Translational Medical Research Commons^™

Do You Know The Pathophysiology Of Cytokine Storm During Covid-19?, Shameera Shaik Masthan, Deekshitha Turaka, Ahmed Abdelhaleem, Mounica Vorla, Steven B. Lippmann

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Evaluation Of Respiratory Function Using Blood Gas Parameters In Yucatan Minipigs Following Spinal Cord Injury, Jackson Gallagher, Monique Morgan, Chase Knibbe, Destiny Gibson, Maxwell Boakye

The Cardinal Edge

There are approximately 17,810 new spinal cord injuries (SCI) in the U.S. each year [1]. Physical damage to the spinal cord has the potential to interfere with normal motor, sensory, and/or autonomic function, such as impairment of the respiratory system. In fact, respiratory insufficiency is the number one cause of mortality and morbidity after SCI. The more rostral the injury, the more likely there will be disruption to normal ventilation (generally rostral to T6) [2]. To conduct relevant preclinical research, it has been shown that large animal models, such as the Yucatan minipig, have a better success rate of translating …

Emergency Care For Youth Who Experience Suicidality And Identify As Lesbian Gay Bisexual Transgender Queer/Questioning (Lgbtq+): An Interpretive Phenomenology, Theresa Schultz

Electronic Theses and Dissertations

Purpose: Suicide is a leading cause of death in children; youth who identify as LGBTQ+ are at an exponentially higher risk of suicide. The purpose of this study was to explore the lived experiences of young adults who identify as LGBTQ+ and sought emergency care for suicidality when they were adolescents.

Methods: Heideggerian hermeneutics phenomenology is the research method used in this study. Youth, ages 18-25 years, who identify as LGBTQ+ and sought emergency treatment for suicidality when they were adolescents (13-17 years) were recruited to participate;fifteen youth enrolled. Individuals ranged in age from 20 to 25 years. Participants described …

Comparing Outcomes For Community-Acquired Pneumonia Between Females And Males: Results From The University Of Louisville Pneumonia Study, Pavani Nathala, Simrat Sarai, Vidyulata Salunkhe, Mahder A. Tella, Stephen P. Furmanek, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

Introduction: Male sex is currently considered to be a risk factor for worsened community-acquired pneumonia (CAP) outcomes compared to female sex; hence, female sex equates to a lower score on the Pneumonia Severity Index. There is no recent update on sex-based outcomes of patients with CAP. The objective of this study was to compare the outcomes of CAP between females and males.

Methods: This was a secondary analysis of the University of Louisville Pneumonia Study database. It was a prospective population-based cohort study of all hospitalized adults with CAP who were residents of Jefferson County in the city of Louisville, …

Grk2 Regulates Adp Signaling In Platelets Via P2y1 And P2y12., Xuefei Zhao, Matthew Cooper, James V Michael, Yanki Yarman, Aiden Baltz, J Kurt Chuprun, Walter J Koch, Steven E. Mckenzie, Maurizio Tomaiuolo, Timothy J Stalker, Li Zhu, Peisong Ma

Department of Medicine Faculty Papers

The critical role of G protein-coupled receptor kinase 2 (GRK2) in regulating cardiac function has been well documented for >3 decades. Targeting GRK2 has therefore been extensively studied as a novel approach to treating cardiovascular disease. However, little is known about its role in hemostasis and thrombosis. We provide here the first evidence that GRK2 limits platelet activation and regulates the hemostatic response to injury. Deletion of GRK2 in mouse platelets causes increased platelet accumulation after laser-induced injury in the cremaster muscle arterioles, shortens tail bleeding time, and enhances thrombosis in adenosine 5'-diphosphate (ADP)-induced pulmonary thromboembolism and in FeCl3-induced carotid …

Role Of Deep Learning Techniques In Non-Invasive Diagnosis Of Human Diseases., Hisham Abouelseoud Elsayem Abdeltawab

Electronic Theses and Dissertations

Machine learning, a sub-discipline in the domain of artificial intelligence, concentrates on algorithms able to learn and/or adapt their structure (e.g., parameters) based on a set of observed data. The adaptation is performed by optimizing over a cost function. Machine learning obtained a great attention in the biomedical community because it offers a promise for improving sensitivity and/or specificity of detection and diagnosis of diseases. It also can increase objectivity of the decision making, decrease the time and effort on health care professionals during the process of disease detection and diagnosis. The potential impact of machine learning is greater than …

A Microfluidics-Based Approach For Isolation Of Antigen-Specific Cd8+ T Cells, Meredith Frank

Dissertations and Theses (Open Access)

Cancer is a global epidemic: there are predicted to be 200 million new cases this year alone. Almost a quarter of all cancer-related deaths are caused by lung cancer, for which 5-year survival rates are just above 20%. 85% of lung cancer diagnoses are classified as non-small cell lung cancer (NSCLC) for which 5-year survival rates in metastatic disease are less than 10%. Early detection and targeted therapies have improved prognoses, yet relapse is still common among patients.

Immunotherapies that leverage tumor-specific CD8⁺ cytotoxic T cells have shown great promise for the treatment of NSCLC. However, although highly promising, …

Absolute Quantification Of Tc-99m Activity Distributions Using A Planar Molecular Breast Imaging Commercial System, Benjamin P. Lopez

Dissertations and Theses (Open Access)

Molecular breast imaging (MBI) uses two dedicated-breast semiconductor detectors to visualize the preferential uptake of technetium-99m-sestamibi (^99mTc-sestamibi) by breast cancer cells relative to surrounding benign breast tissues. Clinically, MBI is used primarily as a supplementary tool to standard-of-care mammography because of its improved detection of breast cancers, especially in women with mammographically-dense breasts. Because of a lack of image corrections, MBI applications are currently limited to qualitative evaluations of relative pixel intensities between image regions with suspected lesions and normal tissue.

The objective of this dissertation was to use Monte Carlo simulations to better characterize the MBI imaging …

Unraveling The Effects Of Aerobic Exercise And Erk5 Signaling In The Solid Tumor Microenvironment Using Murine Models, Hannah Savage

Dissertations and Theses (Open Access)

Solid tumors are comprised of multiple cell types which communicate and work together to promote tumor progression. Advances in the treatment of solid tumors have armed clinicians with more efficacious pharmacologic agents and combinations. However, a focus on drug adjuvants in the treatment of solid cancer has left gaps in knowledge regarding non-pharmacologic treatment adjuvants, like aerobic exercise. The current dissertation investigates pharmacologic and non-pharmacologic based approaches to remodel the solid tumor microenvironment landscape and alter therapeutic efficacy. We disassemble compartments of the tumor microenvironment, including tumor vasculature and immune infiltrate, using mouse models and single cell techniques, to elucidate …

Bhlhe40: Required For Tumor Microenvironment Remodeling And Immune Checkpoint Therapy Efficacy, Avery Salmon, Avery J. Salmon

Dissertations and Theses (Open Access)

Advancements in immunotherapy treatments have become essential in the treatment of various cancers, such as those with high tumor burden like melanoma(Brahmer et al., 2012; Hodi et al., 2010). Immunotherapy, specifically immune checkpoint therapy (ICT) provides antagonist effect on specific immune checkpoints to control effector T cell functions(Pardoll, 2012). This therapy allows for the modulation of anti-tumor responses through the use of monoclonal antibodies, such as anti-CTLA-4 or anti-PD-1 that block the receptors from binding with their ligands, thus allowing for CD4⁺ and CD8⁺ T cell priming and activation(Wei et al., 2017). However, the required epigenetic and transcriptional …

Cell-Free Dna Sequencing In Multiple Myeloma, Russell Irwin

Dissertations and Theses (Open Access)

Multiple myeloma (MM) is an incurable plasma cell dyscrasia. Recent advances in MM therapy, including CAR-T therapy, have increased survival and shown the value of assessing treatment response with great sensitivity, both in acute and long-term settings. Cell-free DNA, DNA fragments which are released into circulation as a part of normal cellular turnover, is a useful and dynamic biomarker in cancer patients due to the presence of circulating tumor DNA (ctDNA), which is readily identified using next generation sequencing. Here we report the analytical sensitivity, applicability, consistency, and prognostic ability of M5Seq, a novel hybrid capture panel designed for MM …

Development Of A Decellularized Hydrogel Composite And Its Application In A Novel Model Of Disc-Associated Low Back Pain In Female Sprague Dawley Rats, David Lillyman

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

Chronic low back pain is a global socioeconomic crisis compounded by an absence of reliable, curative treatments. The predominant pathology associated with chronic low back pain is degeneration of intervertebral discs in the lumbar spine. During degeneration, nerves can sprout into the intervertebral disc tissue and be chronically subjected to inflammatory and mechanical stimuli, resulting in pain. Pain arising from the intervertebral disc, or disc-associated pain, is a complex, multi-faceted disorder which necessitates valid animal models to screen therapeutics and study pathomechanisms of pain.

While many research teams have created animal models of disc degeneration, the translation of these platforms …

Radiation Therapy For Older Women With Early Breast Cancer: An Unnecessary Hardship, Lauren E. Shawver

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising:

Kunkler IH, Williams LJ, Jack WJ, Cameron DA, Dixon JM; PRIME II investigators. Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial [published correction appears in Lancet Oncol. 2015 Mar;16(3):e105]. Lancet Oncol. 2015;16(3):266-273. https://doi.org/10.1016/S1470-2045(14)71221-5

for an older patient seeking treatment for Stage 1 Ductal Breast Carcinoma

Lisdexamfetamine Is An Effective Monotherapy For Moderate To Severe Binge Eating Disorder, Benjamin Young

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using

McElroy SL, Hudson J, Ferreira-Cornwell MC, Radewonuk J, Whitaker T, Gasior M. Lisdexamfetamine dimesylate for adults with moderate to severe binge eating disorder: Results of two pivotal phase 3 randomized controlled trials. Neuropsychopharmacology. 2016;41(5):1251-1260. https://doi.org/10.1038/npp.2015.275

for a young woman requesting a novel pharmacological intervention for a Binge Eating Disorder (BED).

Enhanced Recovery After Surgery (Eras) Protocols Decrease Length Of Hospital Stay And Maintain Functional Independence In Elderly Patients Undergoing Colorectal Surgery, Kristen Hawes

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using

Ostermann S, Morel P, Chalé JJ, et al. Randomized controlled trial of enhanced recovery program dedicated to elderly patients after colorectal surgery. Dis Colon Rectum. 2019;62(9):1105-1116. https://doi.org/10.1097/DCR.0000000000001442

for an elderly patient undergoing colorectal surgery.

What About Anosmia From Covid-19 ?, Sharanya S E Santhi, Sara Elnour, Steven B Lippmann

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Management Of Non-Compressible Torso Hemorrhage Of The Abdomen In Austere/Remote Environments By Non-Surgeon Using Truncal Hemorrhage Control, Donald Adams Mpas, Pa-C

Doctor of Philosophy in Translational Health Sciences Dissertations

Background: Non-compressible torso hemorrhage (NCTH) of the abdomen is a potentially preventable cause of death due to injury. Over the last 26 years, the trauma community has not developed a temporizing or definitive intervention to preserve life in patients with non-compressible torso hemorrhage of the abdomen due to trauma. Individuals who sustain survivable injuries that are associated with non-compressible torso hemorrhage of the abdomen will, on average bleed out or hemorrhage within 30 minutes of sustaining injury. Truncal hemorrhage control is the intervention this research study would implement by non-surgeons managing patients with non-compressible torso hemorrhage of the abdomen in …

Prognostic Serum Biomarkers In Cancer Patients With Covid-19: A Systematic Review, Te-An Lee, Shih-Han Wang, Chun-Tse Kuo, Chia-Wei Li, Louise D Mccullough, Dhimiter Bello, Yun-Ju Lai

Faculty, Staff and Student Publications

Purpose: Cancer patients with COVID-19 likely express biomarker changes in circulation. However, the biomarkers used in SARS-CoV-2 infected cancer patients for COVID-19 severity and prognosis are largely unclear. Therefore, this systematic review aims to determine what biomarkers were measured in cancer patients with COVID-19 and their prognostic utility.

Methods: A systematic literature review in PubMed, Embase, and Scopus was performed on June 16th, 2021. The search keywords coronavirus, neoplasm, biomarkers, and disease progression were used to filter out 17 eligible studies, which were then carefully evaluated.

Results: A total of 4,168 patients, 16 types of cancer, and 60 biomarkers were …

Lost In Translation? Communicating Nutrition Science, Lindsay Yarabek Datlow

Doctor of Philosophy in Translational Health Sciences Dissertations

Diet is directly correlated with overall health; therefore, nutrition is a critical piece of the obesity-epidemic puzzle. The news media has become a primary source for nutrition information yet results from International Food Information Council surveys indicate that the majority of Americans view the nutrition news they read as inconsistent and confusing. Very recent inquiry provides empirical evidence that nutrition confusion could be fueled by media. Nutrition confusion has been causally linked to “nutrition backlash,” which is complete disregard for even the most strongly supported nutrition advice. Understanding how nutrition research is translated in the news media and the mechanisms …

Characterization And Assessment Of Barriers And Facilitators To The Decision-Making Process For Blood And Blood Donor Safety In The United States: A Collective Case Study, Lauren A. Crowder

Doctor of Philosophy in Translational Health Sciences Dissertations

Background: Over 16 million blood components are transfused to patients in need every year in the United States (Jones et al., 2021). Because of the reliance on human blood donors, the donation and transfusion of blood will always be associated with some level of risk for both donors and recipients; the tolerability of these risks may vary from stakeholder to stakeholder. While the U.S. Food and Drug Administration (FDA) concedes that attaining a blood supply with zero risk for transmission of infectious diseases may be unattainable (U.S. Food and Drug Administration, 2019), they continue to strive for the lowest …

Treating Cytokine Storm In Patients With Covid-19, Ahmed Abdelhaleem, Deekshitha Turaka, Shameera Shaik Masthan, Steven B Lippmann

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Neoadjuvant Immunotherapy Across Cancers: Meeting Report From The Immunotherapy Bridge-December 1st–2nd, 2021, Elizabeth M Burton, Rodabe N Amaria, Tina Cascone, Myriam Chalabi, Neil D Gross, Elizabeth A Mittendorf, Richard A Scolyer, Padmanee Sharma, Paolo A Ascierto

Faculty, Staff and Student Publications

After the success of immunotherapy in the treatment of advanced metastatic cancer, further evaluation in earlier settings, including high-risk, surgically-resectable disease is underway. Potential benefits of a neoadjuvant immunotherapeutic approach include presurgical tumor shrinkage, reduced surgical morbidity, early eradication of micrometastases and prevention of distant disease, and greater antigen-specific T cell response. For some cancers, pathologic response has been established as a surrogate measure for long-term outcomes, therefore offering the ability for early and objective assessment of treatment efficacy and the potential to inform and personalize adjuvant treatment clinical decision-making. Leveraging the neoadjuvant treatment setting offers the ability to deeply …

Antimicrobial Stewardship Meets Transitions Of Care: Defining Length Of Therapy For Community-Acquired Pneumonia (Cap), Christopher Whitman, Sarah E. Moore, Matthew Song, Brian C. Bohn, Ashley M. Wilde

The University of Louisville Journal of Respiratory Infections

Introduction: Hospital-based antimicrobial stewardship efforts have traditionally focused on inpatient settings. Antibiotic prescribing at discharge is often an overlooked area of focus for antimicrobial stewardship programs. Discharge prescribing optimization is necessary to combat antibiotic overuse.

Methods: This was an observational, retrospective cohort study at a four–adult community hospital system. Four hundred adult patients admitted with community-acquired pneumonia and discharged with antibiotics were included. The primary outcome was overall (inpatient and discharge) antibiotic length of therapy. The secondary outcome was percentage of patients discharged on a fluoroquinolone who had not received one in the hospital. Descriptive statistics were utilized.

Results: The …

Covid-19 Case Complicated With Organizing Pneumonia And Pneumothorax: Correspondence, Hammad A. Bhatti, Minh Q. Ho

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Regulation Of Oxidative Phosphorylation Of Liver Mitochondria In Sepsis, Pierre Eyenga, Benjamin Rey, Lilia Eyenga, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

The link between liver dysfunction and decreased mitochondrial oxidative phosphorylation in sepsis has been clearly established in experimental models. Energy transduction is plastic: the efficiency of mitochondrial coupling collapses in the early stage of sepsis but is expected to increase during the recovery phases of sepsis. Among the mechanisms regulating the coupling efficiency of hepatic mitochondria, the slipping reactions at the cytochrome oxidase and ATP synthase seem to be a determining element, whereas other regulatory mechanisms such as those involving proton leakage across the mitochondrial membrane have not yet been formally proven in the context of sepsis. If the dysfunction …

Akt Inhibition In The Central Nervous System Induces Signaling Defects Resulting In Psychiatric Symptomatology, Apostolia-Maria Tsimberidou, Antonis Skliris, Alan Valentine, Jamie Shaw, Ursula Hering, Henry Hiep Vo, Tung On Chan, Roger S Armen, Jeffrey R Cottrell, Jen Q Pan, Philip N Tsichlis

Center for Translational Medicine Faculty Papers

Background: Changes in the expression and activity of the AKT oncogene play an important role in psychiatric disease. We present translational data assessing the role of AKT in psychiatric symptoms.

Methods: (1) We assessed the protein activity of an AKT3 mutant harboring a PH domain mutation (Q60H) detected in a patient with schizophrenia, the corresponding AKT1 mutant (Q61H), and wild-type AKT1 and AKT3 transduced in AKT-null mouse fibroblasts and modeled the Q61H mutation onto the crystal structure of the Akt1 PH domain. (2) We analyzed the results of earlier genome-wide association studies to determine the distribution of schizophrenia-associated single-nucleotide polymorphisms …

Covid-19, Vaccination, And Heart Transplantation, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

No abstract provided.

A Survey To Highlight Areas Of Focus For Patient Care In Settings Utilizing Medical Interpretation, Azayzel Deregis

Undergraduate Honors Theses

This thesis recounts my personal experience working as a volunteer medical interpreter for the Language and Culture Resource Center at East Tennessee State University. The result of my time spent volunteering as a medical interpreter, shadowing professional medical interpreters, and witnessing patient-provider interactions during interpreted sessions was an inspiration to study medical interpretation further and delve into the challenges faced by patients who require medical interpreters. During my time researching this topic, I found that the United States is severely lacking in Spanish medical interpreters—with some healthcare facilities employing no medical interpreters—even though the size of the Hispanic population is …

Summary Of: Understanding The Role Of Misinformation In Covid-19 Vaccine Hesitancy In A Rural State, Ann Marie Hess, Colin T. Waters, Elizabeth A. Jacobs, Kerri L. Barton, Kathleen M. Fairfield

Northern New England Clinical & Translational Research

Findings from this study regarding COVID-19 vaccine hesitancy and sources of trusted information are important for developing public health strategies to increase vaccination rates. Understanding the concerns of individuals as assessed in this study provides opportunities for trusted health professionals, friends and family to reinforce facts about the importance of being vaccinated.

Study found @ "Understanding the Role of Misinformation in COVID-19 Vaccine Hesitancy" by Ann Marie Hess, Colin T. Waters et al.

Adipose-Derived Stromal Vascular Fraction Therapy Improves Age-Related Adrenergic Mediated Microvascular Dysfunction And Increases Revascularization Potential Following Injury., Gabrielle Brown

Electronic Theses and Dissertations

The role of the microcirculation is to balance blood flow and oxygen delivery to meet local metabolic and oxygen demands. With advancing age, the health of the endothelium declines leading to improper augmentation of the microcirculation; decreasing vasoreactivity and angiogenic potential which can further increase the risk of ischemia. The multiple contributing factors that drive the decline in endothelial health with age make traditional pharmacological interventions challenging whereas cell-based therapies can exert multifactorial gains. Adipose-derived stromal vascular fraction (SVF) is an emerging therapeutic for its easily accessible, autologous, anti-inflammatory, and angiogenic properties. It is a heterogenous population comprised of leukocyte …