Translational Medical Research Commons^™

Glypican-3 And Cd81 Promote Development Of Hepatocellular Carcinoma And Hepatoblastoma Through Negative Selection., Yuhua Xue, Wendy Mars, William Bowen, Aatur D. Singhi, Sarangarajan Ranganathan, George K. Michalopoulos

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.

Frontiers In Precision Medicine Ii: Cancer, Big Data And The Public, Emily Coonrod, Jorge L. Contreras, Willard Dere, Jeffrey Botkin, Leslie Francis, Jim Tabery

Utah Law Faculty Scholarship

Precision medicine is being developed within a complex landscape of public policy, science, economics, law, and regulation. In these and other policy areas, the goal of developing individually-tailored therapies poses novel challenges for health care research, delivery and policy. In this symposium, a range of experts in genetics, medicine, bioinformatics, intellectual property, health economics and bioethics identified and discussed many of the pressing questions raised by the development and practice of precision medicine. These and other issues will need to be taken into account as precision medicine moves ahead and becomes the standard of medical practice and care in the …

New Insights Into Post-Sepsis Muscle Weakness Elucidated Using A Novel Animal Model, Allison M. Steele

Theses and Dissertations--Physiology

Sepsis is a severe life-threatening critical illness that damages multiple physiological systems. After hospital discharge, more than 70% of severe sepsis survivors report profound weakness which significantly impacts quality of life. Such weakness gives rise to new limitations of daily living, which ultimately leads to loss of independence in many patients. Despite wide recognition of this serious issue by clinicians and researchers alike, the mechanisms contributing to chronic skeletal muscle dysfunction after sepsis are not well understood. Lack of progress in this field is largely due to the absence of an appropriate animal model; current models are either too mild …

Maine Medical Center Research Institute: 2017 Year In Review, Maine Medical Center Research Institute

Annual Reports

Annual Report: Bench to Bedside to Community, Basic Research->Translational & Clinical Research->Patient-Centered Outcomes Research

The Mechanical Properties Of Non-Failing And Failing Human Myocardium, Cheavar A. Blair

Theses and Dissertations--Physiology

Heart failure is a clinical syndrome that manifests when there are structural and functional impairments to the heart that reduces the ability of the ventricles to fill or eject blood. The syndrome affects ~6 million Americans and is responsible for nearly 300,000 deaths annually. At the core of the syndrome are dysfunctional sarcomeres, the machinery that drives cardiac contraction and relaxation. By assessing the mechanical properties of human cardiac tissue, the information provided in this dissertation will provide data that demonstrates how sarcomeric dysfunction contributes to heart failure in the left and right ventricles. Additionally, these data will supply information …

Efficacy Of Nutritional Interventions To Lower Circulating Ceramides In Young Adults: Fruvedomic Pilot Study, Alice T. Matthews, Oluremi A. Famodu, Melissa D. Olfert, Pamela J. Murray, Christopher F. Cuff, Marianne T. Downes, Norman J. Haughey, Sarah E. Colby, Paul D. Chantler, I. Mark Olfert, Joseph W. Mcfadden

Faculty & Staff Scholarship

The 2010 USDA Dietary Guidelines for Americans (DGA) recommends a diet largely composed of fruit and vegetables. Consuming a diet high in fruit and vegetables and low in refined carbohydrates and saturated fat may reduce an individual’s risk for type 2 diabetes, nonalcoholic fatty liver disease, low-grade chronic inflammation, and metabolic syndrome (MetS). Several recent studies have implicated the bioactive sphingolipid ceramide as an associative and causative biomarker for the development of these conditions. Considering that the intake of fruit and vegetables is frequently inadequate in young adults, we performed a pilot investigation to assess the efficacy of a free-living …

Bladder Antimuscarinics And Cognitive Decline In Elderly Patients, Daniela Claudia Moga, Erin L. Abner, Qishan Wu, Gregory A. Jicha

Pharmacy Practice and Science Faculty Publications

Introduction: The evidence on the impact of bladder antimuscarinics initiation on cognitive function in older adults is inconsistent.

Methods: A retrospective analysis of data from the National Alzheimer's Coordinating Center (NACC) on enrollees 65 years and older evaluated the association between antimuscarinic initiation and cognitive decline. We defined decline from baseline (yes/no) for cognitive assessments included in the NACC Uniform Data Set 2.0 battery. New users were matched on year of enrollment and time in the cohort to randomly selected nonusers. Analyses were conducted using inverse probability of treatment weights based on baseline propensity scores.

Results: Our analyses included 698 …

The Mitochondrial Ca(2+) Uniporter: Structure, Function, And Pharmacology., Jyotsna Mishra, Bong Sook Jhun, Stephen Hurst, Jin O-Uchi, György Csordás, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex.

Decellularized Wharton's Jelly From Human Umbilical Cord As A Novel 3d Scaffolding Material For Tissue Engineering Applications., Sushma Jadalannagari, Gabriel Converse, Eric Buse, Michael Filla, Maria T. Villar, Antonio Artigues, Adam J. Mellot, Jinxi Wang, Michael S. Detamore, Richard A. Hopkins, Omar S. Aljitawi, C Mcfall

Manuscripts, Articles, Book Chapters and Other Papers

In tissue engineering, an ideal scaffold attracts and supports cells thus providing them with the necessary mechanical support and architecture as they reconstruct new tissue in vitro and in vivo. This manuscript details a novel matrix derived from decellularized Wharton's jelly (WJ) obtained from human umbilical cord for use as a scaffold for tissue engineering application. This decellularized Wharton's jelly matrix (DWJM) contained 0.66 ± 0.12 μg/mg sulfated glycosaminoglycans (GAGs), and was abundant in hyaluronic acid, and completely devoid of cells. Mass spectroscopy revealed the presence of collagen types II, VI and XII, fibronectin-I, and lumican I. When seeded onto …

Person-Centered Treatment To Optimize Psychiatric Medication Adherence, Natalie Bareis

Theses and Dissertations

Objectives: Adherence to psychotropic medication is poor among individuals with bipolar disorder (BD). To understand treatment experiences and associated adherence among these individuals, we developed a novel construct of Clinical Net Benefit (CNB) using psychiatric symptoms, adverse effects and overall functioning assessments. We tested whether adherence differed across classes of CNB, whether individuals transitioned between classes over time, and whether these transitions were differentially associated with adherence.

Methods: Data come from individuals aged 18+ during five years of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Latent class analysis identified groups of CNB. Latent transition analysis determined probabilities of …

Characterization Of The Role Of Insulin-Like Growth Factor Binding Protein 7 (Igfbp7) Using A Genetic Knockout Mouse Model, Maaged A. Akiel

Theses and Dissertations

In the US, the incidence and mortality rates of hepatocellular carcinoma (HCC) are alarmingly increasing since no effective therapy is available for the advanced disease. Activation of IGF signaling is a major oncogenic event in diverse cancers, including HCC. Insulin-like growth factor binding protein-7 (IGFBP7) inhibits IGF signaling by binding to IGF-1 receptor (IGF-1R) and functions as a potential tumor suppressor for hepatocellular carcinoma (HCC). IGFBP7 abrogates tumors by inducing cancer-specific senescence and apoptosis and inhibiting angiogenesis. We now document that Igfbp7 knockout (Igfbp7-/- ) mouse shows constitutive activation of IGF signaling, presents with pro-inflammatory and immunosuppressive microenvironment, and develops …

Effect Of Arginine On Oligomerization And Stability Of N-Acetylglutamate Synthase., N Haskins, A Mumo, P H Brown, Mendel Tuchman, Hiroki Morizono, L Caldovic

Genomics and Precision Medicine Faculty Publications

N-acetylglutamate synthase (NAGS; E.C.2.3.1.1) catalyzes the formation of N-acetylglutamate (NAG) from acetyl coenzyme A and glutamate. In microorganisms and plants, NAG is the first intermediate of the L-arginine biosynthesis; in animals, NAG is an allosteric activator of carbamylphosphate synthetase I and III. In some bacteria bifunctional N-acetylglutamate synthase-kinase (NAGS-K) catalyzes the first two steps of L-arginine biosynthesis. L-arginine inhibits NAGS in bacteria, fungi, and plants and activates NAGS in mammals. L-arginine increased thermal stability of the NAGS-K from Maricaulis maris (MmNAGS-K) while it destabilized the NAGS-K from Xanthomonas campestris (XcNAGS-K). Analytical gel chromatography and ultracentrifugation indicated tetrameric structure of the …

Inflammatory Gene Expression In Women Diagnosed With Polycystic Ovarian Syndrome, Myles K. Taylor

Electronic Theses & Dissertations

Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The pathophysiology of PCOS has conventionally thought to originate from androgen excess. However, recent evidence suggests that androgen excess is a downstream consequence to inflammatory dysregulation and subsequent metabolic abnormalities. Inflammatory mRNA gene expression of TNFa and IL-1ß in mononuclear cells isolated from women diagnosed with PCOS was explored using qPCR. Additionally, the correlations between body mass index (BMI) and fasting glucose on mRNA expression of TNFa and IL-1ß were explored. mRNA expression of both TNFa and IL-1ß were found to be significantly higher in PCOS …

Adoption Of Perioperative Lidocaine Infusion For The Reduction Of Postoperative Pain, Brandon Scott Figueiredo

Doctoral Projects

Laparoscopic capability provides numerous benefits to patients requiring abdominal surgical procedures. However, the use of these techniques has presented the anesthesia provider with a unique set of challenges in terms of perioperative management and postoperative pain reduction. No standardized method has existed to reduce postoperative pain and improve recovery following these procedures. There were three primary goals of this project. The first goal was to conduct a meta-analysis of randomized controlled trials to determine the benefit of the use of intravenous lidocaine infusions to reduce postoperative pain in laparoscopic abdominal surgery. Twelve articles were included in the meta-analysis that pertained …

Perceptual Variations In Thermoregulation During Exercise In A Hot Environment, William C. Alger

Electronic Theses and Dissertations

ABSTRACT

Professionals are seeking to find ways to prevent exertional heat illness (EHI) in populations working in hot environments as well as populations that are physically active. The purpose of the present study was to evaluate individuals’ ability to accurately perceive core temperature ranges associated with homeothermic and EHI temperatures during exercise. Ten physically active males exercised on a treadmill at a self-selected rate until core temperature reached 39°C. Participants rated perceived core and skin temperature on 100 mm scales each time core temperature increased 0.25˚ C (37.5-39.0˚ C), along with thermal comfort and sweating sensation. During exercise core temperature …

The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary

Electronic Theses and Dissertations

The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current …

Her4 Promotes A Stem-Like Phenotype In Osteosarcoma, Rocio K. Rivera-Valentin

Dissertations and Theses (Open Access)

Metastatic disease to the lungs is the primary cause of death for patients with pediatric osteosarcoma (OS). OS has a high degree of heterogeneity and genomic instability, making understanding the pathogenesis and drivers of metastasis of this disease challenging. In an effort to explain tumoral heterogeneity, the tumor initiating cell model (TIC) states that tumors are composed of cells that form the majority of the tumor and are terminally differentiated. This model however, attributes tumorigenesis, metastasis and chemoresistance to a distinct cell population with a stem-like phenotype that can be identified using selective markers. OS appears to follow this model …

Educating Clinician Scientists Once Again—A Societal Need, James Peter Meza

Clinical Research in Practice: The Journal of Team Hippocrates

The Faculty Editor advocates for the training of clinician scientists again, using the body of clinical research as the laboratory.

Network Inference Driven Drug Discovery, Gergely Zahoránszky-Kőhalmi, Tudor I. Oprea, Cristian G. Bologa, Subramani Mani, Oleg Ursu

Biomedical Sciences ETDs

The application of rational drug design principles in the era of network-pharmacology requires the investigation of drug-target and target-target interactions in order to design new drugs. The presented research was aimed at developing novel computational methods that enable the efficient analysis of complex biomedical data and to promote the hypothesis generation in the context of translational research. The three chapters of the Dissertation relate to various segments of drug discovery and development process.

The first chapter introduces the integrated predictive drug discovery platform „SmartGraph”. The novel collaborative-filtering based algorithm „Target Based Recommender (TBR)” was developed in the framework of this …

Seniors Welcome! Avoiding The Trap Of Age Limits In Health Research, Arshad Jahangir

Journal of Patient-Centered Research and Reviews

The guest editor introduces this specialty issue of the Journal of Patient-Centered Research and Reviews, which focuses on cardiovascular diseases in the elderly. The reality of an aging population has increased the need for better evidence-based medicine in older patients. However, randomized controlled trials frequently exclude such patients, especially those with comorbidities, from study. This practice ignores the fact that physiologic changes to the cardiovascular system caused by the aging process and aging-associated diseases create clinical dilemmas distinct from those in younger patients. Considering the rising costs of health care and growing incidence of cardiovascular disease, research efforts and …

Earth Suit, Bowhee Gwak, Young Park

Clinical Research in Practice: The Journal of Team Hippocrates

The authors reflect on an experience learning at the feet of a spirited patient.

Assessing Feasibility And Readiness To Address Obesity Through Policy In American Indian Reservations, Valarie Blue Bird Jernigan, Gail Boe, Carolyn Noonan, Leslie Carroll, Dedra Buchwald

Journal of Health Disparities Research and Practice

The Institute of Medicine and Centers for Disease Control and Prevention (CDC) have identified policy and environmental strategies as critical to the prevention and control of obesity. However such strategies are rare in American Indian communities despite significant obesity-related disparities. Tribal policymaking processes differ by tribal nation and are often poorly understood by researchers and public health practitioners, hindering the dissemination, implementation, and successful scale-up of evidence-base obesity strategies in tribal communities. To address these gaps in knowledge we surveyed 138 diverse stakeholders in two American Indian reservations to assess the feasibility of and readiness to implement CDC-recommended obesity policy …

An Examination Of Cultural Competence Training In Us Medical Education Guided By The Tool For Assessing Cultural Competence Training, Valarie Blue Bird Jernigan

Journal of Health Disparities Research and Practice

In the United States, medical students must demonstrate a standard level of “cultural competence,” upon graduation. Cultural competence is most often defined as a set of congruent behaviors, attitudes, and policies that come together in systems, organizations, and among professionals to enable effective work in cross-cultural situations. The Association of American Medical Colleges developed the Tool for Assessing Cultural Competence Training (TACCT) to assist schools in developing and evaluating cultural competence curricula to meet these requirements. This review uses the TACCT as a guideline to describe and assess pedagogical approaches to cultural competence training in US medical education and identify …

Cycle Training Modulates Satellite Cell And Transcriptional Responses To A Bout Of Resistance Exercise, Kevin A. Murach, R. Grace Walton, Christopher S. Fry, Sami L. Michaelis, Jason S. Groshong, Brian S. Finlin, Philip A. Kern, Charlotte A. Peterson

Clinical and Translational Science Faculty Publications

This investigation evaluated whether moderate-intensity cycle ergometer training affects satellite cell and molecular responses to acute maximal concentric/eccentric resistance exercise in middle-aged women. Baseline and 72 h postresistance exercise vastus lateralis biopsies were obtained from seven healthy middle-aged women (56 ± 5 years, BMI 26 ± 1, VO_2max 27 ± 4) before and after 12 weeks of cycle training. Myosin heavy chain (MyHC) I- and II-associated satellite cell density and cross-sectional area was determined via immunohistochemistry. Expression of 93 genes representative of the muscle-remodeling environment was also measured via NanoString. Overall fiber size increased ~20% with cycle training ( …

Critical Appraisal Is A Skill That Takes Practice: Our Patients Are Counting On Us, Dorothy Bourdet

Clinical Research in Practice: The Journal of Team Hippocrates

A fumbling attempt at critical analysis in support of a clinical decision crystallizes the author's understanding that skillful analysis of research is crucial to good practice.

Early Haart Should Be Used For Treatment-Naive Hiv Patients With Pneumocystis Pneumonia, Maxwell L. Winkler

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Manzardo C, Esteve A, Ortega N, et al. Optimal timing for initiation of highly active antiretroviral therapy in treatment-naïve human immunodeficiency virus-1-infected individuals presenting with AIDS-defining diseases: the experience of the PISCIS Cohort. Clin. Microbiol. Infect. 2013 July;19(7):646-653. doi: 10.1111/j.1469-0691.2012.03991.x

Pharmacologic Diuresis Is Safer Than Ultrafiltration For Cardiorenal Syndrome, Grace Choong

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Bart BA, Goldsmith SR, Lee KL et al. Ultrafiltration in decompensated heart failure with cardiorenal syndrome. N Engl J Med. 2012;367:2296-2304. doi: 10.1056/NEJMoa1210357

Spinal Compression Fractures: No Additional Pain Relief With Use Of Back Braces, Kayla A. Berigan, Brandon Baker, Zakaria Ahmad, Aaron Simpson

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Li M, Law SW, Cheng J, Kee HM, Wong MS. A comparison study on the efficacy of SpinoMed® and soft lumbar orthosis for osteoporotic vertebral fracture. J. Prosthet. Orthot. Int. 2015;39(4):270-276. doi: 10.1177/0309364614528204

Anticancer Effect Of Moringa Oleifera Leaf Extract In Human Cancer Cell Lines, María Del Mar Zayas-Viera, Pablo Vivas-Mejia, Ph.D, Jeyshka Reyes, Phd

Journal of Health Disparities Research and Practice

Many medicinal plants are used as chemo preventives and antitumor agents in numerous experimental models of carcinogenesis. Moringa oleifera is a plant that contains several phytochemicals, which have been used for medical purposes including anti-inflammatory, analgesic, metabolism activator, anti-asthmatic, anti-anemia, hormone-producing, liver protector, and detoxifier, among others. Moringa oleifera extracts have also been proposed as potential anticancer agents. Cancer is one of the main causes of deaths worldwide. Although many drugs exist against several types of cancer, more specific agents with lower side effects are necessary. Few reports exist regarding the antitumor activity of Moringa oleifera leaf extract in cancer …

The Role Of Sumo And Coilin In The Cajal Body, Shanya Whitehorse, Mario Izaguirre-Sierra, Phd

Journal of Health Disparities Research and Practice

Our lab is solely based on learning about the molecular biology of the cell nucleus using basic model organism such as plants and flies. We focus on the study of the Cajal Body (CB) and specifically, we are interested to know how nuclear bodies can be formed without a membrane. The CB and the nucleolus are conserved nuclear bodies in all eukaryotic cells. CBs contain multiple proteins and RNA species involved in many pathways such as splicing, ribosome biogenesis and telomere maintenance.

Coilin is one of the main proteins in the nucleus and it is known to be required for …