Translational Medical Research Commons^™

Regulation Of Skeletal Muscle Plasticity By The Gut Microbiome, Taylor R. Valentino

Theses and Dissertations--Physiology

Recent evidence suggests that the gut microbiome could play a role in skeletal muscle plasticity, providing novel treatments for muscle wasting diseases and/or performance enhancements. I first sought to determine if the gut microbiome is necessary for skeletal muscle adaptation to exercise. Forty-two, four-month old, female C57Bl/6J underwent nine weeks of weighted wheel running or remained in cage with a locked wheel, without or without the administration of antibiotics (treated). In response to wheel running, I found that antibiotic depletion of the microbiome led to a blunted hypertrophic response in the soleus muscle as measured by normalized muscle wet weight …

The Three-Way Interplay Among Early Life Exposures, The Gut Microbiome, And Outcomes In Infancy, Yuka Moroishi

Dartmouth College Ph.D Dissertations

The bidirectional relationship between the gut microbiome and immune system plays an important role in host immune status: the immune system provides the gut microbiome the optimal environment to thrive in, and the gut microbiome helps regulate the immune system. This relationship is especially important in infants, whose immune system is still premature and rely on innate immunity.

We investigated the three-way interplay among early-life exposures, the developing gut microbiome, and outcomes in infancy from the general population in New Hampshire, US. We used prospective cohort data from the New Hampshire Birth Cohort study to 1) determine whether timing of …

Research Annual Report Fy2022, Children's Mercy Kansas City

Research Annual Reports

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

Vaping During Pregnancy: Effects On Vascular And Behavioral Outcomes In Offspring, Eiman A. Aboaziza

Graduate Theses, Dissertations, and Problem Reports

Electronic cigarette (e-cig) use is increasing due to aggressive marketing, tempting flavors, and seemingly higher acceptability in the community (lesser perceived social stigma) despite unproven claims of safety. In an alarming trend, pregnant women smokers have turned to novel “modified risk” products, such as e-cigs, in response to heavy marketing of e-cigs as safer alternatives to cigarettes and a tool to help quit smoking. This is despite proven detrimental effects of nicotine on a growing fetus, and scarcity of information regarding toxicity of e-liquid (with and without nicotine) on child development. Moreover, rampant e-cig use among youth (nearly 4 million …

Recolonization Of Microbiomes’ Influence On Autism Spectrum Disorder, Hattie Cole

Capstone Showcase

In recent years, there has been an increase in the number of studies conducted on the complications of gastrointestinal (GI) comorbidities associated with autism spectrum disorder (ASD) in children. Some of these GI issues include irritable bowel syndrome (IBS), diarrhea and constipation. The causes of these disorders are poorly understood. The dominant gut phyla are Firmicutes and Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria and Verrucomicrobia. Research conducted on children with ASD compared with typical developing (TD) children showed higher ratios of Firmicutes/Bacteroidetes in the ASD group. Biflobacterium, Actinobacteria phyla, has been shown to be a good intestinal bacterium that may help with …

Exosome- And Microrna-Based Therapeutic Approach For Tendinopathy, Angela Wang Ilaltdinov

Dissertations and Theses

Tendinopathy, characterized by degeneration and chronic inflammation, is a significant clinical burden. Current treatments focus on symptom management but do not sufficiently address its underlying pathology; however, stem cell-based approaches aimed at repairing diseased tissues may overcome this limitation. Therapeutic effects of stem cells may be due in part to paracrine actions, including some mediated by exosomes – extracellular vesicles secreted by cells that play a role in cell communication. MicroRNA (miRNA), small non-coding RNA carried by exosomes, are likely responsible for many exosome effects. Exosomes and miRNA therapies show promise in treating diseases such as cancer and arthritis, but …

Consultation/Liaison Psychiatry During Covid-19, Robert Frierson, Steven B Lippmann

The University of Louisville Journal of Respiratory Infections

Consultation/liaison psychiatrists care for people with co-existing medical and psychologic difficulties. The coronavirus pandemic is stressful for patients and their psychiatric caregivers. Patients have lost support systems and harbor fears about exposing family to the virus. COVID-19 sometimes exacerbates previous psychiatric conditions, while diminishing intimacy with physicians. Everyone is oversaturated with COVID-19-related news focusing on rising concerns about the illness and about jobs, school, and housing insecurities.

The psychiatrist maintains a hospital presence despite fear of contracting the disease. Challenges include addressing staff morale, evidencing empathy despite telecommunication devices, and treating anxiety, depression, sleep phobias, post intubation flashbacks, COVID-19-induced cognitive …

Barriers And Facilitators To Implementing Simulation-Based Translational Research: A Qualitative Study, Lisa Ann Paganotti

Doctor of Philosophy in Translational Health Sciences Dissertations

Translational simulation research has the potential to inform the way simulation is used to impact patient care and patient outcomes. Understanding how to approach translational simulation and the barriers and facilitators that can be used throughout the process can inform novice simulation and translational researchers. This qualitative dissertation sought to answer the following research questions: How do simulation experts describe the barriers and facilitators to implementing translational simulation programs? How do simulation experts describe their various approaches to implementing translational simulation programs? What recommendations do simulation experts describe for overcoming barriers to implementing translational simulation programs? The key findings include …

Micro-Computed Tomographic Analysis Of The Shaping Ability Of Xp-Endo Shaper In Oval-Shaped Distal Root Canals Of Mandibular Molars, Ane Poly, Wei-Ju Louis Tseng, Fernando Marques, Frank Carsten Setzer, Bekir Karabucak

Center for Translational Medicine Faculty Papers

Objective: To compare the shaping ability of the XP-endo Shaper (XPS) system to the ProTaper Next (PTN) system in oval-shaped distal root canals.

Methods: From 12 mandibular molars, distal roots with moderately curved single oval canals were randomly assorted to be instrumented with XPS (experimental group) or PTN (control group) and then scanned using micro-computed tomography [Scan 1]. The root canals of the XPS samples were prepared following the manufacturer's instructions using 15 insertions (XPS15) and rescanned [Scan 2]. An additional 10 insertions to the working length were applied, totalling 25 insertions (XPS25), and the roots were rescanned again [Scan …

Ogr1-Dependent Regulation Of The Allergen-Induced Asthma Phenotype, Ajay P Nayak, Deepak A. Deshpande, Phd, Sushrut D. Shah, Dominic R Villalba, Roslyn Yi, Nadan Wang, Raymond B. Penn

Division of Pulmonary and Critical Care Medicine Faculty Papers

The proton-sensing receptor, ovarian cancer G protein-coupled receptor (OGR1), has been shown to be expressed in airway smooth muscle (ASM) cells and is capable of promoting ASM contraction in response to decreased extracellular pH. OGR1 knockout (OGR1KO) mice are reported to be resistant to the asthma features induced by inhaled allergen. We recently described certain benzodiazepines as OGR1 activators capable of mediating both procontractile and prorelaxant signaling in ASM cells. Here we assess the effect of treatment with the benzodiazepines lorazepam or sulazepam on the asthma phenotype in wild-type (WT) and OGR1KO mice subjected to inhaled house dust mite (HDM; …

Activation Of Crtc2/Creb1 In Skeletal Muscle Enhances Weight Loss During Intermittent Fasting, Nelson E Bruno, Jerome C Nwachukwu, David C Hughes, Sathish Srinivasan, Richard Hawkins, David Sturgill, Gordon L Hager, Stephen Hurst, Shey-Shing Sheu, Sue C Bodine, Michael D Conkright, Kendall W Nettles

Department of Medicine Faculty Papers

The Creb-Regulated Transcriptional Coactivator (Crtc) family of transcriptional coregulators drive Creb1-mediated transcription effects on metabolism in many tissues, but the in vivo effects of Crtc2/Creb1 transcription on skeletal muscle metabolism are not known. Skeletal muscle-specific overexpression of Crtc2 (Crtc2 mice) induced greater mitochondrial activity, metabolic flux capacity for both carbohydrates and fats, improved glucose tolerance and insulin sensitivity, and increased oxidative capacity, supported by upregulation of key metabolic genes. Crtc2 overexpression led to greater weight loss during alternate day fasting (ADF), selective loss of fat rather than lean mass, maintenance of higher energy expenditure during the fast and reduced binge-eating …

Adult Spiny Mice (Acomys) Exhibit Endogenous Cardiac Recovery In Response To Myocardial Infarction, Hsuan Peng, Kazuhiro Shindo, Renée R. Donahue, Erhe Gao, Brooke M. Ahern, Bryana M. Levitan, Himi Tripathi, David Powell, Ahmed Noor, Garrett A. Elmore, Jonathan Satin, Ashley W. Seifert, Ahmed K. Abdel-Latif

Physiology Faculty Publications

Complex tissue regeneration is extremely rare among adult mammals. An exception, however, is the superior tissue healing of multiple organs in spiny mice (Acomys). While Acomys species exhibit the remarkable ability to heal complex tissue with minimal scarring, little is known about their cardiac structure and response to cardiac injury. In this study, we first examined baseline Acomys cardiac anatomy and function in comparison with commonly used inbred and outbred laboratory Mus strains (C57BL6 and CFW). While our results demonstrated comparable cardiac anatomy and function between Acomys and Mus, Acomys exhibited a higher percentage of cardiomyocytes displaying …

The Role Of Mathematics In 21st Century Medicine, Reinhard Laubenbacher

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Using Adaptive Research Design To Define The Proper Methodology To Use A Data Peek For Power: Step By Step Process, Tom Wasser

Advances in Clinical Medical Research and Healthcare Delivery

When planning or conducting research in the hospital setting, often termed Real-World Environment (RWE), therapeutic assumptions and outcomes are often different than in the Randomized Clinical Trial (RCT) where medications, devices and therapies are tested and developed. This is because RWE research has a lack of experimental control, additional confounding due to patient complications and comorbid conditions, lack of pure patient selection and compliance with therapy in the patients being treated and many other factors as well. However, when RWE experiments are conducted, sample size determination using data from the RCT is common because that is the only data that …

Patient Satisfaction While Enrolled In Clinical Trials: A Literature Review, Ilufredo Y. Tantoy, Andrea N. Bright, Evan Paelmo, Emily I. Moreland, Ashley N. Trost, Joan Pasquesi, Charlotta Weaver, Richard T. D'Aquila

Patient Experience Journal

Patient satisfaction surveys may not adequately reflect organizations that conduct research in patients who enroll in clinical trials. The purpose of this systematic literature review was to summarize the current state of knowledge of patient satisfaction while enrolled in clinical trials utilizing a widely used, validated patient satisfaction instrument. A comprehensive literature search was conducted using CINAHL, EMBASE, PsycInfo, PubMed and Web of Science. Studies were evaluated in terms of clinical trial participation; assessment conducted during or after participation; utilization of a validated instrument; a pharmacological intervention; and the paper was published in English. Only nine studies met this review’s …

Human Immunodeficiency Virus Type-1 (Hiv-1) Transcriptional Regulation, Latency And Therapy In The Central Nervous System, Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Priya Tyagi, Alok Bhushan, Mudit Tyagi

College of Pharmacy Faculty Papers

The central nervous system (CNS) is highly compartmentalized and serves as a specific site of human immunodeficiency virus (HIV) infection. Therefore, an understanding of the cellular populations that are infected by HIV or that harbor latent HIV proviruses is imperative in the attempts to address cure strategies, taking into account that HIV infection and latency in the CNS may differ considerably from those in the periphery. HIV replication in the CNS is reported to persist despite prolonged combination antiretroviral therapy due to the inability of the current antiretroviral drugs to penetrate and cross the blood–brain barrier. Consequently, as a result …

Development Of A Novel Mir-3648-Related Gene Signature As A Prognostic Biomarker In Esophageal Adenocarcinoma, Donglei Zhang, Hang Yin, Thomas L. Bauer, Michael P. Rogers, Jeffrey B. Velotta, Clinton T. Morgan, Weijia Du, Ping Xu, Xiaozhe Qian

Surgery Faculty Publications

Background: Esophageal adenocarcinoma (EA) is a typical immunogenic malignant tumor with a dismal 5-year survival rate lower than 20%. Although miRNA-3648 (miR-3648) is expressed abnormally in EA, its impact on the tumor immune microenvironment remains unknown. In this study, we sought to identify immune-related genes (IRGs) that are targeted by miR-3648 and develop an EA multigene signature.

Methods: The gene expression data of 87 EA tumor samples and 67 normal tissue samples from The Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database were downloaded, respectively. Weighted gene co-expression network analysis (WGCNA), the CIBERSORT algorithm, and Cox regression …

A Research Framework For Evaluating Next Generation Sequencing In Community-Acquired Pneumonia, Ashley M. Wilde, Elena Swingler, Sarah E. Moore Pharmd, Brian C. Bohn Pharmd, Matthew Song Pharmd, Bcidp, Ruth Carrico, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Conference Proceedings: Select Abstracts Presented At 2021 Advocate Aurora Health Scientific Day

Journal of Patient-Centered Research and Reviews

Abstracts published within this supplement were presented at the 47th annual Advocate Aurora Health Scientific Day, held virtually on May 26, 2021. This research symposium provides a forum for disseminating results from studies conducted by faculty, fellows, residents, and other allied health professionals associated with Midwest-based health system Advocate Aurora Health, which publishes the Journal of Patient-Centered Research and Reviews.

Covid-19-Associated Pulmonary Aspergillosis: A Case Report From The Covid-19 Surveillance Program., Mohamad Belal Aldaas, Dylan Goldsmith, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

A 72-year-old male was brought to the hospital following a motorcycle crash and was admitted for multiple trauma management. His initial course of hospitalization was complicated by mild hypoxemia and altered mental status. Respiratory workup and imaging were consistent with SARS-CoV-2 pneumonia. He completed a five-day course of remdesivir and a ten-day course of dexamethasone. Twenty days later, he developed a low-grade fever. His chest computerized tomography (CT) showed gas and fluid containing parenchymal collection in the anteromedial right middle lobe measuring up to 4.8 cm, most consistent with a pulmonary abscess. Antimicrobial treatment was started.

The patient became hypoxic …