Translational Medical Research Commons^™

A Woman With A Lung Infiltrate And Brain Abscesses: Case Discussion From The University Of Louisville Hospital, Veronica Corcino, Viswanathan Nagarajan, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

No abstract provided.

The Effect Of Arm Swing On Countermovement Vertical Jump Performance, Arash Mohammadzadeh Gonabadi

UNO Student Research and Creative Activity Fair

Vertical jumping is one of the popular ways to evaluate ankle-knee efficiency in athletic population. Arm swing can play a crucial role in enhancing vertical jump performance. This study aimed to address the differences in kinetic and kinematic parameters during countermovement jump motion with arm swing (AS) and no arm swing (NAS). We used OpenSim to examine the efficacy of AS in reducing the impulse applied to the body and changes in range of lower limb joint angles at landing instant. We calculated the maximum vertical peak of the ground reaction force and impulse generated at landing in two different …

Assessment Of Pneumonia Severity Indices As Mortality Predictors, Connor L. English, Thomas Chandler, Brian E. Guinn, Stephen P. Furmanek, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

BACKGROUND

The leading cause of infectious disease death in the United States is community-acquired pneumonia (CAP). Several pneumonia severity indices exist and are widely used as tools to assist physicians regarding site of care based on risk of death. However, limited data exists that discerns which of the most commonly used severity scores is the best predictor of mortality across multiple time points. The objective of this study is to determine the best mortality predictor at different time points between four of the most commonly used pneumonia severity scores.

METHODS

This was a secondary analysis of a prospective, multicenter, population-based, …

A Man With Acute Severe Pneumonia: Case Discussion From The University Of Louisville Hospital, Viswanathan Nagarajan, Srinivas R. Dontineni, Veronica Corcino, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Current And Future Antiviral Medications To Treat Influenza: Mechanisms Of Action, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Sphk2−/− Mice Are Protected From Obesity And Insulin Resistance, Shwetha Ravichandran, Brian S. Finlin, Philip A. Kern, Sabire Özcan

Clinical and Translational Science Faculty Publications

Sphingosine kinases phosphorylate sphingosine to sphingosine 1‑phosphate (S1P), which functions as a signaling molecule. We have previously shown that sphingosine kinase 2 (Sphk2) is important for insulin secretion. To obtain a better understanding of the role of Sphk2 in glucose and lipid metabolism, we have characterized 20- and 52-week old Sphk2^−/− mice using glucose and insulin tolerance tests and by analyzing metabolic gene expression in adipose tissue. A detailed metabolic characterization of these mice revealed that aging Sphk2^−/− mice are protected from metabolic decline and obesity compared to WT mice. Specifically, we found that 52-week old …

Development Of A Real-Time Pcr Assay For Pneumocystis Jirovecii On The Luminex Aries® Platform, Subathra Marimuthu, Kuldeep Ghosh, Leslie A Wolf

The University of Louisville Journal of Respiratory Infections

Pneumocystis pneumonia (PCP) is an opportunistic infection caused by the fungus Pneumocystis jirovecii. Infection with P. jirovecii can result in serious illness in patients with a weakened immune system, and can lead to death if it is not properly diagnosed and treated. Direct detection of P. jirovecii in lower respiratory tract specimens such as bronchoalveolar lavage (BAL) is preferred for rapid diagnosis, a laboratory service currently not available locally. We report here the development of a diagnostic real-time Polymerase Chain Reaction (PCR) assay using BAL specimens to detect P. jirovecii. By targeting the multi-copy mitochondrial large subunit ribosomal …

A Guide For Using Nih Image J For Single Slice Cross-Sectional Area And Composition Analysis Of The Thigh From Computed Tomography, Douglas E. Long, Alejandro G. Villasante Tezanos, James N. Wise, Phillip A. Kern, Marcas M. Bamman, Charlotte A. Peterson, Richard A. Dennis

Clinical and Translational Science Faculty Publications

Reports using computed tomography (CT) to estimate thigh skeletal muscle cross-sectional area and mean muscle attenuation are often difficult to evaluate due to inconsistent methods of quantification and/or poorly described analysis methods. This CT tutorial provides step-by-step instructions in using free, NIH Image J software to quantify both muscle size and composition in the mid-thigh, which was validated against a robust commercially available software, SliceOmatic. CT scans of the mid-thigh were analyzed from 101 healthy individuals aged 65 and older. Mean cross-sectional area and mean attenuation values are presented across seven defined Hounsfield unit (HU) ranges along with the percent …

My First Experience Using Clinical Evidence To Change Patient Care, Alec Aiello

Clinical Research in Practice: The Journal of Team Hippocrates

This third year medical student reflects upon how his observations and subsequent research into a clinical question was able to influence the way his team thought about administering care in their day-to-day practice.

Npo Or Ama? Patients Allowed Clear Liquids Up To 2 Hours Pre-Procedure Have Equivalent Aspiration Risk And Increased Patient Satisfaction, Erich Smith

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Itou K, Fukuyama T, Sasabuchi Y, et al. Safety and efficacy of oral rehydration therapy until 2 h before surgery: a multicenter randomized controlled trial. Journal of Anesthesia. 2012;26(1):20-27. doi: 10.1007/s00540-011-1261-x.

Icatibant Is Not Helpful For The Treatment Of Ace Inhibitor-Induced Angioedema, Samantha R. Schwartz

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Sinert R, Levy P, Bernstein JA, et al. Randomized trial of icatibant for angiotensin-converting enzyme inhibitor-induced upper airway angioedema. J Allergy Clin Immunol Pract. 2017; 5(5): 1402-1409. doi: 10.1016/j.jaip.2017.03.003.

Renal Angioplasty Does Not Improve Clinical Outcomes Compared To Standard Medical Therapy In Patients With Atherosclerotic Renal Artery Stenosis, Alexandra Morris

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Cooper CJ, Murphy T, Cutlip D, Jamerson K, Henrich W. Stenting and medical therapy for atherosclerotic renal-artery stenosis. New Eng J Med. 2014;370(1):13-22. doi: 10.1056/NEJMoa1310753.

Early Dexamethasone Administration In Adults With Suspected Meningitis Lowers Morbidity And Mortality, Dana Siegel

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of de Gans J, van de Beek D, Investigators EDiABMS. Dexamethasone in adults with bacterial meningitis. New Eng J Med. 2002;347(20):1549-1556. doi: 10.1056/NEJMoa021334.

Memantine Unproven To Provide Any Clinical Benefit In Cases Of Vascular Cognitive Impairment, Irene Kitromelides

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Wilcock G, Möbius HJ, Stöffler A. A double-blind, placebo-controlled multicentre study of memantine in mild to moderate vascular dementia (MMM500). Int Clin Psychopharmacol. 2002 Nov;17(6):297-305. doi: 10.1097/00004850-200211000-00005.

Roflumilast Does Not Decrease Copd Exacerbations In Adequately Treated Patients, But Subgroup Analysis Allows For Shared Decision Making, Nathanael Sanchez

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Martinez FJ, Rabe KF, Sethi S, et al. Effect of Roflumilast and Inhaled Corticosteroid/Long-Acting beta2-Agonist on Chronic Obstructive Pulmonary Disease Exacerbations (RE(2)SPOND). A Randomized Clinical Trial. Am J Respir Crit Care Med. Sep 1 2016;194(5):559-567. doi: 10.1164/rccm.201607-1349OC.

Confirmation Bias By Consumers Of Clinical Research Demonstrates The Need For Implementation Science, James Peter Meza

Clinical Research in Practice: The Journal of Team Hippocrates

The Journal's Editor holds that, although Evidence-based medicine typically only looks for bias of the research design, still evidence-based practice must also include the biases of those using the research evidence and how it is deployed in clinical practice.

Towards Multi-Lingual Pneumonia Research Data Collection Using The Community-Acquired Pneumonia International Cohort Study Database, William A. Mattingly, Kimberley A. Buckner, Senen Pena

The University of Louisville Journal of Respiratory Infections

Background: Although multilingual interfaces are preferred by most users when they have a choice, organizations are often unable to support and troubleshoot problems involving multiple user languages. Software that has been structured with multiple languages and data interlinking considerations early in its development is more likely to be easily maintained. We describe the process of adding multilingual support to the CAPO international Cohort study database using REDCap.

Methods: Using Google Translate API we extend the supported Spanish language version of REDCap to the most recent version used by CAPO, 8.1.4. We then translate the English data dictionary for CAPO to …

Clinical Research In Pneumonia: Role Of Artificial Intelligence, Timothy L. Wiemken, Robert R. Kelley, William A. Mattingly, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Carbapenem-Resistant Enterobacteriaceae Infections: A Review Of Epidemiology And Treatment Options, Julie Harting

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Defining Patient-Oriented Research For The Average Person (And Potential Research Partner), Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

In this introduction to the first issue of 2019, the editor-in-chief of Journal of Patient-Centered Research and Reviews offers additional context to the findings of Kaur and Pluye (p. 7), who methodically formalized an operational definition of patient-oriented research for the purposes of searching bibliographic databases. A possible succinct, lay definition of patient-oriented research for the average “person on the street” is proposed.

Coordinating An Oncology Precision Medicine Clinic Within An Integrated Health System: Lessons Learned In Year One, Michael A. Thompson, Jennifer J. Godden, Deborah Wham, Antony Ruggeri, Michael P. Mullane, Amanda Wilson, Shamsuddin Virani, Scott M. Weissman, Brenda Ramczyk, Pamela Vanderwall, James L. Weese

Journal of Patient-Centered Research and Reviews

Precision medicine is a term describing strategies to promote health and prevent and treat disease based on an individual’s genetic, molecular, and lifestyle characteristics. Oncology precision medicine (OPM) is a cancer treatment approach targeting cancer-specific genetic and molecular alterations. Implementation of an OPM clinical program optimally involves the support and collaboration of multiple departments, including administration, medical oncology, pathology, interventional radiology, genetics, research, and informatics. In this review, we briefly introduce the published evidence regarding OPM’s potential effect on patient outcomes and discuss what we have learned over the first year of operating an OPM program within an integrated health …

Lipid Uptake By Alveolar Macrophages Drives Fibrotic Responses To Silica Dust., Xiaomin Hou, Ross Summer, Ziying Chen, Ying Tian, Jingjing Ma, Jie Cui, Xiaohui Hao, Lingli Guo, Hong Xu, Hongli Wang, Heliang Liu

Center for Translational Medicine Faculty Papers

Silicosis is a common occupational disease and represents a significant contributor to respiratory morbidity and mortality worldwide. Lipid-laden macrophages, or foam cells, are observed in the lungs of patients with silicosis but the mechanisms mediating their formation remain poorly understood. In this study, we sought to elucidate the mechanisms by which silica promotes foam cell formation in the lung, and to determine whether uptake of lipids alone is sufficient to drive TGF-β production by alveolar macrophages. Consistent with previous reports, we found that foam cells were markedly increased in the lungs of patients with silicosis and that these findings associated …

How Do Teachers Use Comics To Promote Engagement, Equity, And Diversity In Science Classrooms?, Camilla Matuk, Talia Hurwich, Amy Spiegel, Judy Diamond

World of Viruses

Equitable learning opportunities are critical to the goals of science education. However, major curriculum standards are vague on how to achieve equity goals, and educators must often develop their own resources and strategies to achieve equity goals. This study examines how educators used a comic book series designed to interest youth in virology as a way to make science more broadly appealing to their diverse students. We begin with the notion of Pedagogical Design Capacity, which describes a dynamic relationship between teachers and their tools and the ability for teachers to perceive and leverage affordances of artifacts as tools in …

A Brain-Computer Interface For Closed-Loop Sensory Stimulation During Motor Training In Patients With Tetraplegia, Sarah Helen Thomas

Theses and Dissertations--Biomedical Engineering

Normal movement execution requires proper coupling of motor and sensory activation. An increasing body of literature supports the idea that incorporation of sensory stimulation into motor rehabilitation practices increases its effectiveness. Paired associative stimulation (PAS) studies, in which afferent and efferent pathways are activated in tandem, have brought attention to the importance of well-timed stimulation rather than non-associative (i.e., open-loop) activation. In patients with tetraplegia resulting from spinal cord injury (SCI), varying degrees of upper limb function may remain and could be harnessed for rehabilitation. Incorporating associative sensory stimulation coupled with self-paced motor training would be a means for supplementing …

Integrin Α5Β1 As A Novel Target With The Small Peptide, Atn-161, In The Treatment Of Ischemic Stroke, Danielle Nichele Edwards

Theses and Dissertations--Neuroscience

Stroke is the 5^th leading cause of death and the leading cause of disability in the United States, but there are only two available therapies, tissue plasminogen activator and endovascular thrombectomy. As both therapies focus on removal of the clot, the subsequent pathologic processes, i.e. inflammation, cerebrovascular breakdown, ATP depletion, etc. are left untreated, contributing to worsened patient outcome. Many clinical trials have unsuccessfully attempted to address these mechanisms. The blood-brain barrier (BBB), a system of non-fenestrated endothelial cells, extracellular matrix, and astrocytic endfeet, is significantly impacted after ischemic stroke in its role of preventing the free movement of …

Autologous Peripheral Nerve Grafts To The Brain For The Treatment Of Parkinson's Disease, Andrew Welleford

Theses and Dissertations--Neuroscience

Parkinson’s disease (PD) is a disorder of the nervous system that causes problems with movement (motor symptoms) as well as other problems such as mood disorders, cognitive changes, sleep disorders, constipation, pain, and other non-motor symptoms. The severity of PD symptoms worsens over time as the disease progresses, and while there are treatments for the motor and some non-motor symptoms there is no known cure for PD. Thus there is a high demand for therapies to slow the progressive neurodegeneration observed in PD. Two clinical trials at the University of Kentucky College of Medicine (NCT02369003, NCT01833364) are currently underway that …

Development Of Mithramycin Analogues With Improved Efficacy And Reduced Toxicity For Treatment Of Ets-Dependent Tumors In Ewing Sarcoma And Prostate Cancer, Joseph Michael Eckenrode

Theses and Dissertations--Pharmacy

Introduction: Genetic rearrangements in Ewing sarcoma, prostate, and leukemia cells result in activation of oncogenic ETS transcription factor fusions. Mithramycin (MTM) has been identified as an inhibitor of EWS-FLI1 transcription factor, a gene fusion product responsible for oncogenesis in Ewing sarcoma. Despite preclinical success, a phase I/II clinical trial testing MTM therapy in refractory Ewing sarcoma was terminated. Liver and blood toxicities resulted in dose de-escalation and sub-therapeutic exposures. However, the promise of selectively targeting oncogenic ETS transcription factors like EWS-FLI1 prompted us to undertake the discovery of more selective, less toxic analogues of MTM. MTM is a potent inhibitor …

A Pilot Study Of A Multiple Health Behavior Change Intervention For Smokers, Srihari Seshadri

Theses and Dissertations--Clinical and Translational Science

Background: Being both obese and a smoker increases the probability of developing type 2 diabetes, cardiovascular disease, and cancer, diseases that impact Kentucky residents disproportionately. Kentucky (KY) has a high incidence of obesity (34.2%) and smoking (24.5 %). Weight gain associated with smoking cessation also can undermine health benefits of quitting, and may lead to smoking relapse.

Aim: The aim of the pilot study was to implement and evaluate a Multiple Health Behavioral Change (MHBC) program that combines Cooper Clayton Method to Stop Smoking (CCMSS) and the Diabetes Prevention Program (DPP) for weight control.

Method: A 15-week intervention was administered …

Beta-Lactam Plus Macrolide Vs Fluoroquinolone For Empiric Therapy Of Hospitalized Patients With Cap: Results From The University Of Louisville Pneumonia Study, Vidyulata Salunkhe, Stephen P. Furmanek, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

Background

Current guidelines recommend a β-lactam plus a macrolide or fluoroquinolone monotherapy as initial empiric antibiotic therapy for treatment of patients hospitalized with community-acquired pneumonia (CAP). Multiple studies have shown different results comparing the two regimens for the treatment of CAP. Our objective, in a city-wide prospective study, was to compare outcomes among hospitalized patients with CAP who received empiric treatment either with a β-lactam plus a macrolide or fluoroquinolone monotherapy.

Methods

This was a propensity score matched case-control study of the University of Louisville Pneumonia Study. It was a prospective population-based cohort study of all hospitalized adults with CAP. …

Effects Of The Dual Orexin Receptor Antagonist Dora-22 On Sleep In 5xfad Mice, Marilyn J. Duncan, Hannah Farlow, Chairtra Tirumalaraju, Do-Hyun Yun, Chanung Wang, James A. Howard, Madison N. Sanden, Bruce F. O'Hara, Kristen J. Mcquerry, Adam D. Bachstetter

Neuroscience Faculty Publications

Introduction: Sleep disruption is a characteristic of Alzheimer's disease (AD) that may exacerbate disease progression. This study tested whether a dual orexin receptor antagonist (DORA) would enhance sleep and attenuate neuropathology, neuroinflammation, and cognitive deficits in an AD-relevant mouse model, 5XFAD.

Methods: Wild-type (C57Bl6/SJL) and 5XFAD mice received chronic treatment with vehicle or DORA-22. Piezoelectric recordings monitored sleep and spatial memory was assessed via spontaneous Y-maze alternations. Aβ plaques, Aβ levels, and neuroinflammatory markers were measured by immunohistochemistry, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction, respectively.

Results: In 5XFAD mice, DORA-22 significantly increased light-phase sleep without reducing Aβ levels, …