Translational Medical Research Commons^™

Intra-Articular Tranexamic Acid During Total Knee Arthroplasty, Ahmed F. Khan

Clinical Research in Practice: The Journal of Team Hippocrates

An informed consent conversation regarding bleeding risk prior to total knee arthroplasty in an elderly patient with chronic kidney disease.

Cognitive Behavioral Therapy For Patients With Psychogenic Non-Epileptic Seizures, Andrew Brown

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Goldstein L., Chalder T., et al. Cognitive-behavioral therapy for psychogenic non-epileptic seizures: A pilot RCT. Neurology. 2010;74(24):1986-1994. doi: 10.1212/WNL.0b013e3181e39658

Rad Gtpase Deletion Atenuates Post-Ischemic Cardiac Dysfunction And Remodeling, Janet R. Manning, Lakshman Chelvarajan, Bryana R. Levitan, Catherine Nicole Kaminski Withers, Prabhakara R. Nagareddy, Christopher M. Haggerty, Brandon K. Fornwalt, Erhe Gao, Himi Tripathi, Ahmed Abdel-Latif, Douglas A. Andres, Jonathan Satin

Physiology Faculty Publications

The protein Rad interacts with the L-type calcium channel complex to modulate trigger Ca²⁺ and hence to govern contractility. Reducing Rad levels increases cardiac output. Ablation of Rad also attenuated the inflammatory response following acute myocardial infarction. Future studies to target deletion of Rad in the heart could be conducted to establish a novel treatment paradigm whereby pathologically stressed hearts would be given safe, stable positive inotropic support without arrhythmias and without pathological structural remodeling. Future investigations will also focus on establishing inhibitors of Rad and testing the efficacy of Rad deletion in cardioprotection relative to the time of …

Microrna 1207-3p In Prostate Cancer, Dibash Das

Dissertations, Theses, and Capstone Projects

Prostate cancer (PCa) is the most commonly diagnosed male cancer and the second leading cause of cancer-related death for men in the United States. Understanding the molecular mechanisms involved in progression from the asymptomatic androgen-dependent PCa to the lethal castration resistant prostate cancer (CRPC) is a major challenge. MicroRNAs (miRNAs), are known to be dysregulated in PCa. MicroRNA-1207-3p (miR-1207-3p) is encoded by the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, the role of miR-1207-3p in PCa is unclear. We have discovered that miR-1207-3p is significantly underexpressed in PCa cell lines …

Implementation Of A Low-Cost Unna Boot Alternative As Adjunctive Treatment For Kaposi Sarcoma, Alexander Robert Mills, Edith Tonui, Sonak Pastakia, Rakhi Karwa, Phelix Were

Engagement & Service-Learning Summit

There are 6 million people living with HIV; 70% reside in Sub-Saharan Africa (SSA). Furthermore, 1.1 million deaths occur due to opportunistic infections (OIs) that can be minimized with antiretroviral therapy. In Kenya, Kaposi Sarcoma (KS) is an especially debilitating OI that presents with dermatologic lesions; magnifying the stigma that patients with HIV face physically and psychosocially. Dermatology research is underway to determine the effectiveness of an unna boot (medicated, layered compression dressing) to speed the healing of these lesions with anecdotal success. Commercially available unna boot products are too expensive and not readily available in SSA. Clinicians from Purdue …

Beta-Catenin Cleavage Enhances Transcriptional Activation, Tatiana Goretsky, Emily M. Bradford, Qing Ye, Olivia F. Lamping, Tomas Vanagunas, Mary Pat Moyer, Patrick C. Keller, Preetika Sinh, Josep M. Llovet, Tianyan Gao, Qing-Bai She, Linheng Li, Terrence A. Barrett

Internal Medicine Faculty Publications

Nuclear activation of Wnt/β-catenin signaling is required for cell proliferation in inflammation and cancer. Studies from our group indicate that β-catenin activation in colitis and colorectal cancer (CRC) correlates with increased nuclear levels of β-catenin phosphorylated at serine 552 (pβ-Cat⁵⁵²). Biochemical analysis of nuclear extracts from cancer biopsies revealed the existence of low molecular weight (LMW) pβ-Cat⁵⁵², increased to the exclusion of full size (FS) forms of β-catenin. LMW β-catenin lacks both termini, leaving residues in the armadillo repeat intact. Further experiments showed that TCF4 predominantly binds LMW pβ-Cat⁵⁵² in the nucleus of inflamed and …

Electrotransfer Of Different Control Plasmids Elicits Different Antitumor Effectiveness In B16.F10 Melanoma, Masa Bosnjak, Tanjo Jesenko, Urska Kamensek, Gregor Sersa, Jaka Lavrencak, Loree Heller, Maja Cemazar

Bioelectrics Publications

Several studies have shown that different control plasmids may cause antitumor action in different murine tumor models after gene electrotransfer (GET). Due to the differences in GET protocols, plasmid vectors, and experimental models, the observed antitumor effects were incomparable. Therefore, the current study was conducted comparing antitumor effectiveness of three different control plasmids using the same GET parameters. We followed cytotoxicity in vitro and the antitumor effect in vivo after GET of control plasmids pControl, pENTR/U6 scr and pVAX1 in B16.F10 murine melanoma cells and tumors. Types of cell death and upregulation of selected cytosolic DNA sensors and cytokines were …

Effects Of The Na-Cl Co-Transporter (Ncc) In Western Diet Induced Metabolic And Cardiac Dysfunction, Zachary S. Cutter

Theses and Dissertations

Interleukin-18 (IL-18) is a pro-inflammatory cytokine known to be involved in maintaining metabolic homeostasis; however, also capable of inducing cardiac dysfunction. Additionally, IL-18, has been shown to bind to a novel receptor, the Na-Cl Co-transporter (NCC). We hypothesized that NCC mediates IL-18 metabolic and cardiac signaling in mice. Using male C57BL/6J mice, we compared the metabolic and cardiac function changes after at least 8 weeks of high-saturated fat high sugar diet (Western Diet) in NCC knockout (NCCKO), IL-18 knockout (IL-18KO), and wild-type mice. We show that NCCKO mice have significantly increased body weight gain from baseline, no difference in fasting …

Type 1 Diabetes Alters Lipid Handling And Metabolism In Human Fibroblasts And Peripheral Blood Mononuclear Cells, Albert R. Jones Iv, Emily L. Coleman, Nicholas R. Husni, Jude T. Deeney, Forum Raval, Devin Steenkamp, Hans Dooms, Barbara S. Nikolajczyk, Barbara E. Corkey

Clinical and Translational Science Faculty Publications

Triggers of the autoimmune response that leads to type 1 diabetes (T1D) remain poorly understood. A possibility is that parallel changes in both T cells and target cells provoke autoimmune attack. We previously documented greater Ca²⁺ transients in fibroblasts from T1D subjects than non-T1D after exposure to fatty acids (FA) and tumor necrosis factor α (TNFα). These data indicate that metabolic and signal transduction defects present in T1D can be elicited ex vivo in isolated cells. Changes that precede T1D, including inflammation, may activate atypical responses in people that are genetically predisposed to T1D. To identify such cellular differences …

Hmgcs2 Is A Key Ketogenic Enzyme Potentially Involved In Type 1 Diabetes With High Cardiovascular Risk., Sanket Kumar Shukla, Weijing Liu, Kunal Sikder, Sankar Addya, Amrita Sarkar, Yidong Wei, Khadija Rafiq

Center for Translational Medicine Faculty Papers

Diabetes increases the risk of Cardio-vascular disease (CVD). CVD is more prevalent in type 2 diabetes (T2D) than type 1 diabetes (T1D), but the mortality risk is higher in T1D than in T2D. The pathophysiology of CVD in T1D is poorly defined. To learn more about biological pathways that are potentially involved in T1D with cardiac dysfunction, we sought to identify differentially expressed genes in the T1D heart. Our study used T1D mice with severe hyperglycemia along with significant deficits in echocardiographic measurements. Microarray analysis of heart tissue RNA revealed that the T1D mice differentially expressed 10 genes compared to …

Impact Of Kras/Nras Mutational Heterogeneity On Clinical Outcomes In Colorectal Cancer, Jonathan M. Loree

Dissertations and Theses (Open Access)

Introduction: Mutations in KRAS/NRAS (RAS) predict a lack of benefit from anti-EGFR agents in metastatic colorectal cancer (mCRC). As next generation sequencing (NGS) has advanced, we are discovering atypical and low allele frequency mutations. We aimed to evaluate how NGS can optimally define RAS mutant CRC and the role of relative mutant allele frequency (rMAF) as a biomarker.

Methods: Using institutional and public cohorts of mCRC patients with NGS results, we described the prevalence and clinical impact of atypical (not in current guidelines) and low rMAF RAS mutations (RAS MAF by the MAF of the mutated gene with …

Membrane Bound Il21 Promotes Natural Killer Cell Expansion Through Mir 124-3p Mediated Regulation, Anitha Somanchi

Dissertations and Theses (Open Access)

Natural Killer (NK) cells are cells of the innate immune system that act as first line of defense against viral infections and participate in tumor immune surveillance. NK cells do not cause graft versus host disease (GvHD), or require prior antigen exposure to exert anti-tumor activity, hence are an attractive choice for immunotherapy applications. Owing to small numbers of NK cells in peripheral blood (1-32%, with a 6% median), ex vivo expansion of NK cells is critical for NK cell adoptive immunotherapy, various expansion platforms have been explored over the decades. We developed a robust platform for ex vivo expansion …

Conference Proceedings: Aurora Scientific Day 2017

Journal of Patient-Centered Research and Reviews

This supplement includes select abstracts presented at the 43rd Annual Aurora Scientific Day research symposium on May 24, 2017. Aurora Scientific Day hosts a forum for original research conducted by faculty, fellows, residents, and other allied health professionals affiliated with Aurora Health Care, an integrated health system headquartered in Milwaukee, Wisconsin.

Generation Of A Patient-Derived Brain Metastasis Breast Cancer Cell Line Via Novel Orthotopic Injection Placement And Serial Mouse Transplantation To Develop Pdx Mouse Model, Amber L. Lacrosse, Denise M. Coley, Paul J. Mintz, Santhi D. Konduri, Richard A. Rovin, Amin B. Kassam

Journal of Patient-Centered Research and Reviews

Background: The incidence of brain metastasis appears to be increasing, potentially due to advanced technology that aids early diagnosis. Patient-derived xenografts (PDX) have high translational value, as these models retain key functional characteristics of the patient tumor. PDX models are useful to understand the molecular basis of tumorigenesis and to identify new treatment targets. However, generating a first-line PDX model is challenging as engraftment failure is high. Serial transplanting tumor tissue via mouse-to-mouse propagation increases engraftment rates and decreases PDX development time. Herein we report methods to generate a PDX cell line from patient-derived tumor tissue that includes the cerebral …

Lung Cytokines And Systemic Inflammation In Patients With Copd., Alessandra Morello Gearhart, Rodrigo Cavallazzi, Paula Peyrani, Timothy L. Wiemken, Stephen P. Furmanek, Andrea Reyes-Vega, Umair Gauhar, Hiram Rivas-Perez, Jesse Roman, Julio A. Ramirez, Rafael Fernandez-Botran

Faculty and Staff Scholarship

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by lung and systemic inflammation. The role of cytokines in local and systemic inflammation in COPD is not well understood. This study aimed to compare plasma and bronchoalveolar lavage (BAL) fluid cytokine levels in COPD and non-COPD subjects with the intent of better understand their potential roles in driving local and systemic inflammation.

Methods: This cross-sectional study analyzed data from 65 subjects: 31 with COPD confirmed by spirometry and 34 non-COPD controls. All subjects underwent spirometry, plasma sample collection, and bronchoscopy/BAL. Levels of 21 inflammatory cytokines were measured in the plasma (systemic …

Hydroxyurea Lowers The Frequency Of Sickle Cell Vaso-Occlusive Crises, Corey S. Macrander

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Charache S, Terrin ML, Moore RD, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. N Engl J Med 1995;(332):1317-1322 doi: 10.1056/nejm199505183322001

Clopidogrel Alone Is Safer Than Clopidogrel And Aspirin For Secondary Prevention Of Acute Ischemic Stroke., Bradford J. Woelke, Daniel Angell Do, Katherine Litow Md

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Diener HC, Bogousslavsky J, Brass LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet. 2004;364(9431):331-337. doi: 10.1016/s0140-6736(04)16721-4

Quality? Safety? Stop Being Naïve., Rana K. Zaban Do, Steven Istephan, Jonathan Serman Md

Clinical Research in Practice: The Journal of Team Hippocrates

The first day of our inpatient medicine rotation, the Emergency Department (ED) admitted a patient to a general medical floor without notifying our rounding team. We used the institution’s system improvement tracking software to draw attention to communication breakdown in the interest of patient safety. This piece illustrates how there is a prominent hierarchy in medicine; it is inherent to the framework of the way in which hospitals function. A discussion ensues with our attending physician supervisor on our patient medicine service. During this discussion, we ponder whether it is possible to impact quality and safety from our position as …

Treating Diabetic Ketoacidosis With Subcutaneous Insulin?, Marlene Aziza Azar

Clinical Research in Practice: The Journal of Team Hippocrates

The author examines the evidence for treating diabetic ketoacidosis with subcutaneous insulin vs IV insulin.

Improving Nk Cell Therapy For Osteosarcoma, Jennifer Foltz

Dissertations and Theses (Open Access)

Osteosarcoma (OS) is the most common primary bone tumor. Despite new treatment options, 5-year survival for metastatic OS has remained at only 30% for the last 30 years. Adoptive transfer of Natural Killer (NK) cells holds promise for a new, non-toxic therapy for OS. NK cells are part of the innate immune system and readily kill metastatic and chemotherapy-resistant OS in vitro and in murine models. However, there is little data regarding their efficacy in animal models with an intact immune system. In addition, the OS tumor microenvironment is highly suppressive, producing TGFβ which impedes NK cell killing of solid …

Motor Learning And Adaptation In People With Knee Osteoarthritis And Chronic Pain, Heather Turcotte, Katherine S. Rudolph

Osteopathic Medicine Student Research Posters

Osteoarthritis (OA) affects an estimated 50 million people in the US, and approximately 43% have limitations in daily function due to arthritis pain.3 Individuals with knee osteoarthritis (OA) have heightened sensitization to pain2,5 as well as reduced strength, diminished function and quality of life1 that prompts them to seek care from health care providers. Physical therapists commonly work with patients to improve function and quality of life by helping them learn to move without pain. Unfortunately, chronic pain causes changes to the nervous system that may impact the ability to learn new ways but the extent to which chronic pain …

Analysis Of The Local And Systemic Cytokine Response Profiles In Patients With Community-Acquired Pneumonia. Relationship With Disease Severity And Outcomes., Rafael Fernandez-Botran, Timothy Lee Wiemken, Robert R. Kelley, Paula Peyrani, Jose Bordon, Rodrigo Cavallazzi, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

The goals of this study were to investigate the relationship of systemic and local cytokine responses with time to clinical stability (TCS) in patients with community-acquired pneumonia (CAP) and to develop a model to integrate multiple cytokine data into “cytokine response profiles” based on local vs. systemic and pro- vs. anti-inflammatory cytokine patterns in order to better understand their relationships with measures of CAP severity and outcomes. Forty hospitalized patients enrolled through the Community Acquired Pneumonia Inflammatory Study Group (CAPISG) were analyzed. Based on the ranked distribution of the levels of eight different pro-inflammatory cytokines and chemokines (IL-1b, IL-6, IL-8, …

Cyclin B1 Mediates The Effect Of Uchl1 In Promoting Cell Cycle Progression In Uterine Papillary Serous Carcinoma, Suet Ying Kwan

Dissertations and Theses (Open Access)

Uterine papillary serous carcinoma (UPSC) is an aggressive form of endometrial cancer with poor survival rates and a high risk of recurrence. The rarity of UPSC poses challenges to the discovery of novel targeted therapies. Therefore, the purpose of this dissertation was to identify novel therapeutic targets that could aid in the management of UPSC. To do so, we began with the relatively large cohort of UPSC cases in the TCGA data set, which was used to identify differentially expressed genes between UPSC and low-grade endometrioid endometrial carcinoma (EEC) and normal tissue.

We identified Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1 …

Low Molecular-Weight Heparin Is Better Than Warfarin For Prevention Of Recurrent Venous Thromboembolism In Cancer Patients, Sarah Choi

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Lee AYY, Levin MN, Bake RI, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003;349:146-153. doi: 10.1056/NEJMoa025313

The Impact Of The Patient-Centered Medical Home On Health Disparities In Adults: A Systematic Review Of The Evidence, J. Nwando Olayiwola 2062970, Sonali Sheth, Victor Mleczko, Anna L. Choi, Anjana E. Sharma

Journal of Health Disparities Research and Practice

Introduction: The objective of this study was to review the empirical evidence on Patient-Centered Medical Home (PCMH) impact on health disparities in adults.

Methods: We searched PubMed, Scopus, and Google Scholar to identify studies on PCMH/health homes and health disparities published in English between January 1, 2009 and December 31, 2014. Articles met inclusion criteria if they investigated at least one component of PCMH or health homes in vulnerable populations, defined by PROGRESS-PLUS criteria, and reported differences in one of five clinical quality measures.

Results: 964 articles were identified through database searching and subsequent snowballing. 60 articles underwent full text …

Correcting The Trajectory Of Stroke Therapeutic Research, Keith R. Pennypacker, Gregory J. Bix, Justin F. Fraser

Neurology Faculty Publications

No abstract provided.

The Ethics Of Offering Futile Treatment, Rebekah L. Eddy, Viktoria Krajnc, Lauren Smith

Clinical Research in Practice: The Journal of Team Hippocrates

It important to acknowledge our own emotional biases and be cognizant of how we present evidence-based options to patients and their families, so that they may provide truly informed consent.

Stem Cell Therapy For End Stage Copd: A Cautionary Tale Of Direct-To-Consumer Advertising, Blake J. Arthurs, Scott Yaekle

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Weiss DJ, Casaburi R, Flannery R, LeRoux-Williams M, Tashkin DP. A placebo-controlled, randomized trial of mesenchymal stem cells in COPD. Chest. 2013;143(6):1590-1598. doi: 10.1378/chest.12-2094

It Is Reasonable To Recommended Intrapleural Alteplase For Loculated Pleural Effusions, Tricia Fernandez

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Thommi G, Shehan J, Robison K, Christensen M, Backemeyer L, McLeay M. A double blind randomized cross over trial comparing rate of decortication and efficacy of intrapleural instillation of alteplase vs placebo in patients with empyemas and complicated parapneumonic effusions. Respir Med. 2012;17(2):716-723. doi: 10.1016/j.rmed.2012.02.005

Combination Octreotide, Midodrine, And Albumin May Improve Survival In Patients With Hepatorenal Syndrome, But The Evidence Is Weak, Jacob Szafranski

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Skagen C, Einstein M, Lucey MR, Said A. Combination treatment with octreotide, midodrine, and albumin improves survival in patients with type 1 and type 2 hepatorenal syndrome. J Clin Gastroenterol. 2009 Aug;43(7):680-5. doi: 10.1097/MCG.0b013e318188947c