Translational Medical Research Commons^™

Selective Generation Of Dopaminergic Precursors From Human Fibroblasts By Direct Lineage Conversion, Miao He

Theses & Dissertations

Transplantation of dopaminergic precursors (DPs) is a promising therapeutic strategy of Parkinson’s disease (PD). However, limited cell source for dopaminergic precursors has become a major obstacle for transplantation therapy. In the first part of the study, we demonstrated that Foxa2 is superior to Lmx1a in inducing dopaminergic neuronal differentiation from induced neural progenitor cells (iNPCs). Based on the results above and some other published results, our group demonstrated that mouse fibroblasts can be reprogrammed into induced dopaminergic precursors (iDPs) through ectopic expression of transcription factors Brn2, Sox2 and Foxa2(1). In the current study, we hypothesized that similar strategy …

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 …

Muc4 Based Immunotherapy For Pancreatic Cancer, Kasturi Banerjee

Theses & Dissertations

Pancreatic Cancer (PC) is a lethal disease claiming approximately 45000 lives in the US in 2018, and it establishes an elaborate immunosuppressive tumor microenvironment that aids in disease pathogenesis. Immunotherapy has emerged as a strategy to target tumor cells by reprogramming patient’s immune system. Challenges present in PC immunotherapy are: i) identifying a tumor-associated antigen that could be targeted, ii) identifying adjuvants that could efficiently deliver antigens, iii) eliciting robust anti-tumor responses and iv) overcoming peripheral tolerance and immunosuppression elicited by the tumor.

Firstly, we detected circulating autoantibodies to MUC4 present in PC patients and observed that IgM autoantibodies to …

Strain Differences In Susceptibility To Cisplatin-Induced Renal Fibrosis, Gabrielle B. Oropilla

College of Arts & Sciences Senior Theses

Cisplatin is a potent chemotherapeutic; the dose-limiting side effect of this drug is nephrotoxicity, causing acute kidney injury (AKI) in 30% of adult patients. Patients with cisplatin-induced AKI are more likely to develop end stage renal diseases, particularly chronic kidney disease (CKD), which is marked by the development of fibrosis. Currently, there are no therapeutic interventions for cisplatin-induced kidney injury, which may be due to limitations in the mouse model used to study this type of injury. We have previously developed a repeated dosing regimen of cisplatin (mice treated with 7 mg/kg once a week for 4 weeks, mice sacrificed …

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 …

Efficacy Of Antibiotic Treatments For Klebsiella And Esbl Pneumonia, Harry Snow

Clinical and Translational Science Center Scholarly Output

There is a dearth of knowledge and studies about empiric antibiotic treatment for Extended Spectrum-β-Lactamase (ESBL) bacterial pneumonia.

This study is meant to improve quality of evidence to “medium” levels from the current level of “very-low” quality.

Improved methods for treating Klebsiella Pneumoniae infection.

Primary outcome:Mortality

Aim:To assess differences in patient survival probability due to different antibiotic regimens, considering all classes of antibiotics.

Genomic Evolution Of Chemoresistance In Triple-Negative Breast Cancer Delineated By Single Cell Sequencing, Charissa Kim

Dissertations and Theses (Open Access)

Triple-negative breast cancer (TNBC) is an aggressive subtype that displays extensive intratumor heterogeneity and frequently (46%) develops resistance to neoadjuvant chemotherapy (NAC). Currently, the genomic basis of chemoresistance remains poorly understood. An important question is whether resistance to chemotherapy is driven by the selection of rare pre-existing subclones with genomic mutations and transcriptional programs that confer resistance to chemotherapy (adaptive resistance) or by the spontaneous induction of new mutations and expression changes that confer a resistant phenotype (acquired resistance). To investigate this question we applied single cell DNA and RNA sequencing methods and deep-exome sequencing to longitudinal time-point samples collected …

Genotype-Specific Insertion Of Cytotoxic Genetic Elements Into Cancer Cells, Ryan Englander

University Scholar Projects

The new gene editing system CRISPR/Cas9, composed of a complex composed of a guide RNA and the Cas9 endonuclease, promises to revolutionize biological research and potentially allow clinicians to directly modify patient DNA in vivo. While its applications in the treatment of genetic diseases and in modifying immune cells for immunotherapy are currently being explored, CRISPR/Cas9’s potential utility as a modular system for targeting tumor-specific mutated sequences has not as of yet been explored. While CRISPR/Cas9 is specific enough to target small insertions and deletions or gross chromosomal rearrangements, it is not specific enough to reliably restrict editing to …

Cognitive Changes Following Multiple-Modality Exercise And Mind-Motor Training In Older Adults With Subjective Cognitive Complaints: The M4 Study, Narlon Cassio Boa Sorte Silva, Dawn P. Gill, Adrian M. Owen, Teresa Liu-Ambrose, Vladimir Hachinski, Ryosuke Shigematsu, Robert Petrella

Lifestyle Research Team

Background

We investigated the effects of multiple-modality exercise with additional mind-motor training on cognition in community-dwelling older adults with subjective cognitive complaints.

Methods

Participants (n = 127, mean age 67.5 [7.3] years, 71% women) were randomized to receive 45 minutes of multiple-modality exercise with additional 15 minutes of either mind-motor training (M4, n = 63) or control (balance, range of motion and breathing exercises [M2, n = 64]). In total, both groups exercised 60 minutes/day, 3 days/week, for 24 weeks. Standardized global cognitive functioning (GCF), concentration, reasoning, planning, and memory were assessed at 24 weeks and after a 28-week no-contact …

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

Visualization Of Fibronectin Assembly Using Crispr And Fluorescence Imaging, Brenda French, Sophie Astrof

Sigma Xi Student Research Day

Objectives

Surprisingly, the mechanisms of fibronectin assembly remain largely unknown. This project aims to elucidate the process by which fibronectin assembles through fluorescent labeling. Fluorescent tags allow for the visualization of fibronectin to clarify how this extracellular matrix protein may influence migration and signaling.

Adult Patients Living With Human Immunodeficiency Virus Hospitalized For Community-Acquired Pneumonia In The United States: Incidence And Outcomes, Leslie A. Beavin, Stephen P. Furmanek, Paula Peyrani, Anupama Raghuram, Forest W. Arnold, Mark Burns, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Background: Community-acquired pneumonia (CAP) is a common infectious reason for hospitalization of adults in the United States (US), including those with Human Immunodeficiency Virus (HIV). While there are studies detailing the incidence and outcomes for all adults with CAP we are not aware of a recent study detailing incidence and outcomes in adult HIV patients hospitalized with CAP. The objectives of this study were (1) to define the current incidence and outcomes of adult HIV patients hospitalized with CAP in Louisville, Kentucky, and (2) to estimate the burden of CAP in the US HIV adult population.

Methods: This was a …

A Software Tool For Automated Upload Of Large Clinical Datasets Using Redcap And The Capo Database, William A. Mattingly, Christopher Sinclair, Danna Williams, Matthew Grassman, Stephen Furmanek, Kimberley Buckner, Mohammad Tahboub

The University of Louisville Journal of Respiratory Infections

Introduction: Obtaining clinical data from healthcare sources is necessary for conducting clinical research. New technologies now allow for connecting a research database to Electronic Medical Records remotely, allowing the automatic import of clinical research data. In this paper we design and evaluate a REDCap extension to import clinical records from an external health database.

Methods: Many hospital EHRs are designed to use secure file transfer protocol (SFTP) repositories for data communication. We develop a REDCap plugin to connect to an external SFTP file repository for the import of clinical record data. We use the CAPO instance of REDCap and a …

Bacteremic Pneumococcal Pneumonia: A Longitudinal Study In 279 Adult Patients From A Single Center, Jorge H. Gentile, Claudia Hernandez, Monica D. Sparo, Edgardo M. Rodriguez, Carolina Ceriani, Florencia Bruggesser

The University of Louisville Journal of Respiratory Infections

Background: Bacteremic pneumococcal pneumonia (BPP) is the most common clinical presentation of invasive pneumococcal disease (IPD). Although it has been extensively studied, there is little knowledge in our region in relation to burden of disease, demographic and outcome features.

Methods: We conducted a prospective, longitudinal, observational study from 1989 to 2015 in adult patients with BPP, in order to deepen our knowledge of the characteristics of this disease in our community hospital in Tandil, Argentina.

Results: 279 patients were included. The mean incidence was 2.8/1000 admissions with a sharp decrease in the last two years, reaching 0.8/1000 admissions. Mean patient …

An Hiv-Positive Patient With Copd Admitted To The Icu With Respiratory Failure, Bhavani Puskur, Veronica Corcino, Srikant Ramachandruni, Viswanathan Nagarajan, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Non-Resolving Community Acquired Pneumonia (Cap) Due To Blastomyces Dermatitidis (Pulmonary Blastomycosis): Case Report And Review Of Literature, Johnson Britto

The University of Louisville Journal of Respiratory Infections

In this case report, we describe a case of progressive acute pulmonary blastomycosis in a healthy adult living in Kentucky, initially presenting with flu like illness with a left sided consolidation, who did not respond to antibiotic therapy. Patient’s clinical condition deteriorated with development of necrotizing bronchopneumonia, mediastinal lymphadenopathy, tree-in-bud reticulonodularity and pleural effusion. A diagnosis of progressive pulmonary blastomycosis was established by radiological findings as well as transbronchial needle aspiration cytology and bronchoalveolar lavage culture demonstrating Blastomyces dermatitidis. Patient showed significant clinical improvement with resolution of pulmonary lesions on antifungal treatment. Since symptoms of blastomycosis are often similar to …

Effectiveness Of The Influenza Vaccine In Preventing Hospitalizations Of Patients With Influenza Community-Acquired Pneumonia, Thomas Chandler, Stephen P. Furmanek, Connor L. English, Connor Glick, Wesley Trail, Lara Daniels, Ugochukwu Owolabi, Ruth Carrico, Julio A. Ramirez, Timothy L. Wiemken

The University of Louisville Journal of Respiratory Infections

Introduction: Influenza vaccination is the primary strategy for prevention of influenza infection. Influenza infection can vary from mild or even asymptomatic illness to severe community-acquired pneumonia (CAP). Although many national and international investigators and organizations report annual estimates of influenza vaccine effectiveness for prevention of influenza infection in the community, few studies report estimates for the prevention of hospitalizations due to influenza CAP, the most severe form of the infection. The objective of this study is to determine the effectiveness of the influenza vaccine for prevention of hospitalization in patients with influenza-associated CAP.

Methods: This was a test-negative study using …

Duration Of Antibiotic Therapy For Patients With Bacteremic Staphylococcus Aureus Community-Acquired Pneumonia, Julio A. Ramirez, Thomas File, Daniel Musher

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Real-Time Pcr Detection Of Mycoplasma Pneumoniae, Chlamydia Pneumoniae And Legionella Pneumophila In Respiratory Specimens Using The Aries® System, Subathra Marimuthu, Leslie A. Wolf, James T. Summersgill

The University of Louisville Journal of Respiratory Infections

Background: Mycoplasma pneumoniae (Mpn), Chlamydia pneumoniae (Cpn), and Legionella pneumophila (Lpn) can cause both epidemic and endemic occurrences of acute respiratory disease and are responsible for up to 22% of cases of community acquired pneumonia. Due to the limited availability of FDA-approved molecular diagnostic assays, we developed and evaluated a multiplexed Real-time PCR assay for the detection of these agents in two respiratory specimen types on the Luminex ARIES® instrument. The instrument provides for nucleic acid extraction plus PCR amplification and target detection in the same cassette. The ARIES® instrument generates a cycle threshold value and a confirmatory melt curve …

Communication Between Clinicians And The Hospital-Based Microbiology Laboratory: Strategies For 2018 And Beyond, Hans H. Liu

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Mycobacterium Kansasii As The Primary Etiology Of Pulmonary Infections Due To Non-Tuberculous Mycobacterium (Ntm) In Patients Without Human Immunodeficiency Virus (Hiv): Experience From A Center In Buenos Aires, Argentina, Gabriel Yusti, Marcela Heres, Alejandra González, Mariano Fielli, Adrian Ceccato, Alejandra Zapata

The University of Louisville Journal of Respiratory Infections

Introduction: Pulmonary diseases due to non-tuberculous mycobacterium (NTM) lung infection in HIV-negative patients are rarely described in the literature. Currently, NTM consist of more than 150 species, and they are globally ubiquitous in both natural and man-made environments.The objective of this study was to define the most frequent species of NTM causing pulmonary disease in HIV-negative patients in the city of Buenos Aires, Argentina. The prevalence of pulmonary diseases caused by NTM is difficult to determine since the isolation of NTM does not necessarily indicate disease.

Methods: A retrospective review of all the respiratory cultures positive for NTM in the …

Research Support Infrastructure: Implementing A Clinical Research Coordinating Center, Julio A. Ramirez, Paula Peyrani, William A. Mattingly, Forest W. Arnold, Timothy L. Wiemken, Robert R. Kelley, Leslie A. Wolf, Ruth M. Carrico, The Clinical Research Coordinating Center Team

The University of Louisville Journal of Respiratory Infections

Insufficient infrastructure is one of the challenges facing investigators in the field of clinical research. At the University of Louisville (UofL) Division of Infectious Diseases, we developed a multidisciplinary coordinating center with the aim to support investigators in all aspects of the clinical research process. The objective of this article is to describe the composition and the role of the different units of the UofL Clinical Research Coordinating Center. The different components of the Center can serve as a template for institutions interested in developing a clinical research support infrastructure.

Clinical Research: From Idea To Publication, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Julio A. Ramirez, M.D., FACP, Professor of Medicine/Associate Professor of Microbiology and Immunology; Chief, Division of Infectious Diseases; Director, Infectious Diseases Fellowship Training Program and Founding Director, Global Health Initiative at The University of Louisville, presented "Clinical Research: From Idea to Publication" at University of Louisville Department of Medicine Grand Rounds on February 15, 2018. The talk focused on performing an overview of clinical study designs, describing the planning and performing of a clinical study, reviewing the process for statistical and clinical analysis, and presenting the structure of a Clinical Research Coordinating Center.

Research Support Infrastructure: Implementing A Clinical Research Coordinating Center, Julio A. Ramirez, Paula Peyrani, William A. Mattingly, Forest W. Arnold, Timothy L. Wiemken, Robert R. Kelley, Leslie A. Wolf, Ruth M. Carrico, Andrea Reyes-Vega

Faculty and Staff Scholarship

Insufficient infrastructure is one of the challenges facing investigators in the field of clinical research. At the University of Louisville (UofL) Division of Infectious Diseases, we developed a multidisciplinary coordinating center with the aim to support investigators in all aspects of the clinical research process. The objective of this article is to describe the composition and the role of the different units of the UofL Clinical Research Coordinating Center. The different components of the Center can serve as a template for institutions interested in developing a clinical research support infrastructure.

Similarity Based Classification Of Adhd Using Singular Value Decomposition, Taban Eslami, Fahad Saeed

Parallel Computing and Data Science Lab Technical Reports

Attention deficit hyperactivity disorder (ADHD) is one of the most common brain disorders among children. This disorder is considered as a big threat for public health and causes attention, focus and organizing difficulties for children and even adults. Since the cause of ADHD is not known yet, data mining algorithms are being used to help discover patterns which discriminate healthy from ADHD subjects. Numerous efforts are underway with the goal of developing classification tools for ADHD diagnosis based on functional and structural magnetic resonance imaging data of the brain. In this paper, we used Eros, which is a technique for …

Transformative And Translational: Supporting A New Phd Program, Alexandra Gomes, Anne Linton

Himmelfarb Library Faculty Posters and Presentations

No abstract provided.

Pim-1 Kinase Phosphorylates Cardiac Troponin I And Regulates Cardiac Myofilament Function., Ni Zhu, Bing Yi, Zhifu Guo, Guanxin Zhang, Shengdong Huang, Yongwen Qin, Xianxian Zhao, Jianxin Sun

Center for Translational Medicine Faculty Papers

BACKGROUND/AIMS: Pim-1 is a serine/threonine kinase that is highly expressed in the heart, and exerts potent cardiac protective effects through enhancing survival, proliferation, and regeneration of cardiomyocytes. Its myocardial specific substrates, however, remain unknown. In the present study, we aim to investigate whether Pim-1 modulates myofilament activity through phosphorylation of cardiac troponin I (cTnI), a key component in regulating myofilament function in the heart.

METHODS: Coimmunoprecipitation and immunofluorescent assays were employed to investigate the interaction of Pim-1 with cTnI in cardiomyocytes. Biochemical, site directed mutagenesis, and mass spectrometric analyses were utilized to identify the phosphorylation sites of Pim1 in cTnI. …

Development Of Health Rehabilitation In Mainland China: From Traditional Chinese Medicine To Modern Western Rehabilitation Methods, Michelle Moy

Independent Study Project (ISP) Collection

The aim of this study is to understand the changes occurring in China, leading to the development of health rehabilitation. This study will portray the shift of traditional Chinese medicine to modern influences of Western rehabilitation, and will also introduce the idea of an integrated model of TCM and Western Rehabilitation.

Observations were held at a TCM hospital, a rehabilitation hospital, as well as a TCM hospital that provided modern rehabilitation services. Two online questionnaire surveys were sent out to rehabilitation health professionals working in mainland China, one of which collected quantitative data while the other collected both qualitative and …

Investigating Ampk Signalling Regulation Of Autophagy In A Model Of Ovarian Tumour Dormancy, Jeremi Laski

Western Research Forum

Investigating AMPK signalling regulation of autophagy in a model of ovarian tumour dormancy

Jeremi Laski and Trevor G. Shepherd

Background:

Ovarian cancer is the most deadly gynecologic malignancy in women. A particular subset of this disease, epithelial ovarian cancer (EOC), is responsible for over 70% of all diagnosed ovarian cancer cases, yet the mechanisms governing disease progression are poorly understood. One of the unique hallmarks of EOC metastasis lies in the process of spheroid formation, whereby tumour cells aggregate into larger 3D structures. These EOC spheroids have been shown to be metabolically dormant, while concurrently up-regulating autophagy (cellular waste …

Evaluating Disparities In The U.S. Technology Transfer Ecosystem To Improve Bench To Business Translation, James Weis, Ashvin Bashyam, Gregory J. Ekchian, Kathryn Paisner, Nathan L. Vanderford

Markey Cancer Center Faculty Publications

Background: A large number of highly impactful technologies originated from academic research, and the transfer of inventions from academic institutions to private industry is a major driver of economic growth, and a catalyst for further discovery. However, there are significant inefficiencies in academic technology transfer. In this work, we conducted a data-driven assessment of translational activity across United States (U.S.) institutions to better understand how effective universities are in facilitating the transfer of new technologies into the marketplace. From this analysis, we provide recommendations to guide technology transfer policy making at both the university and national level.

Methods: Using data …