Translational Medical Research Commons^™

Is Sars-Cov-2 A Neurotropic Virus And A Potential Facilitator Of Cns Infection For Other Pathogens?, Jose Bordon

The University of Louisville Journal of Respiratory Infections

No abstract provided.

The Importance Of Cycle Threshold Values In The Evaluation Of Patients With Persistent Positive Pcr For Sars-Cov-2: Case Study And Brief Review, Jose Bordon, Donghoon Chung, Priya Krishnan, Ruth Carrico, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Some patients recover from COVID-19, but their reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 remains persistently positive. In the evaluation of these patients, it is important to define the cycle threshold (Ct) value of the RT-PCR test. This article will present a case study, address relevant findings and interpretation of the RT-PCR test, and explain the use of Ct values in defining when a healthcare worker may return to work. Our current approach is to allow health care workers with persistently positive RT-PCR to return to work if the Ct value is greater than 35.

Covid-19 Surveillance Testing Of Healthcare Personnel Drives Universal Masking Practice, Paul S. Schulz, Ashley M. Wilde, Steve T. Hester, Jim Frazier, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Health care professionals (HCP) are at increased risk of COVID-19 infection due to the unpredictable clinical presentation of COVID-19 disease, limited SARS-CoV-2 testing, personal protective equipment (PPE) shortages, and the inherent inability to distance from patients. Infected HCP may infect others, including coworkers, leading to a simultaneous increase in the number of infections and decrease in the availability of HCP in a community. Due to PPE shortages, many healthcare systems have faced difficult decisions regarding utilization of PPE to protect HCP, patients, and the communities they serve. We describe Norton Healthcare’s success utilizing surveillance COVID-19 testing of HCP to inform …

Why Every Hospital Needs A Covid-19 Clinical Case Review Team, Ashley M. Wilde, Paul Schulz, Brian C. Bohn, Sarah E. Moore, Matthew Song, Clayton J. Patross, Bryan Denham, Jim Frazier, Steve T. Hester, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

A hospital’s response to a global pandemic requires a coordinated effort to provide consistent guidance as information rapidly changes. In the early months of the COVID-19 pandemic, diagnosis and subsequent containment was challenging due to unfamiliarity with disease presentation, unknown reverse transcription-polymerase chain reaction sensitivity, and inconsistent access to testing supplies. A centralized COVID-19 clinical case review team can provide guidance on test interpretation, isolation, resource coordination and more.

The Nurse Practitioner In The Time Of Covid, Julie Marfell, Lynn Kelso

The University of Louisville Journal of Respiratory Infections

No abstract provided.

An Overview Of Current Clinical Trials Of Agents For The Treatment And Prevention Of Covid-19 In The United States, Kenneth Schot Hannan, William P. Mckinney

The University of Louisville Journal of Respiratory Infections

Introduction: Given the rapid worldwide spread of SARS-CoV-2 and the attendant risks for severe complications and mortality, numerous clinical trials for its treatment and prevention have been generated in a short period. This report focuses on the categories of the wide spectrum of agents being studied in the United States and the intensity of effort involved with each so that clinicians may consider whether suggesting enrollment may be appropriate for their patients.

Methods: A search was completed of the ClinicalTrials.gov database on May 28, 2020, for all such trials underway as of that date in the US. A total 190 …

Vaccine-Preventable Diseases In The Time Of Covid, Thaddeus Zajdowicz, Margan Zajdowicz

The University of Louisville Journal of Respiratory Infections

No abstract provided.

The Strengths, Weaknesses, Opportunities And Threats (Swot) Analysis Of The Severe Acute Respiratory Syndrome Coronavirus 2 Of Covid-19, Michael Oluyemi Babalola Ph.D

The University of Louisville Journal of Respiratory Infections

Introduction: SARS-CoV-2 is the etiologic agent of Coronavirus Disease 2019 (COVID-19), a highly contagious, emergent, acute, viral pneumonia that emanated sporadically in Wuhan, China, in December 2019. COVID-19 became a pandemic in February 2020, leading to 4,942,687 confirmed cases and over 321,987 deaths and grounding several economies around the world as of May 2020. Although global researchers, epidemiologists, virologists, and medical professionals rose steadily to contain the disease, in-depth knowledge of the virus and concerted efforts to combat it are still evolving. This research sought to elucidate the biological Strengths, Weaknesses, Opportunities, and Threats to SARS-CoV-2, with a view to …

Metformin Enhances Autophagy And Normalizes Mitochondrial Function To Alleviate Aging-Associated Inflammation, Leena P. Bharath, Madhur Agrawal, Grace Mccambridge, Dequina A. Nicholas, Hatice Hasturk, Jing Liu, Lao Jiang, Rui Liu, Zhenheng Guo, Jude T. Deeney, Caroline M. Apovian, Jennifer Snyder-Cappione, Gregory S. Hawk, Rebecca M. Fleeman, Riley M. F. Pihl, Katherine Thompson, Anna C. Belkina, Licong Cui, Elizabeth A. Proctor, Philip A. Kern, Barbara S. Nikolajczyk

Clinical and Translational Science Faculty Publications

Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and bioinformatic analyses showed that Th17 cytokine production differentiates CD4+ T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Metformin ameliorated the Th17 inflammaging profile by increasing autophagy and improving mitochondrial bioenergetics. By contrast, autophagy-targeting siRNA disrupted redox balance in T cells from young subjects and activated the Th17 …

False-Negative Sars-Cov-2 Reverse Transcriptase Polymerase Chain Reaction (Rt-Pcr) Is An Important Consideration For Patient Management And Infection Prevention: A Case Report From The Louisville Covid-19 Epidemiology Study, Matthew Song Pharmd, Bcidp, Ashley M. Wilde, Sarah E. Moore Pharmd, Brian C. Bohn Pharmd, Clayton J. Patross, Bryan Denham, Paul Schulz, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

We report a case of false-negative SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) on a nasopharyngeal swab. Treating clinicians and infection preventionists should maintain a high suspicion for COVID-19 in the appropriate clinical setting despite negative test results. Utilization of chest computed tomography (CT) should be strongly considered in the diagnostic work-up for suspected COVID-19, particularly in areas with limited RT-PCR availability.

Concomitant Invasive Pneumococcal Disease In A Patient With Covid-19 – A Case Report From The Louisville Epidemiology Study, Clayton J. Patross, Brian C. Bohn Pharmd, Sarah E. Moore Pharmd, Paul Schulz, Matthew Song Pharmd, Bcidp, Ashley M. Wilde, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

A 60-year-old male presented to the emergency department (ED) with a 1–2 day history of confusion, headache, and subjective fever. Because he had met with a contact two days prior to admission who had recently traveled from the Bahamas, a COVID-19 nasopharyngeal (NP) and oropharyngeal (OP) polymerase chain reaction (PCR) test was ordered. He was diagnosed with bacterial meningitis based on presenting neurologic symptoms and the identification of Streptococcus pneumoniae from blood cultures. The COVID-19 NP and OP test returned positive, although he never developed shortness of breath, cough, other respiratory symptoms, diarrhea, abdominal pain, nausea, vomiting, or any change …

Foundational Research And Nih Funding Enabling Emergency Use Authorization Of Remdesivir For Covid-19, Ekaterina Galkina Cleary, Matthew J. Jackson, Zoë Folchman-Wagner, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

Emergency Use Authorization for remdesivir months after discovery of COVID-19 is unprecedented. Typically, decades of research and public-sector funding are required to establish the mature body of foundational research requisite for efficient, targeted drug discovery and development. This work quantifies the body of research related to remdesivir’s biological target, RNA-dependent RNA polymerase (RdRp), or parent chemical structure, nucleoside analogs (NcAn), through 2019, as well as NIH funding for this research 2000–2019. There were 6,567 RdRp-related publications in PubMed, including 1,263 with NIH support, and 11,073 NcAn-related publications, including 2,319 with NIH support. NIH support for RdRp research comprised 2,203 Project …

A Comparison Efficacy Study Of Commercial Nasopharyngeal Swabs Versus A Novel 3d Printed Swab For The Detection Of Sars-Cov-2, Forest W. Arnold, Gerald Grant, Phillip F. Bressoud, Stephen P. Furmanek, Donghoon Chung, Nadine Sbaih, Dipan Karmali, Meredith Cahill, George Pantalos

The University of Louisville Journal of Respiratory Infections

Introduction: The large volume of diagnostic tests required by the response to the COVID-19 pandemic resulted in a shortage of commercial nasopharyngeal swabs. In an effort to alleviate the shortage, swabs created by 3D printing may be a solution.

Methods: We designed and produced 3D printed swabs and sought to compare their ability to detect SARS-CoV-2 in patients admitted for COVID-19 or who were suspected of having COVID-19.

Results: A total of 30 patients were swabbed with a commercial and a 3D printed swab. Results matched in 27 of 30 patients (90%). Two patients were discordant with a positive commercial …

Stroke Management In The Time Of Covid, Marwa Elnazeir, Siddharth Narayanan, Kerri Remmel

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Covid-19 Radiological Library, Forest W. Arnold, Tracy Vanmeter, Lachlan Smith, Danny Mcgrath, Matthew Grassman, Nishant Patel, William Mattingly

The University of Louisville Journal of Respiratory Infections

No abstract provided.

A Patient With Escherichia Coli Bacteremia And Covid-19 Co-Infection: A Case Report For The Louisville Covid-19 Epidemiology Study, Sarah E. Moore Pharmd, Ashley M. Wilde Pharmd, Bcps-Aqid, Matthew Song Pharmd, Bcidp, Brian C. Bohn Pharmd, Clayton J. Patross Pharmd, Bcps, Bryan Denham Md, Paul Schulz, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Patients with COVID-19 may have co-infections with other microorganisms. Here we report a case of a patient with an Escheria coli bacteremia secondary to a urinary tract infection, who experienced fevers while on active antimicrobial therapy. The patient was eventually tested for COVID-19 and found to be positive. This case emphasizes the need to suspect COVID-19 even in patients with documented bacterial infection.

Sars-Cov-2 And Bacterial Co-Infection, Rodrigo Cavallazzi

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Life In The Time Of Covid, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Healthcare Workers In The Time Of Covid, Julio A. Ramirez, Ruth Carrico

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Nih Funding For Research Underlying New Cancer Therapies, Ekaterina Galkina Cleary, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

Contemporary discovery and development of cancer drugs are based on the model that investments in basic biomedical science will provide insights that can be translated into new cures. In the USA, basic research is primarily funded by the National Institutes of Health (NIH),1 which allocates half of its research budget to basic science,2 with smaller amounts contributed by philanthropy, academics, or industry.1 Basic science is formally defined as the “systematic study directed toward fuller knowledge or understanding of the fundamental aspects of phenomena and observable facts without specific application towards processes or products in mind”.3 However, science is often useinspired,4 …

Abo Blood Group Type And Susceptibility To Covid-19 Infection, G. Rafael Fernandez-Botran

The University of Louisville Journal of Respiratory Infections

Since December 2019, the SARS-CoV-2 (COVID-19) pandemic has extended its reach over most of the world, infecting over four million people and causing well over 300,000 deaths so far.[1] A significant percentage of infected patients develop severe symptoms and life-threatening conditions. While COVID-19 infection can affect all ages, available evidence points to older age and pre-existing comorbidities, such as hypertension, diabetes, and coronary heart disease, as important risk factors related to increased mortality rates.[2-4] Moreover, recent reports from China and the U.S. have suggested that susceptibility, and perhaps even mortality, to COVID-19 infection might be influenced by the ABO blood …

Causes Of Challenges In Implementing Computer-Based Knowledge Management Systems In Healthcare Institutions: A Case Study Of Private Hospitals In Johannesburg, South Africa, George Maramba, Alfred Coleman, Felix F. Ntawanga

The African Journal of Information Systems

The advent of computer-based knowledge management systems has changed the world, especially in the way businesses operate, making them an integral aspect to modern economies and the drivers of success. Studies show that the implementation of computer-based knowledge management systems is challenging, particularly in healthcare institutions. This paper presents a study that was undertaken to identify the causes of challenges encountered when implementing computer-based knowledge management systems in healthcare institutions. A case was used as this study’s research methodology in which three private hospitals based in Johannesburg, South Africa, were utilized. Six participants, two from each private hospital, were purposively …

Implementation Of The Louisville Covid-19 Surveillance Protocol: Experiences From The University Of Louisville Center Of Excellence For Research In Infectious Diseases [Cerid], Ruth Carrico, Dawn Balcom, William Johnson, Amr Aboelnasr, Mutasem Abuhalaweh, Stephen Furmanek, Montray Smith, Amanda Lasnik, Donghoon Chung, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

The lack of available testing for SARS-CoV-2 has been one of the primary challenges in the development and implementation of a comprehensive approach to infection prevention and transmission in the United States (US). In response to the need for increased testing capacities and capabilities, the University of Louisville (UofL) Division of Infectious Diseases Center of Excellence for Research in Infectious Diseases (CERID) initiated the Louisville Coronavirus Surveillance Program, a comprehensive approach to surveillance and testing of patients and healthcare workers. The first specimens were accepted on March 12, 2020, and parallel testing was done using a high-capacity testing process at …

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 …

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., …

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, …

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 …