Translational Medical Research Commons^™

Awareness & Prevention Of Health Hazards For Americans Embarking In Space Tourism, Krzysztof Zembrzuski

Rowan-Virtua Research Day

Since the beginning of spaceflight, keeping humans healthy has been a serious concern. Prior to 2021, astronauts had to undergo an elite selection process to embark in space travel. Now that commercial spaceflight is a reality, the criteria to experience space has been significantly loosened, raising health concerns to a larger and unhealthier pool of travelers. Most commercial spaceflight clients are anticipated to be middle-aged adults, which implies many will suffer from high blood pressure and heart disease, both of which are frequent ailments in this age group. Because of the massive compression the body undergoes during takeoff and return, …

Extravasated Brain-Reactive Autoantibodies Perturb Neuronal Surface Protein Expression In Alzheimer's Pathology, Wardah Bajwa, Mary Kosciuk, Randel L. Swanson, Anuradha Krishnan, Venkat Venkataraman, Robert Nagele, Nimish Acharya

Rowan-Virtua Research Day

Background: Increased blood-brain barrier (BBB) permeability is reported in both the neuropathological and in vivo studies in both Alzheimer’s Disease (AD) and age matched cognitively normal, no cognitive impairment (NCI), subjects. Impaired BBB allows various vascular components such as immunoglobulin G (IgG) to extravasate into the brain and specifically bind to various neuronal surface proteins (NSP), also known as brain reactive autoantibodies (BrABs). This interaction is predicted to further enhance deposition of amyloid plaques.

Hypothesis: Interaction between extravasated BrABs and its cognate NSPs lower the expression of that NSPs in AD patients.

Methods: We selected Western blotting technique to study …

Application Of Informatics Tools To Facilitate The Practice Of Precision Medicine With Genomic Testing And Clinical Data, Michael Sayer

Pharmaceutical Sciences (PhD) Dissertations

The practice of precision medicine considers a variety of sources of information to optimize patient care. Factors such as patient demographics, clinical history, and lab test values have well understood effects on treatment outcomes and influence decision making. However, effective inclusion of biomolecular data such as protein expression and DNA sequencing data within the practice of precision medicine needs continued study. Informatics tools offer solutions to allow these complex data sources to be effectively embraced. Utilization of informatics tools to visualize data pertaining to the gene selection practices of pharmacogenomic (PGx) tests effectively communicated large amounts of information into concise …

Beyond Covid-19: The Impact Of Recent Pandemics On Medical Students And Their Education: A Scoping Review, Moneb Bughrara, Stephanie Swanberg, Victoria Lucia, Keaton Schmitz, Dawn Jung, Tracy Wunderlich-Barillas

Posters

Over the past two years, COVID-19 has greatly altered undergraduate medical education (UME) as well as daily life. Medical schools across the world were disrupted and had to immediately adapt the educational experience to the online environment in order to continue the delivery of quality UME. However, COVID-19 was not the only recent pandemic. This posed the question, were similar disruptions and adaptations also seen in recent past pandemics such as Severe Acute Respiratory Syndrome (SARS) or Middle East Respiratory Syndrome (MERS) that could have prepared UME for COVID-19? This scoping review investigated the educational and personal impact of recent …

Identification Of Molecular Markers Associated With Copd In Non-Smokers And Smokers: A Bioinformatics Analysis, Agede O. Ayodele, Isa M. Wasagu, Ademola E. Fawibe, Alakija K. Salami

The University of Louisville Journal of Respiratory Infections

Background

Even though the proportional burden of COPD among never-smokers is significant in both developing and developed nations, accounting for around 30% of all COPD in the community, there is little awareness of the prevalence of COPD in this population. Understanding the molecular processes that underlie COPD in nonsmokers is essential.

Methods

Dataset (GSE146560) was acquired from the Gene Expression Omnibus (GEO). The limma and clusterProfiler software tools were used to identify differentially expressed genes (DEGs) and conduct a functional enrichment analysis respectively.

Results

In all, 10,583 DEGs were found, of which 1,065 were up-regulated and 9,518 were down-regulated. The …

Targeting Metabolic Alterations Associated With Smooth Muscle Α-Actin Pathogenic Variant Attenuates Moyamoya-Like Cerebrovascular Disease, Anita Kaw

Dissertations and Theses (Open Access)

Heterozygous pathogenic variants in ACTA2, encoding smooth muscle α-actin (α-SMA), predispose to thoracic aortic aneurysms and dissections. De novo missense variants disrupting ACTA2 arginine 179 (p.Arg179) cause a multisystemic disease termed smooth muscle dysfunction syndrome (SMDS), which is characterized by early onset thoracic aortic disease and moyamoya disease-like (MMD) cerebrovascular disease. The MMD-like cerebrovascular disease in SMDS patients is marked by bilateral steno-occlusive lesions in the distal internal carotid arteries (ICAs) and their branches. To study the molecular mechanisms that underlie the ACTA2 p.Arg179 variants, a smooth muscle-specific Cre-lox knock-in mouse model of the heterozygous Acta2 R179C variant, termed …

Regenerative Medicine For Tendon/Ligament Injuries: De Novo Equine Tendon/Ligament Neotissue Generation And Application, Takashi Taguchi

LSU Doctoral Dissertations

Tendon and ligament injuries are debilitating conditions across species. Poor regenerative capacities of these tissues limit restoration of original functions. The first study evaluated the effect of cellular administration on tendon/ligament injuries in horses using meta-analysis. The cellular administration was effective in restoring ultrasonographic echogenicity and increasing vascularity during early phase of healing. Additionally, it improved microstructural organization of healed tissue in terms of cellularity and fiber alignment. However, the study did not support its use for increasing rate of return to performance, expression/deposition of tendon-specific genes/proteins, or mechanical properties.

The findings led to the second study that engineered implantable …

Persistently Elevated Hbv Viral-Host Junction Dna In Urine As A Biomarker For Hepatocellular Carcinoma Minimum Residual Disease And Recurrence: A Pilot Study, Selena Y Lin, Dina Halegoua-De Marzio, Peter Block, Yu-Lan Kao, Jesse M. Civan, Fwu-Shan Shieh, Wei Song, Hie-Won Hann, Ying-Hsiu Su

Department of Medicine Faculty Papers

Hepatitis B virus (HBV)-host junction sequences (HBV-JSs) has been detected in the urine of patients with HBV infection. This study evaluated HBV-JSs as a marker of minimum residual disease (MRD) and tumor recurrence after treatment in HBV-hepatocellular carcinoma (HCC) patients. Archived serial urine DNA from two HBV–HCC with recurrence as confirmed by MRI and four HBV-related cirrhosis (LC) patients were used. Urinary HBV-JSs were identified by an HBV-targeted NGS assay. Quantitative junction-specific PCR assays were developed to investigate dynamic changes of the most abundant urinary HBV-JS. Abundant urinary HBV-JSs were identified in two cases of tumor recurrence. In case 1, …

I Finally Understand How Applying The Fagan Nomogram Can Change Medical Decision-Making, David Salvatori, Do

Clinical Research in Practice: The Journal of Team Hippocrates

The author reflects on the case that changed his opinion on the efficacy of the Fagan nomogram.

Glut1 Is Redundant In Hypoxic And Glycolytic Nucleus Pulposus Cells Of The Intervertebral Disc, Shira N. Johnston, Elizabeth S. Silagi, Vedavathi Madhu, Duc H. Nguyen, Irving M. Shapiro, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Glycolysis is central to homeostasis of nucleus pulposus (NP) cells in the avascular intervertebral disc. Since the glucose transporter, GLUT1, is a highly enriched phenotypic marker of NP cells, we hypothesized that it is vital for the development and postnatal maintenance of the disc. Surprisingly, primary NP cells treated with 2 well-characterized GLUT1 inhibitors maintained normal rates of glycolysis and ATP production, indicating intrinsic compensatory mechanisms. We showed in vitro that NP cells mitigated GLUT1 loss by rewiring glucose import through GLUT3. Of note, we demonstrated that substrates, such as glutamine and palmitate, did not compensate for glucose restriction resulting …

Advancing Health Equity In The Us Military, James D. Mancuso, John Young, Jennifer Rusiecki, Shauna Stahlman, Natasha Schvey, Toya Randolph, Candy Wilson, Catherine Witkop, Patrick Hyde, Althea Green, Patcho Santiago, Donald Shell, Tracy Sbrocco

Journal of Health Disparities Research and Practice

Eliminating health disparities and achieving health equity are central to US national health objectives and the Military Health System’s “quadruple aim,” which has readiness as its core aim. Because military service members enjoy universal eligibility for health care, it is sometimes assumed that health disparities do not exist in the Department of Defense (DoD). However, while some studies have shown that disparities have been attenuated or eliminated in the DoD, others suggest that significant disparities remain. Reasons these disparities may remain include that universal eligibility for care does not necessarily result in equal to access to care, and that equal …

Umbilical Cord Blood Transplantation: Connecting Its Origin To Its Future, Gabriela Sanchez-Petitto, Katayoun Rezvani, May Daher, Hind Rafei, Partow Kebriaei, Elizabeth J Shpall, Amanda Olson

Faculty, Staff and Student Publications

Transplantation of umbilical cord blood (UCB) is an attractive alternative source of hematopoietic stem cells (HSCs). The unique properties of cord blood and its distinct immune tolerance and engraftment kinetics compared to bone marrow (BM) and peripheral blood progenitor cells, permit a wider disparity in human leukocyte antigen levels between a cord blood donor and recipient after an unrelated umbilical cord blood transplant (UCBT). In addition, it is readily available and has a lowered risk of graft-versus-host disease (GvHD), with similar long-term clinical outcomes, compared to BM transplants. However, the relatively low number of cells administered by UCB units, as …

Narrative Review Of Single Ventricle: Where Are We After 40 Years?, Antonio F Corno, Tina O Findley, Jorge D Salazar

Faculty, Staff and Student Publications

Background and objective: Key medical and surgical advances have been made in the longitudinal management of patients with "functionally" single ventricle physiology, with the principles of Fontan circulation applied to other complex congenital heart defects. The purpose of this article is to review all of the innovations, starting from fetal life, that led to a change of strategy for single ventricle.

Methods: Our literature review included all full articles published in English language on the Cochrane, MedLine, and Embase with references to "single ventricle" and "univentricular hearts", including the initial history of the treatments for this congenital heart defects as …

Performance Of A Sars-Cov-2 Rt-Pcr Assay With Non-Traditional Specimen Types, Subathra Marimuthu, Holly Aliesky, Heather Ness, Daniya Sheikh, Sathya Rashmit, Dawn Balcom, Leslie A. Wolf

The University of Louisville Journal of Respiratory Infections

During the first two years of the coronavirus disease 2019 (COVID-19) pandemic, nasopharyngeal (NP) specimens were the gold standard for clinical diagnostic testing. As information about the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the pandemic continued to be shared, it was clear that the virus could be detected in other specimen types during an active infection. The University of Louisville Infectious Diseases Laboratory accepted non-traditional specimen types, most without a paired, positive NP result, for research purposes only to support local epidemiology efforts. A real-time reverse transcription-polymerase chain reaction (RT-PCR) assay originally validated for NP specimens was used …

What? Now A Respiratory Syncytial Virus Epidemic, Aya Allam, Steven B Lippmann

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Research Annual Report Fy2023, Children's Mercy Kansas City

Research Annual Reports

Annual report of the research at Children's Mercy Kansas City in Kansas City MO, a pediatric medical center.

Developing Ecologically Valid Clinical Tools For Persons With Tbi: Understanding The Role And Impact Of Distractions, Deanna Pinnow

Theses and Dissertations--Rehabilitation Sciences

There is a critical need for the development of ecologically valid clinical tools to assess real-life cognitive functioning in persons impacted by traumatic brain injury (TBI). Chronic cognitive impairments that are exacerbated by distractions are one of the core factors contributing to poor home and community re-integration post injury. Simulation-based digital platforms (i.e., virtual reality, augmented reality, and mixed reality) have become potential solutions for eliciting real-world cognitive performance in clinical settings. Yet, there is a paucity of research investigating the role and impact of distractions on cognition. As a result, there is no clear framework of measuring distractions to …

N-Of-1 Trials: The Epitome Of Personalized Medicine?, Joyce P Samuel, Susan H Wootton, Jon E Tyson

Faculty, Staff and Student Publications

Observational studies are notoriously susceptible to bias, and parallel-group randomized trials are important to identify the best overall treatment for eligible patients. Yet, such trials can be expected to be a misleading indicator of the best treatment for some subgroups or individual patients. In selected circumstances, patients can be treated in n-of-1 trials to address the inherent heterogeneity of treatment response in clinical populations. Such trials help to accomplish the ultimate goal of all biomedical research, to optimize the care of individual patients.

Role Of Histone Deacetylase (Hdac) In Epithelial To Mesenchymal Transition (Emt) In A Human Cholangiocyte Model Of Ischemic Cholangiopathy, Priyanshi Pragnesh Parikh

Theses and Dissertations

Organ transplants are a vital intervention for many diseases that result in end stage organ failure. Currently, the donation pool is not meeting the demands of the transplant list. Expanding this pool to include donation after cardiac death (DCD) is highly sought-after. However, the use of DCD livers can lead to increased odds of graft failure and ischemic cholangiopathy. The loss of epithelialization and fibrosis that occurs during ischemic cholangiopathy is characteristic of these cells undergoing epithelial-to-mesenchymal transition (EMT). The biological changes the cell experiences enhance migratory capacity, invasiveness, and increased resistance to apoptosis. Our earlier studies have shown differential …

Partial Outpatient Oral Antibiotic Treatment Of Infective Endocarditis Is Non-Inferior To Inpatient Intravenous Antibiotic Therapy, Nicholas J. Murphy

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Iversen K, Ihlemann N, Gill SU, et al. Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis. N Engl J Med. 2019; 380:415-424. https://doi.org/10.1056/NEJMoa1808312

for a patient with infective endocarditis and intravenous drug use with desire to leave the hospital.

Indwelling Pleural Catheterization Maximizes Functionality And Quality Of Life In Management Of Recurrent Malignant Pleural Effusions, Avinash Ramkissoon

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Davies HE, Mishra EK, Kahan BC, et al. Effect of an indwelling pleural catheter vs chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: The TIME2 randomized controlled trial. J Am Med Assoc. 2012;307(22):2383-2389. https://doi.org/10.1001/jama.2012.5535

for the management of recurrent malignant pleural effusions in a patient with metastatic renal cell carcinoma.

Exploring Alternative Treatment Options For A Patient With Heavy Menstrual Bleeding And Mistrust Of The Healthcare System, Rachel A. O'Dell

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Tinelli A, Gustapane S, D’Oria O, Licchelli M, Panese G. Nutraceuticals in fibroid management after ulipristal acetate administration: An observational study on patients’ compliance. International Journal of Gynecology and Obstetrics; 2022;156(1):133-138. https://doi.org/10.1002/ijgo.13692

for a patient with chronic, symptomatic anemia with menorrhagia and uterine fibroid.

The Importance Of Stigma Theory For Clinical Decisions Related To Diabetic Foot Amputations, Rachael Garcia, Callie Bartkowiak, Alison Nesbitt Do

Clinical Research in Practice: The Journal of Team Hippocrates

The authors examine the unconsidered impact of social stigma theory on the shared clinical decision-making process for a patient with foot osteomyelitis and MRSA bacteremia facing the prospect of an amputation.

Expansion Of The Detrusor Muscular Ring Surrounding The Bladder Neck On Mri: Moving Beyond The Prostate As An Etiology Of Lower Urinary Tract Symptoms Due To Benign Prostatic Hyperplasia, Kiran Nandalur, David Walker, Hong Ye, Sayf A. Al-Katib, Brian Seifman, David Gangwish, Abhay Dhaliwal, Connor Ervin, Kayla Dobies, Channing Sesoko, Sirisha Nandalur, Bernadette Zwaans, Jennifer Nguyen, Jason Hafron

Conference Presentation Abstracts

Purpose: The etiology of lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH) remains uncertain. The purpose of our study was to quantitatively analyze pelvic anatomic characteristics on magnetic resonance imaging (MRI) to assess for independent factors for symptoms.
*Methods and Materials: This retrospective single-institution study evaluated treatment-naïve men who underwent prostate MRI within 3 months of International Prostate Symptom Score (IPSS) from June 2021 to February 2022. Factors measured on MRI included: detrusor muscular ring surrounding the bladder neck measured as area and alternatively diameter, central gland (CG) mean apparent diffusion coefficient (ADC), levator hiatus (LH) volume, intrapelvic …

Triple Blockade Of Ido-1, Pd-L1 And Mek As A Potential Therapeutic Strategy In Nsclc, Carminia Maria Della Corte, Vincenza Ciaramella, Kavya Ramkumar, Giovanni Vicidomini, Alfonso Fiorelli, Valerio Nardone, Salvatore Cappabianca, Immacolata Cozzolino, Federica Zito Marino, Gaetano Di Guida, Qi Wang, Robert Cardnell, Carl Michael Gay, Davide Ciardiello, Erika Martinelli, Teresa Troiani, Giulia Martini, Stefania Napolitano, Jing Wang, Lauren Averett Byers, Fortunato Ciardiello, Floriana Morgillo

Faculty, Staff and Student Publications

BACKGROUND: Despite the recent progress in the treatment and outcome of Non Small Cell Lung Cancer (NSCLC), immunotherapy has still significant limitations reporting a significant proportion of patients not benefiting from therapy, even in patients with high PD-L1 expression. We have previously demonstrated that the combined inhibition of MEK and PD-L1 in NSCLC patients derived three dimensional cultures exerted significant synergistic effect in terms of immune-dependent cancer cell death. However, subsequent experiments analyzing the expression of Indoleamine 2,3-dioxygenase-1 (Ido-1) gene expression demonstrated that Ido-1 resulted unaffected by the MEK inhibition and even increased after the combined inhibition of MEK and …

A Moment Of Reflection As We Move Forward, Bruce Morgenstern

Journal of Patient-Centered Research and Reviews

The newly appointed editor-in-chief of the Journal of Patient-Centered Research and Reviews reflects on the original editorial mission of the journal and its continuing commitment to publish patient-centered scholarly works that exhibit respect for each patient’s values and preferences; coordinated and integrated care; patient and family education; alleviation of pain, fear, and anxiety; continuity through care-site transitions; and access to care. The reasoning behind the pursuit of well-developed patient-centered care models, through the dissemination of peer-reviewed research findings and patient perspectives, has only been reinforced since the journal’s launch in 2014.

The Decision I Never Thought I Would Have To Make, Mary Nixon

Clinical Research in Practice: The Journal of Team Hippocrates

A brief essay on how the COVID pandemic has changed how we think about medicine and our patients.

Regulation Of Airway Smooth Muscle Cell Proliferation By Diacylglycerol Kinase: Relevance To Airway Remodeling In Asthma, Miguel Angel Hernandez-Lara, Santosh K Yadav, Sushrut D. Shah, Mariko Okumura, Yuichi Yokoyama, Raymond B. Penn,, Taku Kambayashi, Deepak A. Deshpande

Center for Translational Medicine Faculty Papers

Airway remodeling in asthma involves the hyperproliferation of airway smooth muscle (ASM) cells. However, the molecular signals that regulate ASM growth are not completely understood. Gq-coupled G protein-coupled receptor and receptor tyrosine kinase signaling regulate ASM cell proliferation via activation of phospholipase C, generation of inositol triphosphate (IP3) and diacylglycerol (DAG). Diacylglycerol kinase (DGK) converts DAG into phosphatidic acid (PA) and terminates DAG signaling while promoting PA-mediated signaling and function. Herein, we hypothesized that PA is a pro-mitogenic second messenger in ASM, and DGK inhibition reduces the conversion of DAG into PA resulting in inhibition of ASM cell proliferation. We …

What? Is Epstein–Barr Virus Infection Linked To Multiple Sclerosis?, Asha Mahajan, Steven B Lippmann

The University of Louisville Journal of Respiratory Infections

No abstract provided.

A Population-Based Meta-Analysis Of Circulating Gfap For Cognition And Dementia Risk, Mitzi M Gonzales, Crystal Wiedner, Chen-Pin Wang, Qianqian Liu, Joshua C Bis, Zhiguang Li, Jayandra J Himali, Saptaparni Ghosh, Emy A Thomas, Danielle M Parent, Tiffany F Kautz, Matthew P Pase, Hugo J Aparicio, Luc Djoussé, Kenneth J Mukamal, Bruce M Psaty, William T Longstreth, Thomas H Mosley, Vilmundur Gudnason, Djass Mbangdadji, Oscar L Lopez, Kristine Yaffe, Stephen Sidney, R Nick Bryan, Ilya M Nasrallah, Charles S Decarli, Alexa S Beiser, Lenore J Launer, Myriam Fornage, Russell P Tracy, Sudha Seshadri, Claudia L Satizabal

Faculty, Staff and Student Publications

Objective: Expression of glial fibrillary acidic protein (GFAP), a marker of reactive astrocytosis, colocalizes with neuropathology in the brain. Blood levels of GFAP have been associated with cognitive decline and dementia status. However, further examinations at a population-based level are necessary to broaden generalizability to community settings.

Methods: Circulating GFAP levels were assayed using a Simoa HD-1 analyzer in 4338 adults without prevalent dementia from four longitudinal community-based cohort studies. The associations between GFAP levels with general cognition, total brain volume, and hippocampal volume were evaluated with separate linear regression models in each cohort with adjustment for age, sex, education, …