Therapeutics Commons^™

Investigating The Therapeutic Potential Of Targeting Lrrc15 In Endometrial Cancer, Christopher Pathoulas

All College Thesis Program, 2016-2019

Endometrial cancer is the most common gynecological malignancy and accounts for 6% of all cancers in women. In 2018, there were an estimated 63,280 new cases of endometrial cancer resulting in 11,350 deaths. In advanced stages, aggressive forms of endometrial cancer are able to invade the peritoneum and metastasize to the omentum and bowel. Shridhar et al. have identified leucine rich repeat containing 15 (LRRC15), a protein involved in cell adhesion and interactions with the extracellular matrix (ECM), as a potential therapeutic target due to its significantly higher expression in ovarian cancer tumors that have metastasized to the omentum and …

Innovative Care Of Individuals In The Athletic Training Room: A Case Series, Kathryn E. Young

Senior Honors Projects, 2010-2019

This work follows three unique cases of athletic injuries and/or injuries in patients. These cases were selected because of the innovative nature of the rehabilitation process conducted by the sports medicine team via the athletic training room or the unique nature of the injury/case.

The first is a concussion sustained from a motor vehicle accident in a collegiate female thrower. This is unique because it’s a non-sport related concussion handled as an athletic trainer would handle a sports related concussion. It also demonstrates a new unique protocol for concussion management.

The second case is a patient with two complete anterior …

Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman

Theses & Dissertations

Dolutegravir (DTG) is a potent human immunodeficiency virus type 1 (HIV-1) integrase strand-transfer inhibitor (INSTI) with a high barrier to viral drug resistance. However, opportunities to improve its profile abound. These include extending the drug’s apparent half-life, increasing penetrance to “putative” viral reservoirs, and reducing inherent toxicities. These highlight, in part, the need for long-acting, slow effective release antiretroviral therapy (LASER ART) delivery schemes. A long-acting (LA) DTG was made by synthesizing a hydrophobic and lipophilic prodrug encased with poloxamer (P407) surfactant. This modified DTG (MDTG) reduced systemic metabolism and polarity, increased lipophilicity and membrane permeability, improved encapsulation, and formed …

Multimodality Somatostatin Analog For Fluorescence-Guided Surgery In Cancer, Servando Hernandez Vargas

Dissertations and Theses (Open Access)

Cancer surgery remains the primary curative treatment for most solid cancers and has major therapeutic implications for patients with neuroendocrine tumors (NETs). Anatomical and functional imaging technologies are widely used during the pre- and postoperative stages, but intraoperative disease recognition relies on direct visual inspection and the hands of surgeons. The limited number of clinical tools for real-time intraoperative visual feedback restricts the ability to remove the complete cancer source and is partially responsible for the high rate of disease recurrence in patients. Intraoperative imaging with fluorescent contrast agents has the potential to improve the ability of surgeons to detect …

Experiences Of Veterans With Ptsd And Sud In An Outpatient Setting, Andrew Breault, Hannah Shifflett-Kohler

Thinking Matters Symposium Archive

In 2014, there were approximately 7.9 million adults in the United States with co-occurring Post Traumatic Stress Disorder (PTSD) and Substance Use Disorders (SUD) (SAMHSA, 2014). Of the veterans who served in the conflicts in Iraq and Afghanistan alone, 30% of those in SUD treatment also meet the criteria for PTSD (Seal et al, 2008, pp. 476). Furthermore, statistics show that about 20 Veterans in the United States complete suicide daily (Spiva, 2019, p. 8). The Department of Veterans Affairs is urgently seeking successful approaches to addressing the high incidence of suicides among all veterans along with the low retention …

Prophylactic Use Of Lmwh Vs Ufh In Pe Patients, Kyleigh Grieshaber, Barbara Mcclaskey

Posters

As a result of deep vein thrombosis (DVT), a pulmonary embo­lism (PE) can occur which creates a blockage in the body’s pulmonary circulation, leading to cell death. PE is the third leading cause of death in the U.S., while being the most common, most preventable cause of death in hospitalized patients. Understanding the signs and symptoms of PE is essential in order to save patients’ lives. The objective of this research study was to compare the prophylactic use of Unfractionated Heparin (UFH) and Low Molecular Weight Heparin (LMWH) in patients effected with PE. Information for this research project was gathered …

Tamsulosin Use After Shock Wave Lithotripsy: A Systematic Review, Katherine Harte

Senior Honors Projects

Urolithiasis, or the formation of stones in the urinary tract, is a potentially painful process that impacts many people across the world. However, the results of clinical trials disagree on the proper treatment and management of kidney stones. One way to help those who have kidney stones is to perform extracorporeal shock wave lithotripsy (SWL), a medical procedure in which shock waves are directed towards kidney stones to prevent them from migrating and causing pain. Following SWL, patients are sometimes given additional medications, such as alpha blockers (e.g., tamsulosin), to aid in the passage of the stones. However, the benefits …

New Internal Medicine Residency Program At A Community Hospital Improves Mortality Without Increasing The Cost Or Length Of Stay: A Two-Year Follow Up., Javad Savoj, Christine Mikhail, Rajesh Gulati, Napatkamon Ayutyanont, Alina Popa

Medical Education

Opening new residency programs in community hospitals is one strategy to address to address physician shortage. Previous reports have shown better mortality outcomes in university based hospitals. However, less is known about teaching community hospitals. Disrupting well-established workflows in community hospitals is feared to cause an increased cost and possibly a slide in quality of care. Our aim was to assess the impact of starting a new Internal Medicine residency program in a Graduate Medical Education (GME) naive community hospital.

Successful Extracorporeal Membrane Oxygenation In The Management Of Acute Respiratory Distress Syndrome And Cardiopulmonary Collapse Secondary To Amniotic Fluid Embolism, Sumon Roy, Nishit A. Biniwale, Venkata S. Pendela, Patricia Oates, Katrina Wojciechowski, Scott C. Feitell

The VAD Journal

Amniotic fluid embolism (AFE) is one of the most devastating complications of pregnancy that typically manifests as acute cardiopulmonary collapse during delivery or in the postpartum period. The potential role of extracorporeal membrane oxygenation (ECMO) as a management technique in severe cases of AFE remains largely unknown given the limited literature available. In this report, we present the first case, to our knowledge, of successful implementation of ECMO as a life-saving measure in a case of hemorrhagic shock due to postpartum bleeding complicated by severe AFE leading to acute respiratory distress syndrome (ARDS) ultimately requiring tracheostomy. Hemodynamic decompensation is often …

A Case Of Flecainide Toxicity In A Young Male, Ifrah Butt, Umair Shaikh, Marlena Fernandez, Sameer Shaharyar, Daniel Heller

Internal Medicine

No abstract provided.

Management Of Patients With Brain Metastases From Non-Small Cell Lung Cancer And Adverse Prognostic Features: Multi-National Radiation Treatment Recommendations Are Heterogeneous, Minesh Mehta

All Publications

No abstract provided.

Transforming Growth Factor-Β1 Decreases Β2-Agonist–Induced Relaxation In Human Airway Smooth Muscle, Christie A. Ojiaku, Elena Chung, Vishal Parikh, Jazmean K. Williams, Anthony Schwab, Ana Lucia Fuentes, Maia L. Corpuz, Victoria Lui, Sam Paek, Natalia M. Bexiga, Shreya Narayan, Francisco J. Nunez, Kwangmi An, Rennolds S. Ostrom, Steven S. An, Reynold A. Pannettieri Jr.

Pharmacy Faculty Articles and Research

Helper T effector cytokines implicated in asthma modulate the contractility of human airway smooth muscle (HASM) cells. We have reported recently that a profibrotic cytokine, transforming growth factor (TGF)-β1, induces HASM cell shortening and airway hyperresponsiveness. Here, we assessed whether TGF-β1 affects the ability of HASM cells to relax in response to β₂-agonists, a mainstay treatment for airway hyperresponsiveness in asthma. Overnight TGF-β1 treatment significantly impaired isoproterenol (ISO)-induced relaxation of carbachol-stimulated, isolated HASM cells. This single-cell mechanical hyporesponsiveness to ISO was corroborated by sustained increases in myosin light chain phosphorylation. In TGF-β1–treated HASM cells, ISO evoked markedly lower …

Memantine Unproven To Provide Any Clinical Benefit In Cases Of Vascular Cognitive Impairment, Irene Kitromelides

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Wilcock G, Möbius HJ, Stöffler A. A double-blind, placebo-controlled multicentre study of memantine in mild to moderate vascular dementia (MMM500). Int Clin Psychopharmacol. 2002 Nov;17(6):297-305. doi: 10.1097/00004850-200211000-00005.

The Promises And Challenges Of Erythropoietin For Treatment Of Alzheimer's Disease, Jiahong Sun, Jan Michelle Martin, Victoria Vanderpoel, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder in the world, and intracellular neurofibrillary tangles and extracellular amyloid-beta protein deposits represent the major pathological hallmarks of the disease. Currently available treatments provide some symptomatic relief but fail to modify primary pathological processes that underlie the disease. Erythropoietin (EPO), a hematopoietic growth factor, acts primarily to stimulate erythroid cell production, and is clinically used to treat anemia. EPO has evolved as a therapeutic agent for neurodegeneration and has improved neurological outcomes and AD pathology in rodents. However, penetration of the blood–brain barrier (BBB) and negative hematopoietic effects are the two …

Dr. Seuss Fine Motor Development Club, Nicole Borcyk, Madelyn Beck

Honors Program: Expanded Learning Clubs

After school club that helps students develop fine motor skills by doing hands-on activities relating to Dr. Seuss's most popular books.

Genomic Prediction Of Relapse In Recipients Of Allogeneic Haematopoietic Stem Cell Transplantation., J Ritari, K Hyvärinen, S Koskela, M Itälä-Remes, R Niittyvuopio, A Nihtinen, U Salmenniemi, M Putkonen, L Volin, T Kwan, T Pastinen, J Partanen

Manuscripts, Articles, Book Chapters and Other Papers

Allogeneic haematopoietic stem cell transplantation currently represents the primary potentially curative treatment for cancers of the blood and bone marrow. While relapse occurs in approximately 30% of patients, few risk-modifying genetic variants have been identified. The present study evaluates the predictive potential of patient genetics on relapse risk in a genome-wide manner. We studied 151 graft recipients with HLA-matched sibling donors by sequencing the whole-exome, active immunoregulatory regions, and the full MHC region. To assess the predictive capability and contributions of SNPs and INDELs, we employed machine learning and a feature selection approach in a cross-validation framework to discover the …

A Brain-Computer Interface For Closed-Loop Sensory Stimulation During Motor Training In Patients With Tetraplegia, Sarah Helen Thomas

Theses and Dissertations--Biomedical Engineering

Normal movement execution requires proper coupling of motor and sensory activation. An increasing body of literature supports the idea that incorporation of sensory stimulation into motor rehabilitation practices increases its effectiveness. Paired associative stimulation (PAS) studies, in which afferent and efferent pathways are activated in tandem, have brought attention to the importance of well-timed stimulation rather than non-associative (i.e., open-loop) activation. In patients with tetraplegia resulting from spinal cord injury (SCI), varying degrees of upper limb function may remain and could be harnessed for rehabilitation. Incorporating associative sensory stimulation coupled with self-paced motor training would be a means for supplementing …

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 …

Integrating Alexander Technique Into Treatment Of Adolescent Idiopathic Scoliosis To Improve Patient Quality Of Life, Ana Nishioka

Scripps Senior Theses

The following thesis posits training in the Alexander Technique as a possible solution to address the comorbidities of poor body image and reduced feelings of efficacy in patients treated for adolescent idiopathic scoliosis (AIS). Both literature and personal accounts of AIS highlight that current conservative methods of treating AIS offered by the Western medical sphere, including observation, bracing, and physical therapy, do not adequately address, and may actually exacerbate, negative mental health symptoms. Patients are often represented as their external orthopedic diagnosis and receive limited emotional guidance in exploring their internal feelings about their body and its capabilities. Alexander Technique …

Hematologic Safety Of Chronic Brain-Penetrating Erythropoietin Dosing In App/Ps1 Mice, Jiahong Sun, Joshua Yang, Kathrine Whitman, Charlene Zhu, David H. Cribbs, Ruben J. Boado, William M. Pardridge, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Introduction: Low blood-brain barrier (BBB) penetration and hematopoietic side effects limit the therapeutic development of erythropoietin (EPO) for Alzheimer's disease (AD). A fusion protein of EPO and a chimeric monoclonal antibody targeting the mouse transferrin receptor (cTfRMAb) has been engineered. The latter drives EPO into the brain via receptor-mediated transcytosis across the BBB and increases its peripheral clearance to reduce hematopoietic side effects of EPO. Our previous work shows the protective effects of this BBB-penetrating EPO in AD mice but hematologic effects have not been studied. Herein, we investigate the hematologic safety and therapeutic effects of chronic cTfRMAb-EPO dosing, …