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Current Understanding Of The Mechanism Of Action Of The Antiepileptic Drug Lacosamide, Michael A. Rogawski, Azita Tofighy, H Steve White, Alain Matagne, Christian Wolff 2015 University of California - Davis

Current Understanding Of The Mechanism Of Action Of The Antiepileptic Drug Lacosamide, Michael A. Rogawski, Azita Tofighy, H Steve White, Alain Matagne, Christian Wolff

Michael A. Rogawski

The antiepileptic drug lacosamide [(R)-2-acetamido-N-benzyl-3-methoxypropanamide], a chiral functionalized amino acid, was originally identified by virtue of activity in the mouse and rat maximal electroshock (MES) test. Attention was drawn to lacosamide because of its high oral potency and stereoselectivity. Lacosamide is also active in the 6 Hz seizure model but inactive against clonic seizures in rodents induced by subcutaneous pentylenetetrazol, bicuculline and picrotoxin. It is also ineffective in genetic models of absence epilepsy. At doses greater than those required to confer protection in the MES test, lacosamide inhibits behavioral and electrographic seizures in hippocampal kindled rats. It also effectively ...


Ngo's Bpa Report Intended To Frighten, Not Enlighten., Robert L. Brent Dr. 2015 duPont Hosp for Children

Ngo's Bpa Report Intended To Frighten, Not Enlighten., Robert L. Brent Dr.

The Selected Works of Robert Brent

None


Early Mobilization In The Critical Care Unit: A Review Of Adult And Pediatric Literature., Saoirse Cameron, Ian Ball, Gediminas Cepinskas, Karen Choong, Timothy J Doherty, Christopher G Ellis, Claudio M Martin, Tina S Mele, Michael Sharpe, J Kevin Shoemaker, Douglas D Fraser 2015 Western University

Early Mobilization In The Critical Care Unit: A Review Of Adult And Pediatric Literature., Saoirse Cameron, Ian Ball, Gediminas Cepinskas, Karen Choong, Timothy J Doherty, Christopher G Ellis, Claudio M Martin, Tina S Mele, Michael Sharpe, J Kevin Shoemaker, Douglas D Fraser

Medical Biophysics Publications

Early mobilization of critically ill patients is beneficial, suggesting that it should be incorporated into daily clinical practice. Early passive, active, and combined progressive mobilizations can be safely initiated in intensive care units (ICUs). Adult patients receiving early mobilization have fewer ventilator-dependent days, shorter ICU and hospital stays, and better functional outcomes. Pediatric ICU data are limited, but recent studies also suggest that early mobilization is achievable without increasing patient risk. In this review, we provide a current and comprehensive appraisal of ICU mobilization techniques in both adult and pediatric critically ill patients. Contraindications and perceived barriers to early mobilization ...


Low Level Lead Exposure Impairs Attentional Set Shifting Task Performance Depending Upon Sex And Developmental Periods Of Exposure, L.S. Neuwirth, D.W. Anderson, J. S. Schneider 2015 Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia PA

Low Level Lead Exposure Impairs Attentional Set Shifting Task Performance Depending Upon Sex And Developmental Periods Of Exposure, L.S. Neuwirth, D.W. Anderson, J. S. Schneider

Department of Pathology, Anatomy and Cell Biology Faculty Papers

Introduction

Exposure to low levels of lead (Pb) impairs a variety of cognitive processes. Although children exposed to Pb developmentally present with a variety of cognitive impairments that include deficits in learning, memory, language, and executive functioning, experimental work on Pb toxicity in rats has focused mostly on learning and memory deficits and less on executive functions. However, detrimental effects on executive functioning could lead to or even underlie a variety of other cognitive problems attributed to Pb exposure. In this study, we examined the ability of Long Evans rats (control and Pb-exposed: 150ppm Pb-acetate in food given perinatally (gestation ...


Strategic Distribution Of The Mitochondrial Ca2+ Uniporter In Cardiac Mitochondria, Sergio De La Fuente, Caitlin Vail, Elorm J. Agra, Kira Holmstrom, Junhui Sun, Jyotsna Mishra, Toren Finkel, Elizabeth Murphy, Shey-Shing Sheu, György Csordás 2015 Pathology, Anatomy & Cell Biol., Thomas Jefferson University, Philadelphia, PA, USA

Strategic Distribution Of The Mitochondrial Ca2+ Uniporter In Cardiac Mitochondria, Sergio De La Fuente, Caitlin Vail, Elorm J. Agra, Kira Holmstrom, Junhui Sun, Jyotsna Mishra, Toren Finkel, Elizabeth Murphy, Shey-Shing Sheu, György Csordás

Department of Pathology, Anatomy and Cell Biology Faculty Papers

Background:

1) Control of the mitochondrial ATP production by SR-derived Ca2+ signals includes local, nanodomain Ca2+ transfer from ryanodine receptors (RyR2) to the mitochondrial matrix (excitation-bioenergetics coupling).

2) Ca2+ crosses the inner mitochondrial membrane (IMM) via the mtCU, a low-affinity Ca2+-activated Ca2+ channel complex.

3) The surface area of cardiac IMM is extensively enhanced by cristae folding; however, mitoplast patch clamp studies showed mtCU current density the lowest amongst a range of tissues (Fieni 2012. Nat Commun).


He Started The Whole World Singing A Song, Brian R. Cates 2015 Cedarville University

He Started The Whole World Singing A Song, Brian R. Cates

Musical Offerings

Throughout history, music has moved people in powerful ways, so much so that, at times, it leaves them speechless. They realize that it is a song, full of notes and rhythms, yet at the same time, it makes them become profoundly aware that there is something more, humming just below the surface. My presentation seeks to enter into this music moment by asking why these types of moments even occur. Does music speak or communicate? If so, does it communicate something meaningful and significant? What is the mechanism by which music conveys this meaning? How can this meaning be articulated ...


Cationic Cell-Penetrating Peptides Are Potent Furin Inhibitors, Bruno Ramos-Molina, Adam N. Lick, Amir Nasrolahi Shirazi, Donghoon Oh, Rakesh Tiwari, Naglaa Salem El-Sayed, Keykavous Parang, Iris Lindberg 2015 University of Maryland-Baltimore

Cationic Cell-Penetrating Peptides Are Potent Furin Inhibitors, Bruno Ramos-Molina, Adam N. Lick, Amir Nasrolahi Shirazi, Donghoon Oh, Rakesh Tiwari, Naglaa Salem El-Sayed, Keykavous Parang, Iris Lindberg

Pharmacy Faculty Articles and Research

Cationic cell-penetrating peptides have been widely used to enhance the intracellular delivery of various types of cargoes, such as drugs and proteins. These reagents are chemically similar to the multi-basic peptides that are known to be potent proprotein convertase inhibitors. Here, we report that both HIV-1 TAT47-57 peptide and the Chariot reagent are micromolar inhibitors of furin activity in vitro. In agreement, HIV-1 TAT47-57 reduced HT1080 cell migration, thought to be mediated by proprotein convertases, by 25%. In addition, cyclic polyarginine peptides containing hydrophobic moieties which have been previously used as transfection reagents also exhibited potent furin inhibition in vitro ...


Nicotinamde Riboside Delivery Generates Nad+ Reserves To Protect Vascular Cells Against Oxidative Damage, Krista M. Hawrylyshyn 2015 The University of Western Ontario

Nicotinamde Riboside Delivery Generates Nad+ Reserves To Protect Vascular Cells Against Oxidative Damage, Krista M. Hawrylyshyn

University of Western Ontario - Electronic Thesis and Dissertation Repository

The ability of vascular cells to withstand oxidative insults is critical to vascular health. NAD+, which drives poly (ADP-ribose) polymerase (PARP) and sirtuin (SIRT) reactions, can be compromised and strategies for overcoming this limitation in the vasculature do not exist. This study determines if nicotinamide riboside (NR) delivery can augment NAD+ stores and fuel resistance to oxidative stress. I established that oxidative-stress insult on vascular cells decreased NAD+ levels, accompanied by a striking increase in nuclear PAR-chain accumulation. PARP inhibition abolished PAR-chain formation and preserved NAD+ levels, establishing PARP in NAD+ consumption in this model. NR delivery protected against cell-shrinkage ...


The Cerebellar Gabaa Receptor Contribution To Alcohol Intake And Intoxication, Joshua Steven Kaplan 2015 Oregon Health & Science University

The Cerebellar Gabaa Receptor Contribution To Alcohol Intake And Intoxication, Joshua Steven Kaplan

Scholar Archive

Alcohol use disorders (AUDs) are a leading cause of preventable death and illness that contribute significant social and economic costs to society. Genetic factors contribute substantially to AUD development but identifying and characterizing their phenotypic expression at the cellular level has been incomplete. One of the greatest challenges in treating problem alcohol (ethanol; EtOH) use is our poor understanding of the diversity of factors that promote sensitivity to EtOH reward and intoxication. The cerebellum has long been ignored as a brain region that could influence EtOH intake. However, recent functional, anatomical, and behavioral studies have established a cerebellar link to ...


No Enhancement Of 24-Hour Visuomotor Skill Retention By Post-Practice Caffeine Administration, Sara Hussain, Kelly Cole 2015 University of Iowa Physical Therapy and Rehab Science

No Enhancement Of 24-Hour Visuomotor Skill Retention By Post-Practice Caffeine Administration, Sara Hussain, Kelly Cole

Department of Health and Human Physiology Publications

Caffeine is widely consumed throughout the world and appears to indirectly facilitate learning and memory through effects on attention and motivation. Animal work indicates that post-training caffeine administration augments inhibitory avoidance memory, spatial memory, and object memory. In humans, post-training caffeine administration enhances the ability to discern between familiar images and new, similar images. However, the effect of post-training caffeine administration on motor memory has not been examined. Therefore, we tested two groups of low caffeine consumers (average weekly consumption ≤500 mg) in a double-blind, placebo-controlled study involving acquisition of a continuous isometric visuomotor tracking skill. On Day 1, subjects ...


Cloning And Characterization Of The Escherichia Coli Heptosyltransferase Iii: Exploring Substrate Specificity In Lipopolysaccaride Core Biosynthesis, Jagadesh Mudapaka, Erika A. Taylor 2015 Wesleyan University

Cloning And Characterization Of The Escherichia Coli Heptosyltransferase Iii: Exploring Substrate Specificity In Lipopolysaccaride Core Biosynthesis, Jagadesh Mudapaka, Erika A. Taylor

Erika A. Taylor, Ph.D.

Bacterial lipopolysaccharide (LPS) molecules are an important cell surface component that enables adhesion to surfaces and cell motility, amongst other functions. In Escherichia coli, there are multiple Heptosyltransferase enzymes involved in the biosynthesis of the core region of LPS. Here we describe the first ever cloning, expression, purification and characterization of Heptosyltransferase III (HepIII) from E. coli, which catalyzes the addition of an l-glycero-d-manno-heptose (Hep) residue to the growing LPS core via an α(1→7) bond. Inspired by results from our lab on the E. coli HepI, we assessed the catalytic efficiency with phospho-Hep2-Kdo2-Lipid A (PH2K2LA) and two deacylated ...


Neural Correlates Of Post-Conventional Moral Reasoning: A Voxel-Based Morphometry Study, Kristin Prehn, Marc Korczykowski, Hengyi Rao, Zhuo Fang, John A. Detre, Diana C. Robertson 2015 University of Pennsylvania

Neural Correlates Of Post-Conventional Moral Reasoning: A Voxel-Based Morphometry Study, Kristin Prehn, Marc Korczykowski, Hengyi Rao, Zhuo Fang, John A. Detre, Diana C. Robertson

Neuroethics Publications

Going back to Kohlberg, moral development research affirms that people progress through different stages of moral reasoning as cognitive abilities mature. Individuals at a lower level of moral reasoning judge moral issues mainly based on self-interest (personal interests schema) or based on adherence to laws and rules (maintaining norms schema), whereas individuals at the post-conventional level judge moral issues based on deeper principles and shared ideals. However, the extent to which moral development is reflected in structural brain architecture remains unknown. To investigate this question, we used voxel-based morphometry and examined the brain structure in a sample of 67 Master ...


Robotic Joint Replacement Surgery: Does Technology Improve Outcomes, Chelsea Hill, Reem El-Bash, Leslie Johnson, Alberto Coustasse 2015 Marshall University

Robotic Joint Replacement Surgery: Does Technology Improve Outcomes, Chelsea Hill, Reem El-Bash, Leslie Johnson, Alberto Coustasse

Management Faculty Research

Introduction: Osteoarthritis is a common disease that leads patients to seek Total Joint Replacement (TJR). Component misalignments leads to failure of TJR. Computer navigation enhances the precision of component alignment, but the addition of robotic guidance, can boost TJR to a higher level of accuracy.

Methodology: This literature reviewed 29 English language peer reviewed articles from 2002 – 2013 and one website. A conceptual framework was adapted to explain benefits and barriers of adoption of robotic TJR.

Results: A total of ten studies were reviewed with focus on more precise alignment, outcomes, length of stay, and costs. Cost to obtain robotic ...


Beliefs About Hospice Care Among Helping Professionals, Teresa Y. Phinazee 2015 California State University - San Bernardino

Beliefs About Hospice Care Among Helping Professionals, Teresa Y. Phinazee

Electronic Theses, Projects, and Dissertations

ABSTRACT

Centered on interviews with 13 hospice care professionals from two large hospice organizations in Southern California, this thesis project examines the challenges that arise in hospice work. Hospice’s delivery of end-of-life care is becoming even more significant as the population lives longer. According to the National Institute on Aging (2014), the face of aging in the United States is changing dramatically. This examination discloses some of the challenges that hospice workers face in a continuously changing health care system, while trying to provide extraordinary service to the terminally ill.

Hospice regards dying as a conventional progression, and neither ...


Parp Inhibitor : Abrogation Of Chromosomal Radial-Induced Mitotic Cell Death And Induction Of Multipolar Division Via Loss Of Centrosome Integrity, Nichole M. Owen 2015 Oregon Health & Science University

Parp Inhibitor : Abrogation Of Chromosomal Radial-Induced Mitotic Cell Death And Induction Of Multipolar Division Via Loss Of Centrosome Integrity, Nichole M. Owen

Scholar Archive

Fanconi anemia (FA) and Bloom syndrome (BS) are disorders defined by the genome instability that leads to chromosomal abnormalities known as radials. This instability is thought to be a large factor contributing to increased predisposition to cancer seen in these patients. However, the exquisite sensitivity of these cells to most DNA damaging agents limits the available chemotherapeutics that can be tolerated. Thus it is imperative that new chemotherapeutic agents be identified, and that new drugs are studied thoroughly to determine if they are safe specifically for these patients. The information presented here is a collection of manuscripts pertaining to chromosomal ...


A Role For Mpdz In Ethanol Withdrawal But Not Binge-Like Ethanol Drinking, Lauren C. Kruse 2015 Oregon Health & Science University

A Role For Mpdz In Ethanol Withdrawal But Not Binge-Like Ethanol Drinking, Lauren C. Kruse

Scholar Archive

Alcoholism is a debilitating disease, influenced by both biological (genetic) and environment factors. Unfortunately, the genetic determinants of risk remain largely unknown, hindering effective prevention and treatment of dependent individuals. Recent quantitative trait mapping studies have identified the Mpdz gene, which encodes the multiple Post-synaptic density-95, Discs Large, Zona Occludens protein 1 MUPP1, in predisposition to ethanol withdrawal (EWD) in mice. The aim of my dissertation was to assess the caudolateral substantia nigra pars reticulata (clSNr) as a region through which Mpdz affects EWD, and assess the potential role of the Mpdz gene in predisposition to binge-like ethanol drinking. Further ...


Serum Vitamin D Status Is Associated With The Presence But Not The Severity Of Primary Open Angle Glaucoma., Aurélien Goncalves, Dan Milea, Philippe Gohier, Ghislaine Jallet, Stéphanie Leruez, Mani Baskaran, Tin Aung, Cédric Annweiler 2015 Western University

Serum Vitamin D Status Is Associated With The Presence But Not The Severity Of Primary Open Angle Glaucoma., Aurélien Goncalves, Dan Milea, Philippe Gohier, Ghislaine Jallet, Stéphanie Leruez, Mani Baskaran, Tin Aung, Cédric Annweiler

Medical Biophysics Publications

OBJECTIVES: Vitamin D is involved in visual health and function. Our objective was to determine whether age-related vitamin D insufficiency was associated with the presence and the severity of primary open angle glaucoma (POAG) in a case-control study of older adults.

STUDY DESIGN: Case-control study.

MAIN OUTCOME MEASURES: One hundred fifty cases diagnosed with moderate-to-severe POAG (mean, 75.1±8.5 years; 42.0% female) and 164 healthy controls (mean, 73.0±7.9 years; 59.8% female) were included. POAG diagnosis was based on classical diagnostic criteria of optic nerve cupping and/or RNFL thinning, measured with optical coherence ...


Granulocyte Colony-Stimulating Factor: Its Role In Gut-Homing Macrophage Generation And Colitis, And Production By Probiotics, Shahab Meshkibaf 2015 The University of Western Ontario

Granulocyte Colony-Stimulating Factor: Its Role In Gut-Homing Macrophage Generation And Colitis, And Production By Probiotics, Shahab Meshkibaf

University of Western Ontario - Electronic Thesis and Dissertation Repository

The pleiotropic cytokine granulocyte-colony stimulatory factor (G-CSF) is mainly required for the generation of neutrophils, but its role in macrophage generation has also been reported. In addition, G-CSF is effective for the down-regulation of inflammatory cytokines and ameliorating gut disorders, such as colitis. However, the G-CSF function in macrophage generation and gut immunity remains unclear. The first focus of this thesis was to assess the role of G-CSF in macrophage generation and its contribution to gut immunity. G-CSF was found to promote the generation of Gr-1high/F4/80+ macrophages in macrophage (M)-CSF-treated bone marrow cells, most likely through suppressing ...


Ventilation Heterogeneity In Ex-Smokers Without Airflow Limitation., Damien Pike, Miranda Kirby, Fumin Guo, David G McCormack, Grace Parraga 2015 Western University

Ventilation Heterogeneity In Ex-Smokers Without Airflow Limitation., Damien Pike, Miranda Kirby, Fumin Guo, David G Mccormack, Grace Parraga

Medical Biophysics Publications

RATIONALE AND OBJECTIVES: Hyperpolarized (3)He magnetic resonance imaging (MRI) ventilation abnormalities are visible in ex-smokers without airflow limitation, but the clinical relevance of this is not well-understood. Our objective was to phenotype healthy ex-smokers with normal and abnormally elevated ventilation defect percent (VDP).

MATERIALS AND METHODS: Sixty ex-smokers without airflow limitation provided written informed consent to (3)He MRI, computed tomography (CT), and pulmonary function tests in a single visit. (3)He MRI VDP and apparent diffusion coefficients (ADCs) were measured for whole-lung and each lung lobe as were CT measurements of emphysema (relative area [RA] with attenuation ≤-950 ...


Novel Advances In Alzheimer's Disease, Jacob P. Naumann 2015 Cleveland State University

Novel Advances In Alzheimer's Disease, Jacob P. Naumann

The Downtown Review

Alzheimer’s disease, the most common form of dementia in adults, is a progressive degenerative neurological disease that affects memory, cognition, and behavior. Dr. Alois Alzheimer discovered and diagnosed the irreversible disease in 1906 after documenting the famous case of Auguste Deter.1 Since the discovery of the disease, numerous advances have made it possible to not only better understand the causal factors, but also to improve the medical diagnosis and preventative measures that healthcare providers can implement. For the first time since 1984, the National Institute on Aging (NIAA) and the Alzheimer’s Association (AA) proposed and published new ...


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