Translational Medical Research Commons^™

Quantitative Systems Pharmacology Model Of Chimeric Antigen Receptor T-Cell Therapy, Deni Hardiansyah, Chee Meng Ng

Pharmaceutical Sciences Faculty Publications

Chimeric antigen receptor T‐cell (CART) therapy is a new and promising cancer therapy. However, severe toxicity due to cytokine release syndrome (CRS) in CART‐treated patients highlighted the possible danger of this new therapy. Disease burden and CART doses are the potential factors associated with CRS but the detail relationships between these factors and the severity of the CRS remain largely unknown. In this study, the quantitative systems pharmacology (QSP) approach is used to quantify the complex relationships among CART doses, disease burden, and pro inflammatory cytokines in human subjects and to gain relevant insights into the determinant of clinical toxicity/efficacy …

Glucocorticoids And Airway Smooth Muscle: A Few More Answers, Still More Questions, Ajay P. Nayak

Center for Translational Medicine Faculty Papers

No abstract provided.

Cell-Free Dna Release During Programmed Cell Death In Ischemia Reperfusion Injury, Alexander Dionne, Anthony M. Jevnikar, Zhu-Xu Zhang

Western Research Forum

Transplantation is invariably associated with acute allograft injury caused by ischemia reperfusion injury (IRI). This injury causes cells of the allograft to undergo various forms of programmed cell death including apoptosis and necroptosis. During programmed cell death, immunogenic molecules are released from cells, one of which is cell-free DNA (cfDNA). We hypothesize that cfDNA is released by microvascular endothelial cells (MVECs) during programmed cell death of IRI and that cfDNA acts as both a biomarker for cellular injury as well as a biologically active molecule capable of amplifying inflammation and organ injury.

Our results indicate that cfDNA is released by …

C1q/Tnf-Related Protein 3 (Ctrp3) And 9 (Ctrp9) Concentrations Are Decreased In Patients With Heart Failure And Are Associated With Increased Morbidity And Mortality., Chao Gao, Shasha Zhao, Kun Lian, Baibing Mi, Rui Si, Zhijun Tan, Feng Fu, Shuai Wang, Rutao Wang, Xin-Liang Ma, Ling Tao

Center for Translational Medicine Faculty Papers

BACKGROUND: Biochemical marker has revolutionized the approach to the diagnosis of heart failure. However, it remains difficult to assess stability of the patient. As such, novel means of stratifying disease severity are needed. C1q/TNF-Related Protein 3 (CTRP3) and C1q/TNF-Related Protein 9 (CTRP9) are novel adipokines that contribute to energy homeostasis with additional anti-inflammatory and anti-ischemic properties. The aim of our study is to evaluate concentrations of CTRP3 and CTRP9 in patients with HFrEF (heart failure with reduced ejection fraction) and whether associated with mortality.

METHODS: Clinical data and plasma were obtained from 176 healthy controls and 168 patients with HFrEF. …

Technical Freediving: An Emerging Breath-Hold Diving Technique, Derek Covington, Robert H. Lee, Steven Toffel, Alberto Bursian, Kirk Krack, Chris Giordano

Journal of Human Performance in Extreme Environments

Technical freediving can be defined as freediving augmented by the use of oxygen-enriched gases or oxygen before, during, or after a freedive. As a result of these techniques, breath-hold divers can visit and enjoy underwater wrecks, reefs, and other diving locations previously located at depths unreachable to apnea divers. By pre-breathing oxygen-enriched gases in conjunction with hyperventilation—which decreases the partial pressure of carbon dioxide (PCO2)—the technical freediver now has additional oxygen to facilitate aerobic respiration during the dive. In addition, pre-breathing oxygen decreases tissue nitrogen tensions, which limits inert gas loading and decreases the risk of decompression sickness (DCS). Finally, …

Preventing Osteosarcoma Progression With Small Molecular Inhibitors Targeting Macrophage Migration Inhibitory Factor : Cd74 Interaction, Sana Farooki

Research Days

No abstract provided.

21st Century Clinical Trials: Rethinking Best Practices Challenges And Opportunities, William E Truog

Presentations

Panel discussion at the Pediatric Academic Societies 2019 annual meeting.

Implications Of Genetic Variation Of Common Drug Metabolizing Enzymes And Abc Transporters Among The Pakistani Population, Nasir Ali Afsar, Henrike Bruckmueller, Anneke Nina Werk, Muhammad Kashif Nisa, H R. Ahmad, Ingolf Cascorbi

Department of Biological & Biomedical Sciences

Genetic polymorphism of drug metabolizing enzymes and transporters may influence drug response. The frequency varies substantially between ethnicities thus having implications on appropriate selection and dosage of various drugs in different populations. The distribution of genetic polymorphisms in healthy Pakistanis has so far not been described. In this study, 155 healthy adults (98 females) were included from all districts of Karachi. DNA was extracted from saliva and genotyped for relevant SNVs in CYP1A1, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4 and CYP3A5 as well as ALDH3A1, GSTA1, ABCB1 and ABCC2. About 64% of the participants were born to parents who were unrelated …

Differential Iron Regulatory Genetics In 2d & 3d Culture Of Breast Cancer Cells, Tyler Hanna, Suzy Torti Ph. D, Frank Torti M.D., Mph, Nicole Farra Ph. D.

Honors Scholar Theses

The iron regulatory axis has consistently been shown to be perturbed in cancer cell lines relative to non-cancerous cell lines. As cancer cells rapidly divide and grow, they require iron to fuel many intracellular processes, including DNA replication and protein synthesis. Three-dimensional cell culture is an increasingly popular method of culture that purportedly more accurately mimics the in vivo microenvironment of cancers over traditional two-dimensional culture. This project was prompted by previous lab results to investigate differential iron regulatory gene expression in 2D and 3D spheroid culture models. We replicated the findings that the gene hepcidin is induced in 3D …

Computational Genomic Models For Spatio-Temporal Investigation Of Early Lung Cancer Pathology, Smruthy Sivakumar

Dissertations and Theses (Open Access)

Lung cancer, of which non-small cell lung cancer (NSCLC) is the most common form, is the second most prevalent cancer and the leading cause of cancer-related deaths. NSCLCs primarily comprise adenocarcinomas (LUAD) and squamous cell carcinomas (LUSC). Advances in early detection and prevention have been limited by the lack of early-stage biomarkers and targets. A comprehensive molecular characterization of premalignant lesions and tumor-adjacent normal tissue can aid in better understanding NSCLC pathogenesis. However, these investigations are further challenged by limited tissue availability and low cellular fractions of detectable somatic mutations.

Therefore, there is a dearth of knowledge about the pathogenesis …

Increasing Upstream Chromatin Long-Range Interactions May Favor Induction Of Circular Rnas In Lysopc-Activated Human Aortic Endothelial Cells., Angus Li, Yu Sun, Charles Drummer, Yifan Lu, Daohai Yu, Yan Zhou, Xinyuan Li, Simone J. Pearson, Candice Johnson, Catherine Yu, William Y. Yang, Kevin Mastascusa, Xiaohua Jiang, Jianxin Sun, Thomas Rogers, Wenhui Hu, Hong Wang, Xiaofeng Yang

Center for Translational Medicine Faculty Papers

Circular RNAs (circRNAs) are non-coding RNAs that form covalently closed continuous loops, and act as gene regulators in physiological and disease conditions. To test our hypothesis that proatherogenic lipid lysophosphatidylcholine (LPC) induce a set of circRNAs in human aortic endothelial cell (HAEC) activation, we performed circRNA analysis by searching our RNA-Seq data from LPC-activated HAECs, and found: (1) LPC induces significant modulation of 77 newly characterized cirRNAs, among which 47 circRNAs (61%) are upregulated; (2) 34 (72%) out of 47 upregulated circRNAs are upregulated when the corresponding mRNAs are downregulated, suggesting that the majority of circRNAs are upregulated presumably via …

Quantification Of Contrast-Enhanced Ultrasound, Joseph Pathoulas

All College Thesis Program, 2016-2019

The aim of this experiment was to investigate the effect of manipulating ultrasound scanner settings on time-intensity curve parameters in a tube perfusion phantom system using contrast-enhanced ultrasound imaging. Imaging was performed using a Philips LOGIQ E9 ultrasound scanner equipped with a C1-6VN transducer and utilized two different microbubble contrast agents: Definity and Lumason. The ultrasound scanner settings manipulated included: gain, dynamic range, and frequency. Additionally, relative microbubble concentration, microbubble type, and perfusion flow rate were manipulated. Four time-intensity curve parameters (time to peak, area under curve, gradient, peak intensity) were measured from linearized pixel data. Time to peak was …

Abstracts From The 25th Annual Health Care Systems Research Network Conference, April 8–10, 2019, Portland, Oregon

Journal of Patient-Centered Research and Reviews

The Health Care Systems Research Network (HCSRN) is made up of nonprofit health systems with embedded research departments whose scientists are dedicated to public domain research. The network’s annual conference serves as a forum for research teams to disseminate study findings, stimulate new collaborations, and share insights about conducting research in real-world care settings. Abstracts accepted for presentation at HCSRN 2019 are published in this supplement of Journal of Patient-Centered Research and Reviews, the official scientific journal of the conference.

Talking To Children About Their Terminal Disease And Ultimate Death, Alyssa Nesbitt

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Kreicbergs U, Valdimarsdóttir U, Onelöv E, Henter J, Steineck G. Talking about death with children who have severe malignant disease. New Eng J Med. 2004;351(12):1175-1186. doi: 10.1056/nejmoa040366.

Outcomes Of Robotic-Assisted Laparoscopic Prostatectomy Versus Open Prostatectomy In Surgical Intervention Of Localized Prostate Cancer, Hojun Lee, Brandon Ahlgren

Clinical Research in Practice: The Journal of Team Hippocrates

An informed consent conversation regarding robotic-assisted laparoscopic prostatectomy versus open prostatectomy in patients with localized prostate cancer.

Evidence Doesn’T Change Prescribing Patterns…So What Does?, Ali Rida, Anthony Brooks

Clinical Research in Practice: The Journal of Team Hippocrates

The authors write in support of critical analysis of clinical research, as a corrective to the physician's urge to "do something" even when no evidence of benefit exists.

Changes In The Left Atrial-Esophageal Relationship With The Insertion Of An Esophageal Protective Device: A Cadaveric Imaging Study, Akmal Shahzad, Charys M. Martin, Michele L. Barbeau

Western Research Forum

Background: Atrial fibrillation is the most common cardiac rhythm disorder in North America and is frequently treated by a minimally invasive procedure called catheter ablation. A rare, but often fatal complication of this procedure is development of an atrial-esophageal fistula (AEF) due to the proximity of the esophagus to the left atrium (LA) of the heart. Esophageal protective devices may potentially mitigate the risk of developing an AEF but their impact on the relationship between the esophagus and LA is unknown. This study will investigate the relevant anatomical changes that occur upon insertion of an esophageal protective device.

Methods: 13 …

Empiric Antibiotic Use For Infectious Conjunctivitis Provides Little Clinical Benefit, Matthew M. Rolain

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Rose PW, Harnden A, Brueggemann AB, et al. Chloramphenicol treatment for acute infective conjunctivitis in children in primary care: a randomised double-blind placebo-controlled trial. Lancet. 2005;366(9479):37-43. doi: 10.1016/S0140-6736(05)66709-8.

Bisphosphonates Can Be Safely Given To Patients With Hypercalcemia And Renal Insufficiency Secondary To Multiple Myeloma, Matthew J. Miller

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.

Social Inequity Is A Life And Death Situation For Our Patients, Stephanie Clough, Mira Hamame, Elizabeth Bavers

Clinical Research in Practice: The Journal of Team Hippocrates

Advocating for change in the economic structure of health care in the United States is a moral imperative.

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.