Translational Medical Research Commons^™

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 …

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, …

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. …

Inflammatory Serine Proteases Play A Critical Role In The Early Pathogenesis Of Diabetic Cardiomyopathy., Mikhail A Kolpakov, Kunal Sikder, Amrita Sarkar, Shaswati Chaki, Sanket K Shukla, Xinji Guo, Zhao Qi, Carlos Barbery, Abdelkarim Sabri, Khadija Rafiq

Center for Translational Medicine Faculty Papers

BACKGROUND/AIMS: Diabetic cardiomyopathy (DCM) is characterized by structural and functional alterations that can lead to heart failure. Several mechanisms are known to be involved in the pathogenesis of DCM, however, the molecular mechanism that links inflammation to DCM is incompletely understood. To learn about this mechanism, we investigated the role of inflammatory serine proteases (ISPs) during the development of DCM.

METHODS: Eight weeks old mice with deletion of dipeptidyl peptidase I (DPPI), an enzyme involved in the maturation of major ISPs, and wild type (WT) mice controls were injected with streptozotocin (50 mg/kg for 5 days intraperitoneally) and studied after …

Behavioral And Anti-Inflammatory Effects Of Magl Inhibition In A Mouse Model Of Inflammatory Arthritis, Floyd Franklin Steele Iii

Graduate Theses, Dissertations, and Problem Reports (ETD)

Cannabinoids have analgesic and anti-inflammatory properties. For example, in preclinical models of acute inflammatory pain, cannabinoid receptor subtype 2 (i.e., CB_2, Table 1) agonists decrease paw inflammation and resulting pain. Yet, the anti-inflammatory properties of cannabinoid receptor manipulation in chronic inflammatory pain states are unknown. Monoacylglycerol lipase (MAGL) is the primary catabolic enzyme of the endocannabinoid (i.e., endogenous cannabinoid ligand) 2-arachidonoyl glycerol (i.e., 2-AG). Compounds that inhibit MAGL indirectly increase tissue levels of 2-AG by preventing its catabolism. MAGL inhibitors demonstrate efficacy in acute models of inflammatory/rheumatic disease. Thus, in this study, the MAGL inhibitor JZL184 was tested …

A Study Of Gastrointestinal Pathophysiology, Emily Minor

Graduate Theses, Dissertations, and Problem Reports (ETD)

Though the duodenum is the primary site of iron absorption, the colon also contains iron transporters and participates in iron absorption. The purpose of this study was to characterize colonic iron absorption in control patients and those with ulcerative colitis (UC), a disease that frequently results in iron deficiency. Using RT-qPCR and western blot analysis, we found that colonic expression of the apical iron importer, divalent metal transporter 1 (DMT1), is equal to duodenal expression. However, colonic expression of ferroportin 1 (FPN1), an iron exporter, is only about one-quarter that of the duodenum. Patients with active ulcerative colitis were found …

Translational Modeling Of Non-Invasive Electrical Stimulation, Dennis Quangvinh Truong

Dissertations and Theses

Seminal work in the early 2000’s demonstrated the effect of low amplitude non-invasive electrical stimulation in people using neurophysiological measures (motor evoked potentials, MEPs). Clinical applications of transcranial Direct Current Stimulation (tDCS) have since proliferated, though the mechanisms are not fully understood. Efforts to refine the technique to improve results are on-going as are mechanistic studies both in vivo and in vitro. Volume conduction models are being applied to these areas of research, especially in the design and analysis of clinical montages. However, additional research on the parameterization of models remains.

In this dissertation, Finite Element Method (FEM) models of …