Medicine and Health Sciences Commons^™

Identification And Molecular Analysis Of Dna In Exosomes, Jena Tavormina

Dissertations & Theses (Open Access)

Exosomes are heterogeneous nanoparticles 50-150nm in diameter. Exosomes contain many functional cargo components, such as protein, DNA, and RNA. While protein and RNA exosome content has been extensively studied, very little work has been done to characterize exosomal DNA. Here, we demonstrate that exosomal DNA is heterogeneous and its packaging into exosomes is dependent on the cell of origin. Furthermore, through a rigorous assessment of various isolation methods, we identify Size Exclusion Chromatography (SEC) as the best method for the isolation of exosomal DNA for downstream applications. Additionally, we evaluate the methylation status of exosomal DNA and demonstrate that exosomal …

The Non-Coding Rnome After Splenectomy, Mihnea P Dragomir, Stefan Tudor, Keishi Okubo, Masayoshi Shimizu, Meng Chen, Dana Elena Giza, William Ruixian He, Cristina Ivan, George A Calin, Catalin Vasilescu

Journal Articles

Splenectomy is a common surgical procedure performed in millions of people worldwide. Epidemiologic data show that splenectomy is followed by infectious (sepsis) and non-infectious complications, with unknown mechanisms. In order to explore the role of the non-coding transcripts involved in these complications, we analysed a panel of circulating microRNAs (miRNAs), which were previously reported to be deregulated in sepsis, in the plasma of splenectomized patients. MiR-223 was overexpressed immediately and late after splenectomy, while miR-146a was overexpressed immediately after splenectomy, returning latter to basal levels; and miR-16, miR-93, miR-26a and miR-26b were overexpressed only late after splenectomy, suggesting similarities with …

Integrating Primary Care Into Community Mental Health Centres In Texas, Usa: Results Of A Case Study Investigation, Rebecca Wells, Ellen D Breckenridge, Sasha Ajaz, Aman Narayan, Daniel Brossart, James H Zahniser, Jolene Rasmussen

Journal Articles

INTRODUCTION: Despite evidence that people with serious mental illness benefit from receiving primary care within mental health care settings, there is little research on this type of integration. The objective of this study was to characterize how providers and patients experienced implementation of primary care into specialty mental health services.

METHODS: During site visits, study team members interviewed staff and conducted focus groups with patients at 10 United States community mental health centres then beginning to integrate primary into their practices. One year later, follow up phone interviews with key centre staff informants validated and updated findings. Data analysis included …

Safety Climate, Safety Climate Strength, And Length Of Stay In The Nicu, Daniel S Tawfik, Eric J Thomas, Timothy J Vogus, Jessica B Liu, Paul J Sharek, Courtney C Nisbet, Henry C Lee, J Bryan Sexton, Jochen Profit

Journal Articles

BACKGROUND: Safety climate is an important marker of patient safety attitudes within health care units, but the significance of intra-unit variation of safety climate perceptions (safety climate strength) is poorly understood. This study sought to examine the standard safety climate measure (percent positive response (PPR)) and safety climate strength in relation to length of stay (LOS) of very low birth weight (VLBW) infants within California neonatal intensive care units (NICUs).

METHODS: Observational study of safety climate from 2073 health care providers in 44 NICUs. Consistent perceptions among a NICU's respondents, i.e., safety climate strength, was determined via intra-unit standard deviation …

Oral Delivery Of Xenon For Cardiovascular Protection, Xing Yin, Melanie R Moody, Valeria Hebert, Melvin E Klegerman, Yong-Jian Geng, Tammy R Dugas, David D Mcpherson, Hyunggun Kim, Shao-Ling Huang

Journal Articles

Cardiac hypertrophy often causes impairment of cardiac function. Xenon (Xe), a naturally occurring noble gas, is known to provide neurological and myocardial protection without side effects. The conventional method of Xe delivery by inhalation is not feasible on a chronic basis. We have developed an orally deliverable, effective Xe formulation for long-term administration. We employed 2-hydroxypropyl)-β-cyclodextrin (HPCD), which was dissolved in water to increase the Xe concentration in solution. The beneficial effects of long-term oral administration of Xe-enriched solutions on cardiovascular function were evaluated in vivo. HPCD increased Xe solubility from 0.22 mM to 0.67 mM (3.8-fold). Aged ApoE knockout …

Unexpected Diagnosis, Gauravpal S Gill, Rukma R Govindu, Ragai Fouda, Hussam M Ammar

Journal Articles

A 74-year-old man presented to the ER with an eight-month history of shortness of breath, cough, anorexia, and weight loss. He had emigrated from sub-Saharan African to the USA, where he was diagnosed and treated for coronary artery disease, heart failure, and stroke; was hospitalized several times; and underwent hernia surgery. Despite the complex care that he received in the USA for many years, the diagnosis of AIDS was continually missed for years, and the patient was eventually diagnosed at the age of 74.

Nuclear Receptor Subfamily 4 Group A Member 2 Inhibits Activation Of Erk Signaling And Cell Growth In Response To Β-Adrenergic Stimulation In Adult Rat Cardiomyocytes, Sadia Ashraf, Yassmin K Hegazy, Romain Harmancey

Journal Articles

Sustained elevation of sympathetic activity is an important contributor to pathological cardiac hypertrophy, ventricular arrhythmias, and left ventricular contractile dysfunction in chronic heart failure. The orphan nuclear receptor NR4A2 is an immediate early-response gene activated in the heart under β-adrenergic stimulation. The goal of this study was to identify the transcriptional remodeling events induced by increased NR4A2 expression in cardiomyocytes and their impact on the physiological response of those cells to sustained β-adrenergic stimulation. Treatment of adult rat ventricular myocytes with isoproterenol induced a rapid (<4 >h) increase in NR4A2 levels that was accompanied by a transient (<24 >h) increase …

Indications For Lung Transplant Referral And Listing, Omar Shweish, Goutham Dronavalli

Journal Articles

Lung transplantation is a valuable therapeutic option for many patients with severe lung disease who have exhausted other medical or surgical therapies. However, since lungs are not a manufacturable organ like artificial heart valves or left ventricular assist devices, and since they are a limited resource compared to number of patients requiring the organs, the Department of Health and Human Services set the Final Rule of organ allocation in 1998. This led to development and implementation of Lung Allocation Score (LAS) in 2005. The score broadly divides lung diseases into 4 diagnostic criteria with a coefficient factor given to each …

Drunk Without Drinking: A Case Of Auto-Brewery Syndrome, Bobak J Akhavan, Luis Ostrosky-Zeichner, Eric J Thomas

Journal Articles

Information on auto-brewery syndrome is limited in the medical literature. This rare syndrome occurs when yeast overgrowth leads to ethanol fermentation in the gut. We present a patient presenting with symptoms of alcohol intoxication with objective laboratory data of elevated blood ethanol levels without a history of alcohol consumption. We reviewed the literature and have discussed the current diagnostic and therapeutic options.

Vitamin D Status And Risk Of Incident Tuberculosis Disease: A Nested Case-Control Study, Systematic Review, And Individual-Participant Data Meta-Analysis, Omowunmi Aibana, Chuan-Chin Huang, Said Aboud, Alberto Arnedo-Pena, Mercedes C Becerra, Juan Bautista Bellido-Blasco, Ramesh Bhosale, Roger Calderon, Silvia Chiang, Carmen Contreras, Ganmaa Davaasambuu, Wafaie W Fawzi, Molly F Franke, Jerome T Galea, Daniel Garcia-Ferrer, Maria Gil-Fortuño, Barbará Gomila-Sard, Amita Gupta, Nikhil Gupte, Rabia Hussain, Jesus Iborra-Millet, Najeeha T Iqbal, Jose Vicente Juan-Cerdán, Aarti Kinikar, Leonid Lecca, Vidya Mave, Noemi Meseguer-Ferrer, Grace Montepiedra, Ferdinand M Mugusi, Olumuyiwa A Owolabi, Julie Parsonnet, Freddy Roach-Poblete, Maria Angeles Romeu-García, Stephen A Spector, Christopher R Sudfeld, Mark W Tenforde, Toyin O Togun, Rosa Yataco, Zibiao Zhang, Megan B Murray

Journal Articles

BACKGROUND: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk.

METHODS AND FINDINGS: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. …

Low-Cost, High-Resolution Imaging For Detecting Cervical Precancer In Medically-Underserved Areas Of Texas, Sonia G Parra, Ana M Rodriguez, Katelin D Cherry, Richard A Schwarz, Rose M Gowen, Laura B Guerra, Andrea M Milbourne, Paul A Toscano, Susan P Fisher-Hoch, Kathleen M Schmeler, Rebecca R Richards-Kortum

Journal Articles

OBJECTIVE: Cervical cancer rates in the United States have declined since the 1940's, however, cervical cancer incidence remains elevated in medically-underserved areas, especially in the Rio Grande Valley (RGV) along the Texas-Mexico border. High-resolution microendoscopy (HRME) is a low-cost, in vivo imaging technique that can identify high-grade precancerous cervical lesions (CIN2+) at the point-of-care. The goal of this study was to evaluate the performance of HRME in medically-underserved areas in Texas, comparing results to a tertiary academic medical center.

METHODS: HRME was evaluated in five different outpatient clinical settings, two in Houston and three in the RGV, with medical providers …

Low-Cost, High-Resolution Imaging For Detecting Cervical Precancer In Medically-Underserved Areas Of Texas, Sonia G Parra, Ana M Rodriguez, Katelin D Cherry, Richard A Schwarz, Rose M Gowen, Laura B Guerra, Andrea M Milbourne, Paul A Toscano, Susan P Fisher-Hoch, Kathleen M Schmeler, Rebecca R Richards-Kortum

Journal Articles

OBJECTIVE: Cervical cancer rates in the United States have declined since the 1940's, however, cervical cancer incidence remains elevated in medically-underserved areas, especially in the Rio Grande Valley (RGV) along the Texas-Mexico border. High-resolution microendoscopy (HRME) is a low-cost, in vivo imaging technique that can identify high-grade precancerous cervical lesions (CIN2+) at the point-of-care. The goal of this study was to evaluate the performance of HRME in medically-underserved areas in Texas, comparing results to a tertiary academic medical center.

METHODS: HRME was evaluated in five different outpatient clinical settings, two in Houston and three in the RGV, with medical providers …

Nuclear Receptor Subfamily 4 Group A Member 2 Inhibits Activation Of Erk Signaling And Cell Growth In Response To Β-Adrenergic Stimulation In Adult Rat Cardiomyocytes, Sadia Ashraf, Yassmin K Hegazy, Romain Harmancey

Journal Articles

Sustained elevation of sympathetic activity is an important contributor to pathological cardiac hypertrophy, ventricular arrhythmias, and left ventricular contractile dysfunction in chronic heart failure. The orphan nuclear receptor NR4A2 is an immediate early-response gene activated in the heart under β-adrenergic stimulation. The goal of this study was to identify the transcriptional remodeling events induced by increased NR4A2 expression in cardiomyocytes and their impact on the physiological response of those cells to sustained β-adrenergic stimulation. Treatment of adult rat ventricular myocytes with isoproterenol induced a rapid (<4 >h) increase in NR4A2 levels that was accompanied by a transient (<24 >h) increase …

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

Dissertations & 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 …

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

Dissertations & 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 …

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

Dissertations & 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 …

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

Dissertations & 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 …

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

Dissertations & 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 …

Health Coaching To Encourage Obese Adults To Enroll In Commercially-Available Weight Management Programs: The Path To Health Study, Natalia I Heredia, Minjae Lee, Kevin O Hwang, Belinda M Reininger, Maria E Fernandez, Lorna H Mcneill

Journal Articles

Physicians are recommended to screen and refer obese patients to weight management programs (WMPs). There are often limited referral options for physicians, though commercially-available WMPs could be a potential solution. The purpose of this study (Path to Health) was to evaluate the efficacy of health coaching to promote enrollment in commercially-available WMPs through a two-arm, RCT with obese patients (n = 168) randomly assigned to intervention (n = 84) or control groups (n = 84). Intervention participants received phone health coaching to help them select and enroll in WMPs. We collected data on program enrollment, weight, self-reported physical activity (PA), …

The Significance Of So-Called Equivocal Immunohistochemical Staining For Cytomegalovirus In Colorectal Biopsies, Manju Ambelil, David M Saulino, Atilla Ertan, Andrew W Dupont, Mamoun Younes

Journal Articles

CONTEXT.—: Recent studies examining immunohistochemical staining of colorectal biopsies for cytomegalovirus (CMV) reported that some cases showed only occasional small positive nuclei that were called equivocal for CMV.

OBJECTIVES.—: To determine the extent and clinical significance of equivocal CMV staining in colorectal biopsies.

DESIGN.—: Two-hundred twenty-one consecutive cases of colon and rectal biopsies that were stained for CMV by immunohistochemistry were retrieved from our files and reviewed. Staining results were recorded as negative, unequivocal, or equivocal. Results were correlated with clinicopathologic data, results of polymerase chain reaction studies for CMV, and treatment history.

RESULTS.—: Fifty-two cases (24% of all tested, …

Datagauge: A Practical Process For Systematically Designing And Implementing Quality Assessments Of Repurposed Clinical Data, Jose-Franck Diaz-Garelli, Elmer V Bernstam, Minjae Lee, Kevin O Hwang, Mohammad H Rahbar, Todd R Johnson

Journal Articles

The well-known hazards of repurposing data make Data Quality (DQ) assessment a vital step towards ensuring valid results regardless of analytical methods. However, there is no systematic process to implement DQ assessments for secondary uses of clinical data. This paper presents DataGauge, a systematic process for designing and implementing DQ assessments to evaluate repurposed data for a specific secondary use. DataGauge is composed of five steps: (1) Define information needs, (2) Develop a formal Data Needs Model (DNM), (3) Use the DNM and DQ theory to develop goal-specific DQ assessment requirements, (4) Extract DNM-specified data, and (5) Evaluate according to …

Pyroglutamic Acidemia: An Underrecognized And Underdiagnosed Cause Of High Anion Gap Metabolic Acidosis - A Case Report And Review Of Literature, Sidish S Venkataraman, Rachel Regone, Hussam M Ammar, Rukma R Govindu

Journal Articles

Pyroglutamic acidemia (oxoprolinemia) is an underrecognized cause of high anion gap acidosis resulting from derangement in the gamma-glutamyl cycle. Pyroglutamic acidemia is most commonly diagnosed in the pediatric population in patients with inherited autosomal recessive enzyme deficiencies. However, acquired pyroglutamic acidemia can present in the adult population. Patients often present with confusion, nausea, and vomiting as well as an elevated anion gap metabolic acidosis. This article describes a case of acquired pyroglutamic acidemia and emphasizes the need to consider this entity.

In Vitro Characterization Of Sonothrombolysis And Echocontrast Agents To Treat Ischemic Stroke, Himanshu Shekhar, Robert T Kleven, Tao Peng, Arunkumar Palaniappan, Kunal B Karani, Shaoling Huang, David D Mcpherson, Christy K Holland

Journal Articles

The development of adjuvant techniques to improve thrombolytic efficacy is important for advancing ischemic stroke therapy. We characterized octafluoropropane and recombinant tissue plasminogen activator (rt-PA)-loaded echogenic liposomes (OFP t-ELIP) using differential interference and fluorescence microscopy, attenuation spectroscopy, and electrozone sensing. The loading of rt-PA in OFP t-ELIP was assessed using spectrophotometry. Further, it was tested whether the agent shields rt-PA against degradation by plasminogen activator inhibitor-1 (PAI-1). An in vitro system was used to assess whether ultrasound (US) combined with either Definity or OFP t-ELIP enhances rt-PA thrombolysis. Human whole blood clots were mounted in a flow system and visualized …

Integrating Diverse Disciplines To Enhance Interprofessional Competency In Healthcare Delivery, Tiffany Champagne-Langabeer, Lee Revere, Mariya Tankimovich, Erica Yu, Robert Spears, Jennifer Lee Swails

Journal Articles

Interprofessional education (IPE) typically involves clinical simulation exercises with students from medical and nursing schools. Yet, healthcare requires patient-centered teams that include diverse disciplines. Students from public health and informatics are rarely incorporated into IPE, signaling a gap in current educational practices. In this study, we integrated students from administrative and non-clinical disciplines into traditional clinical simulations and measured the effect on communication and teamwork. From July 2017-July 2018, 408 students from five schools (medicine, nursing, dentistry, public health, and informatics) participated in one of eight three-hour IPE clinical simulations with Standardized Patients and electronic health record technologies. Data were …

Adam Christian Thebesius' Channels Into The Human Heart: The Thebesian Veins And The Thebesian Valve, Magdalena Mazurak, Jacek Kusa

The Texas Heart Institute Journal

In 1708, Adam Christian Thebesius, a 22-year-old student at Leiden University, presented his graduate thesis, Disputatio medica inauguralis de circulo sanguinis in corde. More than a doctoral dissertation, this groundbreaking work opened new channels into the study of the human coronary venous system. Thebesius' theory about the vascular communication between the coronary arteries and the chambers of the heart helped to advance understanding of hemodynamic principles and to clarify the physiologic pathways of the coronary circulation. The following article—the third in a trilogy about Lower Silesian scientists—provides an overview of the life story and achievements of this Silesian physician …

Goosebumps, Efrain Rodriguez

The Texas Heart Institute Journal

No abstract provided.

Percutaneous Coronary Intervention For Interposed Coronary Graft Stenosis After Modified Bentall Procedure In A Teenaged Boy With Takayasu Arteritis, Hiroki Ikenaga, Satoshi Kurisu, Yasuki Kihara

The Texas Heart Institute Journal

Anastomotic occlusion of an interposed coronary artery graft after a Bentall procedure is rare and catastrophic. It can lead to myocardial infarction or sudden cardiac death. We found several reports of occlusion and stenosis of a coronary-graft anastomosis, but few describe occlusion of the interposed coronary graft itself, as evaluated with use of intracoronary ultrasonography and computed tomography. We report the case of a 17-year-old boy with Takayasu arteritis who had a myocardial infarction caused by severe ostial stenosis in an interposed left coronary graft. The graft occlusion was confirmed by results of electrocardiography, aortography, and intracoronary ultrasonography. The patient …

The Man With 2 Hearts: 25 Years From Heterotopic To Orthotopic Heart Transplantation, Elizabeth L Godfrey, Michael L Kueht, Abbas Rana, O H Frazier

The Texas Heart Institute Journal

Substantial technological advances in mechanical circulatory support have caused a shift in the management of end-stage heart failure. From the 1970s through the 1990s, heterotopic heart transplantation was routinely performed in patients in whom orthotopic transplantation was likely to fail. Heterotopic heart transplantation is now performed less often because modern mechanical circulatory assist devices are routinely used as bridges to orthotopic transplantation; regardless, the operation has helped numerous patients who would not otherwise have received adequate allografts. We describe the case of a man with idiopathic nonischemic cardiomyopathy who, at age 17, was given an ABO- and size-matched heterotopic allograft …

Osborn Waves: Differential Diagnosis, Akriti G Jain, Hammad Zafar, Sanjay Jain, Jason D'Souza

The Texas Heart Institute Journal

No abstract provided.

Anomalous Origin Of The Right Coronary Artery From The Pulmonary Artery In A Neonate With Turner Syndrome And Aortic Arch Hypoplasia, Bryan P Stefek, Jason R Imundo, Joseph B Clark

The Texas Heart Institute Journal

Anomalous origin of the right coronary artery from the pulmonary artery, a rare congenital cardiac defect, is typically not diagnosed during infancy. On the other hand, Turner syndrome is usually diagnosed early, and it is classically associated with bicuspid aortic valve and aortic coarctation. Individuals with Turner syndrome are also at increased risk for coronary artery anomalies. We present a case of anomalous right coronary artery from the pulmonary artery in a week-old neonate who also had Turner syndrome, patent ductus arteriosus, transverse aortic arch hypoplasia, and impaired ventricular function. Prostaglandin therapy through the ductus increased the patient's myocardial perfusion. …