Translational Medical Research Commons^™

Shedding Light On The Role Of Extracellular Vesicles In Hiv Infection And Wound Healing., Aseel Alqatawni, Adhikarimayum Lakhikumar Sharma, Beatrice Attilus, Mudit Tyagi, Rene Daniel

Center for Translational Medicine Faculty Papers

Extracellular vesicles (EVs) play an important role in intercellular communication. They are naturally released from cells into the extracellular environment. Based on their biogenesis, release pathways, size, content, and function, EVs are classified into exosomes, microvesicles (MVs), and apoptotic bodies (ApoBDs). Previous research has documented that EVs, specifically exosomes and MVs, play an important role in HIV infection, either by promoting HIV infection and pathogenesis or by inhibiting HIV-1 to a certain extent. We have also previously reported that EVs (particularly exosomes) from vaginal fluids inhibit HIV at the post-entry step (i.e., reverse transcription, integration). Besides the role that EVs …

Possible Role Of Tetracyclines On Covid-19: Recycling Well-Known Old Drugs From The Shelf, Martin Gnoni, Raul Vasquez-Gararatti, Angel Mena

The University of Louisville Journal of Respiratory Infections

We are in the midst of a pandemic due to the novel coronavirus SARS-CoV-2. Innovative therapies are in the lookup around the world. Recently, chloroquine and hydroxychloroquine in addition to azithromycin were proposed to be used in patients with severe disease even though strong evidence is lacking. We propose the use of tetracyclines in addition to anti-virals early in the curse of the disease in order to prevent the cytokine storm syndrome associated with COVID-19 and prevent ARDS. The proposed mechanisms of tetracyclines are: 1) anti-apoptotic properties; 2) decrease the Myeloperoxidase and ROS releaser from immune cells; 3) decrease neutrophil …

Variability In Naltrexone Biotransformation, Stephani L. Stancil

Research Days

No abstract provided.

The Short Variant Of Optic Atrophy 1 (Opa1) Improves Cell Survival Under Oxidative Stress., Hakjoo Lee, Sylvia B Smith, Shey-Shing Sheu, Yisang Yoon

Center for Translational Medicine Faculty Papers

Optic atrophy 1 (OPA1) is a dynamin protein that mediates mitochondrial fusion at the inner membrane. OPA1 is also necessary for maintaining the cristae and thus essential for supporting cellular energetics. OPA1 exists as membrane-anchored long form (L-OPA1) and short form (S-OPA1) that lacks the transmembrane region and is generated by cleavage of L-OPA1. Mitochondrial dysfunction and cellular stresses activate the inner membrane-associated zinc metallopeptidase OMA1 that cleaves L-OPA1, causing S-OPA1 accumulation. The prevailing notion has been that L-OPA1 is the functional form, whereas S-OPA1 is an inactive cleavage product in mammals, and that stress-induced OPA1 cleavage causes mitochondrial fragmentation …

The Role Of Inter-Enlargement Propriospinal Neurons In Locomotion Following Spinal Cord Injury., Courtney Therese Shepard

Electronic Theses and Dissertations

The focus of this dissertation is to explore the functional role of two anatomically-defined pathways in the adult rat spinal cord before and after spinal cord injury (SCI). To do this, a Tet^On dual virus system was used to selectively and reversibly silence neurons with cell bodies at spinal segment L2 and projections to spinal segment C6 (long ascending propriospinal neurons, LAPNs) and neurons that originate in the C6 spinal segment and terminate at L2 spinal segment (long descending propriospinal neurons, LDPNs). This dissertation is divided into five chapters. Chapter One provides background information regarding spinal cord injury, locomotion, …

Depression Is Associated With Decreased Severity And Lower Mortality In Non-Elderly Hospitalized Adults With Influenza In The United States, Timothy L. Wiemken, Daniel Hoft, Jeffrey Scherrer

The University of Louisville Journal of Respiratory Infections

Background: Depression is associated with risk for chronic disease, though its relationship with infectious diseases is less understood. Depression may modify the clinical outcomes of patients with infectious diseases such as influenza via its association with inflammation. The objective of this study was to evaluate the relationships between depression and clinical outcomes in non-elderly adults with influenza infection.

Methods: This was a secondary analysis of the Nationwide Inpatient Sample database, years 2012–2016. Hospitalized adults aged 18–65 admitted during each influenza season were included. Depression status was documented via ICD-10 codes. The association between depression and clinical outcomes (e.g., …

Preclinical Studies Of A Novel Idh1 Inhibitor In Acute Myeloid Leukemia (Aml), Vivian Salama

Dissertations and Theses (Open Access)

LY3410738, a novel covalent Isocitrate Dehydrogenase 1 (IDH1) inhibitor in Acute Myeloid Leukemia, it is more effective than Ivosidenib (AG120) and has a potent anti-leukemic effect against IDH1 mutant acute myeloid leukemia in combination with Venetoclax (ABT-199).

Acute myeloid Leukemia (AML) is an aggressive neoplastic blood disorder characterized by proliferation of poorly differentiated cells of myeloid lineage. IDH1 is a cytoplasmic enzyme that catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG) in the citric acid cycle. Somatic gain-of-function mutations in IDH1 occur in ~10% of the newly diagnosed AML patients. The neo-enzymatic activity of mutant IDH1 results in accumulation …

Receptor Tyrosine Kinases-Mediated Acquired Parp Inhibitor Resistance In Breast Cancer, Mei-Kuang Chen

Dissertations and Theses (Open Access)

Leveraging compromised DNA damage repair (DDR) pathways commonly found in tumor cells, a classic strategy in cancer therapy is inducing excessive DNA damage to cause cancer cell death. Small molecule poly(ADP-ribose) polymerase (PARP) inhibitors (PARP-is) have been approved for clinical use in treating breast cancer and ovarian cancer patients bearing DDR-deficient tumors with mutations in breast cancer susceptibility genes (BRCA^m). However, accumulating evidences show that both intrinsic and acquired resistances to PARP-is exist in clinic and pre-clinical animal models. Therefore, I developed panels of cells with acquired PARP-is resistance from PARP-is-sensitive triple negative breast cancer (TNBC) cell …

Development Of Fully Balanced Ssfp And Computer Vision Applications For Mri-Assisted Radiosurgery (Mars), Jeremiah Sanders

Dissertations and Theses (Open Access)

Prostate cancer is the second most common cancer in men and the second-leading cause of cancer death in men. Brachytherapy is a highly effective treatment option for prostate cancer, and is the most cost-effective initial treatment among all other therapeutic options for low to intermediate risk patients of prostate cancer. In low-dose-rate (LDR) brachytherapy, verifying the location of the radioactive seeds within the prostate and in relation to critical normal structures after seed implantation is essential to ensuring positive treatment outcomes.

One current gap in knowledge is how to simultaneously image the prostate, surrounding anatomy, and radioactive seeds within the …

A Call For Grounding Implicit Bias Training In Clinical And Translational Frameworks, Nao Hagiwara, Frederick W. Kron, Mark W. Scerbo, Ginger S. Watson

Psychology Faculty Publications

Since the publication of Unequal Treatment in 2003,¹ the number of studies investigating the implicit bias of health-care providers and its troubling consequences has increased exponentially. Bias can occur in all three psychological components: affects (ie, prejudice), cognition (ie, stereotypes), and behaviour (ie, discrimination). Implicit bias refers to prejudicial attitudes towards and stereotypical beliefs about a particular social group or members therein. These prejudicial attitudes and stereotypical beliefs are activated spontaneously and effortlessly, which often result in discriminatory behaviours.² This definition is consistent with how implicit bias is defined in psychology³ and in literature on health disparities. …

How Immune T-Cell Augmentation Can Help Prevent Covid-19: A Possible Nutritional Solution Using Ketogenic Lifestyle, Ravi K. Kamepalli Md,Fidsa,Cwsp

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Covid-19, Colleagues, Confusion, And Conversations, Nathanael R. Sanchez M.D., Katherine S. Lee , M.D., Karen Weaver M.D.

Clinical Research in Practice: The Journal of Team Hippocrates

During the COVID-19 pandemic, doctors in a community hospital reflect on their decision-making regarding treatment options for COVID-19. Whether to use hydroxychloroquine is the treatment discussed in most detail.

When Rationing Becomes Part Of Clinical Decision-Making, Christopher A. Hopper, Mitra Bahaee

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical practice-based reflection on Noack DP, Newton G. Compared to maximal current management standards, oscillating positive expiratory pressure devices have not been shown to improve clinically relevant outcomes in COPD patients with acute exacerbation. Clin. Res. Prac. 2017;3(2):eP1516. doi: 10.22237/crp/149886732.

Clinical Decision Science Suggests Different Research Questions Need To Be Asked Related To Informed Consent, John K. Geddes

Clinical Research in Practice: The Journal of Team Hippocrates

The author examines the literature relating to informed consent for early cardiac catheterization to treat Non-ST-segment elevation acute coronary syndrome, and considers whether Clinical Decision Science might provide new directions for applying the clinical research literature.

Valbenazine Has A Small But Meaningful Benefit For Tardive Dyskinesia, Joseph Friedli, Ryan Quick, Reem Sobh, Samantha Cowing

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of

Hauser RA, Factor SA, Marder SR, et al. KINECT 3: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia. Am J Psychiatry. 2017;174(5):476-484. https://doi.org/10.1176/appi.ajp.2017.16091037

and

Factor SA, Remington G, Comella CL, et al. The Effects of Valbenazine in Participants with Tardive Dyskinesia: Results of the 1-Year KINECT 3 Extension Study. J Clin Psychiatry. 2017;78(9):1344-1350. https://doi.org/10.4088/JCP.17m11777

exploring the efficacy of a newer therapy for tardive dyskinesia, and describing recommendations for a patient with acute medical problems and longstanding tardive dyskinesia.

From The Editor: Defining The Scholarship Of Clinical Decision Science, James Peter Meza

Clinical Research in Practice: The Journal of Team Hippocrates

The Editor refines the focus of the journal to a new area of scholarship, Clinical Decision Science, exploring how the complex interacting aspects of clinical care are described, understood, shared, and explained in the context of the doctor-patient relationship.

Copd Exacerbation Caused By Sars-Cov-2: A Case Report From The Louisville Covid-19 Surveillance Program, Forest W. Arnold, Kamran Mahmood, Angeline Prabhu, Darmaan Aden, Anupama Raghuram, Mark Burns, Leslie A. Beavin, Donghoon Chung, Kenneth E. Palmer, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

A 53-year-old male with a history of chronic obstructive pulmonary disease (COPD) on home oxygen presented to the hospital with worsening shortness of breath plus cough. He was admitted to the intensive care unit for COPD exacerbation and respiratory failure. A routine evaluation was performed, including a nasopharyngeal swab for a respiratory viral panel, which was negative. His symptoms improved over 48 hours, after which time a surveillance test for SARS-CoV-2 returned as positive. After clinical improvement, he was discharged to home isolation.

How To Prevent Covid-19 In Nurses And Physicians In The Hospital Setting: Universal Test-And-Isolate For All Patients Admitted To Hospitals, Julio A. Ramirez, Ruth Carrico, Forest W. Arnold, Paul Schulz

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Defining The Burden Of Covid-19 In The Kentuckiana Area: Incidence, Epidemiology & Clinical Outcomes Of Patients With Covid-19, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Rationale: Early evaluation of the burden of disease that COVID-19 may produce in a community is critical to appropriately allocate resources for COVID-19 prevention and treatment.

Objective: The primary objective of this study is to define the incidence, epidemiology, and clinical outcomes of patients with COVID-19 in the Louisville, Kentucky, and southern Indiana region (Kentuckiana) of the USA.

Methods: This will be a retrospective observational study of patients in the Kentuckiana region with the diagnosis of COVID-19.

Louisville Coronavirus Surveillance Program, Julio A. Ramirez, Kenneth E. Palmer, Ruth Carrico, Forest W. Arnold, Donghoon Chung, Leslie A Wolf

The University of Louisville Journal of Respiratory Infections

An important feature of COVID-19, the disease produced by the new coronavirus SARS-CoV-2, is the high number of health care workers (HCWs) that acquire the disease. In an initial report of 138 patients hospitalized with COVID-19 pneumonia in China, 40 patients (29%) were HCWs. One reason why HCWs are at higher risk of acquiring COVID-19 is that some patients with COVID-19 are admitted to the hospital without the classical presentation and are therefore not tested for the disease early during hospitalization. Presently in the US, it is recommended to test for COVID-19 when physicians suspect the disease. This subjective approach …