Translational Medical Research Commons^™

The Histone Deacetylase Inhibitor Tubacin Mitigates Endothelial Dysfunction By Up-Regulating The Expression Of Endothelial Nitric Oxide Synthase., Jihui Chen, Jian Zhang, Noor F. Shaik, Bing Yi, Xin Wei, Xiao-Feng Yang, Ulhas P. Naik, Ross Summer, Guijun Yan, Xinyun Xu, Jianxin Sun

Center for Translational Medicine Faculty Papers

Endothelial nitric oxide (NO) synthase (eNOS) plays a critical role in the maintenance of blood vessel homeostasis. Recent findings suggest that cytoskeletal dynamics play an essential role in regulating eNOS expression and activation. Here, we sought to test whether modulation of cytoskeletal dynamics through pharmacological regulation of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation affects eNOS expression and endothelial function in vitro and in vivo.Wefound that tubulin acetylation inducer (tubacin), a compound that appears to selectively inhibit HDAC6 activity, dramatically increased eNOS expression in several different endothelial cell lines, as determined by both immunoblotting and NO production assays. Mechanistically, we found …

A Drive To Driven Model Of Mapping Intraspecific Interaction Networks., Libo Jiang, Jian Xu, Mengmeng Sang, Yan Zhang, Meixia Ye, Hanyuan Zhang, Biyin Wu, Youxiu Zhu, Peng Xu, Ruyu Tai, Zixia Zhao, Yanliang Jiang, Chuanju Dong, Lidan Sun, Christopher H. Griffin, Claudia Gragnoli, Rongling Wu

Division of Endocrinology, Diabetes and Metabolic Diseases Faculty Papers

Community ecology theory suggests that an individual's phenotype is determined by the phenotypes of its coexisting members to the extent at which this process can shape community evolution. Here, we develop a mapping theory to identify interaction quantitative trait loci (QTL) governing inter-individual dependence. We mathematically formulate the decision-making strategy of interacting individuals. We integrate these mathematical descriptors into a statistical procedure, enabling the joint characterization of how QTL drive the strengths of ecological interactions and how the genetic architecture of QTL is driven by ecological networks. In three fish full-sib mapping experiments, we identify a set of genome-wide QTL …

The Role Of Histone Chaperone Fact Complex In Base Excision Repair Pathway And Its Therapeutic Potential In Colon Cancer And Medulloblastoma, Heyu Song

Theses & Dissertations

Base excision repair (BER) pathway is required for the removal of damaged bases caused by alkylation, oxidation and ring-saturation. Human apurinic/apyrimidinic endonuclease 1 (APE1) plays a central role in BER pathway. Although repair of damaged bases by recombinant APE1 has been well investigated in vitro, how APE1 gains access to damaged bases in the context of chromatin is largely unknown. A prominent member of the histone chaperone family, FACT (Facilitates Chromatin Transcription) is thought to reorganize nucleosomes through the destabilization of multiple intra-nucleosome contacts. FACT complex is composed of two polypeptides identified as SPT16 (Suppressor of Ty 16) and SSRP1 …

An Analysis Of Abdominal Stability Following Hyperthermic Exercise In Euhydrated And Dehydrated Conditions, Carli Ceckanowicz

Honors Scholar Theses

Core stability is essential for maintaining safety and optimizing performance during exercise and sport. The purpose of this study is to analyze how heat and hydration status (euhydrated USG<1.025 or dehydrated USG>1.025) can impair trunk stability in males and females (in both follicular and luteal phases) using the Trunk Stability Test (TST). Participants complete three blocks of 30 minutes of hyperthermic (35±1.299 ^oC and 49.418±5.0329% relative humidity) treadmill exercise. Exercise intensity is equivalent to 15 minutes at either 11W/kg or 7W/kg and the following 15 minutes at either 7W/kg or 4W/kg, respectively, based on individual heat production data. TST data will …

The Biomedical Application Of Chimeric Antigen Receptor T Cell Therapy, Jessica Devenport

Arts & Sciences Electronic Theses and Dissertations

No abstract provided.

Preparing Healthcare Staff For Cardiac Arrest Codes In The Outpatient Clinical Setting: Code Drill Training Improves Patient Outcomes, Rowan Edwards, Rn

Master's Projects and Capstones

Preparing Healthcare Staff for Cardiac Arrest Codes in the Outpatient Clinical Setting: Code Drill Training Improves Patient Outcomes

The acuity of care provided in outpatient clinical settings across the United States continues to rise. It is estimated that more than 350,000 cardiac arrests occur outside of a hospital each year (AHA, 2019). For the purpose of this clinical nurse leader (CNL)-lead quality improvement project, the relevant focus is directed towards improving the knowledge, physical skills and perceptions of healthcare staff within an urgent care center (UCC) regarding the application of advanced rescue skills. It is important to note that the …

Underreporting Of Patient-Reported Outcomes In Myeloproliferative Neoplasms Clinical Trials, Anthony Messina, Quentin O'Brien

Clinical Research and Leadership Faculty Posters and Presentations

Introduction

Improvements in overall survival (OS) and quality of life (QoL) are clinically relevant outcomes that should guide clinical decision-making. Patients with MPNs can live with their disease for a long period of time, which increases the importance of understanding the impact of treatment in regards to a patients’ Health-Related QoL. Therefore, including PROs in clinical trials has become paramount in facilitating informed treatment decisions made by health care providers and patients. Furthermore, the FDA encourages the implementation of patient-centric measures in clinical trials.

Objective

We aimed to evaluate the frequency at which PRO measures are utilized as study endpoints …

Relevance Of Fgfr1 And Its Isoforms In Prostate Cancer Bone Metastases, Estefania Labanca

Dissertations & Theses (Open Access)

The fibroblast growth factor receptor (FGFR) 1 is implicated in prostate cancer (PCa) progression. Various FGFR1 isoforms have been described and we demonstrate here that the well-characterized FGFR1 a and b isoforms are correlated with the expression of different genes and pathways in human PCa. Direct injection of PC3 PCa cells overexpressing FGFR1 isoforms into the femur of mice resulted in enhanced tumor growth and reduction in bone volume when compared with PC3 expressing empty vector. However, only PC3 overexpressing FGFR1 b was associated with increased osteoclast parameters, suggesting that each isoform may mediate diverse biological effects (similar findings were …

A Recombinant Cholera Toxin B Subunit Variant (Ctb-Kdel) Exhibits Unique Colon Mucosal Healing Effects That Have Therapeutic Implications For Inflammatory Bowel Disease., Joshua Mark Royal

Electronic Theses and Dissertations

This dissertation uncovers the mechanism and explores the utility of a recombinant cholera toxin B subunit (CTB) variant containing a KDEL endoplasmic reticulum (ER) retention motif (CTB-KDEL) as a drug candidate for the treatment of inflammatory bowel disease (IBD). CTB is a mucosal immunomodulatory protein that induces robust mucosal and systemic antibody responses. This well-known biological activity has been exploited in cholera prevention (as a component of Dukoral® vaccine) and vaccine development for decades. On the other hand, several studies have investigated CTB’s immunotherapeutic potential in the treatment of inflammatory diseases such as Crohn’s disease and asthma. Here, we reveal …

Hypothyroidism, Sex And Age Predict Future Thromboembolic Events Among Younger People, Supplementary Table 1, Jay A. Martinez, Fares Qeadan, Mark R. Burge

Clinical and Translational Science Center Scholarly Output

This is Supplementary Table 1 for a forthcoming publication in the Journal of Clinical Endocrinology and Metabolism, entitled "Hypothyroidism, Sex and Age Predict Future Thromboembolic Events Among Younger People," by Authors Jay A. Martinez, Fares Qeadan, PhD, and Mark R. Burge, MD

Supplement Table 1: ICD-9 and ICD-10 codes employed in this study for inclusion and exclusion purposes.

Community-Acquired Pneumonia Pathogenesis In Patients With Chronic Obstructive Pulmonary Disease, Julio A. Ramirez, Rodrigo Cavallazzi

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Twenty Novel Disease Group-Specific And 12 New Shared Macrophage Pathways In Eight Groups Of 34 Diseases Including 24 Inflammatory Organ Diseases And 10 Types Of Tumors., Bin Lai, Jiwei Wang, Alexander Fagenson, Yu Sun, Jason Saredy, Yifan Lu, Gayani Nanayakkara, William Y Yang, Daohai Yu, Ying Shao, Charles Drummer, Candice Johnson, Fatma Saaoud, Ruijing Zhang, Qian Yang, Keman Xu, Kevin Mastascusa, Ramon Cueto, Hangfei Fu, Susu Wu, Lizhe Sun, Peiqian Zhu, Xuebin Qin, Jun Yu, Daping Fan, Ying H Shen, Jianxin Sun, Thomas Rogers, Eric T Choi, Hong Wang, Xiaofeng Yang

Center for Translational Medicine Faculty Papers

The mechanisms underlying pathophysiological regulation of tissue macrophage (Mφ) subsets remain poorly understood. From the expression of 207 Mφ genes comprising 31 markers for 10 subsets, 45 transcription factors (TFs), 56 immunometabolism enzymes, 23 trained immunity (innate immune memory) enzymes, and 52 other genes in microarray data, we made the following findings. (1) When 34 inflammation diseases and tumor types were grouped into eight categories, there was differential expression of the 31 Mφ markers and 45 Mφ TFs, highlighted by 12 shared and 20 group-specific disease pathways. (2) Mφ in lung, liver, spleen, and intestine (LLSI-Mφ) express higher M1 Mφ …

Association Of Urine Levels Of C-Reactive Protein With Clinical Outcomes In Patients With Pneumonia: A Pilot Study, Subathra Marimuthu, Vidyulata Salunkhe, Stephen P. Furmanek, Leslie A Wolf

The University of Louisville Journal of Respiratory Infections

Finding relevant biomarkers as a potential predictor of severity for patients hospitalized with community acquired pneumonia (CAP), in addition to the clinical scoring system, could advance progress towards more effective patient management. The inflammatory marker, C-reactive protein (CRP), which is elevated in the pathogenesis of many infectious diseases, may be a key biomarker target for CAP. Previous studies have shown that serum CRP may be a useful diagnostic marker for pneumonia in hospitalized patients with acute respiratory symptoms. The main aims of this study were to determine the correlation between serum and urine CRP levels in hospitalized patients with CAP, …

Managing A Conflict-Related, Open Fracture With Drug-Resistant Infections: The Case Of A Wounded Syrian Refugee In The Hashemite Kingdom Of Jordan, Alex Green

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Uruc V, Ozden R, Duman IG, Dogramaci Y, Yengil E, Karapinar S, Karakus A, Kalaci A. Major musculoskeletal injuries and applied treatments in the current conflicts in Syria. Acta Medica Mediterranea. 2014;30(3):637-644.

Fondaparinux Is An Effective Alternative To Other Non-Heparin Anticoagulants In The Treatment Of Heparin-Induced Thrombocytopenia, Allan J. Brazier Jr.

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Kang M, Alahmadi M, Sawh S, Kovacs MJ, Lazo-Langner A. Fondaparinux for the treatment of suspected heparin-induced thrombocytopenia: a propensity score-matched study. Blood. 2014;125(6):924-929. doi: 10.1182/blood-2014-09-599498.

The Value Of Innovation To Implementation Program (Vi2p): A Strategic Approach To Aligning And Leveraging Academic Research And Clinical Care Missions, Jing Li, Mark V. Williams, Cecilia Page, Lisa A. Cassis, Philip A. Kern, Robert S. Dipaola

Clinical and Translational Science Faculty Publications

Problem: Inefficient implementation of evidence-based care garners increasing attention as a source of suboptimal value of clinical care, and integration of quality improvement methodology into clinical practice represents a potential solution. Academic medical centers (AMCs) often have expertise in implementation science, yet it is not leveraged effectively to solve operational inefficiencies or to rapidly implement evidence-based practices (EBPs).

Approach: To leverage in-house research expertise, the University of Kentucky (UK) College of Medicine and Center for Health Services Research (CHSR) launched a pilot awards program—Value of Innovation to Implementation Program (VI2P)—across its health system and six health professional colleges. Criteria for …

Amantadine Minimally Improves Arousal In Patients With Severe Traumatic Brain Injury, Michelle Eventov

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Giacino JT, Whyte J, Bagiella E, et al. Placebo-Controlled Trial of Amantadine for Severe Traumatic Brain Injury. New England Journal of Medicine. 2012;366(9):819-826. doi: 10.1056/nejmoa1102609.

Pyk2 Expression And Localization In Cardiac Mitochondria And Its Role In Mitochondrial Calcium Regulation, Ariele Baggett, Celia Fernandez-Sanz, Sergio De La Fuente, Johannes Hoek, Shey-Shing Sheu

Center for Translational Medicine Posters

TRPM2 is a non-selective cation channel located in the plasma membrane of the cell. Upon activation, the channel opens, allowing calcium to enter into the cytosol of the cell, leading ultimately to the phosphorylation and activation of the enzyme Pyk2 (proline-rich tyrosine kinase 2). Once phosphorylated, Pyk2 translocates from the cytosol to the mitochondria, where it regulates the formation of the pore component of the mitochondrial calcium uniporter (MCU) complex. Consequently, this interaction is a key factor in mitochondrial calcium uptake and therefore mitochondrial bioenergetics.

Gsk3Β-Dependent Phosphorylation Of Cypd And Regulation Of Mptp Opening During Myocardial Infarction, Stephen Hurst, Ludovic Gomez, Shey-Shing Sheu

Center for Translational Medicine Posters

Background

Mitochondrial calcium overload and oxidative stress during ischemia reperfusion (I/R) injury remains a major obstacle during percutaneous coronary intervention after acute myocardial infarction. It often leads to an increased susceptibility for mitochondria permeability transition pore (mPTP) opening leading to cell death. Mitochondrial calcium overload and ROS have been identified as key triggers to open the mPTP for over 30 years, yet the exact mechanism has remained elusive. Additionally, glycogen synthase kinase 3β; (GSK-3β;) is proposed as one of the key molecules that regulate mitochondrial dysfunction and injury during I/R. Indeed inhibition of GSK-3β has been shown to be required …

Metformin Blunts Muscle Hypertrophy In Response To Progressive Resistance Exercise Training In Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial: The Masters Trial, R. Grace Walton, Cory M. Dungan, Douglas E. Long, S. Craig Tuggle, Kate Kosmac, Bailey D. Peck, Heather M. Bush, Alejandro G. Villasante Tezanos, Gerald Mcgwin, Samuel T. Windham, Fernando Ovalle, Marcas M. Bamman, Philip A. Kern, Charlotte A. Peterson

Clinical and Translational Science Faculty Publications

Progressive resistance exercise training (PRT) is the most effective known intervention for combating aging skeletal muscle atrophy. However, the hypertrophic response to PRT is variable, and this may be due to muscle inflammation susceptibility. Metformin reduces inflammation, so we hypothesized that metformin would augment the muscle response to PRT in healthy women and men aged 65 and older. In a randomized, double-blind trial, participants received 1,700 mg/day metformin (N = 46) or placebo (N = 48) throughout the study, and all subjects performed 14 weeks of supervised PRT. Although responses to PRT varied, placebo gained more lean body …

Reflection: Reducing Long-Term Mortality In Suicidal Adolescents, Nina R. Bihani

Clinical Research in Practice: The Journal of Team Hippocrates

A transformative method to reducing mortality in suicidal adolescents involves a novel approach of educating and empowering their loved ones.

Reduced Doses Of Direct Oral Anticoagulation Are Safe In Atrial Fibrillation Patients With Mild Thrombocytopenia, Matthew Gross

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Janion-Sadowska A, Papuga-Szela E, Łukaszuk R, et al. Non–Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation and Thrombocytopenia. Journal of Cardiovascular Pharmacology. 2018;72(3):153-160. doi: 10.1097/fjc.0000000000000607

Nsaid Use Increases Risk Of Miscarriage In Early Pregnancy, Leigh Durudogan

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Li D, Ferber J, Odouli R, Quesenberry C. Use of nonsteroidal anti-inflammatory drugs during pregnancy and the risk of miscarriage. Am J Ob Gyn. 2018; 219(3): 275.e1–275.e8. doi: 10.1016/j.ajog.2018.06.002.

Fecal Microbiota Therapy In Recurrent And Refractory Clostridium Difficile Infections Has Been Associated With Positive Results In Immunocompromised Patients, Eric Applebach

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Kelly CR, Ihunnah C, Fischer M, et al. Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients. The American Journal of Gastroenterology, 2014;109(7):1065-71. doi: 10.1038/ajg.2014.133

Intravenous Iodinated Contrast Is Not Associated With Acute Kidney Injury In Adult Patients With Nephrotic Syndrome, Andrew Bacyinski

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Tao SM, Kong X, Schoepf UJ, et al. Acute kidney injury in patients with nephrotic syndrome undergoing contrast-enhanced CT for suspected venous thromboembolism: a propensity score-matched retrospective cohort study. European Radiology. 2018;28(4):1585-1593. doi: 10.1007/s00330-017-5109-0

Getting Sexual And Gender Minority Health “Into The Brick And Mortar”: A Mixed Methods Implementation Study, Mandi Pratt-Chapman

Doctor of Philosophy in Translational Health Sciences Dissertations

Sexual and gender minorities (SGM) have unique health risks and health care needs, but medical students receive little training on SGM health (Obedin-Maliver, et al., 2011). This mixed methods study sought to learn from curricular champions in diverse settings to apply lessons learned at the George Washington University (GW). Exploratory models that included eight potential predictor variables for six criterion variables were tested using multiple linear regression. Criterion variables were: knowledge, attitudes, and clinical preparedness measured by the Lesbian, Gay, Bisexual, and Transgender Development of Clinical Skills Scale (LGBT-DOCSS; Bidell, 2017); attitudes measured by the Attitudes Toward LGBT Patients Scale …

Carvedilol Is Not Superior To Metoprolol For Heart Failure Patients When Given At Equivalent Doses, Adam Gorman

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Lazarus DL, Jackevicius CA, Behlouli H, et al. Population-Based Analysis of Class Effect of β Blockers in Heart Failure. The American Journal of Cardiology 2011;107(8):1196-1202. doi: 10.1016/j.amjcard.2010.12.017.

Weighing Harms, Benefits, And Alternatives For A Young Man With A Recent Flare Of Ulcerative Colitis, Louise B. Welsh

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Sandborn WJ, Su C, Sands B, et al. Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med. 2017 May 4;376(18):1723-1736. doi: 10.1056/NEJMoa1606910

Thrombosis Prevention In Atrial Fibrillation With Concomitant Cirrhosis: Oral Anticoagulation May Not Be Worth The Risks, Madeline Berschback

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Kuo L, Chao TF, Liu CJ, et al. Liver cirrhosis in patients with atrial fibrillation: Would oral anticoagulation have a net clinical benefit for stroke prevention? J Am Heart Assoc. 2017;6(6):e005307. doi: 10.1161/jaha.116.005307

Andexanet Alfa Is An Effective Reversal Agent For Factor Xa Inhibitors In Patients That Develop Intracranial Hemorrhage, Joseph Friedli

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Connolly SJ, Milling TJ, Eikelboom JW, et al. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med. 2016;375(12):1131-1141. doi: 10.1056/NEJMoa1607887.