Translational Medical Research Commons^™

The Histone Deacetylase Inhibitor Tubacin Mitigates Endothelial Dysfunction By Up-Regulating The Expression Of Endothelial Nitric Oxide Synthase., Jihui Chen, Jian Zhang, Noor F. Shaik, Bing Yi, Xin Wei, Xiao-Feng Yang, Ulhas P. Naik, Ross Summer, Guijun Yan, Xinyun Xu, Jianxin Sun

Center for Translational Medicine Faculty Papers

Endothelial nitric oxide (NO) synthase (eNOS) plays a critical role in the maintenance of blood vessel homeostasis. Recent findings suggest that cytoskeletal dynamics play an essential role in regulating eNOS expression and activation. Here, we sought to test whether modulation of cytoskeletal dynamics through pharmacological regulation of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation affects eNOS expression and endothelial function in vitro and in vivo.Wefound that tubulin acetylation inducer (tubacin), a compound that appears to selectively inhibit HDAC6 activity, dramatically increased eNOS expression in several different endothelial cell lines, as determined by both immunoblotting and NO production assays. Mechanistically, we found …

An Analysis Of Abdominal Stability Following Hyperthermic Exercise In Euhydrated And Dehydrated Conditions, Carli Ceckanowicz

Honors Scholar Theses

Core stability is essential for maintaining safety and optimizing performance during exercise and sport. The purpose of this study is to analyze how heat and hydration status (euhydrated USG<1.025 or dehydrated USG>1.025) can impair trunk stability in males and females (in both follicular and luteal phases) using the Trunk Stability Test (TST). Participants complete three blocks of 30 minutes of hyperthermic (35±1.299 ^oC and 49.418±5.0329% relative humidity) treadmill exercise. Exercise intensity is equivalent to 15 minutes at either 11W/kg or 7W/kg and the following 15 minutes at either 7W/kg or 4W/kg, respectively, based on individual heat production data. TST data will …

Fondaparinux Is An Effective Alternative To Other Non-Heparin Anticoagulants In The Treatment Of Heparin-Induced Thrombocytopenia, Allan J. Brazier Jr.

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Kang M, Alahmadi M, Sawh S, Kovacs MJ, Lazo-Langner A. Fondaparinux for the treatment of suspected heparin-induced thrombocytopenia: a propensity score-matched study. Blood. 2014;125(6):924-929. doi: 10.1182/blood-2014-09-599498.

Amantadine Minimally Improves Arousal In Patients With Severe Traumatic Brain Injury, Michelle Eventov

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Giacino JT, Whyte J, Bagiella E, et al. Placebo-Controlled Trial of Amantadine for Severe Traumatic Brain Injury. New England Journal of Medicine. 2012;366(9):819-826. doi: 10.1056/nejmoa1102609.

Weighing Harms, Benefits, And Alternatives For A Young Man With A Recent Flare Of Ulcerative Colitis, Louise B. Welsh

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Sandborn WJ, Su C, Sands B, et al. Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med. 2017 May 4;376(18):1723-1736. doi: 10.1056/NEJMoa1606910

Andexanet Alfa Is An Effective Reversal Agent For Factor Xa Inhibitors In Patients That Develop Intracranial Hemorrhage, Joseph Friedli

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Connolly SJ, Milling TJ, Eikelboom JW, et al. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med. 2016;375(12):1131-1141. doi: 10.1056/NEJMoa1607887.

Cannabidiol Is Beneficial In Management Of Drug-Resistant Dravet Syndrome, Nikita Desai

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Devinsky O, Cross H, Laux L, et al. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med. 2017;376(21):2011-2020. doi: 10.1056/NEJMoa1611618.

Developing Drug Therapies: Cognitive Damage In Mice Following Brain Radiation, Rachel Yuska

The Journal of Purdue Undergraduate Research

Pediatric brain cancer patients are at a high risk for radiation-induced cognitive impairment due to white matter changes in the brain. Half of six-month radiotherapy survivors develop significant changes in white matter. Previous research has shown that a mouse model can be used to show similar cognitive and behavioral deficits in human patients. The purpose of this work is to evaluate the effectiveness of two drug therapies, Donepezil and 3,3-Diindolylmethane (DIM), that could be used to either protect the brain from radiation injury or cure the cognitive injury and behavioral deficits that result from whole-brain irradiation. This project consisted of …

Towards Stable Electrochemical Sensing For Wearable Wound Monitoring, Sohini Roychoudhury

FIU Electronic Theses and Dissertations

Wearable biosensing has the tremendous advantage of providing point-of-care diagnosis and convenient therapy. In this research, methods to stabilize the electrochemical sensing response from detection of target biomolecules, Uric Acid (UA) and Xanthine, closely linked to wound healing, have been investigated. Different kinds of materials have been explored to address such detection from a wearable, healing platform. Electrochemical sensing modalities have been implemented in the detection of purine metabolites, UA and Xanthine, in the physiologically relevant ranges of the respective biomarkers. A correlation can be drawn between the concentrations of these bio-analytes and wound severity, thus offering probable quantitative insights …

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 …

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, …

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 …

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 …

Electroencephalogram As A Diagnostic Tool In Acquired Brain Injury, Michael Zarra

Senior Theses and Projects

The ability of electroencephalogram (EEG) to be used as a diagnostic device for acquired brain injuries (ABI) has been conceptualized previously. Averaged event-related potentials (ERP) derived from an EEG are suitable as markers of dysfunction however, distinctive properties in the frequency domain have not been established previously. In the present study, we examined pre- existing EEG signal data of healthy adults (HA), mild ABI (mABI), and severe ABI (sABI) human groups. Through Fourier analysis performed in MATLAB, we found that individuals in our sample population (n=80) were able to be categorized into their respective group based on common neuronal activity …

Icatibant Is Not Helpful For The Treatment Of Ace Inhibitor-Induced Angioedema, Samantha R. Schwartz

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Sinert R, Levy P, Bernstein JA, et al. Randomized trial of icatibant for angiotensin-converting enzyme inhibitor-induced upper airway angioedema. J Allergy Clin Immunol Pract. 2017; 5(5): 1402-1409. doi: 10.1016/j.jaip.2017.03.003.

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 …

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 …

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 …