Translational Medical Research Commons^™

Cbf-1 Promotes The Establishment And Maintenance Of Hiv Latency By Recruiting Polycomb Repressive Complexes, Prc1 And Prc2, At Hiv Ltr., Adhikarimayum Lakhikumar Sharma, Joseph Hokello, Shilpa Sonti, Sonia Zicari, Lin Sun, Aseel Alqatawni, Michael Bukrinsky, Gary Simon, Ashok Chauhan, René Daniel, Mudit Tyagi

Center for Translational Medicine Faculty Papers

The C-promoter binding factor-1 (CBF-1) is a potent and specific inhibitor of the human immunodeficiency virus (HIV)-1 LTR promoter. Here, we demonstrate that the knockdown of endogenous CBF-1 in latently infected primary CD4+ T cells, using specific small hairpin RNAs (shRNA), resulted in the reactivation of latent HIV proviruses. Chromatin immunoprecipitation (ChIP) assays using latently infected primary T cells and Jurkat T-cell lines demonstrated that CBF-1 induces the establishment and maintenance of HIV latency by recruiting polycomb group (PcG/PRC) corepressor complexes or polycomb repressive complexes 1 and 2 (PRC1 and PRC2). Knockdown of CBF-1 resulted in the dissociation of PRCs …

Covid-19 Is Associated With Increased Severity In Pregnant Women, Zahid Imran, Vidyulata Salunkhe, Ahmed A. Eladely, Ahmed Abdelhaleem, Satya Durugu, Daisy Sangroula

The University of Louisville Journal of Respiratory Infections

Introduction: The COVID-19 pandemic originated in China in late 2019; the number of cases is increasing with 2,104,346 cases and 116,140 deaths in the United States as of June 16, 2020. Pregnant women are a vulnerable population in epidemics or pandemics. This review is designed to look in detail at the severity of COVID-19 in pregnant women compared to non-pregnant women of reproductive age.

Methods: Literature searches on PubMed, Google Scholar, the Lancet, and Web of Science were conducted.

Results: We found evidence of increased risk for severe disease and distinctive symptoms among pregnant women diagnosed with COVID-19 compared …

Simultaneous Analytical Determination Of Methyl Salicylate And Thymol In Selected Malaysian Traditional Medicines, Muhammad Shahariz Mohamad Adzib

Student Works (2020-2029)

Various topical formulations comprise of methyl salicylate and thymol due to their analgesic and anti-inflammatory properties. The huge demand has led traditional medicines being susceptible to adulteration with synthetic drugs or their analogues to enhance their efficacy and to minimise the cost of obtaining the limited natural substance. The objectives of this study are to analyse a suitable analytical method for simultaneous determination of methyl salicylate and thymol in selected Malaysian traditional medicines using High Performance Liquid Chromatography (HPLC) and to screen the selected Malaysian traditional medicines for possible methyl salicylate and thymol adulteration using the analytical method. Most literature …

The Incidence Of Common Respiratory Viruses During The Covid-19 Pandemic: Results From The Louisville Covid-19 Epidemiology Study, Brian C. Bohn Pharmd, Bcidp, Ashley M. Wilde Pharmd, Bcps-Aq Id, Sarah E. Moore Pharmd, Matthew Song Pharmd, Bcidp, Clayton J. Patross Pharmd, Bcps, Alan D. Junkins Phd, D(Abmm), Paul Schulz Md, Julio A. Ramirez Md Facp

The University of Louisville Journal of Respiratory Infections

Introduction: Social distancing has been utilized during the COVID-19 pandemic to reduce the spread of SARS-CoV-2; it is also expected to reduce the spread of common respiratory viruses.

Methods: This retrospective, descriptive study assessed the rate of positivity of common respiratory viruses from a commercially available respiratory pathogen panel across a five-hospital health system during four-week periods within March to April of 2019 and 2020.

Results: During the four-week period in 2019, the percent positivity of common respiratory viruses from week 1 to week 4 decreased from 6 to 32% among the four included viruses. In the comparator period in …

Opioid Dependency And Its Effects On Alcohol Consumption, Emily V. Flores

Psychology and Counseling Theses

Previous research has found dualistic effects on alcohol consumption with low doses of buprenorphine increasing alcohol and higher doses of buprenorphine reducing alcohol consumption in rats (Ciccocioppo et al., 2006). Other existing research on naloxone treatment and alcohol consumption in opioid use has demonstrated that alcohol consumption decreases after naloxone treatment in rats (Hyytia & Sinclair, 1993). Yet, no research has been conducted on either rats or humans on the effects of buprenorphine and naloxone medication combined. The effects of opioid maintenance therapy are controversial and the relationship between alcohol consumption and opioid dependency treatment is mainly based on literature …

The Generation Of An Engineered Interleukin-10 Protein With Improved Stability And Biological Function, Faisal Minshawi, Sebastian Lanvermann, Edward Mckenzie, Rebecca Jeffery, Kevin Couper, Stamatia Papoutsopoulou, Axel Roers, Werner Muller

Center for Translational Medicine Faculty Papers

Interleukin-10 (IL-10) is an immunoregulatory cytokine that plays a pivotal role in modulating inflammation. IL-10 has inhibitory effects on proinflammatory cytokine production and function in vitro and in vivo; as such, IL-10 is viewed as a potential treatment for various inflammatory diseases. However, a significant drawback of using IL-10 in clinical application is the fact that the biologically active form of IL-10 is an unstable homodimer, which has a short half-life and is easily degraded in vivo. Consequently, IL-10 therapy using recombinant native IL-10 has had only limited success in the treatment of human disease. To improve the therapeutic potential …

Efficient Non-Epigenetic Activation Of Hiv Latency Through The T-Cell Receptor Signalosome., Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Human immunodeficiency virus type-1 (HIV-1) can either undergo a lytic pathway to cause productive systemic infections or enter a latent state in which the integrated provirus remains transcriptionally silent for decades. The ability to latently infect T-cells enables HIV-1 to establish persistent infections in resting memory CD4+ T-lymphocytes which become reactivated following the disruption or cessation of intensive drug therapy. The maintenance of viral latency occurs through epigenetic and non-epigenetic mechanisms. Epigenetic mechanisms of HIV latency regulation involve the deacetylation and methylation of histone proteins within nucleosome 1 (nuc-1) at the viral long terminal repeats (LTR) such that the inhibition …

Sexual Dysfunction After Rectal Cancer Treatment, Sarah M. Popek

Clinical and Translational Science Center Scholarly Output

Introduction: Treatment for rectal cancer results in sexual dysfunction. Sexual function is a component of the HR-QOL (health related quality of life) measures. The incidence of sexual dysfunction following treatment for rectal cancer and its impact on the HR-QOL is not well delineated, particularly on women.

Objectives: To prospectively assess the degree of sexual dysfunction that occurs after treatment for Stage I-III rectal cancer and the corresponding short term (<3 months) and long term (<2 years) effect on the Quality of Life measure for oncology (QOL-30).

Methods: Validated questionnaires will be administered to assess sexual function and quality of life. The International Index of Erectile Dysfunction will be administered to male patients and …

Modeling, Fabrication And Characterization Of Coated Calcium Phosphate Scaffolds Produced By 3d-Printing For Tissue Engineering Application, Touri Maria

Student Works (2020-2029)

A fully interconnected 3-dimensional scaffold with pre-determined dimensions and porosity can be attained by design-dependent rapid prototyping techniques which possess precise control over the internal and external architecture of the scaffolds thus they can overcome the problems associated with the process-dependent classical approaches. Interruption of vascular flow with fracture or surgical osteotomy results in a transient hypoxic gradient within the wound and subsequent tissue necrosis. Tissue engineering scaffolds with oxygen generating elements have shown to be able to increase the level of oxygen and cell survivability. In this study, biphasic calcium phosphate (BCP) scaffolds with the composition of 60% hydroxyapatite …

Anesthesia Services In The Time Of Covid, James Chen, Daisy Sangroula, Katelyn Williams, Sydney Pham, Ozan Akca, Jiapeng Huang, Sean Clifford

The University of Louisville Journal of Respiratory Infections

Our hospital is a 400-bed, Level-1 trauma center with 78 intensive care unit (ICU) beds serving the greater Louisville metropolitan area. The COVID-19 pandemic forced our hospital to re-evaluate our core business operations and to develop a coherent response to a fluid situation. Between March 15 and May 15, 2020, the University of Louisville Hospital admitted more than 100 COVID-19 inpatients; approximately 30 were admitted to the ICU, and most required endotracheal intubation. The following review describes our Department of Anesthesiology \& Perioperative Medicine foci, actions, and rationale during the COVID-19 pandemic. While we hope not to experience another pandemic …

Severe Covid-19, Arpan H. Chawala, Shivam Gulati, Bettina Sinanova, Jose Bordon

The University of Louisville Journal of Respiratory Infections

Introduction: There is substantial variation in the clinical characteristics and outcomes of severe coronavirus disease (COVID-19), making it difficult to do an optimal assessment of this condition. We reviewed the current English literature to identify the findings concerning the baseline characteristics and health outcomes of patients with severe COVID-19, primarily those with acute respiratory distress syndrome (ARDS).

Methods: We examined only studies that assessed patients with confirmed COVID-19 by reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with at least one of the following severity criteria: treated in the intensive care unit (ICU), ARDS, and/or invasive …

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 …