Translational Medical Research Commons^™

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.

Augmented Immunomodulation Of Endogenous Marrow-Derived Stem Cells In The Setting Of Acl Rupture, Mackenzie Fleischer, Michael Newton, Samantha Hartner, John A. Driscoll, Anthony Arveschoug, Chritopher C. Vasileff, Kevin Baker

Conference Presentation Abstracts

PURPOSE: Augmentation of MSC immunomodulation is an unexplored, potentially useful therapeutic to combat PTOA following ACLR. Lower kynurenine-to-tryptophan ratios observed in synovial fluid of ACL rupture (ACLR) rats suggests decreased activity of tryptophan metabolizing enzyme, Ido, known to be secreted by MSCs to promote T-reg expansion and Th17 suppression. This study aims to characterize the immunomodulatory capacity of pharmacologically mobilized MSCs in conjunction with exogenously delivered Ido. METHODS: Rats (N = 48) underwent ACLR to evaluate the effects of mobilized MCSs on Ido1 and inflammatory cytokine expression profiles in the synovial fluid. Additionally, rats (N = 160) underwent ACLR to …

Evaluating Simulation-Based Tobacco Treatment Scenarios For Providers Delivering Treatment For People Living With Mental Illnesses, Chizimuzo T. C. Okoli, Janet Otachi, Sarret Seng, Bassema Abufarsakh, Lovoria B. Williams

Clinical and Translational Science Faculty Publications

Background: People living with mental illnesses (PMI) experience elevated tobacco use and related morbidity and mortality. Despite the availability of effective and safe tobacco treatments along with evidence that PMI are motivated and able to quit successfully, few Mental and behavioral healthcare providers (MHPs) engage PMI in such treatment. MHPs may lack the confidence or skills to engage their clients in tobacco treatment. Currently, there are limited training modalities to prepare MHPs in delivering tobacco treatment for PMI. However, animated scenario-based simulated encounters can bridge this gap to effectively provide tailored MHP training to enhance treatment delivery. Hence, the purpose …

Tumor Suppressor Par-4 Regulates Complement Factor C3 And Obesity, Nathália Araujo, James Sledziona, Sunil K. Noothi, Ravshan Burikhanov, Nikhil Hebbar, Saptadwipa Ganguly, Tripti Shrestha-Bhattarai, Beibei Zhu, Wendy S. Katz, Yi Zhang, Barry S. Taylor, Jinze Liu, Li Chen, Heidi L. Weiss, Daheng He, Chi Wang, Andrew J. Morris, Lisa A. Cassis, Mariana N. Nikolova‑Karakashian, Prabhakara R. Nagareddy, Olle Melander, B. Mark Evers, Phillip A. Kern, Vivek M. Rangnekar

Clinical and Translational Science Faculty Publications

Prostate apoptosis response-4 (Par-4) is a tumor suppressor that induces apoptosis in cancer cells. However, the physiological function of Par-4 remains unknown. Here we show that conventional Par-4 knockout (Par-4^-/-) mice and adipocyte-specific Par-4 knockout (AKO) mice, but not hepatocyte-specific Par-4 knockout mice, are obese with standard chow diet. Par-4^-/- and AKO mice exhibit increased absorption and storage of fat in adipocytes. Mechanistically, Par-4 loss is associated with mdm2 downregulation and activation of p53. We identified complement factor c3 as a p53-regulated gene linked to fat storage in adipocytes. Par-4 re-expression in adipocytes or c3 deletion reversed …

Aorta In Pathologies May Function As An Immune Organ By Upregulating Secretomes For Immune And Vascular Cell Activation, Differentiation And Trans-Differentiation-Early Secretomes May Serve As Drivers For Trained Immunity, Yifan Lu, Yu Sun, Keman Xu, Fatma Saaoud, Ying Shao, Charles Drummer, Sheng Wu, Wenhui Hu, Jun Yu, Satya P Kunapuli, John R Bethea, Roberto I Vazquez-Padron, Jianxin Sun, Xiaohua Jiang, Hong Wang, Xiaofeng Yang

Center for Translational Medicine Faculty Papers

To determine whether aorta becomes immune organ in pathologies, we performed transcriptomic analyses of six types of secretomic genes (SGs) in aorta and vascular cells and made the following findings: 1) 53.7% out of 21,306 human protein genes are classified into six secretomes, namely, canonical, caspase 1, caspase 4, exosome, Weibel-Palade body, and autophagy; 2) Atherosclerosis (AS), chronic kidney disease (CKD) and abdominal aortic aneurysm (AAA) modulate six secretomes in aortas; and Middle East Respiratory Syndrome Coronavirus (MERS-CoV, COVID-19 homologous) infected endothelial cells (ECs) and angiotensin-II (Ang-II) treated vascular smooth muscle cells (VSMCs) modulate six secretomes; 3) AS aortas upregulate …