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https://www.readbyqxmd.com/read/27798153/t-cell-independent-mechanisms-associated-with-neutrophil-extracellular-trap-formation-and-selective-autophagy-in-il-17a-mediated-epidermal-hyperplasia
#1
Erika Suzuki, Emanual Maverakis, Ritu Sarin, Laura Bouchareychas, Vijay K Kuchroo, Frank O Nestle, Iannis E Adamopoulos
IL-17A has been strongly associated with epidermal hyperplasia in many cutaneous disorders. However, because IL-17A is mainly produced by αβ and γδT cells in response to IL-23, the role of T cells and IL-23 has overshadowed any IL-17A-independent actions. In this article, we report that IL-17A gene transfer induces epidermal hyperplasia in Il23r(-/-)Rag1(-/-)- and Tcrδ-deficient mice, which can be prevented by neutrophil depletion. Moreover, adoptive transfer of CD11b(+)Gr-1(hi) cells, after IL-17A gene transfer, was sufficient to phenocopy the disease...
December 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27747458/acute-on-chronic-liver-failure
#2
Shiv Kumar Sarin, Ashok Choudhury
Acute-on-chronic liver failure (ACLF) is a distinct entity that differs from acute liver failure and decompensated cirrhosis in timing, presence of treatable acute precipitant, and course of disease, with a potential for self-recovery. The core concept is acute deterioration of existing liver function in a patient of chronic liver disease with or without cirrhosis in response to an acute insult. The insult should be a hepatic one and presentation in the form of liver failure (jaundice, encephalopathy, coagulopathy, ascites) with or without extrahepatic organ failure in a defined time frame...
December 2016: Current Gastroenterology Reports
https://www.readbyqxmd.com/read/27717426/the-racial-paradox-in-multiarterial-conduit-utilization-for-coronary-artery-bypass-grafting
#3
W Brent Keeling, Jose Binongo, Michael E Halkos, Bradley G Leshnower, Duc Q Nguyen, Edward P Chen, Eric L Sarin, Jeffrey S Miller, Steven Macheers, Omar M Lattouf, Robert A Guyton, Vinod H Thourani
BACKGROUND: It has been established that outcomes for black patients undergoing coronary artery bypass graft surgery (CABG) are inferior to those of their white counterparts. The purpose of this study was to determine (1) whether rates of multiarterial grafting are different among black patients and white patients, and (2) whether racial differences exist in postoperative outcomes after accounting for grafting strategy. METHODS: A retrospective review of black patients (n = 2,810) and white patients (n = 13,569) who underwent isolated, primary CABG from January 2002 to June 2014 at a US academic institution was performed...
October 4, 2016: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/27705071/sarin-gb-o-isopropyl-methylphosphonofluoridate-neurotoxicity-critical-review
#4
Mohamed B Abou-Donia, Briana Siracuse, Natasha Gupta, Ashly Sobel Sokol
Sarin (GB, O-isopropyl methylphosphonofluoridate) is a potent organophosphorus (OP) nerve agent that inhibits acetylcholinesterase (AChE) irreversibly. The subsequent build-up of acetylcholine (ACh) in the central nervous system (CNS) provokes seizures and, at sufficient doses, centrally-mediated respiratory arrest. Accumulation of ACh at peripheral autonomic synapses leads to peripheral signs of intoxication and overstimulation of the muscarinic and nicotinic receptors, which is described as "cholinergic crisis" (i...
November 2016: Critical Reviews in Toxicology
https://www.readbyqxmd.com/read/27681292/corrigendum-meta-analysis-of-375-000-individuals-identifies-38-susceptibility-loci-for-migraine
#5
Padhraig Gormley, Verneri Anttila, Bendik S Winsvold, Priit Palta, Tonu Esko, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Terho Lehtimäki, Antti-Pekka Sarin, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Paul M Ridker, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Jouke-Jan Hottenga, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Reedik Mägi, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea E Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G Eriksson, Veikko Salomaa, Kauko Heikkilä, Elizabeth Loehrer, Andre G Uitterlinden, Albert Hofman, Cornelia M van Duijn, Lynn Cherkas, Linda M Pedersen, Audun Stubhaug, Christopher S Nielsen, Minna Männikkö, Evelin Mihailov, Lili Milani, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J Aromaa, Olli Raitakari, M Arfan Ikram, Tim Spector, Marjo-Riitta Järvelin, Andres Metspalu, Christian Kubisch, David P Strachan, Michel D Ferrari, Andrea C Belin, Martin Dichgans, Maija Wessman, Arn M J M van den Maagdenberg, John-Anker Zwart, Dorret I Boomsma, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J Daly, Benjamin M Neale, Jes Olesen, Daniel I Chasman, Dale R Nyholt, Aarno Palotie
No abstract text is available yet for this article.
September 28, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27663781/current-and-former-smokers-use-of-electronic-cigarettes-for-quitting-smoking-an-exploratory-study-of-adolescents-and-young-adults
#6
Deepa R Camenga, Grace Kong, Dana A Cavallo, Suchitra Krishnan-Sarin
BACKGROUND: This exploratory study examines the prevalence and predictors of current and former smokers' use of electronic (e-) cigarettes for smoking cessation among a sample of adolescent and young adult established smokers. METHODS: We conducted school-wide surveys in two middle (n = 1166) and four high schools (n = 3614) in fall 2013 and one public college (n = 625) in spring 2014. We analyzed data from 189 established smokers (reported smoking 100 cigarettes in their lifetime) who also reported ever-use of e-cigarettes (50...
September 23, 2016: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
https://www.readbyqxmd.com/read/27639501/blaptica-dubia-as-sentinels-for-exposure-to-chemical-warfare-agents-a-pilot-study
#7
Franz Worek, Thomas Seeger, Katharina Neumaier, Timo Wille, Horst Thiermann
The increased interest of terrorist groups in toxic chemicals and chemical warfare agents presents a continuing threat to our societies. Early warning and detection is a key component for effective countermeasures against such deadly agents. Presently available and near term solutions have a number of major drawbacks, e.g. lack of automated, remote warning and detection of primarily low volatile chemical warfare agents. An alternative approach is the use of animals as sentinels for exposure to toxic chemicals...
September 14, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27639427/propagation-of-damage-in-the-rat-brain-following-sarin-exposure-differential-progression-of-early-processes
#8
Shlomi Lazar, Inbal Egoz, Rachel Brandeis, Shira Chapman, Eugenia Bloch-Shilderman, Ettie Grauer
Sarin is an irreversible organophosphate cholinesterase inhibitor and a highly toxic warfare agent. Following the overt, dose-dependent signs (e.g. tremor, hyper secretion, seizures, respiratory depression and eventually death), brain damage is often reported. The goal of the present study was to characterize the early histopathological and biochemical events leading to this damage. Rats were exposed to 1LD50 of sarin (80μg/kg, i.m.). Brains were removed at 1, 2, 6, 24 and 48h and processed for analysis. Results showed that TSPO (translocator protein) mRNA increased at 6h post exposure while TSPO receptor density increased only at 24h...
November 1, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27592270/nicotine-concentration-of-e-cigarettes-used-by-adolescents
#9
Meghan E Morean, Grace Kong, Dana A Cavallo, Deepa R Camenga, Suchitra Krishnan-Sarin
OBJECTIVE: E-cigarettes are popular among youth, but little is known about the nicotine concentrations of e-liquids used by adolescents. MATERIALS AND METHOD: In Spring, 2014, we conducted cross-sectional surveys in four Connecticut high schools and two middle schools. Among past-30-day e-cigarette users (n=513, 45% female, mean age 15.9 [SD=1.4]), we examined what nicotine concentration adolescents typically used in their e-cigarettes (range 0-30mg/mL and "I don't know")...
October 1, 2016: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/27582056/sar-study-to-find-optimal-cholinesterase-reactivator-against-organophosphorous-nerve-agents-and-pesticides
#10
Lukas Gorecki, Jan Korabecny, Kamil Musilek, David Malinak, Eugenie Nepovimova, Rafael Dolezal, Daniel Jun, Ondrej Soukup, Kamil Kuca
Irreversible inhibition of acetylcholinesterase (AChE) by organophosphates leads to many failures in living organism and ultimately in death. Organophosphorus compounds developed as nerve agents such as tabun, sarin, soman, VX and others belong to the most toxic chemical warfare agents and are one of the biggest threats to the modern civilization. Moreover, misuse of nerve agents together with organophosphorus pesticides (e.g. malathion, paraoxon, chlorpyrifos, etc.) which are annually implicated in millions of intoxications and hundreds of thousand deaths reminds us of insufficient protection against these compounds...
August 31, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27571779/assessment-of-the-regulatory-methods-for-the-comparison-of-highly-variable-dissolution-profiles
#11
Victor Mangas-Sanjuan, Sarin Colon-Useche, Isabel Gonzalez-Alvarez, Marival Bermejo, Alfredo Garcia-Arieta
The objective is to compare the performance of dissolution-profile comparison methods when f 2 is inadequate due to high variability. The 90% confidence region of the Mahalanobis distance and the 90% bootstrap confidence interval (CI) of the f 2 similarity factor (f 2-bootstrap) were explored. A modification of the Mahalanobis distance (new D-Mahalanobis) in which those points >85% were not taken into account for calculation was also used. A population kinetic approach in NONMEM was used to simulate dissolution profiles with the first-order or Weibull kinetic models...
August 29, 2016: AAPS Journal
https://www.readbyqxmd.com/read/27551784/naturally-occurring-genetic-variants-of-human-acetylcholinesterase-and-butyrylcholinesterase-and-their-potential-impact-on-the-risk-of-toxicity-from-cholinesterase-inhibitors
#12
Oksana Lockridge, Robert B Norgren, Rudolph C Johnson, Thomas A Blake
Acetylcholinesterase (AChE) is the physiologically important target for organophosphorus toxicants (OP) including nerve agents and pesticides. Butyrylcholinesterase (BChE) in blood serves as a bioscavenger that protects AChE in nerve synapses from inhibition by OP. Mass spectrometry methods can detect exposure to OP by measuring adducts on the active site serine of plasma BChE. Genetic variants of human AChE and BChE do exist, but loss of function mutations have been identified only in the BCHE gene. The most common AChE variant, His353Asn (H322N), also known as the Yt blood group antigen, has normal AChE activity...
September 19, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27503349/reasons-for-trying-e-cigarettes-and-risk-of-continued-use
#13
Krysten W Bold, Grace Kong, Dana A Cavallo, Deepa R Camenga, Suchitra Krishnan-Sarin
BACKGROUND: Longitudinal research is needed to identify predictors of continued electronic cigarette (e-cigarette) use among youth. We expected that certain reasons for first trying e-cigarettes would predict continued use over time (eg, good flavors, friends use), whereas other reasons would not predict continued use (eg, curiosity). METHODS: Longitudinal surveys from middle and high school students from fall 2013 (wave 1) and spring 2014 (wave 2) were used to examine reasons for trying e-cigarettes as predictors of continued e-cigarette use over time...
September 2016: Pediatrics
https://www.readbyqxmd.com/read/27403844/engineering-bacteria-to-catabolize-the-carbonaceous-component-of-sarin-teaching-e-coli-to-eat-isopropanol
#14
Margaret E Brown, Aindrila Mukhopadhyay, Jay D Keasling
We report an engineered strain of Escherichia coli that catabolizes the carbonaceous component of the extremely toxic chemical warfare agent sarin. Enzymatic decomposition of sarin generates isopropanol waste that, with this engineered strain, is then transformed into acetyl-CoA by enzymatic conversion, with a key reaction performed by the acetone carboxylase complex (ACX). We engineered the heterologous expression of the ACX complex from Xanthobacter autotrophicus PY2 to match the naturally occurring subunit stoichiometry and purified the recombinant complex from E...
July 12, 2016: ACS Synthetic Biology
https://www.readbyqxmd.com/read/27387540/efficacy-of-novel-phenoxyalkyl-pyridinium-oximes-as-brain-penetrating-reactivators-of-cholinesterase-inhibited-by-surrogates-of-sarin-and-vx
#15
Janice E Chambers, Howard W Chambers, Kristen E Funck, Edward C Meek, Ronald B Pringle, Matthew K Ross
Pyridinium oximes are strong nucleophiles and many are effective reactivators of organophosphate-inhibited cholinesterase (ChE). However, the current oxime reactivators are ineffective at crossing the blood-brain barrier and reactivating brain ChE in the intact organism. Our laboratories have developed a series of substituted phenoxyalkyl pyridinium oximes (US patent 9,227,937 B2) with the goal of identifying reactivators effective in crossing the blood-brain barrier. The first 35 of the series were found to have similar in vitro efficacy as reactivators of ChE inhibited by a sarin surrogate (phthalimidyl isopropyl methylphosphonate, PIMP) or a VX surrogate (nitrophenyl ethyl methylphosphonate, NEMP) in bovine brain preparations as previously observed in rat brain preparations...
July 4, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27371808/creation-of-a-protective-pulmonary-bioshield-against-inhaled-organophosphates-using-an-aerosolized-bioscavenger
#16
Yvonne J Rosenberg, James B Fink
In addition to the global use of organophosphate (OP) pesticides for agriculture, OP nerve agents and pesticides have been employed on battlefields and by terrorists (e.g., a recent sarin attack in Syria). These occurrences highlight the need for an effective countermeasure against OP exposure. Human butyrylcholinesterase (HuBChE) is a leading candidate, but injection of the high doses required for protection present pharmacokinetic challenges. An aerosolized recombinant form (aer-rHuBChE) that can neutralize inhaled OPs at the portal of entry has been assessed for its efficacy in protecting macaques against respiratory toxicity following inhalation exposure to the pesticide paraoxon (aer-Px)...
June 2016: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/27344117/preference-for-gain-or-loss-framed-electronic-cigarette-prevention-messages
#17
Grace Kong, Dana A Cavallo, Deepa R Camenga, Meghan E Morean, Suchitra Krishnan-Sarin
BACKGROUND: Effective electronic cigarette (e-cigarette) prevention messages are needed to combat the rising popularity/uptake of e-cigarettes among youth. We examined preferences for e-cigarette prevention messages that either emphasized gains (e.g., You save money by not using e-cigarettes) or losses (e.g., You spend money by using e-cigarettes) among adolescents and young adults. METHODS: Using surveys in two middle schools, four high schools, and one college in CT (N=5405), we assessed students' preferences for gain- or loss-framed e-cigarette prevention messages related to four themes: financial cost, health risks, addiction potential, and social labeling as a smoker...
November 2016: Addictive Behaviors
https://www.readbyqxmd.com/read/27340741/basosquamous-carcinoma-controversy-advances-and-future-directions
#18
Caroline Z Tan, Kerri E Rieger, Kavita Y Sarin
BACKGROUND: Basosquamous carcinoma is a rare cutaneous neoplasm that has caused considerable controversy as to its classification, pathogenesis, and management. OBJECTIVE: To review and summarize current literature on the definition, pathogenesis, incidence, and management of basosquamous carcinoma. MATERIALS AND METHODS: Through December 2015, an electronic search of the Pubmed database was performed using combinations of basosquamous carcinoma and metatypical basal cell carcinoma as search terms...
June 21, 2016: Dermatologic Surgery: Official Publication for American Society for Dermatologic Surgery [et Al.]
https://www.readbyqxmd.com/read/27330028/autophagy-linked-fyve-containing-protein-wdfy3-interacts-with-traf6-and-modulates-rankl-induced-osteoclastogenesis
#19
Dennis J Wu, Ran Gu, Ritu Sarin, Regina Zavodovskaya, Chia-Pei Chen, Blaine A Christiansen, Iannis E Adamopoulos
Recently, autophagy-related proteins were shown to regulate osteoclast mediated bone resorption, a critical process in autoimmune diseases such as rheumatoid arthritis. However, the role of autophagy-linked FYVE containing protein, WDFY3, in osteoclast biology remains elusive. WDFY3 is a master regulator in selective autophagy for clearing ubiquitinated protein aggregates and has been linked with rheumatoid arthritis. Herein, we used a series of WDFY3 transgenic mice (Wdfy3(lacZ) and Wdfy3(loxP)) to investigate the function of WDFY3 in osteoclast development and function...
September 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27322543/meta-analysis-of-375-000-individuals-identifies-38-susceptibility-loci-for-migraine
#20
Padhraig Gormley, Verneri Anttila, Bendik S Winsvold, Priit Palta, Tonu Esko, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Terho Lehtimäki, Antti-Pekka Sarin, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Paul M Ridker, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Jouke-Jan Hottenga, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Reedik Mägi, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea E Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G Eriksson, Veikko Salomaa, Kauko Heikkilä, Elizabeth Loehrer, Andre G Uitterlinden, Albert Hofman, Cornelia M van Duijn, Lynn Cherkas, Linda M Pedersen, Audun Stubhaug, Christopher S Nielsen, Minna Männikkö, Evelin Mihailov, Lili Milani, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J Aromaa, Olli Raitakari, M Arfan Ikram, Tim Spector, Marjo-Riitta Järvelin, Andres Metspalu, Christian Kubisch, David P Strachan, Michel D Ferrari, Andrea C Belin, Martin Dichgans, Maija Wessman, Arn M J M van den Maagdenberg, John-Anker Zwart, Dorret I Boomsma, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J Daly, Benjamin M Neale, Jes Olesen, Daniel I Chasman, Dale R Nyholt, Aarno Palotie
Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association (GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we carried out a genetic study of migraine on 59,674 affected subjects and 316,078 controls from 22 GWA studies...
August 2016: Nature Genetics
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