Translational Medical Research Commons^™

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 …

Dual-Display Laparoscopic Laser Speckle Contrast Imaging For Real-Time Surgical Assistance, Jaepyeong Cha, Corey Zheng, Lung Wai Lau

Pediatrics Faculty Publications

Laser speckle contrast imaging (LSCI) utilizes the speckle pattern of a laser to determine the blood flow in tissues. The current approaches for its use in a clinical setting require a camera system with a laser source on a separate optical axis making it unsuitable for minimally invasive surgery (MIS). With blood flow visualization, bowel viability, for example, can be determined. Thus, LSCI can be a valuable tool in gastrointestinal surgery. In this work, we develop the first-of-its-kind dual-display laparoscopic vision system integrating LSCI with a commercially available 10mm rigid laparoscope where the laser has the same optical axis as …

Direct Crystal Formation From Micronized Bone And Lactic Acid: The Writing On The Wall For Calcium-Containing Crystal Pathogenesis In Osteoarthritis?, Anna A. Bulysheva, Nardos Sori, Michael P. Francis

Bioelectrics Publications

Introduction

Pathological calcium-containing crystals accumulating in the joints, synovial fluid, and soft tissues are noted in most elderly patients, yet arthritic crystal formation remains idiopathic. Interestingly, elevated lactic acid and bone erosion are frequently among the comorbidities and clinical features of patients with highest incidence of crystal arthropathies. This work shows that bone particulates (modeling bone erosion) dissolve in lactic acid and directly generate crystals, possibly presenting a mechanism for crystal accumulation in osteoarthritis.

Methods and results

Micronized human bone (average particle size of 160 μm x 79 μm ) completely dissolved in lactic acid in 48 hours, and in …

Equal Efficacy Of Clopidogrel Versus Ticagrelor As Monotherapy In Peripheral Artery Disease, Aimee L. Vos

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Hiatt H, Fowkes G, Heizer G, et al. Ticagrelor versus clopidogrel in symptomatic peripheral artery disease. N Engl J Med. 2017;376:32-40. doi: 10.1056/NEJMoa1611688.

Lurasidone Is Not Associated With Risk Of Qtc Prolongation, Halimah Y. Oral

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Meltzer HY, Cucchiaro J, Silva R, Ogasa M, Phillips D, Xu J, Kalali AH, Scheizer E, Pikalov A, Loebel A. Lurasidone in the treatment of schizophrenia: a randomized, double-blind, placebo- and olanzapine-controlled study. Am J Psychiatry. 2011 Sep;168(9):957-67. doi: https://doi.org/10.1176/appi.ajp.2011.10060907.

Autologous Blood Patch After Ct-Guided Lung Biopsy Might Reduce Pneumothorax Requiring Chest Tube Placement, Tiffani Strickland

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Malone LJ, Stanfill RM, Wang H, Fahey KM, Bertino RE. Effect of intraparenchymal blood patch on rates of pneumothorax and pneumothorax requiring chest tube placement after percutaneous lung biopsy. American Journal of Roentgenology. 2013;200(6):1238-1243. doi: 10.2214/ajr.12.8980.

Transcriptional Up-Regulation Of Relaxin-3 By Nur77 Attenuates Β-Adrenergic Agonist-Induced Apoptosis In Cardiomyocytes., Xiaohua You, Zhifu Guo, Fang Cheng, Bing Yi, Fan Yang, Xinzhu Liu, Ni Zhu, Xianxian Zhao, Guijun Yan, Xin-Liang Ma, Jianxin Sun

Center for Translational Medicine Faculty Papers

The relaxin family peptides have been shown to exert several beneficial effects on the heart, including anti-apoptosis, anti-fibrosis, and anti-hypertrophy activity. Understanding their regulation might provide new opportunities for therapeutic interventions, but the molecular mechanism(s) coordinating relaxin expression in the heart remain largely obscured. Previous work demonstrated a role for the orphan nuclear receptor Nur77 in regulating cardiomyocyte apoptosis. We therefore investigated Nur77 in the hopes of identifying novel relaxin regulators. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) data indicated that ectopic expression of orphan nuclear receptor Nur77 markedly increased the expression of latexin-3 (RLN3), but not relaxin-1 …

Anidulafungin: A Noninferior Alternative To Fluconazole For Treatment Of Esophageal Candidiasis, Blake S. Sanford

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Krause DS, Simjee AE, van Rensburg C, et al. A randomized, double-blind trial of anidulafungin versus fluconazole for the treatment of esophageal candidiasis. Clin Infect Dis. 2004;39(6):770-775. doi: 10.1086/423378.

Intravenous Glucocorticoids Provide No Additional Benefit Over Oral Glucocorticoids In Chronic Obstructive Pulmonary Disease Exacerbation, Alexander C. Waselewski

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of de Jong YP, Uil SM, Grotjohan HP, Postma DS, Kerstjens HA, van den Berg JW. Oral or IV prednisolone in the treatment of COPD exacerbations: a randomized, controlled, double-blind study. Chest. 2007;132(6):1741-1747. doi: 10.1378/chest.07-0208

Coping With Chronic Fungal Rhinosinusitis: Diagnosis To Therapy, Veronica Corcino, Leslie Beavin, Shengli Lu, Ashley Ross, Carmen V. Sciortino Jr.

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Continuous Infusion Of Epoprostenol As Salvage Therapy For Severe Pulmonary Arterial Hypertension, Jenna Rousseau, Jie Chi

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Barst RJ, Rubin LJ, Long WA, McGoon MD, Rich S. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. New Eng J Med. 1996;334(5):296-301. doi: 10.1056/nejm199602013340504

The Transfusion Threshold For Upper Gastrointestinal Bleeding Is A Hemoglobin Of 7.0 G/Dl Or Less, Matthew J. Ouellette , D.O., Katherine S. Lee , M.D., Daniel P. Noack, Aaron Simpson , M.D., Rana K. Zaban , D.O., Chelsea Gonzalez , D.O., Racha El-Ladki , D.O.

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Villanueva C, Colomo A, Bosch A, Concepcion M, Hernandez-Gea V, Aracil C. Transfusion strategies for acute upper gastrointestinal bleeding. New Eng J Med. 2013;368(1):11-21. doi: 10.1056/NEJMoa1211801

Fecal Microbiota Transplantation May Have Clinical Utility In Reducing Incidence Of Recurrent Urinary Tract Infection, Jeremy A. Grekin

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Tariq R, Pardi DS, Tosh PK, Walker RC, Razonable RR, Khanna S. Fecal microbiota transplantation for recurrent Clostridium difficile infection reduces recurrent urinary tract infection frequency. Clinical Infectious Diseases. 2017 Oct 30;65(10):1745–1747. doi: 10.1093/cid/cix618

Early Oral Refeeding In Acute Pancreatitis Reduces Length Of Hospital Stay, Sylvie B. Polsky

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Lariño-Noia J, Lindkvist B, Iglesias-García J, Seijo-Ríos S, Iglesias-Canle J, Domínguez-Muñoz J. Early and/or immediately full caloric diet versus standard refeeding in mild acute pancreatitis: A randomized open-label trial. Pancreatology. 2014;14(3):167-173. doi: 10.1016/j.pan.2014.02.008.

Heparin Bridging Therapy Is Not Necessary For Patients With Atrial Fibrillation Undergoing Temporary Interruption Of Warfarin Therapy For Elective Invasive Procedures Or Surgery, Shannon Paquette

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Douketis JD, Spyropoulos AC, Kaatz S, et al. Perioperative bridging anticoagulation in patients with atrial fibrillation. New Engl J Med. Aug 2015;373(9):823-833. doi: 10.1056/NEJMoa1501035

Exploring The Role Of Ceftaroline In The Treatment Of Community-Acquired Pneumonia, Zachary Meyer

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of File TM Jr, Low DE, Eckburg PB, Talbot GH, Friedland HD, Lee J, Llorens L, Critchley IA, Thye DA, FOCUS 1 investigators. FOCUS 1: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia. J Antimicrob Chemother. 2011 Apr;66 Suppl 3:iii19-32. doi: 10.1093/jac/dkr096

Implementing A Pre-Exposure Prophylaxis Intervention For Safer Conception Among Hiv Serodiscordant Couples: Recommendations For Health Care Providers, Mari-Lynn Drainoni, Dea L. Biancarelli, Ashley A. Leech, Meg Sullivan, Angela R. Bazzi

Journal of Health Disparities Research and Practice

Couples in HIV serodiscordant relationships frequently desire children. Although partners who are virally suppressed pose almost no risk of transmitting HIV to their partners, partners who are inconsistently on therapy may transmit HIV to their partners when attempting to conceive. Pre-exposure prophylaxis (PrEP) is an available safer conception strategy for these couples but is not consistently offered. We sought to better understand barriers to PrEP implementation for couples seeking conception and patient perceptions on what providers could do to encourage use. We conducted in-depth, qualitative interviews with 11 participants representing six couples taking PrEP for safer conception in a safety-net …

Endorepellin Remodels The Endothelial Transcriptome Toward A Pro-Autophagic And Pro-Mitophagic Gene Signature., Thomas Neill, Eva Andreuzzi, Zi-Xuan Wang, Stephen C. Peiper, Maurizo Mongiat, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Regulation of autophagy by proteolytically cleaved fragments of heparan sulfate proteoglycans is a novel and current research focus in tumor biology. Endorepellin is the C-terminal angiostatic fragment of the heparan sulfate proteoglycan perlecan and induces autophagy in endothelial cells. To further investigate this property, we used NanoString, a digital PCR platform for measuring pre-defined transcripts in biological samples to analyze a custom subset of 95 autophagy-related genes in human umbilical vein endothelial cells treated with ultrapure human recombinant endorepellin. We discovered an endorepellin-evoked pro-autophagic and pro-mitophagic gene expression signatures, which included two coordinately up-regulated mitochondrial-associated genes encoding the E3 ubiquitin …

Ticagrelor Reduces Thromboinflammatory Markers In Patients With Pneumonia, Travis R. Sexton, Guoying Zhang, Tracy E. Macaulay, Leigh Ann Callahan, Richard Charnigo, Olga A. Vsevolozhskaya, Zhenyu Li, Susan S. Smyth

Gill Heart & Vascular Institute Faculty Publications

Despite treatment advances for sepsis and pneumonia, significant improvements in outcome have not been realized. Antiplatelet therapy may improve outcome in pneumonia and sepsis. In this study, the authors show that ticagrelor reduced leukocytes with attached platelets as well as the inflammatory biomarker interleukin (IL)-6. Pneumonia patients receiving ticagrelor required less supplemental oxygen and lung function tests trended toward improvement. Disruption of the P2Y₁₂ receptor in a murine model protected against inflammatory response, lung permeability, and mortality. Results indicate a mechanistic link between platelets, leukocytes, and lung injury in settings of pneumonia and sepsis, and suggest possible therapeutic approaches …

“Our Lab Is The Community”: Defining Essential Supporting Infrastructure In Engagement Research, Donald E. Nease Jr., Dee Burton, Sarah L. Cutrona, Lauren Edmundson, Alex H. Krist, Michael Barton Laws, Montelle Tamez

Publications and Research

Introduction: Effective patient engagement is central to patient-centered outcomes research. A well-designed infrastructure supports and facilitates patient engagement, enabling study development and implementation. We sought to understand infrastructure needs from recipients of Patient-Centered Outcomes Research Institute (PCORI) pilot grant awards. Methods: We surveyed recipients of PCORI pilot project awards on self-perceived strengths in engagement infrastructure through PCORI’s Ways of Engaging-Engagement Activity Tool survey, and interviewed leaders of 8 projects who volunteered as exemplars. Descriptive statistics summarized the survey findings. We conducted a thematic analysis of the interview transcripts. Results: Of the 50 surveyed pilots, 22 answered the engagement infrastructure questions …

Apoptosis Signal-Regulating Kinase 1 Inhibition Attenuates Human Airway Smooth Muscle Growth And Migration In Chronic Obstructive Pulmonary Disease., Mathew S. Eapen, Anudeep Kota, Howard Vindin, Kielan D. Mcalinden, Dia Xenaki, Brian G. Oliver, Deepak A. Deshpande, Sukhwinder Singh Sohal, Pawan Sharma

Center for Translational Medicine Faculty Papers

Increased airway smooth muscle (ASM) mass is observed in chronic obstructive pulmonary disease (COPD), which is correlated with disease severity and negatively affects lung function in these patients. Thus, there is clear unmet clinical need for finding new therapies which can target airway remodeling and disease progression in COPD. Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K) activated by various stress stimuli, including reactive oxygen species (ROS), tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) and is known to regulate cell proliferation. ASM cells from COPD patients are hyperproliferative to mitogens in vitro. …

Pth1r-Casr Cross Talk: New Treatment Options For Breast Cancer Osteolytic Bone Metastases., Yanmei Yang, Bin Wang

Department of Medicine Faculty Papers

Metastatic breast cancer (BrCa) is currently incurable despite great improvements in treatment of primary BrCa. The incidence of skeletal metastases in advanced BrCa occurs up to 70%. Recent findings have established that the distribution of BrCa metastases to the skeleton is not a random process but due to the favorable microenvironment for tumor invasion and growth. The complex interplay among BrCa cells, stromal/osteoblastic cells, and osteoclasts in the osseous microenvironment creates a bone-tumor vicious cycle (a feed-forward loop) that results in excessive bone destruction and progressive tumor growth. Both the type 1 PTH receptor (PTH1R) and extracellular calcium-sensing receptor (CaSR) …

Hemostatic Nanoparticles Increase Survival, Mitigate Neuropathology And Alleviate Anxiety In A Rodent Blast Trauma Model, W. Brad Hubbard, Margaret Lashof-Sullivan, Shaylen Greenberg, Carly Norris, Joseph Eck, Erin Lavik, Pamela Vandevord

Spinal Cord and Brain Injury Research Center Faculty Publications

Explosions account for 79% of combat related injuries and often lead to polytrauma, a majority of which include blast-induced traumatic brain injuries (bTBI). These injuries lead to internal bleeding in multiple organs and, in the case of bTBI, long term neurological deficits. Currently, there are no treatments for internal bleeding beyond fluid resuscitation and surgery. There is also a dearth of treatments for TBI. We have developed a novel approach using hemostatic nanoparticles that encapsulate an anti-inflammatory, dexamethasone, to stop the bleeding and reduce inflammation after injury. We hypothesize that this will improve not only survival but long term functional …

High-Volume Hemofiltration Is Not Preferred For Hypertriglyceridemia-Induced Pancreatitis, Ian N. Monk

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of He WH, Yu M, Zhu Y, et al. Emergent triglyceride-lowering therapy with early high-volume hemofiltration against low-molecular-weight heparin combined with insulin in hypertriglyceridemic pancreatitis: A prospective randomized controlled trial. J Clin Gastroenterol. 2016;50(9):772-778. doi: 10.1097/MCG.0000000000000552.

Letter To The Editor: Management Of Pfo: More Evidence, Same Recommendation, Halima Ali, Md

Clinical Research in Practice: The Journal of Team Hippocrates

The author offers more evidence to support Zhang's assertion in CRP 3(2) that closure of patent foramen ovale or medical therapy alone are both appropriate choices for preventing recurrent cryptogenic strokes (https://doi.org/10.22237/crp/1518739380).

A Study Of Acoustically Activated Nanodroplets, Songita Choudhury

Theses & Dissertations

Current treatment of acute myocardial infarction (AMI), which is the main pathophysiological event leading to death in the United States, has advanced considerably with the introduction of emergent percutaneous interventions, but there remains an urgent need for novel techniques to rapidly and accurately detect infarcted or ischemic tissue that results from AMI. Ultrasound contrast agents, also known as microbubbles (MB), have become commonplace in echocardiography. However, MBs are purely intravascular tracers and unable to cross endothelial barriers due to size. The limitations of MBs, namely size and short circulation times within the human body, led to the development of phase-change …

Intestinal Permeability And Microbial Dysbiosis In Acute Coronary Syndrome (Miacs Study), Tarik Z. Alhmoud

Biomedical Sciences ETDs

Background: Acute Coronary Syndrome (ACS) is a leading cause of morbidity and mortality. Metabolic syndrome and obesity are major risk factors for atherosclerosis and ACS. Dysbiosis plays an important role in metabolic syndrome and obesity. Studies show a markedly increased risk of heart attacks in patients with high levels of the pro-atherogenic metabolite trimethylamine-N-Oxide (TMAO). TMAO is produced by the intestinal microbial flora through metabolism of dietary phospholipids; Gram-negative bacteria (Phylum Proteobacteria) is the major source of TMAO metabolism. Patients with obesity and metabolic syndrome have a defective intestinal tight-junctional (TJ) barrier, which allows paracellular permeation of luminal antigens such …

Extending The Phenotypic Spectrum Of Sengers Syndrome: Congenital Lactic Acidosis With Synthetic Liver Dysfunction., David B Beck, Kristina Cusmano-Ozog, Nickie Andescavage, Eyby Leon

Pathology Faculty Publications

Sengers syndrome is a rare autosomal recessive mitochondrial disease characterized by lactic acidosis, hypertrophic cardiomyopathy and bilateral cataracts. We present here a case of neonatal demise, within the first day of life, who initially presented with severe lactic acidosis, with evidence of both chorioamnionitis and cardiogenic shock. Initial metabolic labs demonstrated a severe lactic acidosis prompting genetic testing which revealed a homozygous pathogenic variant for Sengers syndrome in

Cyclin D1-Mediated Microrna Expression Signature Predicts Breast Cancer Outcome, Guangxue Wang, Michael Gormley, Jing Qiao, Qian Zhao, Min Wang, Gabriele Disante, Shengqiong Deng, Lin Dong, Timothy G. Pestell, Xiaoming Ju, Mathew C. Casimiro, Sankar Addya, Adam Ertel, Ayden Tozeren, Qinchuan Li, Zuoren Yu, Richard G. Pestell

Department of Cancer Biology Faculty Papers

Background: Genetic classification of breast cancer based on the coding mRNA suggests the evolution of distinct subtypes. Whether the non-coding genome is altered concordantly with the coding genome and the mechanism by which the cell cycle directly controls the non-coding genome is poorly understood.

Methods: Herein, the miRNA signature maintained by endogenous cyclin D1 in human breast cancer cells was defined. In order to determine the clinical significance of the cyclin D1-mediated miRNA signature, we defined a miRNA expression superset from 459 breast cancer samples. We compared the coding and non-coding genome of breast cancer subtypes.

Results: Hierarchical clustering of …

Acute Pressor Response To Psychosocial Stress Is Dependent On Endothelium‐Derived Endothelin‐1, Brandon M. Fox, Bryan K. Becker, Analia S. Loria, Kelly A. Hyndman, Chunhua Jin, Hannah Clark, Robin Johns, Masashi Yanagisawa, David M. Pollock, Jennifer S. Pollock

Pharmacology and Nutritional Sciences Faculty Publications

Background

Acute psychosocial stress provokes increases in circulating endothelin‐1 (ET‐1) levels in humans and animal models. However, key questions about the physiological function and cellular source of stress‐induced ET‐1 remain unanswered. We hypothesized that endothelium‐derived ET‐1 contributes to the acute pressor response to stress via activation of the endothelin A receptor.

Methods and Results

Adult male vascular endothelium‐specific ET‐1 knockout mice and control mice that were homozygous for the floxed allele were exposed to acute psychosocial stress in the form of cage switch stress (CSS), with blood pressure measured by telemetry. An acute pressor response was elicited by CSS in …