Medical Anatomy Commons^™

Constitutive Genetic Deletion Of Hcn1 Increases Alcohol Preference During Adolescence, Michael C. Salling, Neil L. Harrison

School of Medicine Faculty Publications

The hyperpolarization-activated cyclic nucleotide-gated channel (HCN), which underlies the hyperpolarization-activated cation current (Ih), has diverse roles in regulating neuronal excitability across cell types and brain regions. Recently, HCN channels have been implicated in preclinical models of substance abuse including alcohol. In the prefrontal cortex of rodents, HCN expression and Ih magnitude are developmentally regulated during adolescence and may be vulnerable to alcohol’s effects. In mice, binge alcohol consumption during the adolescent period results in a sustained reduction in Ih that coincides with increased alcohol consumption in adulthood, yet the direct role HCN channels have on alcohol consumption are unknown. Here, …

Steered Molecular Dynamic Simulations Reveal Marfan Syndrome Mutations Disrupt Fibrillin-1 Cbegf Domain Mechanosensitive Balcium Binding, Stephen J. Haller, Adrian E. Roitberg, Andrew T. Dudley

Journal Articles: Genetics, Cell Biology & Anatomy

Marfan syndrome (MFS) is a highly variable genetic connective tissue disorder caused by mutations in the calcium binding extracellular matrix glycoprotein fibrillin-1. Patients with the most severe form of MFS (neonatal MFS; nMFS) tend to have mutations that cluster in an internal region of fibrillin-1 called the neonatal region. This region is predominantly composed of eight calcium-binding epidermal growth factor-like (cbEGF) domains, each of which binds one calcium ion and is stabilized by three highly conserved disulfide bonds. Crucially, calcium plays a fundamental role in stabilizing cbEGF domains. Perturbed calcium binding caused by cbEGF domain mutations is thus thought to …

Exosomes Secreted Under Hypoxia Enhance Stemness In Ewing's Sarcoma Through Mir-210 Delivery, Matthew J. Kling, Nagendra K. Chaturvedi, Varun Kesherwani, Don W. Coulter, Timothy R. Mcguire, J. Graham Sharp, Shantaram S. Joshi

Journal Articles: Genetics, Cell Biology & Anatomy

Intercellular communication between tumor cells within the hypoxic microenvironment promote aggressiveness and poor patient prognoses for reasons that remain unclear. Here we show that hypoxic Ewing's sarcoma (EWS) cells release exosomes that promote sphere formation, a stem-like phenotype, in EWS cells by enhancing survival. Analysis of the hypoxic exosomal miRNA cargo identified a HIF-1α regulated miRNA, miR-210, as a potential mediator of sphere formation in cells exposed to hypoxic exosomes. Knockdown of HIF-1α in hypoxic EWS cells led to decreased exosomal miR-210 levels and reduced the capacity of hypoxic exosomes to form spheres. Inhibition of miR-210 in hypoxic spheres attenuated …

Educational Case: A Case Of Transfusion-Transmitted Babesiosis: Diagnostic Perspectives Across The Clinical Laboratory., Kaitlyn Dykes, Alexis R. Peedin

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology.

Stem Crisis Teaching: Curriculum Design With E-Learning Tools, Sonya E. Van Nuland, Elissa Hall, Natalie R. Langley

School of Medicine Faculty Publications

The COVID-19 pandemic and subsequent social distancing protocols have accelerated the shift to online teaching across the globe. In Science, Technology, Engineering, and Mathematics (STEM) programs this means a shift from face-to-face laboratory instruction to self-directed learning with e-learning tools. Unfortunately, selecting and integrating an e-learning tool into a curriculum can be daunting. This article highlights key questions and practical suggestions instructors should consider in choosing the most effective option for their course and learners.

A Fatal Rectus Sheath Hematoma After A Myasthenia Crisis Case Report, Robert G. Michaud, Lesley B. Gordon

Journal of Maine Medical Center

Introduction: Rectus sheath hematomas (RSH) generally occur due to damage to the inferior epigastric artery. They are rare causes of abdominal pain or acute blood loss anemia, but are an important diagnostic consideration because they can be cryptic and are potentially fatal.

Clinical Findings: An 85-year-old female who had been admitted to the hospital for 10 days with a myasthenia crisis was found to be abruptly hypotensive with a tender abdominal mass in the left lower quadrant subtly crossing midline. She was on prophylactic anticoagulation during her hospitalization.

Main diagnosis, therapeutics, interventions, and outcomes: The patient was initially stabilized with …

Tfeb Regulates Murine Liver Cell Fate During Development And Regeneration, Nunzia Pastore, Tuong Huynh, Niculin J Herz, Alessia Calcagni', Tiemo J Klisch, Lorenzo Brunetti, Kangho Ho Kim, Marco De Giorgi, Ayrea Hurley, Annamaria Carissimo, Margherita Mutarelli, Niya Aleksieva, Luca D'Orsi, William R Lagor, David D Moore, Carmine Settembre, Milton J Finegold, Stuart J Forbes, Andrea Ballabio

Faculty, Staff and Students Publications

It is well established that pluripotent stem cells in fetal and postnatal liver (LPCs) can differentiate into both hepatocytes and cholangiocytes. However, the signaling pathways implicated in the differentiation of LPCs are still incompletely understood. Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, is known to be involved in osteoblast and myeloid differentiation, but its role in lineage commitment in the liver has not been investigated. Here we show that during development and upon regeneration TFEB drives the differentiation status of murine LPCs into the progenitor/cholangiocyte lineage while inhibiting hepatocyte differentiation. Genetic interaction studies show that …

Sleep-Wake Disturbances In Mild Traumatic Brain Injury: Meta Analysis Of Literature And Modeling Of Cerebral Tissue Vulnerability, Xiangfu Zhang, Subhendra Sarkar, Mary A. Browne

Publications and Research

Sleep disturbance is a frequent complaint for patients with mild traumatic brain injury (mTBI), it can prolong recovery, and the oxidative stress from lack of sleep could worsen other secondary damages of mTBI. The common types of sleep disturbance of mTBI include insomnia, daytime sleepiness, and obstructive sleep apnea. Conventional imaging often fails to detect any abnormalities in mTBI, and the etiology of sleep disturbance is still unclear. Based on the analysis of current published neurobiological and imaging literature, multiple factors could play a role leading to sleep disturbance in mTBI, however, we have focused on the diencephalon, melatonin and …

Diurnal Patterns Of Gene Expression In The Dorsal Vagal Complex And The Central Nucleus Of The Amygdala - Non-Rhythm-Generating Brain Regions, Mary M Staehle, Sean O'Sullivan, Rajanikanth Vadigepalli, Kate F Kernan, Gregory E Gonye, Babatunde A Ogunnaike, James S. Schwaber

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Genes that establish the circadian clock have differential expression with respect to solar time in central and peripheral tissues. Here, we find circadian-time-induced differential expression in a large number of genes not associated with circadian rhythms in two brain regions lacking overt circadian function: the dorsal vagal complex (DVC) and the central nucleus of the amygdala (CeA). These regions primarily engage in autonomic, homeostatic, and emotional regulation. However, we find striking diurnal shifts in gene expression in these regions of male Sprague Dawley rats with no obvious patterns that could be attributed to function or region. These findings have implications …

Gut Pathophysiology In Mouse Models Of Social Behavior Deficits, Kyla Scott

Undergraduate Honors Theses

Autism spectrum disorders (ASD) encompass neurodevelopment disorders characterized by atypical patterns of development that impact multiple areas of functioning beginning in early childhood. The etiology of ASD is unknown and there are currently no preventative treatment options. Gastrointestinal symptoms are commonly associated comorbidities. The microbiota-gut-brain axis is a multidirectional communication chain that connects the central and enteric nervous system that relates brain function to peripheral intestinal functions. Changes within this axis have been postulated in ASD. For example, the “leaky gut theory” proposes that chronic inflammation is linked to alterations in the bacterial profiles of the gut microbiome and subsequent …

Catabolic Degradation Of Endothelial Vegfa Via Autophagy, Thomas Neill, Carolyn Chen, Simone Buraschi, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Extracellular matrix-evoked angiostasis and autophagy within the tumor microenvironment represent two critical, but unconnected, functions of the small leucine-rich proteoglycan, decorin. Acting as a partial agonist of vascular endothelial growth factor 2 (VEGFR2), soluble decorin signals via the energy sensing protein, AMP-activated protein kinase (AMPK), in the autophagic degradation of intracellular vascular endothelial growth factor A (VEGFA). Here, we discovered that soluble decorin evokes intracellular catabolism of endothelial VEGFA that is mechanistically independent of mTOR, but requires an autophagic regulator, paternally expressed gene 3 (PEG3). We found that administration of autophagic inhibitors such as chloroquine or bafilomycin A1, or depletion …

Tetralogy Of Fallot: A Clinical Review, Jacob Wooten, Joshua Bahos Silva

Student Scholar Showcase

Tetralogy of Fallot is a congenital heart disease that is associated with structural abnormalities during fetal development 1. The incidence of Tetralogy of Fallot in the United States is approximately 3-5 cases per 10,000 live births and is considered one of the most common cyanotic congenital heart diseases 2. The exact etiology of Tetralogy of Fallot is unknown, however it is thought to be associated with untreated maternal diabetes, maternal use of retinoids, as well as chromosomal abnormalities 2. The main components of this disease state include a right ventricular outflow obstruction, interventricular communication in the form of a ventricular …

Dynamic Blood-Brain Barrier Regulation In Mild Traumatic Brain Injury, Eoin O'Keeffe, Eoin Kelly, Yuzhe Liu, Chiara Giordano, Eugene Wallace, Mark Hynes, Stephen Tiernan, Aidan Meagher, Chris Greene, Stephanie Hughes, Tom Burke, John Kealy, Niamh Doyle, Alison Hay, Michael Farrell, Gerald A. Grant, Alon Friedman, Ronel Veksler, Michael G. Molloy, James F. Meaney, Niall Pender, David Camarillo, Colin P. Doherty, Matthew Campbell

Articles

Whereas the diagnosis of moderate and severe traumatic brain injury (TBI) is readily visible on current medical imaging paradigms (magnetic resonance imaging [MRI] and computed tomography [CT] scanning), a far greater challenge is associated with the diagnosis and subsequent management of mild TBI (mTBI), especially concussion which, by definition, is characterized by a normal CT. To investigate whether the integrity of the blood-brain barrier (BBB) is altered in a high-risk population for concussions, we studied professional mixed martial arts (MMA) fighters and adolescent rugby players. Additionally, we performed the linear regression between the BBB disruption defined by increased gadolinium contrast …

Seen In Science: Lgbtq+ Inclusivity In Anatomy & Physiology Texts, Harshini Sirvisetty, Kat Ray King, Linda Catherine Fuselier

Undergraduate Arts and Research Showcase

Biology is unique from other science disciplines in that concepts taught in core classes can inform our student’s understanding of sex and gender. A biology major encounters lessons on sex determination, sexual reproduction, and sex characteristics in their courses. The language used in these units matters. It is imperative that educators consider how the language, examples, and content that we use in classrooms drive (or not) inclusivity for gender- and sexuality-diverse (GSD) (aka LGBTQ+) individuals. We chose to analyze four college-level human anatomy/physiology (AP) textbooks for GSD population inclusivity. We adopted a queer theory framework to critically examine how sex, …

Long Non-Coding Rna Profiling Of Pediatric Medulloblastoma, Varun Kesherwani, Mamta Shukla, Don W. Coulter, J. Graham Sharp, Shantaram Joshi, Nagendra K. Chaturvedi

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: Medulloblastoma (MB) is one of the most common malignant cancers in children. MB is primarily classified into four subgroups based on molecular and clinical characteristics as (1) WNT (2) Sonic-hedgehog (SHH) (3) Group 3 (4) Group 4. Molecular characteristics used for MB classification are based on genomic and mRNAs profiles. MB subgroups share genomic and mRNA profiles and require multiple molecular markers for differentiation from each other. Long non-coding RNAs (lncRNAs) are more than 200 nucleotide long RNAs and primarily involve in gene regulation at epigenetic and post-transcriptional levels. LncRNAs have been recognized as diagnostic and prognostic markers in …

The Quantified Elf, Umico Niwa

Theses and Dissertations

The Quantified Elf is an ongoing collection of scientific, medical, archaeological articles and excerpts from my personal journal. It is a way by which I explore the various ways Western notions of personhood subsume human life into constructs of sexuality and gender, overlooking the various other modes of unbridled existence: plant, microbial. fungal, animal, celestial bodies. The speculative medical papers propose novel forms of body modification to combat gender dysphoria.

Corpus Cavernosum Abscess Secondary To Traumatic Perforation Of Urethral Diverticulum, Thomas C. Gore, Anna Schepcoff, Domenick Sorresso

West Florida Division GME Research Day 2020

A corpus cavernosum abscess is a rare condition. Usual etiologies include penile injection of erectile dysfunction medications or illicit drugs, priapism, sexually transmitted infections, and trauma; however, there have been reported cases of idiopathic etiology. The most common causative organisms include Staphylococcus aureus, Streptococci, and Bacteroides [1]. Diagnosis is typically made clinically and through imaging (computed tomography [CT] and ultrasound). The first-line treatment is the use of intravenous (IV) antibiotics and surgical drainage. More conservative treatment, however, includes aspiration in conjunction with IV antibiotics [2-3]. Urethral diverticulum (UD) is the formation of a saccular outpouching of the urethral lumen. Symptoms …

Combination Of Investigational Cell-Based Therapy And Deep Brain Stimulation To Alter The Progression Of Parkinson’S Disease, Nader El Seblani

Theses and Dissertations--Pharmacy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and the motor symptoms are caused by progressive loss of midbrain dopamine neurons. There is no current treatment that can slow or reverse PD. Our current “DBS-Plus” clinical trial (NCT02369003) features the implantation in vivo of autologous Schwann cells (SCs) derived from a patient’s sural nerve into the substantia nigra pars compacta (SNpc) in combination with Deep Brain Stimulation (DBS) therapy for treating patients with advanced PD.

The central hypothesis of our research is that transdifferentiated SCs within conditioned nerve tissue will deliver pro-regenerative factors to enhance the survival of …

Oral Contraceptives As Possible Acl Injury Prevention Method, Haley Schweizer

Capstone Showcase

ABSTRACT

Introduction: Anterior Cruciate Ligament (ACL) injuries are an upsetting setback for many athletes that require a long and costly recovery process. The injury rates are four times greater in women than men. Preventative measures that help to prevent ACL injuries are limited to stretching and strengthening. Therefore, this review aims to investigate if oral contraceptive [I] usage provides a possible new avenue for prevention of ACL injury [O] in young female athletes (ages 18-30) [P] compared to those that do not take oral contraceptives [C].

Methods: A literature review was performed though PubMed, Google Scholar, SCOPUS Database, and ClinicalKey …

Artificial Reverse Shoulder Arthroplasty Joint Project, Michael Rosen, Bailei Hoyng

Williams Honors College, Honors Research Projects

This proposed project will be developing an artificial reverse shoulder arthroplasty joint that focuses on improvements to the Zimmer Biomet Comprehensive Reverse System by freating a unique feature, or features, to the humeral component that focuses on the prevention of dislocation by not limiting the range of motion of men from ages 45 to 65 years.

The development of the this project will utilize the Food and Drug Administration (FDA) medical device design process. This project will involve a total of four Biomedical Engineering students from the University of Akron. Two students, Michael and Bailei, are in the Honors college …