Translational Medical Research Commons^™

The Increasing Role Of Pragmatic Clinical Trials And Real-World Data In Healthcare Research, Julio A. Ramirez, Ruth Carrico

The University of Louisville Journal of Respiratory Infections

No abstract provided.

A Moral Dilemma: The Use Of Zinc In Patients Hospitalized With Covid Pneumonia, Ebony M. Manigault, Laura Donohue, Elizabeth Moore, Yara Abuaita

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Yao JS, Paguio JA, Dee EC, Tan HC, Moulick A, Milazzo C, Jurado J, Della Penna N, Celi LA. The minimal effect of zinc on the survival of hospitalized patients with COVID-19: an observational study. Chest. 2021 Jan;159(1):108-111. https://doi.org/10.1016/j.chest.2020.06.082

for a patient hospitalized with COVID pneumonia requiring high flow oxygen.

Impact Of Clinical And Pharmacogenetic Variables On The Risk Of Fluoropyrimidine-Related Adverse Events Within Ontario, Theodore J. Wigle

Electronic Thesis and Dissertation Repository

Severe life-threatening adverse events are a major limitation of fluoropyrimidine chemotherapy, these events are disastrous for patients and costly to the healthcare system. Identifying patients at high risk for developing adverse events would allow for preventive dose reduction, improving patient outcomes and reducing healthcare cost. This thesis uses data pulled from provincial databases to quantify the adverse event burden of fluoropyrimidines in Ontario. We found that 31% of Ontario patients treated with fluoropyrimidine systemic chemotherapy developed a severe adverse event that requires acute medical care. Patients that required acute medical therapy were significantly costlier to the public system averaging an …

Improvement Cycles In Medical Education: From Quality Improvement To Patient Care And Clinical Research, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Modulating Immunometabolism To Improve The Activity Of Car-Nk Cells Targeting Cd70 In Renal Cell Carcinoma, Hind Rafei

Dissertations & Theses (Open Access)

Despite the approval of several therapies for metastatic clear cell renal cell carcinoma (ccRCC), disease resistance and relapse are common, and therapies with novel mechanisms of action are urgently needed. Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable responses in hematologic malignancies, but many obstacles hinder success in solid tumors including the paucity of highly specific targets and the hostility of the tumor microenvironment (TME). Moreover, the limitations of generating an autologous cell product, such as cost of manufacture, and the challenges of toxicity with CAR-T cells highlight the need to develop new cell therapy products that are at …

Modulation Of Glucose Homeostasis By Nucleotide P2y2 Receptor And Biological Sex, Hailee Anne Marino

MSU Graduate Theses

Recent insights into the pathological role of Nucleotide P2Y₂ receptor suggest P2Y₂R involvement in high fat diet-induced obesity and potentiates insulin resistance. However, these recent insights do not demonstrate how P2Y₂R modulates glucose homeostasis under physiological conditions. Further, it remains unknown how sex biological factors influence P2Y₂R receptor signaling in the regulation of glucose homeostasis. The research objective for the present study is to elucidate the novel roles of P2Y₂ in fasting blood glucose and glucose tolerance (basal insulin sensitivity) under resting conditions in males and females. We expected that under physiological …

Development Of Vaccines And Antivirals Against Zika Virus, Aryamav Pattnaik

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The re-emergence of Zika virus (ZIKV), an arbovirus, poses a major global human health concern because of its ability to cause congenital abnormalities and neurological diseases. While many candidate vaccines and antiviral drugs are in the developmental pipeline, none have been approved for use against ZIKV infection. This dissertation describes the characterization of one vaccine and two antiviral drug candidates against ZIKV infection. A bacterial ferritin-based nanoparticle vaccine, termed zDIII-F, is designed to display multiple copies of ZIKV E protein domain III on its surface. These stable nanoparticles are shown to induce robust antibody-mediated protection against lethal ZIKV infection in …

Post-Acute Sequelae Of Covid-19 (Pasc): Association With Inflammation And Autoimmunity, Raghava S. Ambadapoodi, Fnu Deepti, Javaria Anwer Mbbs, Rafael Fernandez-Botran

The University of Louisville Journal of Respiratory Infections

It has become increasingly evident that a high percentage of patients that recover from acute COVID-19 infection continue to suffer from a variety of persistent symptoms even months after viral clearance, the most common ones being fatigue, dyspnea, anosmia, dysgeusia, cognitive dysfunction, and psychological problems, including anxiety and depression. This syndrome, known as Post-acute sequelae of COVID-19 (PASC), can severely affect the life quality and represents an important health care concern. The exact causes for the symptoms observed in patients with PASC remain to be adequately characterized, but are likely to be associated with multiple factors, including residual disease and/or …

Hiv-1 Persistence In The Cns: Mechanisms Of Latency, Pathogenesis And An Update On Eradication Strategies., Shilpa Sonti, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Despite four decades of research into the human immunodeficiency virus (HIV-1), a successful strategy to eradicate the virus post-infection is lacking. The major reason for this is the persistence of the virus in certain anatomical reservoirs where it can become latent and remain quiescent for as long as the cellular reservoir is alive. The Central Nervous System (CNS), in particular, is an intriguing anatomical compartment that is tightly regulated by the blood-brain barrier. Targeting the CNS viral reservoir is a major challenge owing to the decreased permeability of drugs into the CNS and the cellular microenvironment that facilitates the compartmentalization …

Genetic Approaches For The Study Of Complex Human Diseases, Julieta Lazarte

Electronic Thesis and Dissertation Repository

The field of human genetics has evolved from its initial narrow focus on single-gene Mendelian disorders, which largely affect children, to our current understanding that for most diseases there is continuum of rare to common variants which can exert a range of phenotypic effects. Despite advances in sequencing capabilities and our overall understanding of diseases, there remains a large proportion of heritability unexplained. Through the use of next-generation sequencing technologies and DNA microarray, I have explored a spectrum of genetic variations from rare, single and structural variants to common variants in individuals with i) “lone” atrial fibrillation; ii) familial hypercholesterolemia; …

European Union Food Law Update, Emilie Majster

Journal of Food Law & Policy

Nutrition is increasingly important in both the European Union (EU) and in global food-related policy making. Governments, which up until recently have focused on regulating food products based on a food safety perspective, are now turning to regulate from a nutritional aspect.

Post-Acute Sequelae Of Covid-19 And Polypharmacy: If You Think There’S Too Much Polypharmacy Now, Just Wait, Demetra Antimisiaris

The University of Louisville Journal of Respiratory Infections

The intersection of increased chronic disease burden worldwide with the COVID-19 pandemic was called the “perfect storm”. This article discusses yet another perfect storm: Post COVID-19 (acute and non-acute) syndrome, high chronic disease burdens, advanced age, and polypharmacy. The expected hyper polypharmacy that should result from the added disease and symptom burden due to post COVID-19 syndrome is discussed, as well as the importance of studying the incidence and characteristics to be able to address avoidable medication-related problems.

Autophagy, Apoptosis, The Unfolded Protein Response, And Lung Function In Idiopathic Pulmonary Fibrosis, Pawan Sharma, Javad Alizadeh, Maya Juarez, Afshin Samali, Andrew J Halayko, Nicholas J Kenyon, Saeid Ghavami, Amir A Zeki

Center for Translational Medicine Faculty Papers

Autophagy, apoptosis, and the unfolded protein response (UPR) are fundamental biological processes essential for manifold cellular functions in health and disease. Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal pulmonary disorder associated with aging that has limited therapies, reflecting our incomplete understanding. We conducted an observational study linking molecular markers of cell stress response pathways (UPR: BiP, XBP1; apoptosis: cleaved caspase-3; autophagy: LC3β) in lung tissues from IPF patients and correlated the expression of these protein markers to each subject's lung function measures. We hypothesized that changes in lung tissue expression of apoptosis, autophagy, and UPR markers correlate with …

The Effect Of Nurse Case Coordination On Management Of Chronic Conditions, Aayush Mittal Ms-Hsm

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Ishani A, Greer N, Taylor BC, et al. Effect of nurse case management compared with usual care on controlling cardiovascular risk factors in patients with diabetes: a randomized controlled trial. Diabetes Care. 2011;34(8):1689-1694. https://doi.org/10.2337/dc10-2121

for a patient requiring care coordination for management of hypertension, diabetes, and hyperlipidemia.

Conjugated Estrogen Is An Effective Option To Manage Chronic Gi Bleeding In A Patient With Atrial Fibrillation And End-Stage Renal Disease, Matthew T. Compton, Krupa Patel

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Livio M, Mannucci PM, Viganò G, Mingardi G, Lombardi R, Mecca G, Remuzzi G. Conjugated estrogens for the management of bleeding associated with renal failure. N Engl J Med. 1986;315:731-735 https://doi.org/10.1056/NEJM198609183151204

for a patient with chronic GI bleeding and complicated pro- and anti-coagulation needs.

Emerging Advances Of Nanotechnology In Drug And Vaccine Delivery Against Viral Associated Respiratory Infectious Diseases (Varid), Amir Seyfoori, Mahdieh Shokrollahi Barough, Pooneh Mokarram, Mazaher Ahmadi, Parvaneh Mehrbod, Alireza Sheidary, Tayyebeh Madrakian, Mohammad Kiumarsi, Tavia Walsh, Kielan D Mcalinden, Chandra C Ghosh, Pawan Sharma, Amir A Zeki, Saeid Ghavami, Mohsen Akbari

Center for Translational Medicine Faculty Papers

Viral-associated respiratory infectious diseases are one of the most prominent subsets of respiratory failures, known as viral respiratory infections (VRI). VRIs are proceeded by an infection caused by viruses infecting the respiratory system. For the past 100 years, viral associated respiratory epidemics have been the most common cause of infectious disease worldwide. Due to several drawbacks of the current anti-viral treatments, such as drug resistance generation and non-targeting of viral proteins, the development of novel nanotherapeutic or nano-vaccine strategies can be considered essential. Due to their specific physical and biological properties, nanoparticles hold promising opportunities for both anti-viral treatments and …

Covid-19 And The Impact On Rural And Black Church Congregants: Results Of The C-M-C Project, Lovoria B. Williams, Anita F. Fernander, Tofial Azam, Maria L. Gomez, Junghee Kang, Cassidy L. Moody, Hannah Bowman, Nancy E. Schoenberg

Clinical and Translational Science Faculty Publications

The COVID‐19 pandemic has had devastating effects on Black and rural populations with a mortality rate among Blacks three times that of Whites and both rural and Black populations experiencing limited access to COVID‐19 resources. The primary purpose of this study was to explore the health, financial, and psychological impact of COVID‐19 among rural White Appalachian and Black nonrural central Kentucky church congregants. Secondarily we sought to examine the association between sociodemographics and behaviors, attitudes, and beliefs regarding COVID‐19 and intent to vaccinate. We used a cross sectional survey design developed with the constructs of the Health Belief and Theory …

Circumcision As An Intervening Strategy Against Hiv Acquisition In The Male Genital Tract, Adhikarimayum Lakhikumar Sharma, Joseph Hokello, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Unsafe sex with HIV-infected individuals remains a major route for HIV transmission, and protective strategies, such as the distribution of free condoms and pre-or post-prophylaxis medication, have failed to control the spread of HIV, particularly in resource-limited settings and high HIV prevalence areas. An additional key strategy for HIV prevention is voluntary male circumcision (MC). International health organizations (e.g., the World Health Organization, UNAIDS) have recommended this strategy on a larger scale, however, there is a general lack of public understanding about how MC effectively protects against HIV infection. This review aims to discuss the acquisition of HIV through the …

A Novel In Vitro Method For Pelvic Floor Dysfunction In Pcos Women, Ruben Vila

University Honors Theses

Background:

Poly Cystic Ovary Syndrome and Pelvic Floor Dysfunction are reproductive diseases with comorbidities whose novel relationship deserves further investigation.

Methods:

Levator Ani Muscle/Paravaginal Attachment was dissected from female Rhesus Macaque and subjected to tissue dissociation. Cells were treated with serum level hormones E2, T, and DHT. PCR, ICC, and IHC were used, followed by statistical analysis.

Results:

RNA analysis show differences in relative expression for endpoints ER, PR, AR, Ki-67, Col1A, and Vimentin. IHC along with ICC showed expression and localization in vivo.

Conclusions:

A novel in vitro model was created from macaque Levator Ani Muscle/Paravaginal Attachment for Pelvic …

An Update On The Hiv Dna Vaccine Strategy, Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi

Center for Translational Medicine Faculty Papers

In 2020, the global prevalence of human immunodeficiency virus (HIV) infection was estimated to be 38 million, and a total of 690,000 people died from acquired immunodeficiency syndrome (AIDS)–related complications. Notably, around 12.6 million people living with HIIV/AIDS did not have access to life-saving treatment. The advent of the highly active antiretroviral therapy (HAART) in the mid-1990s remarkably enhanced the life expectancy of people living with HIV/AIDS as a result of improved immune functions. However, HAART has several drawbacks, especially when it is not used properly, including a high risk for the development of drug resistance, as well as undesirable …

Reflecting On The Now: Race, Gender, Socio-Economic Status And Covid-19, Ariana Montemayor, Sydney M. Scanlon

VA Engage Journal

Early in 2020, we began a project for our Women and Technology class at Old Dominion University to highlight women working in health sciences. However, our original project idea drastically changed with the onset of the COVID-19 pandemic. COVID-19 focused our attention on issues regarding societal inequalities and health disparities. Therefore, we decided to create a new project that emphasized the societal inequalities and the disproportionate impact COVID had on People of Color, women and low-income individuals. In this paper, we critically reflect on the journey of our project from conception to completion, as well as how we, and the …

Impact Of Intratumor Heterogeneity And The Tumor Microenvironment In Shaping Tumor Evolution And Response To Therapy, Akash Mitra

Dissertations & Theses (Open Access)

Intratumor heterogeneity (ITH) is a crucial challenge in cancer treatment. The genotypic and phenotypic heterogeneity underlying diverse cancer types leads to subclonal variation, which may result in mixed or failed response to therapy. The heterogeneity at the tumor level, along with the tumor microenvironment (TME), often shapes tumor evolution and ultimately clinical outcome. Given that modern treatment paradigms increasingly expose patients with metastatic disease to multiple treatment modalities through the course of their disease, there exists a need to characterize robust and predictive biomarkers of response to therapy. In order to accurately characterize tumor evolution, we need to account for …

Neuroplasticity Of The Corticospinal System: Applications Of Neuromodulation-Based Therapies, Alzahraa M. Amer

Dissertations, Theses, and Capstone Projects

The motor cortex and corticospinal tract are necessary for producing skilled movements. I use intermittent theta burst stimulation (iTBS), a high-frequency stimulation protocol known to promote neural plasticity, as a tool to characterize short- and long-term plasticity of the CS system.

Although it is well known that activity-dependent motor cortex (MCX) plasticity produces long-term potentiation (LTP) of local cortical circuits, leading to enhanced motor evoked potentials (MEPs), the effects produced by the corticospinal (CS) projection on spinal cord neurons have not yet been thoroughly studied. In Chapter 2, I determined if the CS tract (CST) is capable of producing LTP …

Interventional Treatment With The Transjugular Intrahepatic Portosystemic Shunt (Tips) Procedure May Offer A Preferable Alternative To Systemic Anticoagulation In Patients With Cirrhosis And Portal Vein Thrombosis, Molly N. Pantelic

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising:

Wang Z, Jiang MS, Zhang HL, et al. Is post-tips anticoagulation therapy necessary in patients with cirrhosis and portal vein thrombosis? A randomized controlled trial. Radiology. 2016;279(3):943-951. https://doi.org/10.1148/radiol.2015150369

for a patient with cryptogenic cirrhosis, gastroesophageal varices, pancreatic cancer, and portal vein thrombosis.

Luspatercept Diminishes The Need For Red Blood Cell Replacement In Transfusion-Dependent Β-Thalassemia Patients, Joudeh B. Freij

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising:

Cappellini MD, Viprakasit V, Taher AT, et al. A phase 3 trial of luspatercept in patients with transfusion-dependent β-thalassemia. N Engl J Med. 2020;382(13):1219-1231. https://doi.org/10.1056/NEJMoa1910182

for a patient with transfusion-dependent beta-thalassemia.

Sleeve Gastrectomy Improves Metabolic Syndrome In Psychologically Stable Patients With Schizophrenia, Irene Chen

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising:

Archid R, Archid N, Meile T, Hoffman J, Wulff D, Teufel M, Muthig M, Quante M, Konigsrainer A, Lange J. Patients with schizophrenia do not demonstrate worse outcome after sleeve gastrectomy: a short-term cohort study. Obesity Surgery. 2019;29:506-510. https://doi.org/10.1007/s11695-018-3578-0

for a patient with schizophrenia and obesity.

External Beam Radiation Therapy Carries Lower Risk Of Sexual Dysfunction As Compared To Radical Prostatectomy In Treatment Of Patients With Localized Prostate Cancer, Aamod S. Dekhne

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising:

Donovan JL, Hamdy FC, Lane JA, et al. Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer. N Engl J Med. 2016;375(15):1425-1437. https://doi.org/10.1056/NEJMoa1606221

for a patient with localized prostate cancer and concerns regarding future sexual dysfunction.

Clinical Decision Science: Experience Can Be Shared; Can It Be Taught?, James Peter Meza

Clinical Research in Practice: The Journal of Team Hippocrates

The editor reflects on the biopsychosocial model of clinical decision making and whether it can be taught in clinical medicine.

The Driving Simulator Visual Field In Glaucoma – A Novel Task To Test Available Field Of View, Deepta Ghate

Theses & Dissertations

Glaucoma causes peripheral vision loss and impaired driving performance. We developed a novel driving simulator visual field task (DSVF) in a panoramic driving simulator to map the available field of view under different perceptual task loads in naturalistic settings. Our hypothesis is that “available field of view” will decrease with increasing task load in both glaucoma subjects and controls. This is a cross-sectional study with 28 glaucoma subjects and 19 controls. DSVF (60̊ x 20̊ visual field at 2.5 m) was tested in a high-fidelity interactive driving simulator in 4 different scenarios: a) no distractions b) no driving condition with …

The Population Affected By The Syndemic Of Covid-19 And Poverty Is More Likely To Be Hospitalized With Sars-Cov-2 Pneumonia, Julio A. Ramirez, Stephen P. Furmanek, Meredith Cahill, Stephen S. Hanson, Ruth Carrico, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

Background

Lockdown measures to control COVID-19 have exacerbated the poverty epidemic. We hypothesized that the synergistic interaction of COVID-19 and poverty epidemics favors the development of more severe forms of COVID-19 in the population living in poverty. To test this hypothesis, we assessed whether an ecological association exists between the geographic distribution of hospitalized patients with SARS-CoV-2 pneumonia and markers of poverty in the city of Louisville, KY.

Methods

Using the geomasked home addresses of hospitalized patients with SARS-CoV-2 pneumonia in the city of Louisville, a kernel density heatmap was created. Kuldorff’s spatial scan statistic was used to calculate areas …