Translational Medical Research Commons^™

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.

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 …

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 …

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 …

Hdac6 Inhibition Reverses Long-Term Doxorubicin-Induced Cognitive Dysfunction By Restoring Microglia Homeostasis, Blake Mcalpin

Dissertations and Theses (Open Access)

One in 8 women in the US will be diagnosed with breast cancer. Currently, doxorubicin is one of the most effective chemotherapies for breast cancer. Unfortunately, up to 60% of survivors report long-term chemotherapy-induced cognitive dysfunction (CICD) characterized by deficits in working memory, processing speed, and executive functioning. Currently, no interventions for CICD have been approved by the US Food and Drug Administration. I show here that a 14-day treatment with a blood-brain barrier permeable histone deacetylase 6 (HDAC6) inhibitor successfully reverses long-term CICD following a therapeutic doxorubicin dosing schedule in female mice, as assessed by the puzzle box test …

Development And Application Of 3d Kinematic Methodologies For Biomechanical Modelling In Adaptive Sports And Rehabilitation, Anne Marie Severyn

All Dissertations

Biomechanical analysis is widely used to assess human movement sciences, specifically using three-dimensional motion capture modelling. There are unprecedented opportunities to increase quantitative knowledge of rehabilitation and recreation for disadvantaged population groups. Specifically, 3D models and movement profiles for human gait analysis were generated with emphasis on post-stroke patients, with direct model translation to analyze equivalent measurements while horseback riding in use of the alternative form of rehabilitation, equine assisted activities and therapies (EAAT) or hippotherapy (HPOT). Significant improvements in gait symmetry and velocity were found within an inpatient rehabilitation setting for patients following a stroke, and the developed movement …

Insulin Therapy Versus Oral Sitagliptin For Treatment Of Latent Autoimmune Diabetes In Adults, Sarah Nasser

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Hals IK, Fiskvik Fleiner H, Reimers N, et al. Investigating optimal β-cell-preserving treatment in latent autoimmune diabetes in adults: Results from a 21-month randomized trial. Diabetes Obes Metab. 2019;21(10):2219-2227. https://doi.org/10.1111/dom.13797

for a patient with an aversion to needles.

Indications For Esophagogastroduodenoscopy In Anemic Patients Without Overt Signs Of Upper Gastrointestinal Bleeding, Geoffrey M. Ginter

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Majid S, Salih M, Wasaya R, Jafri W. Predictors of gastrointestinal lesions on endoscopy in iron deficiency anemia without gastrointestinal symptoms. BMC Gastroenterol. 2008;8:52. https://doi.org/10.1186/1471-230X-8-52

for a patient with a complicated presentation of severe anemia

Exercise Therapy Improves Quality Of Life In Patients With Postural Orthostatic Tachycardia Syndrome (Pots), Heya Batah, Scott L. Baughan

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using

George SA, Bivens TB, Howden EJ, et al. The international POTS registry: Evaluating the efficacy of an exercise training intervention in a community setting. Heart Rhythm. 2016;13(4):943-950. https://doi.org/10.1016/j.hrthm.2015.12.012

for exercise efficacy in patients with POTS.

Sotrovimab: Neutralizing Antibody To Combat Covid-19, Aya Allam, Steven Lippmann

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Are Antipyretic Medications Compatible With Sars-Cov-2 Vaccines?, Sharanya S E Santhi, Niguma Rayamajhi, Steven B Lippmann

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Leptospirosis Presenting As Diffuse Alveolar Hemorrhage, Alejandra González, Paola Alvarez, Mariano Fielli, Analia Santos, Neil Gomez Querales, Elkin Rodriguez Arzuaga

The University of Louisville Journal of Respiratory Infections

Diffuse alveolar hemorrhage (DAH) syndrome has a mortality rate of 30 to 60%. A 15-year-old male patient presented with a seven-day abdominal pain, vomiting, non-dysenteric diarrhea, conjunctival injection, and fever. Chest radiography revealed bilateral interstitial infiltrates predominating in the lower left lobe. The patient’s condition worsened within hours, with the development of massive hemoptysis, acute respiratory distress syndrome (ARDS), arterial hypotension, and hematocrit decline requiring mechanical ventilation. A chest computed tomography (CT) showed ground-glass opacities with consolidation areas in lower lobes, diffuse tree-in-bud opacities, and centrilobular nodules. A bronchoscopy was conducted without endoluminal lesions and bronchoalveolar lavage (BAL) consistent with …

Potential Benefits Of Combined Statin And Metformin Therapy On Resistance Training Response In Older Individuals, Douglas E. Long, Kate Kosmac, Cory M. Dungan, Marcas M. Bamman, Charlotte A. Peterson, Phillip A. Kern

Clinical and Translational Science Faculty Publications

Metformin and statins are currently the focus of large clinical trials testing their ability to counter age-associated declines in health, but recent reports suggest that both may negatively affect skeletal muscle response to exercise. However, it has also been suggested that metformin may act as a possible protectant of statin-related muscle symptoms. The potential impact of combined drug use on the hypertrophic response to resistance exercise in healthy older adults has not been described. We present secondary statin analyses of data from the MASTERS trial where metformin blunted the hypertrophy response in healthy participants (>65 years) following 14 weeks …

Mucormycosis: Covid-19 And Corticosteroids, Mittal Savaliya, Nivedita Jha, Steven B Lippmann

The University of Louisville Journal of Respiratory Infections

No abstract provided.