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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

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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 ...


Compassionate Use Of Experimental Therapies: Who Should Decide?, Patricia J. Zettler 2015 Georgia State University College of Law

Compassionate Use Of Experimental Therapies: Who Should Decide?, Patricia J. Zettler

Faculty Publications By Year

In addition to being an example of unsubstantiated hype about regenerative medicine, the controversy around the Italy-based Stamina Foundation's unproven stem cell therapy represents another chapter in a continuing debate about how to balance patients' requests for early access to experimental medicines with requirements for demonstrating safety and effectiveness. Compassionate use of the Stamina therapy arguably should not have been permitted under Italy's laws, but public pressure was intense and judges ultimately granted access. One lesson from these events is that expert regulatory agencies may be the institutions most competent to make compassionate use decisions and that policies ...


Contribution Of The Dorsolateral Prefrontal Cortex To Attentional And Mnemonic Processes In Visual Search, Brandon Belbeck 2015 The University of Western Ontario

Contribution Of The Dorsolateral Prefrontal Cortex To Attentional And Mnemonic Processes In Visual Search, Brandon Belbeck

Electronic Thesis and Dissertation Repository

A key characteristic of selective visual attention is that it may be deployed on the basis of our knowledge or goals of the task at hand. Here, we used cryogenic deactivation to investigate the contribution of the dorsolateral PFC to cognitive flexibility and working memory, as well as their relation to the deployment of attention. Macaque monkeys performed visual search tasks requiring them to foveate a target in an array of stimuli. These included a feature search, a constant-target conjunction search, a variable-target search and variable-target with delay search task, with each being more cognitively demanding than the last. Bilateral ...


Disruption Of White Matter Integrity In Adult Survivors Of Childhood Brain Tumors: Correlates With Long-Term Intellectual Outcomes, Tricia Z. King, Liya Wang, Hui Mao 2015 Georgia State University

Disruption Of White Matter Integrity In Adult Survivors Of Childhood Brain Tumors: Correlates With Long-Term Intellectual Outcomes, Tricia Z. King, Liya Wang, Hui Mao

Psychology Faculty Publications

Background

Although chemotherapy and radiation treatment have contributed to increased survivorship, treatment-induced brain injury has been a concern when examining long-term intellectual outcomes of survivors. Specifically, disruption of brain white matter integrity and its relationship to intellectual outcomes in adult survivors of childhood brain tumors needs to be better understood.

Methods

Fifty-four participants underwent diffusion tensor imaging in addition to structural MRI and an intelligence test (IQ). Voxel-wise group comparisons of fractional anisotropy calculated from DTI data were performed using Tract Based Spatial Statistics (TBSS) on 27 survivors (14 treated with radiation with and without chemotherapy and 13 treated without ...


Dualism And Doctrine, Dov Fox, Alex Stein 2015 University of San Diego Law School

Dualism And Doctrine, Dov Fox, Alex Stein

Indiana Law Journal

What kinds of harm among those that tortfeasors inflict are worthy of compensation? Which forms of self-incriminating evidence are privileged against government compulsion? What sorts of facts constitute a criminal defendant’s intent? Existing doctrine pins the answer to all of these questions on whether the injury, facts, or evidence at stake are “mental” or “physical.” The assumption that operations of the mind are meaningfully distinct from those of the body animates fundamental rules in our law.

A tort victim cannot recover for mental harm on its own because the law presumes that he is able to unfeel any suffering ...


Higher Hepatic Mir-29 Expression In Undernourished Male Rats During The Postnatal Period Targets The Long-Term Repression Of Insulin-Like Growth Factor 1, Gurjeev Sohi, Andrew Revesz, Julie Ramkumar, Daniel B. Hardy 2015 Western University

Higher Hepatic Mir-29 Expression In Undernourished Male Rats During The Postnatal Period Targets The Long-Term Repression Of Insulin-Like Growth Factor 1, Gurjeev Sohi, Andrew Revesz, Julie Ramkumar, Daniel B. Hardy

Physiology and Pharmacology Publications

A nutritional mismatch in postnatal life of low birth weight offspring increases the risk of developing the metabolic syndrome. Moreover, this is associated with decreased hepatic insulin-like growth factor 1 (Igf1) expression, leading to impaired growth and metabolism. Previously we have demonstrated that the timing of nutritional restoration in perinatal life can differentially programhepatic gene expression. While micro RNAs also play an important role in silencing gene expression, to date, the impact of a nutritional mismatch in neonatal life on their long-term expression has not been evaluated. Given the complementarity of miR-29 to the 3i-UTR of Igf1, we examined how ...


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 ...


Caspase-8 Scaffolding Function And Mlkl Regulate Nlrp3 Inflammasome Activation Downstream Of Tlr3., Seokwon Kang, Teresa Fernandes-Alnemri, Corey Rogers, Lindsey Mayes, Ying Wang, Christopher Dillon, Linda Roback, William Kaiser, Andrew Oberst, Junji Sagara, Katherine A Fitzgerald, Douglas R Green, Jianke Zhang, Edward S Mocarski, Emad S Alnemri 2015 Department of Biochemistry and Molecular Biology, Kimmel Cancer Center, Thomas Jefferson University

Caspase-8 Scaffolding Function And Mlkl Regulate Nlrp3 Inflammasome Activation Downstream Of Tlr3., Seokwon Kang, Teresa Fernandes-Alnemri, Corey Rogers, Lindsey Mayes, Ying Wang, Christopher Dillon, Linda Roback, William Kaiser, Andrew Oberst, Junji Sagara, Katherine A Fitzgerald, Douglas R Green, Jianke Zhang, Edward S Mocarski, Emad S Alnemri

Department of Biochemistry and Molecular Biology Faculty Papers

TLR2 promotes NLRP3 inflammasome activation via an early MyD88-IRAK1-dependent pathway that provides a priming signal (signal 1) necessary for activation of the inflammasome by a second potassium-depleting signal (signal 2). Here we show that TLR3 binding to dsRNA promotes post-translational inflammasome activation through intermediate and late TRIF/RIPK1/FADD-dependent pathways. Both pathways require the scaffolding but not the catalytic function of caspase-8 or RIPK1. Only the late pathway requires kinase competent RIPK3 and MLKL function. Mechanistically, FADD/caspase-8 scaffolding function provides a post-translational signal 1 in the intermediate pathway, whereas in the late pathway it helps the oligomerization of RIPK3 ...


Antibacterial Characterization Of Novel Synthetic Thiazole Compounds Against Methicillin-Resistant Staphylococcus Pseudintermedius, Haroon Mohammad, P.V. N. Reddy, Dennis Monteleone, Abdelrahman S. Mayhoub, Mark S. Cushman, G. Kenitra Hammac, Mohamed N. Seleem 2015 Purdue University

Antibacterial Characterization Of Novel Synthetic Thiazole Compounds Against Methicillin-Resistant Staphylococcus Pseudintermedius, Haroon Mohammad, P.V. N. Reddy, Dennis Monteleone, Abdelrahman S. Mayhoub, Mark S. Cushman, G. Kenitra Hammac, Mohamed N. Seleem

Department of Comparative Pathobiology Faculty Publications

Staphylococcus pseudintermedius is a commensal organism of companion animals that is a significant source of opportunistic infections in dogs. With the emergence of clinical isolates of S. pseudintermedius (chiefly methicillin-resistant S. pseudintermedius (MRSP)) exhibiting increased resistance to nearly all antibiotic classes, new antimicrobials and therapeutic strategies are urgently needed. Thiazole compounds have been previously shown to possess potent antibacterial activity against multidrug-resistant strains of Staphylococcus aureus of human and animal concern. Given the genetic similarity between S. aureus and S. pseudintermedius, this study explores the potential use of thiazole compounds as novel antibacterial agents against methicillin-sensitive S. pseudintermedius (MSSP) and ...


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).


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 ...


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 ...


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