Translational Medical Research Commons^™

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 …

Fatty Acid Metabolites Combine With Reduced Β Oxidation To Activate Th17 Inflammation In Human Type 2 Diabetes, Dequina A. Nicholas, Elizabeth A. Proctor, Madhur Agrawal, Anna C. Belkina, James M. Van Nostrand, Leena Panneerseelan-Bharath, Albert R. Jones Iv, Forum Raval, Blanche C. Ip, Min Zhu, Jose M. Cacicedo, Chloe Habib, Nestor Sanez-Rueda, Leah Persky, Patrick G. Sullivan, Barbara E. Corkey, Caroline M. Apovian, Philip A. Kern, Douglas A. Lauffenburger, Barbara S. Nikolajczyk

Clinical and Translational Science Faculty Publications

Mechanisms that regulate metabolites and downstream energy generation are key determinants of T cell cytokine production, but the processes underlying the Th17 profile that predicts the metabolic status of people with obesity are untested. Th17 function requires fatty acid uptake, and our new data show that blockade of CPT1A inhibits Th17-associated cytokine production by cells from people with type 2 diabetes (T2D). A low CACT:CPT1A ratio in immune cells from T2D subjects indicates altered mitochondrial function and coincides with the preference of these cells to generate ATP through glycolysis rather than fatty acid oxidation. However, glycolysis was not critical for …

Mechanisms Of Simvastatin Myotoxicity: The Role Of Autophagy Flux Inhibition., Arya Emami, Shahla Shojaei, Simone C. Da Silva Rosa, Mahmoud Aghaei, Ehsan Samiei, Amir Reza Vosoughi, Forouh Kalantari, Philip Kawalec, James Thliveris, Pawan Sharma, Amir A. Zeki, Mohsen Akbari, Joseph W. Gordon, Saeid Ghavami

Center for Translational Medicine Faculty Papers

Statins are some of the most widely used drugs worldwide, but one of their major side effects is myotoxicity. Using mouse myoblast (C2C12) and human alveolar rhabdomyosarcoma cell lines (RH30) in both 2-dimensional (2D) and 3-dimensional (3D) cell culture, we investigated the mechanisms of simvastatin's myotoxicity. We found that simvastatin significantly reduced cell viability in C2C12 cells compared to RH30 cells. However, simvastatin induced greater apoptosis in RH30 compared to C2C12 cells. Simvastatin-induced cell death is dependent on geranylgeranyl pyrophosphate (GGPP) in C2C12 cells, while in RH30 cells it is dependent on both farnesyl pyrophosphate (FPP) and GGPP. Simvastatin inhibited …

Developing Drug Therapies: Cognitive Damage In Mice Following Brain Radiation, Rachel Yuska

The Journal of Purdue Undergraduate Research

Pediatric brain cancer patients are at a high risk for radiation-induced cognitive impairment due to white matter changes in the brain. Half of six-month radiotherapy survivors develop significant changes in white matter. Previous research has shown that a mouse model can be used to show similar cognitive and behavioral deficits in human patients. The purpose of this work is to evaluate the effectiveness of two drug therapies, Donepezil and 3,3-Diindolylmethane (DIM), that could be used to either protect the brain from radiation injury or cure the cognitive injury and behavioral deficits that result from whole-brain irradiation. This project consisted of …

P53r245w Mutation Elicits Metastatic Phenotype In Pten Deficient Prostate Cancer, Ky Pham

Dissertations and Theses (Open Access)

Trp53 mutations are the most frequent genetic alterations in prostate cancer and are associated with more aggressive disease and worse overall survival. The majority of Trp53 mutations in prostate cancer are missense mutations, resulting in amino acid substitutions with profound effect. In addition to the loss of wild type function, missense mutations in Trp53 result in a gain-of-function (GOF) phenotype. This GOF phenotype confers biologic advantages to the tumor cells, enabling them to metastasize and invade distant organs. In this study, we generated mice carrying a conditional prostate-specific p53R245W mutant and Pten deletion to access the role of this common …

Spg7 Targets The M-Aaa Protease Complex To Process Mcu For Uniporter Assembly, Ca2 Influx, And Regulation Of Mitochondrial Permeability Transition Pore Opening, Stephen Hurst, Ariele Baggett, György Csordás, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

The mitochondrial matrix ATPase associated with diverse cellular activities (m-AAA) protease spastic paraplegia 7 (SPG7) has been recently implicated as either a negative or positive regulatory component of the mitochondrial permeability transition pore (mPTP) by two research groups. To address this controversy, we investigated possible mechanisms that explain the discrepancies between these two studies. We found that loss of the SPG7 gene increased resistance to Ca²-induced mPTP opening. However, this occurs independently of cyclophilin D (cyclosporine A insensitive) rather it is through decreased mitochondrial Ca² concentrations and subsequent adaptations mediated by impaired formation of functional mitochondrial Ca …

Matrix Metalloproteinase Activity In The Lung Is Increased In Hermansky-Pudlak Syndrome., Ross Summer, Rachana Krishna, Deleila Schriner, Karina Cuevas-Mora, Dominic Sales, Rachel Para, Jesse Roman, Carl Nieweld, Bernadette R. Gochuico, Freddy Romero

Center for Translational Medicine Faculty Papers

BACKGROUND: Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and platelet dysfunction and can sometimes lead to a highly aggressive form of pulmonary fibrosis that mimics the fatal lung condition called idiopathic pulmonary fibrosis (IPF). Although the activities of various matrix metalloproteinases (MMPs) are known to be dysregulated in IPF, it remains to be determined whether similar changes in these enzymes can be detected in HPS.

RESULTS: Here, we show that transcript and protein levels as well as enzymatic activities of MMP-2 and -9 are markedly increased in the lungs of mice carrying the HPS …