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Glibenclamide for the Treatment of Acute CNS Injury

David Kurland, Cigdem Tosun, Adam Pampori, Jason Karimy, Nicholas Caffes, Volodymyr Gerzanich, J. Simard
2013 Pharmaceuticals  
First introduced into clinical practice in 1969, glibenclamide (US adopted name, glyburide) is known best for its use in the treatment of diabetes mellitus type 2, where it is used to promote the release of insulin by blocking pancreatic K ATP [sulfonylurea receptor 1 (Sur1)-Kir6.2] channels. During the last decade, glibenclamide has received renewed attention due to its pleiotropic protective effects in acute CNS injury. Acting via inhibition of the recently characterized Sur1-Trpm4 channel
more » ... rmerly, the Sur1-regulated NC Ca-ATP channel) and, in some cases, via brain K ATP channels, glibenclamide has been shown to be beneficial in several clinically relevant rodent models of ischemic and hemorrhagic stroke, traumatic brain injury, spinal cord injury, neonatal encephalopathy of prematurity, and metastatic brain tumor. Glibenclamide acts on microvessels to reduce edema formation and secondary hemorrhage, it inhibits necrotic cell death, it exerts potent anti-inflammatory effects and it promotes neurogenesis-all via inhibition of Sur1. Two clinical trials, one in TBI and one in stroke, currently are underway. These recent findings, which implicate Sur1 in a number of acute pathological conditions involving the CNS, present new opportunities to use glibenclamide, a well-known, safe pharmaceutical agent, for medical conditions that heretofore had few or no treatment options. OPEN ACCESS Pharmaceuticals 2013, 6 1288 Keywords: glibenclamide; Sur1-Trpm4 channel; cerebral ischemia; traumatic brain injury; spinal cord injury; encephalopathy of prematurity; metastatic brain tumor
doi:10.3390/ph6101287 pmid:24275850 pmcid:PMC3817601 fatcat:qawqxgq24jesrnierk3nai3q5m

Glibenclamide for the Treatment of Ischemic and Hemorrhagic Stroke

Nicholas Caffes, David Kurland, Volodymyr Gerzanich, J. Simard
2015 International Journal of Molecular Sciences  
Marc Simard, or for this project by Remedy Pharmaceuticals. The authors declare no conflict of interest.  ...  Marc Simard holds a US patent (7, 285,574), A novel non-selective cation channel in neural cells and methods for treating brain swelling. J.  ...  Author Contributions Nicholas Caffes, David B. Kurland, Volodymyr Gerzanich and J. Marc Simard contributed to the conception and design of this review. Nicholas Caffes, David B. Kurland, J.  ... 
doi:10.3390/ijms16034973 pmid:25749474 pmcid:PMC4394459 fatcat:h573a7q3uze25ieulfii25b5si

Paid Family and Childbearing Leave Policies at Top US Medical Schools

Nicholas S. Riano, Eleni Linos, Erin C. Accurso, Dawn Sung, Elizabeth Linos, Julia F. Simard, Christina Mangurian
2018 Journal of the American Medical Association (JAMA)  
doi:10.1001/jama.2017.19519 pmid:29450516 pmcid:PMC5838606 fatcat:ctyrtucrfbclranj6tkbgwxtku

Averting a malaria disaster: will insecticide resistance derail malaria control?

Janet Hemingway, Hilary Ranson, Alan Magill, Jan Kolaczinski, Christen Fornadel, John Gimnig, Maureen Coetzee, Frederic Simard, Dabiré K Roch, Clément Kerah Hinzoumbe, John Pickett, David Schellenberg (+3 others)
2016 The Lancet  
World Malaria Day 2015 highlighted the progress made in the development of new methods of prevention (vaccines and insecticides) and treatment (single dose drugs) of the disease. However, increasing drug and insecticide resistance threatens the successes made with existing methods. Insecticide resistance has decreased the efficacy of the most commonly used insecticide class of pyrethroids. This decreased efficacy has increased mosquito survival, which is a prelude to rising incidence of malaria
more » ... and fatalities. Despite intensive research efforts, new insecticides will not reach the market for at least 5 years. Elimination of malaria is not possible without effective mosquito control. Therefore, to combat the threat of resistance, key stakeholders need to rapidly embrace a multifaceted approach including a reduction in the cost of bringing new resistance Correspondence to:
doi:10.1016/s0140-6736(15)00417-1 pmid:26880124 pmcid:PMC6215693 fatcat:x2pq6rheerganpris25wxiebmu

Protocol for a systematic review of screening tools for fear of recurrent illness in common life-threatening diseases

Jenny Jones, Paul Kane, Rob Polson, Stephen J Leslie, Nicholas J Hulbert-Williams, Sébastien Simard, Gozde Ozakinci, Gill Hubbard
2015 Systematic Reviews  
A myocardial infarction (MI) ('heart attack') can be intensely stressful, and the impact of this event can leave patients with clinically significant post-MI stress symptoms. Untreated stress can make heart disease worse. Few tools are available that screen for specific thoughts or beliefs that can trigger post-MI stress responses. In other life-threatening illnesses, fear of recurrence (FoR) of illness has been identified as a key stressor, and screening tools have been developed to identify
more » ... is. The aim of this review is to identify FoR screening tools used in other common life-threatening diseases that report on the development of the tool, to assess if there are any that can be adapted for use in MI survivors so that those with high levels of FoR can be identified and helped. Methods/Design: The review will evaluate full FoR screening tools and methods of measurement used in common life-threatening disease clinical populations. The Campbell and Cochrane Libraries, Cumulative Index of Nursing and Allied Health Literature (CINAHL), PsycINFO, MEDLINE, Embase, Applied Social Sciences Index and Abstracts (ASSIA), Published International Literature on Traumatic Stress (PILOTS), Social Services Abstracts, Sociological Abstracts, Web of Knowledge, Health and Psychosocial Instruments and SCOPUS databases will be searched for relevant studies published from database inception. Reference lists and published reviews/meta-analyses will also be searched. All titles and abstracts will be screened and relevant full-text versions retrieved by two reviewers, who will then extract all the data. Each will independently review all data extracted by the other. Selected studies will also be assessed by two independent researchers using the COnsensus-based standards for the Selection of health status measurement INstruments (COSMIN) checklist and other quality criteria. This will be done to evaluate the degree to which their measurement properties meet the standards for good methodological quality. Disagreement will be resolved through consensus. Discussion: Untreated post-MI stress has a considerable psychological and physical impact on MI survivors. Therefore, there is a critical need to develop a screening tool to identify fear of recurrent MI so that those affected can be identified and directed to appropriate support interventions. This proposed research will enable a tool to be developed and adapted for use in the MI survivor patient population. Systematic review registration: PROSPERO: CRD42014010500
doi:10.1186/2046-4053-4-10 pmid:26187633 pmcid:PMC4506406 fatcat:j4tav2wqbfaqfnawd7phii242m

NIHTS: the near-infrared high throughput spectrograph for the Discovery Channel Telescope

Edward W. Dunham, Thomas A. Bida, Tomas Chylek, Frank Cornelius, Annika Gustafsson, Nicholas Moskovitz, Henry Roe, Hideki Takami, Christopher J. Evans, Luc Simard
2018 Ground-based and Airborne Instrumentation for Astronomy VII  
NIHTS is a first-generation instrument now in use on Lowell Observatory's Discovery Channel Telescope. It is a nearinfrared prism spectrograph of the BASS design featuring high throughput and low dispersion that is intended for observations of faint solar system and astrophysical objects over the YJHK spectral range. An unusual feature is its ability to observe simultaneously with the Large Monolithic Imager, an optical CCD camera, by means of a dichroic fold mirror. This is particularly
more » ... e for time-variable targets such as Kuiper Belt Objects, asteroids, exoplanet transits, and brown dwarfs. We describe its design details and performance both in the lab and on the telescope.
doi:10.1117/12.2313948 fatcat:gymwm4w4wbgg7fbulglghfnh3u

Claudins are essential for cell shape changes and convergent extension movements during neural tube closure

Amanda I. Baumholtz, Annie Simard, Evanthia Nikolopoulou, Marcus Oosenbrug, Michelle M. Collins, Anna Piontek, Gerd Krause, Jörg Piontek, Nicholas D.E. Greene, Aimee K. Ryan
2017 Developmental Biology  
A B S T R A C T During neural tube closure, regulated changes at the level of individual cells are translated into large-scale morphogenetic movements to facilitate conversion of the flat neural plate into a closed tube. Throughout this process, the integrity of the neural epithelium is maintained via cell interactions through intercellular junctions, including apical tight junctions. Members of the claudin family of tight junction proteins regulate paracellular permeability, apical-basal cell
more » ... olarity and link the tight junction to the actin cytoskeleton. Here, we show that claudins are essential for neural tube closure: the simultaneous removal of Cldn3, −4 and −8 from tight junctions caused folate-resistant open neural tube defects. Their removal did not affect cell type differentiation, neural ectoderm patterning nor overall apical-basal polarity. However, apical accumulation of Vangl2, RhoA, and pMLC were reduced, and Par3 and Cdc42 were mislocalized at the apical cell surface. Our data showed that claudins act upstream of planar cell polarity and RhoA/ROCK signaling to regulate cell intercalation and actinmyosin contraction, which are required for convergent extension and apical constriction during neural tube closure, respectively.
doi:10.1016/j.ydbio.2017.05.013 pmid:28545845 pmcid:PMC5523803 fatcat:xkibpigqdfabrhu424rb7pz2jy

ULTIMATE: a deployable multiple integral field unit for Subaru

S. C. Ellis, Ross Zhelem, David Brown, Nicholas F. Staszak, Chris Lidman, David M. Nataf, Andrew R. Casey, Pascal Xavier, Andrew Sheinis, Peter Gillingham, Julia Tims, Jon Lawrence (+5 others)
2016 Ground-based and Airborne Instrumentation for Astronomy VI  
ULTIMATE is an instrument concept under development at the AAO, for the Subaru Telescope, which will have the unique combination of ground layer adaptive optics feeding multiple deployable integral field units. This will allow ULTIMATE to probe unexplored parameter space, enabling science cases such as the evolution of galaxies at z ∼ 0.5 to 1.5, and the dark matter content of the inner part of our Galaxy. ULTIMATE will use Starbugs to position between 7 and 13 IFUs over a 14 x 8 arcmin
more » ... -view, provided by a new wide-field corrector. All Starbugs can be positioned simultaneously, to an accuracy of better than 5 milli-arcsec within the typical slew-time of the telescope, allowing for very efficient re-configuration between observations. The IFUs will feed either the near-infrared nuMOIRCS or the visible/ near-infrared PFS spectrographs, or both. Future possible upgrades include the possibility of purpose built spectrographs and incorporating OH suppression using fibre Bragg gratings. We describe the science case and resulting design requirements, the baseline instrument concept, and the expected performance of the instrument. Downloaded From: on 02/02/2017 Terms of Use: Proc. of SPIE Vol. 9908 99081Q-2 Downloaded From: on 02/02/2017 Terms of Use: Proc. of SPIE Vol. 9908 99081Q-3 Downloaded From: on 02/02/2017 Terms of Use: Proc. of SPIE Vol. 9908 99081Q-4 Downloaded From: on 02/02/2017 Terms of Use:
doi:10.1117/12.2232107 fatcat:dl5h6pi4wrhanfj2mnpwb3e44u

Pain Trajectories Following Subarachnoid Hemorrhage are Associated with Continued Opioid Use at Outpatient Follow-up

Matthew N. Jaffa, Ruchira M. Jha, Jonathan Elmer, Adam Kardon, Jamie E. Podell, Benjamin E. Zusman, Madeleine C. Smith, J. Marc Simard, Gunjan Y. Parikh, Michael J. Armahizer, Neeraj Badjatia, Nicholas A. Morris
2021 Neurocritical Care  
Subarachnoid hemorrhage (SAH) is characterized by the worst headache of life and associated with long-term opioid use. Discrete pain trajectories predict chronic opioid use following other etiologies of acute pain, but it is unknown whether they exist following SAH. If discrete pain trajectories following SAH exist, it is uncertain whether they predict long-term opioid use. We sought to characterize pain trajectories after SAH and determine whether they are associated with persistent opioid
more » ... We reviewed pain scores from patients admitted to a single tertiary care center for SAH from November 2015 to September 2019. Group-based trajectory modeling identified discrete pain trajectories during hospitalization. We compared outcomes across trajectory groups using χ2 and Kruskal-Wallis tests. Multivariable regression determined whether trajectory group membership was an independent predictor of long-term opioid use, defined as continued use at outpatient follow-up. We identified five discrete pain trajectories among 305 patients. Group 1 remained pain free. Group 2 reported low scores with intermittent spikes and slight increase over time. Group 3 noted increasing pain severity through day 7 with mild improvement until day 14. Group 4 experienced maximum pain with steady decrement over time. Group 5 reported moderate pain with subtle improvement. In multivariable analysis, trajectory groups 3 (odds ratio [OR] 3.5; 95% confidence interval [CI] 1.5-8.3) and 5 (OR 8.0; 95% CI 3.1-21.1), history of depression (OR 3.6; 95% CI 1.3-10.0) and racial/ethnic minority (OR 2.3; 95% CI 1.3-4.1) were associated with continued opioid use at follow-up (median 62 days following admission, interquartile range 48-96). Discrete pain trajectories following SAH exist. Recognition of pain trajectories may help identify those at risk for long-term opioid use.
doi:10.1007/s12028-021-01282-5 pmid:34109554 pmcid:PMC8189709 fatcat:mgyghpssarhkhmjc2rnamiqiby

Phosphorylation of Argonaute proteins affects mRNA binding and is essential for microRNA‐guided gene silencing in vivo

Miguel Quévillon Huberdeau, Daniela M Zeitler, Judith Hauptmann, Astrid Bruckmann, Lucile Fressigné, Johannes Danner, Sandra Piquet, Nicholas Strieder, Julia C Engelmann, Guillaume Jannot, Rainer Deutzmann, Martin J Simard (+1 others)
2017 EMBO Journal  
(Ago) proteins form the core of the RNA-induced silencing complex (RISC) and serve as direct binding modules for small RNAs such as short interfering RNAs (siRNAs) or microRNAs (miRNAs) (Hutvagner & Simard  ...  phosphorylation of serine 992 affects ALG-1 function, we first assessed whether its mutation could affect the biogenesis of miRNA as previously observed in alg-1 mutant animals (Grishok et al, 2001; Bouasker & Simard  ... 
doi:10.15252/embj.201696386 pmid:28645918 pmcid:PMC5510005 fatcat:xhd73zevvvbj7erlmkowz2qt24

Reproducibly sampling SARS-CoV-2 genomes across time, geography, and viral diversity

Evan Bolyen, Matthew R. Dillon, Nicholas A. Bokulich, Jason T. Ladner, Brendan B. Larsen, Crystal M. Hepp, Darrin Lemmer, Jason W. Sahl, Andrew Sanchez, Chris Holdgraf, Chris Sewell, Aakash G. Choudhury (+7 others)
2020 F1000Research  
The COVID-19 pandemic has led to a rapid accumulation of SARS-CoV-2 genomes, enabling genomic epidemiology on local and global scales. Collections of genomes from resources such as GISAID must be subsampled to enable computationally feasible phylogenetic and other analyses. We present genome-sampler, a software package that supports sampling collections of viral genomes across multiple axes including time of genome isolation, location of genome isolation, and viral diversity. The software is
more » ... ular in design so that these or future sampling approaches can be applied independently and combined (or replaced with a random sampling approach) to facilitate custom workflows and benchmarking. genome-sampler is written as a QIIME 2 plugin, ensuring that its application is fully reproducible through QIIME 2's unique retrospective data provenance tracking system. genome-sampler can be installed in a conda environment on macOS or Linux systems. A complete default pipeline is available through a Snakemake workflow, so subsampling can be achieved using a single command. genome-sampler is open source, free for all to use, and available at We hope that this will facilitate SARS-CoV-2 research and support evaluation of viral genome sampling approaches for genomic epidemiology.
doi:10.12688/f1000research.24751.2 fatcat:omqolzfwwzbxhcstakbqis577e

Design evolution of the Giant Magellan Telescope Integral Field Spectrograph, GMTIFS

Robert G. Sharp, Gabe Bloxham, Robert Boz, Dave Bundy, Gaston Gausachs, John Hart, Nicholas Herrald, Jon Nielsen, Ellie O'Brien, Chris Onken, Ian Price, Annino Vaccarella (+8 others)
2018 Ground-based and Airborne Instrumentation for Astronomy VII  
We report the design evolution for the GMT Integral Field Spectrograph, (GMTIFS). To support the range of operating modes -a spectroscopic channel providing integral field spectroscopy with variable spaxel scales, and a parallel imaging channel Nyquist sampling the LTAO corrected field of view -the design process has focused on risk mitigation for the demanding operational tolerances. We summarise results from prototype components, confirming concepts are meeting the necessary specifications.
more » ... going review and simulation of the scientific requirements also leads to new demonstrations of the science that will be made possible with this new generation of high performance AO assisted instrumentation.
doi:10.1117/12.2313010 fatcat:34b3ayzktrd3vohekcmlsmb4fm

High-contrast spectroscopy testbed for Segmented Telescopes: instrument overview and development progress

Nemanja Jovanovic, Jacques-Robert Delorme, Daniel Echeverri, Jason Fucik, Dimitri Mawet, Garreth Ruane, James K. Wallace, Carl Coker, Reed L. Riddle, Maxwell A. Millar-Blanchaer, Nicholas Levraud, Alex Delacroix (+5 others)
2018 Ground-based and Airborne Instrumentation for Astronomy VII  
The High Contrast spectroscopy testbed for Segmented Telescopes (HCST) is being developed at Caltech. It aims at addressing the technology gap for future exoplanet imagers and providing the U.S. community with an academic facility to test components and techniques for high contrast imaging, focusing on segmented apertures proposed for future ground-based (TMT, ELT) and space-based telescopes (HabEx, LUVOIR). We present an overview of the design of the instrument and a detailed look at the
more » ... d build and initial alignment. We offer insights into stumbling blocks encountered along the path and show that the testbed is now operational and open for business. We aim to use the testbed in the future for testing of high contrast imaging techniques and technologies with amongst with thing, a TMT-like pupil.
doi:10.1117/12.2314325 fatcat:75cpgvdidna4zauzlrx7fiyguy

Effect of Luteinizing Hormone Releasing Hormone (LHRH) and [d-Trp6, Des-Gly-NH210]LHRH Ethylamide on α-Subunit and LHβ Messenger Ribonucleic Acid Levels in Rat Anterior Pituitary Cells in Culture

Jean-François Hubert, Jacques Simard, Bernard Gagné, Nicholas Barden, Fernand Labrie
1988 Molecular Endocrinology  
The effect of incubation with LHRH and its agonist [D-Trp 6 , des-Gly-NH 2 10 ]LHRH ethylamide has been measured on the concentrations of mRNAs for the common a-subunit of glycoprotein hormones and 0-LH in rat anterior pituitary cells in primary culture. After incubation, total RNA was analyzed by Northern blot or dot blot hybridization with a-and LH0 32 Plabeled cRNA probes and mRNA levels were quantified by autoradiography. Short-term treatment (4-6 h) of pituitary cells with 100 niu LHRH led
more » ... to a marked stimulation of LH release but no effect was observed on a-subunit or LH/3 mRNA levels. Longer (24-72 h) incubation periods with LHRH led to complete desensitization of the LH response to the neurohormone and induced 2-to 3-fold increases in a-mRNA cell content while LH/3 mRNA levels remained unchanged. Maximal induction of amRNA accumulation was observed with an LHRH concentration as low as 0.1 r»M. Incubation with the LHRH agonist [D-Trp 6 , des-Gly-NH 2 ]LHRH ethylamide for 24-72 h also increased amRNA but did not modify LH-/S mRNA levels. It is concluded that long-term exposure of anterior pituitary cells to LHRH or to an LHRH agonist positively regulates a-subunit gene expression in the absence of change in LH/? mRNA levels. This observation can provide an explanation for the high plasma levels of free a-subunits found in patients treated chronically with LHRH agonists. (Molecular Endocrinology 2: 521-527, 1988) 10 ]LHRH ethylamide on a-subunit and LH/3 mRNA levels in rat anterior pituitary cells in primary culture. RESULTS As illustrated by the autoradiograms of Fig. 1 , pituitary RNA separated by electrophoresis in denaturating agarose gel shows single bands for both the a-subunit and LH/3 mRNAs identified by Northern blotting. Moreover, A preliminary report of a part of these results has been presented at the 69th Annual Meeting of The Endocrine Society, Indianapolis, IN, 1987 (Abstract 467).
doi:10.1210/mend-2-6-521 pmid:2458526 fatcat:aqq55iupgzfnbmabhdvnc6mezu

Harnessing Big Data to Support the Conservation and Rehabilitation of Mangrove Forests Globally

Thomas A. Worthington, Dominic A. Andradi-Brown, Radhika Bhargava, Christina Buelow, Pete Bunting, Clare Duncan, Lola Fatoyinbo, Daniel A. Friess, Liza Goldberg, Lammert Hilarides, David Lagomasino, Emily Landis (+11 others)
2020 One Earth  
Initial analyses used correlative approaches linking mangrove AGB to latitude and climate and showed that AGB increased at lower latitudes and with temperature. 41, 49, 50 More recently, Simard et al  ...  Hutchison et al. 41 Mangrove height and biomass canopy height maps based on a digital elevation model and lidar altimetry 2000 30 m Giri et al. 4 ORNLDAAC/1665 Simard  ... 
doi:10.1016/j.oneear.2020.04.018 fatcat:vycddmjtazbnvocbtsyujze6zm
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