Translational Medical Research Commons^™

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.

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 …

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.

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.

Cannabidiol Is Beneficial In Management Of Drug-Resistant Dravet Syndrome, Nikita Desai

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Devinsky O, Cross H, Laux L, et al. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med. 2017;376(21):2011-2020. doi: 10.1056/NEJMoa1611618.

Agenesis Of The Corpus Callosum Is Associated With Developmental Delay And Intellectual Disability, Quinton J. Mandle

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Romaniello R, Marelli S, Giorda R, et al. Clinical characterization, genetics, and long-term follow-up of a large cohort of patients with agenesis of the corpus callosum. Journal of Child Neurology, 2016;32(1):60-71. doi: 10.1177/0883073816664668.

Ranolazine Decreases Weekly Anginal Episodes In Patients With Chronic Stable Angina And Type 2 Diabetes, Hisham Kaddurah

Clinical Research in Practice: The Journal of Team Hippocrates

The author reflects on the meaningful difference between statistical and clinical significance.

Tevar Should Be Considered In Select Patients With Uncomplicated Stanford Type B Aortic Dissection, Mordechai G. Sadowsky

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Nienaber CA, Kische S, Rousseau H, et al. Endovascular repair of type B aortic dissection: long-term results of the randomized investigation of stent grafts in aortic dissection trial. Circ Cardiovasc Interv, 2013;6(4):407-16. doi: 10.1161/circinterventions.113.000463.

Insights Into The Hiv Latency And The Role Of Cytokines., Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Manjari Dimri, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Human immunodeficiency virus-1 (HIV-1) has the ability to infect latently at the level of individual CD4+ cells. Latent HIV-1 proviruses are transcriptionally silent and immunologically inert, but are still capable of reactivating productive lytic infection following cellular activation. These latent viruses are the main obstacle in the eradication of HIV-1, because current HIV-1 treatment regimens are ineffective against them. Normal immunological response against an antigen activates CD4+ naïve T cells. The activated CD4+ naïve T cells undergo cell cycle, resulting in further transformation and profound proliferation to form effector CD4+ T-cells. Notably, in HIV-1 infected individuals, some of the effector …