insula and the amygdala. Insular and amygdalar parcellations were then performed along with diagnostic accuracy of the main findings.

Results: Lower rsFC between the left insula and the left mid-dorsolateral …

Parent-Reported Problematic Sleep Behaviors In Children With Comorbid Autism Spectrum Disorder And Attention-Deficit/Hyperactivity Disorder, Katharine C Reynolds, Michelle Patriquin, Candice A Alfano, Katherine A Loveland, Deborah A Pearson

Staff and Researcher Publications

Background: Sleep problems are frequent and well documented in children with Autism Spectrum Disorders (ASD), children with Attention Deficit/Hyperactivity Disorder (ADHD) and children with internalizing problems, however limited work has examined sleep problems in children presenting with comorbid ASD/ADHD. In healthy children, sleep problems negatively impact social, emotional, and academic functioning. The current study sought to examine diagnostic severity as predictors of sleep problems in children with comorbid ASD/ADHD. Additionally, the association between sleep and "real-life" functional domains (i.e., intellectual functioning, academic achievement, and executive functioning) were assessed.

Method: Sleep, internalizing difficulties, intellectual functioning, academic achievement and executive functioning were …

Reducing Antibiotic Use In Pediatric Upper Respiratory Infection: A Multifaceted Parent-Clinician Approach, Sydnee H. Lucas Dnp, Aprn, Sydney Thompson Dnp, Arnp, Fnp-Bc

Journal of Nursing & Interprofessional Leadership in Quality & Safety

The goal of this QI initiative was to decrease inappropriate antibiotic for the treatment of pediatric upper respiratory infection (URI) in the retail clinic setting. The approach included the use of a protocol to treat viral upper respiratory illness, a visual aid decision-making tool for guideline adherence, prescription pad for nonprescription remedies, and shared decision-making techniques for providers to involve patients and parents in management plans regarding nonprescription remedies, supportive treatment, and signs and symptoms that would warrant a return visit. An improvement trend during the first 3 months of the initiative showed a shift in antibiotic avoidance from a …

Reducing Medication Errors Through Workflow Redesign, Rosslyn W. Blake Dnp, Aprn, Gnp

Journal of Nursing & Interprofessional Leadership in Quality & Safety

Lack of medication reconciliation at the point of transitions between skilled nursing facilities/nursing homes (SNF/NHs) and acute care hospitals (ACHs) is a common point of origin for medical errors that cause harm to patients. The goal of this quality improvement initiative was to improve medication reconciliation at the point of transition from the SNF/NH to the ACH which in turn would reduce medication errors, adverse drug events, and medication-induced injury to the vulnerable elderly population. We implemented a workflow redesign process to reconcile the accuracy of residents’ medications at the time of transfer from the SNF/NH to the ACH. After …

Using Business Modeling To Streamline Cost Of Anesthesia In A Cardiopulmonary Laboratory, Johnny Dang Dnp, Crna, Kristen Starnes-Ott Phd, Crna

Journal of Nursing & Interprofessional Leadership in Quality & Safety

The Time Driven Activity Based Costing (TDABC) measurement system, a model used in the business arena, can capture clinical processes and costs that other costing models often overlook. Use of this system permitted tying costs to time and resources and identified areas of inefficiency such as depleted supplies and health care and emergency supplies placed inconveniently. A multidisciplinary team developed an anesthesia checklist for use in a remote cardiopulmonary laboratory. The compliance rate for checklist completion was approximately 85%. Checklist implementation translated to a decrease in case delays and time expenditure in patient care by 58% with a cost savings …

Education Program Using Non-Pharmacologic Support During Benzodiazepine Reduction In Patients With Anxiety Disorders, Kelly D. Kearney Dnp, Rn, Pmhnp-Bc, Diane Wardell Phd, Whnp-Bc

Journal of Nursing & Interprofessional Leadership in Quality & Safety

A private mental health clinic developed an initiative to aid patients with anxiety disorders to taper their use of benzodiazepines. Based on best practices, a treatment protocol was developed in which patients attended 4 sessions (1 per month) in which they combined instruction in non-pharmaceutical anti-anxiety techniques (guided imagery, mindfulness meditation, deep breathing, progressive muscle relaxation, exercise, emotional freedom) with cognitive behavioral therapy and use of selective serotonin re uptake inhibitors. Participants experienced a reduction in benzodiazepine use. This small scale initiative showed that the holistic approach to anxiety management was an effective plan to decrease the use of benzodiazepines …

Evaluation Of Chest Pain After Implantable Cardioverter-Defibrillator Placement, Amir Gahremanpour, Mohammad Saeed, Yochai Birnbaum

The Texas Heart Institute Journal

No abstract provided.

Transcatheter Tricuspid Valve-In-Valve Replacement With An Edwards Sapien 3 Valve, Pranav Loyalka, Angelo Nascimbene, Benjamin Metz, Igor D Gregoric, Ajay Sundara Raman, Biswajit Kar

The Texas Heart Institute Journal

A few case reports and case series have documented the outcomes in patients with tricuspid bioprosthetic valvular degeneration who underwent transcatheter implantation of the Medtronic Melody and the Edwards Sapien XT and Sapien 3 valves. In this report, we describe the case of a 49-year-old woman with severe bioprosthetic tricuspid valvular stenosis and multiple comorbidities who underwent transcatheter tricuspid valve replacement with a Sapien 3 valve.

White Blood Cell Subtypes Are Associated With A Greater Long-Term Risk Of Death After Acute Myocardial Infarction, Arthur Shiyovich, Harel Gilutz, Ygal Plakht

The Texas Heart Institute Journal

We evaluated the association between white blood cell counts and long-term mortality rates in 2,129 patients (mean age, 65.3 ± 13.5 yr; 69% men) who had survived acute myocardial infarction. We obtained white blood cell counts and differential counts of white blood cell subtypes within the first 72 hours of hospital admission. The primary outcome was all-cause death at 1, 5, and 10 years after acute myocardial infarction.

In regard to death in the long term, we found significant negative linear associations (lymphocytes), positive linear associations (neutrophils and the neutrophil-to-lymphocyte ratio), and nonlinear U-shaped associations (basophils, eosinophils, monocytes, and total …

The Two Anomalies Of Wilhelm Ebstein, Magdalena Mazurak, Jacek Kusa

The Texas Heart Institute Journal

The year 2016 was the 180th anniversary of Wilhelm Ebstein's birth and the 150th anniversary of his description of the congenital tricuspid valve malformation that came to be known as Ebstein anomaly. We present a brief history of the life and work of Dr. Wilhelm Ebstein. Despite his distinguished career, he is seemingly forgotten in his own birthplace. We include a review of the relevant historical medical literature.

Clara's Final Christmas Gift, Gus W Krucke

Faculty, Staff and Student Publications

No abstract provided.

Incremental Validity Of The Pid-5 In Relation To The Five Factor Model And Traditional Polythetic Personality Criteria Of The Dsm-5, J Christopher Fowler, Michelle A Patriquin, Alok Madan, Jon G Allen, B Christopher Frueh, John M Oldham

Staff and Researcher Publications

Background: This study assessed the incremental validity of the Personality Inventory for DSM-5 (PID-5) beyond the impact of demographic, burden of illness, five-factor model of personality, and DSM-5 personality disorder criteria with respect to associations with admission psychiatric symptoms and functional disability.

Methods: Psychiatric inpatients (N = 927) were administered the Big Five Inventory, PID-5, and personality disorder criteria counts. Prior treatment utilization, as well as baseline depression, anxiety, emotion regulation, and functional disability were administered within two days of the personality measures. Hierarchical regression models were used to explore the association of personality functioning with symptom functioning, emotion regulation …

Unproven Stem Cell-Based Interventions: Advancing Policy Through Stakeholder Collaboration, Kirstin R W Matthews, Ana S Iltis

The Texas Heart Institute Journal

No abstract provided.

Factors Influencing Attendance, Postpartum Follow-Up, And Contraceptive Usage Among Teenage Centeringpregnancy® Participants, Latia Hickerson

Dissertations and Theses (Open Access)

Background: Teenage mothers are less likely to obtain postpartum examinations and contraception, increasing risks for negative social and health outcomes. The CenteringPregnancy® prenatal care model has been found to improve outcomes. However, little is known about factors influencing CenteringPregnancy® attendance or how this attendance impacts future pregnancy rates among teenagers.

Aim: The purpose of this study was to explore the association between CenteringPregnancy® attendance, postpartum return, contraception initiation and method selection. Additionally, the Group Care and Perinatal Behaviors Framework was used to assess the association between food insecurity, housing insecurity, intimate partner violence relationship status, partner group attendance and total …

Associations Among Meaning Of Illness, Quality Of Life, Symptom Burden And Depression In Patients With Leptomeningeal Metastasis, Julie Walker

Dissertations and Theses (Open Access)

Background Patients with leptomeningeal metastasis (LM) have symptoms related to disease within the neuroaxis, cancer sites outside the neuroaxis and treatment toxicities. Furthermore, the meaning ascribed to advanced cancer, such as LM, may impact the perceived severity, frequency and distress of symptoms as well as quality of life (QoL) and depression. Our aim was to explore and describe relationships among meaning of illness (MoI), depression, QoL and symptom burden in LM patients and to explore whether adding spine-related items from the MD Anderson Symptom Inventory-Spine (MDASI-SP) to the MDASI-Brain Tumor (BT) enhanced understanding of symptom burden in this population.

Methods …

Cyclin B1 Mediates The Effect Of Uchl1 In Promoting Cell Cycle Progression In Uterine Papillary Serous Carcinoma, Suet Ying Kwan

Dissertations and Theses (Open Access)

Uterine papillary serous carcinoma (UPSC) is an aggressive form of endometrial cancer with poor survival rates and a high risk of recurrence. The rarity of UPSC poses challenges to the discovery of novel targeted therapies. Therefore, the purpose of this dissertation was to identify novel therapeutic targets that could aid in the management of UPSC. To do so, we began with the relatively large cohort of UPSC cases in the TCGA data set, which was used to identify differentially expressed genes between UPSC and low-grade endometrioid endometrial carcinoma (EEC) and normal tissue.

We identified Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1 …

Barriers To Expansion Of Supervision Networks At Genetic Counseling Training Programs, Jordan E. Berg

Dissertations and Theses (Open Access)

Job openings outpace new graduates due to exponential growth in genetic counseling, leading to a workforce shortage. Expanding training slots to meet this demand presumably is linked to the number of supervisors. Thus, there is a need to systematically review barriers to supervision. This study aimed to determine and compare barriers to expansion of supervision networks at genetic counseling training programs as perceived by current supervisors, non-supervisors, and Program Directors. Certified genetic counselors were recruited via National Society of Genetic Counselors e-blast with an invitation to complete an online survey; Program Directors were emailed personal letters of invitation. Twenty-three Program …

Clinical Applicability Of Proposed Algorithm For Identifying Individuals At Risk For Hereditary Hematologic Malignancies, Maggie Clifford

Dissertations and Theses (Open Access)

Over the past decade, more than 12 genes have been identified to cause hereditary predispositions to hematologic malignancies. These syndromes are characterized by an increased risk to develop myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), or aplastic anemia (AA) at young ages, with various phenotypic features including peripheral cytopenias, immune dysfunction and skeletal defects. In 2013, Churpek et al. proposed a referral algorithm which consists of certain criteria for identifying leukemia patients who may benefit from genetic assessment for these hereditary syndromes. These criteria assess personal history of cytopenias, skin or nail abnormalities, immune deficiencies/atypical infections, and other associated clinical …

Molecular Determinants Of Residual Disease In Ovarian Cancer, Kshipra M. Gharpure

Dissertations and Theses (Open Access)

The standard treatment for high grade serous ovarian cancer is primary cytoreductive surgery followed by adjuvant chemotherapy. Residual disease followed by surgery is associated with adverse overall and progression-free survival as well as poor response to adjuvant chemotherapy. Accurate identification of patients at high risk of residual disease will help avoid unnecessary surgeries and help in triaging these patients to neoadjuvant chemotherapy prior to interval surgical debulking. In this study, we address this clinical issue by identifying and validating molecular biomarkers that can predict the likelihood of residual disease in ovarian cancer patients. Using publically available databases and microarray datasets, …

The External Globus Pallidus: Bidirectional Control Over Anxiety-Related Behavior Mediated By Crfr1, Albert J. Hunt Jr

Dissertations and Theses (Open Access)

Abstract

THE EXTERNAL GLOBUS PALLIDUS: BIDIRECTIONAL CONTROL OVER ANXIETY-RELATED BEHAVIOR MEDIATED BY CRFR1

Albert Lee Joseph Hunt, Jr., B.S.

Advisory Professor: Shane Cunha, Ph.D.

Corticotropin-releasing factor receptor 1 (CRFR1), the principle receptor responsible for the anxiogenic activity of the stress peptide CRF, is abundantly expressed in the external globus pallidus (GPe) raising the question whether activity in the GPe is altered in response to stress. I show that CRFR1 expressing neurons are of the “prototypic” subtype of GPe neurons. I provide evidence of novel circuits from CRF neurons in stress-responsive nuclei, including the paraventricular nucleus of the hypothalamus (PVN) and …

Visualizing The Dynamics Of Immune Surveillance In Brain Tumors By Intravital Multiphoton Microscopy, Felix Nwajei

Dissertations and Theses (Open Access)

Visualizing the dynamics of immune surveillance in brain tumors by intravital multiphoton microscopy

By

Felix I. Nwajei, MD

Supervisory Professor: Tomasz Zal, Ph.D.

Brain tumors (BTs) generally have a bad prognosis despite conventional treatment strategies. Immunotherapy is a relatively novel treatment approach that has shown benefit for durable treatment of melanoma, and is a promising candidate for different tumor types including BTs. Immunotherapeutic strategies work by exploiting and/or enhancing natural anti-tumor immune response, a process that is critically dependent on adaptive immunity, T cell infiltration and surveillance of tumor. However, little is known about the dynamics and regulation of T …

Parp Inhibitor Upregulates Pd-L1 Expression And Enhances Cancer-Associated Immunosuppression, Shiping Jiao

Dissertations and Theses (Open Access)

With recent approvals for therapeutic antibodies that block CTLA4, PD-1 and PD-L1, immune checkpoints have emerged as new targets in cancer therapy. In addition, there is accumulating evidence highlighting the role of cancer-associated immunity in patient response to cytotoxic anticancer agents. Inhibitors of poly (ADP-ribose) polymerase (PARP) have shown substantial cytotoxic effects against tumors with defects in DNA damage responses. However, whether a crosstalk between PARP inhibition and immune checkpoints exists remains unclear. Here, it has been shown that PARP inhibitors (PARPis) upregulate PD-L1 expression in multiple cancer cell lines, human xenograft tumors, and syngeneic mouse tumors. Mechanistically, PARPi inactivates …

Effect Of Entinostat On Nk Cell-Mediated Cytotoxicity Against Os Cells And Os Lung Metastsis, Simin Kiany

Dissertations and Theses (Open Access)

The purpose of this study was to investigate the effect of the HDAC inhibitor entinostat on the efficacy of NK cell therapy for OS lung metastasis. The Lung is the most common site of OS metastatic spread in OS and pulmonary metastasis is the main cause of mortality. We have previously demonstrated that NK cell therapy has minimal efficacy against OS metastasis. We wished to determine whether we could augment the killing of OS cells in vitro and improve the efficacy of NK cell therapy in vivo by adding oral administration of entinostat. We elected to use our nude mouse …

The Hypoxic Adenosine Response Modulates Macrophage Differentiation And Contributes To Lung Disease, Kemly Mary Philip

Dissertations and Theses (Open Access)

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease which affects 5 - 8 million individuals worldwide and 200,000 individuals in the United States alone. Although prevalent, we do not know what causes IPF and no effective curative treatment exists for this disease. Our laboratory has shown that extracellular accumulation of adenosine and subsequent activation of the adenosine 2B (ADORA2B) receptor promotes immune cell invasion, airspace destruction, and fibrosis in chronic lung disease. Additionally, alternatively activated alveolar macrophages (AAMs) expressing ADORA2B, have been implicated in mediating adenosine’s pro-fibrotic effects in IPF. However, the exact role of AAMs in the hypoxic …

Role And Regulation Of Sphingosine 1-Phosphate In Erythrocyte, Kaiqi Sun

Dissertations and Theses (Open Access)

Sphingosine 1-phosphate (S1P) is a bioactive signaling sphingolipid produced in every mammalian cell. It plays a variety of important roles both in and outside of cells. S1P is highly enriched in mature erythrocytes because of the high enzymatic activity of the S1P-generating enzyme Sphingosine Kinase 1 (Sphk1) and the absence of S1P degrading enzymes. Erythrocytes are considered only a major reservoir for S1P because they supply S1P to the circulation for the regulation of various physiological processes which include but are not limited to immune cell trafficking, endothelial integrity and hematopoietic stem cell mobilization. However, if S1P plays a role …

Integrative Analysis Of Omics Data In Adult Glioma And Other Tcga Cancers To Guide Precision Medicine, Xin Hu, Xin Hu

Dissertations and Theses (Open Access)

Transcriptomic profiling and gene expression signatures have been widely applied as effective approaches for enhancing the molecular classification, diagnosis, prognosis or prediction of therapeutic response towards personalized therapy for cancer patients. Thanks to modern genome-wide profiling technology, scientists are able to build engines leveraging massive genomic variations and integrating with clinical data to identify “at risk” individuals for the sake of prevention, diagnosis and therapeutic interventions. In my graduate work for my Ph.D. thesis, I have investigated genomic sequencing data mining to comprehensively characterise molecular classifications and aberrant genomic events associated with clinical prognosis and treatment response, through applying high-dimensional …

Tumor-Cell Derived Inhibin, Beta A Is Essential For Adrenergic Effects On Fibroblast Activation, Archana Sidalaghatta Nagaraja

Dissertations and Theses (Open Access)

Objectives: Catecholamine-mediated effects driven by elevated adrenergic signaling are known to increase tumor growth and metastasis by direct effects on tumor cells. However, knowledge of effects of adrenergic signaling on other cells such as cancer-associated fibroblasts (CAFs) within the tumor microenvironment is limited. We hypothesize that adrenergic signaling and norepinephrine can accelerate the induction of CAF-phenotype to promote inflammation and metastasis.

Methods: Ingenuity Pathway Analysis and NetWalker were used to assess gene expression data from patients with known CESD (Center for Epidemiological Studies-Depression)-score alongside microdissected CAFs from primary ovarian cancer. Tumor samples from mice exposed to daily restraint-stress or non-stressed …