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Michael karin

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https://www.readbyqxmd.com/read/27919628/trivalent-pneumococcal-protein-vaccine-protects-against-experimental-acute-otitis-media-caused-by-streptococcus-pneumoniae-in-an-infant-murine-model
#1
Qingfu Xu, Karin Pryharski, Michael E Pichichero
BACKGROUND: Currently licensed serotype-based pneumococcal vaccines are effective in preventing invasive pneumococcal diseases, but less effective in preventing non-bacteremic pneumonia and acute otitis media (AOM). We previously reported that a trivalent pneumococcal protein recombinant vaccine (PPrV) protected against pneumonia in a murine model. Here we evaluated PPrV protection against AOM in an infant murine model. METHODS: C57BL/6J mice were intramuscularly vaccinated at 1-3weeks of age with monovalent pneumococcal histidine triad protein D (PhtD), or pneumococcal choline binding protein A (PcpA), or detoxified pneumolysin (PlyD1), or trivalent vaccine, and transtympanically challenged at 7-8weeks of age with 1×10(2)CFU of pneumococcal strain BG7322 (6A) or 1×10(4)CFU of pneumococcal nontypeable strain 0702064MEF...
December 2, 2016: Vaccine
https://www.readbyqxmd.com/read/27919243/tumour-stage-distribution-and-survival-of-malignant-melanoma-in-germany-2002-2011
#2
Olaf Schoffer, Stefanie Schülein, Gerlinde Arand, Hans Arnholdt, Dieter Baaske, Ralf C Bargou, Nikolaus Becker, Matthias W Beckmann, Yves Bodack, Beatrix Böhme, Tayfun Bozkurt, Regine Breitsprecher, Andre Buchali, Elke Burger, Ulrike Burger, Klaus Dommisch, Gudrun Elsner, Karin Fernschild, Ulrike Flintzer, Uwe Funke, Michael Gerken, Hubert Göbel, Norbert Grobe, Vera Gumpp, Lucie Heinzerling, Lana Raffaela Kempfer, Alexander Kiani, Monika Klinkhammer-Schalke, Sabine Klöcking, Ute Kreibich, Katrin Knabner, Peter Kuhn, Stine Lutze, Uwe Mäder, Tanja Maisel, Jan Maschke, Martin Middeke, Andreas Neubauer, Antje Niedostatek, Anabelle Opazo-Saez, Christoph Peters, Beatrice Schell, Gerhard Schenkirsch, Harald Schmalenberg, Peter Schmidt, Constanze Schneider, Birgit Schubotz, Anika Seide, Paul Strecker, Sabine Taubenheim, Matthias Wackes, Steffen Weiß, Claudia Welke, Carmen Werner, Christian Wittekind, Jörg Wulff, Heike Zettl, Stefanie J Klug
BACKGROUND: Over the past two decades, there has been a rising trend in malignant melanoma incidence worldwide. In 2008, Germany introduced a nationwide skin cancer screening program starting at age 35. The aims of this study were to analyse the distribution of malignant melanoma tumour stages over time, as well as demographic and regional differences in stage distribution and survival of melanoma patients. METHODS: Pooled data from 61 895 malignant melanoma patients diagnosed between 2002 and 2011 and documented in 28 German population-based and hospital-based clinical cancer registries were analysed using descriptive methods, joinpoint regression, logistic regression and relative survival...
December 5, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27916337/nutritionday-10-years-of-growth
#3
REVIEW
Karin Schindler, Claude Pichard, Isabella Sulz, Dorothee Volkert, Melanie Streicher, Pierre Singer, Olle Ljungqvist, Andre Van Gossum, Peter Bauer, Michael Hiesmayr
BACKGROUND & AIMS: Despite high prevalence at hospital admission, disease related malnutrition (DRM) remains under recognized and undertreated. DRM is associated with increased morbidity, hospital readmission rate, and burden for the healthcare system. The compelling need to increase awareness and knowledge through an international survey has triggered the launch of the nutritionDay (ND) concept. METHODS: ND is a worldwide annual systematic collection and analysis of data in hospital wards, intensive care units and nursing homes...
November 11, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/27913448/targeting-inflammation-in-cancer-prevention-and-therapy
#4
REVIEW
Jelena Todoric, Laura Antonucci, Michael Karin
Inflammation is associated with the development and malignant progression of most cancers. As most of the cell types involved in cancer-associated inflammation are genetically stable and thus are not subjected to rapid emergence of drug resistance, the targeting of inflammation represents an attractive strategy both for cancer prevention and for cancer therapy. Tumor-extrinsic inflammation is caused by many factors, including bacterial and viral infections, autoimmune diseases, obesity, tobacco smoking, asbestos exposure, and excessive alcohol consumption, all of which increase cancer risk and stimulate malignant progression...
December 2016: Cancer Prevention Research
https://www.readbyqxmd.com/read/27911767/phosphatidylinositol-3-kinase-inhibition-restores-ca2-release-defects-and-prolongs-survival-in-myotubularin-deficient-mice
#5
Candice Kutchukian, Mirella Lo Scrudato, Yves Tourneur, Karine Poulard, Alban Vignaud, Christine Berthier, Bruno Allard, Michael W Lawlor, Ana Buj-Bello, Vincent Jacquemond
Mutations in the gene encoding the phosphoinositide 3-phosphatase myotubularin (MTM1) are responsible for a pediatric disease of skeletal muscle named myotubular myopathy (XLMTM). Muscle fibers from MTM1-deficient mice present defects in excitation-contraction (EC) coupling likely responsible for the disease-associated fatal muscle weakness. However, the mechanism leading to EC coupling failure remains unclear. During normal skeletal muscle EC coupling, transverse (t) tubule depolarization triggers sarcoplasmic reticulum (SR) Ca(2+) release through ryanodine receptor channels gated by conformational coupling with the t-tubule voltage-sensing dihydropyridine receptors...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27908689/pcsk9-genetic-variants-and-risk-of-type-2-diabetes-a-mendelian-randomisation-study
#6
Amand F Schmidt, Daniel I Swerdlow, Michael V Holmes, Riyaz S Patel, Zammy Fairhurst-Hunter, Donald M Lyall, Fernando Pires Hartwig, Bernardo Lessa Horta, Elina Hyppönen, Christine Power, Max Moldovan, Erik van Iperen, G Kees Hovingh, Ilja Demuth, Kristina Norman, Elisabeth Steinhagen-Thiessen, Juri Demuth, Lars Bertram, Tian Liu, Stefan Coassin, Johann Willeit, Stefan Kiechl, Karin Willeit, Dan Mason, John Wright, Richard Morris, Goya Wanamethee, Peter Whincup, Yoav Ben-Shlomo, Stela McLachlan, Jackie F Price, Mika Kivimaki, Catherine Welch, Adelaida Sanchez-Galvez, Pedro Marques-Vidal, Andrew Nicolaides, Andrie G Panayiotou, N Charlotte Onland-Moret, Yvonne T van der Schouw, Giuseppe Matullo, Giovanni Fiorito, Simonetta Guarrera, Carlotta Sacerdote, Nicholas J Wareham, Claudia Langenberg, Robert Scott, Jian'an Luan, Martin Bobak, Sofia Malyutina, Andrzej Pająk, Ruzena Kubinova, Abdonas Tamosiunas, Hynek Pikhart, Lise Lotte Nystrup Husemoen, Niels Grarup, Oluf Pedersen, Torben Hansen, Allan Linneberg, Kenneth Starup Simonsen, Jackie Cooper, Steve E Humphries, Murray Brilliant, Terrie Kitchner, Hakon Hakonarson, David S Carrell, Catherine A McCarty, H Lester Kirchner, Eric B Larson, David R Crosslin, Mariza de Andrade, Dan M Roden, Joshua C Denny, Cara Carty, Stephen Hancock, John Attia, Elizabeth Holliday, Martin O' Donnell, Salim Yusuf, Michael Chong, Guillaume Pare, Pim van der Harst, M Abdullah Said, Ruben N Eppinga, Niek Verweij, Harold Snieder, Tim Christen, Dennis O Mook-Kanamori, Stefan Gustafsson, Lars Lind, Erik Ingelsson, Raha Pazoki, Oscar Franco, Albert Hofman, Andre Uitterlinden, Abbas Dehghan, Alexander Teumer, Sebastian Baumeister, Marcus Dörr, Markus M Lerch, Uwe Völker, Henry Völzke, Joey Ward, Jill P Pell, Daniel J Smith, Tom Meade, Anke H Maitland-van der Zee, Ekaterina V Baranova, Robin Young, Ian Ford, Archie Campbell, Sandosh Padmanabhan, Michiel L Bots, Diederick E Grobbee, Philippe Froguel, Dorothée Thuillier, Beverley Balkau, Amélie Bonnefond, Bertrand Cariou, Melissa Smart, Yanchun Bao, Meena Kumari, Anubha Mahajan, Paul M Ridker, Daniel I Chasman, Alex P Reiner, Leslie A Lange, Marylyn D Ritchie, Folkert W Asselbergs, Juan-Pablo Casas, Brendan J Keating, David Preiss, Aroon D Hingorani, Naveed Sattar
BACKGROUND: Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk...
November 28, 2016: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/27893080/travel-associated-zika-virus-disease-acquired-in-the-americas-through-february-2016-a-geosentinel-analysis
#7
Davidson H Hamer, Kira A Barbre, Lin H Chen, Martin P Grobusch, Patricia Schlagenhauf, Abraham Goorhuis, Perry J J van Genderen, Israel Molina, Hilmir Asgeirsson, Phyllis E Kozarsky, Eric Caumes, Stefan H Hagmann, Frank P Mockenhaupt, Gilles Eperon, Elizabeth D Barnett, Emmanuel Bottieau, Andrea K Boggild, Philippe Gautret, Noreen A Hynes, Susan Kuhn, R Ryan Lash, Karin Leder, Michael Libman, Denis J M Malvy, Cecilia Perret, Camilla Rothe, Eli Schwartz, Annelies Wilder-Smith, Martin S Cetron, Douglas H Esposito
Background: Zika virus has spread rapidly in the Americas and has been imported into many nonendemic countries by travelers. Objective: To describe clinical manifestations and epidemiology of Zika virus disease in travelers exposed in the Americas. Design: Descriptive, using GeoSentinel records. Setting: 63 travel and tropical medicine clinics in 30 countries. Patients: Ill returned travelers with a confirmed, probable, or clinically suspected diagnosis of Zika virus disease seen between January 2013 and 29 February 2016...
November 22, 2016: Annals of Internal Medicine
https://www.readbyqxmd.com/read/27881883/aquatic-methane-dynamics-in-a-human-impacted-river-floodplain-of-the-danube
#8
Anna Katarzyna Sieczko, Katalin Demeter, Gabriel Andreas Singer, Michael Tritthart, Stefan Preiner, Magdalena Mayr, Karin Meisterl, Peter Peduzzi
River-floodplain systems are characterized by changing hydrological connectivity and variability of resources delivered to floodplain water bodies. Although the importance of hydrological events has been recognized, the effect of flooding on CH4 concentrations and emissions from European, human-impacted river-floodplains is largely unknown. This study evaluates aquatic concentrations and emissions of CH4 from a highly modified, yet partly restored river-floodplain system of the Danube near Vienna (Austria)...
November 2016: Limnology and Oceanography
https://www.readbyqxmd.com/read/27867045/minvar-a-rapid-and-versatile-tool-for-hiv-1-drug-resistance-genotyping-by-deep-sequencing
#9
Michael Huber, Karin J Metzner, Fabienne D Geissberger, Cyril Shah, Christine Leemann, Thomas Klimkait, Jürg Böni, Alexandra Trkola, Osvaldo Zagordi
Genotypic monitoring of drug-resistance mutations (DRMs) in HIV-1 infected individuals is strongly recommended to guide selection of the initial antiretroviral therapy (ART) and changes of drug regimens. Traditionally, mutations conferring drug resistance are detected by population sequencing of the reverse transcribed viral RNA encoding the HIV-1 enzymes target by ART, followed by manual analysis and interpretation of Sanger sequencing traces. This process is labor intensive, relies on subjective interpretation from the operator, and offers limited sensitivity as only mutations above 20% frequency can be reliably detected...
November 17, 2016: Journal of Virological Methods
https://www.readbyqxmd.com/read/27856273/hypermutation-in-pancreatic-cancer
#10
Jeremy L Humphris, Ann-Marie Patch, Katia Nones, Peter J Bailey, Amber L Johns, Skye McKay, David K Chang, David K Miller, Marina Pajic, Karin S Kassahn, Michael C J Quinn, Timothy J C Bruxner, Angelika N Christ, Ivon Harliwong, Senel Idrisoglu, Suzanne Manning, Craig Nourse, Ehsan Nourbakhsh, Andrew Stone, Peter J Wilson, Matthew Anderson, J Lynn Fink, Oliver Holmes, Stephen Kazakoff, Conrad Leonard, Felicity Newell, Nick Waddell, Scott Wood, Ronald S Mead, Qinying Xu, Jianmin Wu, Mark Pinese, Mark J Cowley, Marc D Jones, Adnan M Nagrial, Venessa T Chin, Lorraine A Chantrill, Amanda Mawson, Angela Chou, Christopher J Scarlett, Andreia V Pinho, Ilse Rooman, Marc Giry-Laterriere, Jaswinder S Samra, James G Kench, Neil D Merrett, Christopher W Toon, Krishna Epari, Nam Q Nguyen, Andrew Barbour, Nikolajs Zeps, Nigel B Jamieson, Colin J McKay, C Ross Carter, Euan J Dickson, Janet S Graham, Fraser Duthie, Karin Oien, Jane Hair, Jennifer P Morton, Owen J Sansom, Robert Grützmann, Ralph H Hruban, Anirban Maitra, Christine A Iacobuzio-Donahue, Richard D Schulick, Christopher L Wolfgang, Richard A Morgan, Rita T Lawlor, Borislav Rusev, Vincenzo Corbo, Roberto Salvia, Ivana Cataldo, Giampaolo Tortora, Margaret A Tempero, Oliver Hofmann, James R Eshleman, Christian Pilarsky, Aldo Scarpa, Elizabeth A Musgrove, Anthony J Gill, John V Pearson, Sean M Grimmond, Nicola Waddell, Andrew V Biankin
Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2...
November 15, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27854059/dispersed-oil-decreases-the-ability-of-a-model-fish-dicentrarchus-labrax-to-cope-with-hydrostatic-pressure
#11
Matthieu Dussauze, Karine Pichavant-Rafini, Marc Belhomme, Peter Buzzacott, Killian Privat, Stéphane Le Floch, Philippe Lemaire, Michaël Theron
Data on the biological impact of oil dispersion in deep-sea environment are scarce. Hence, the aim of this study was to evaluate the potential interest of a pressure challenge as a new experimental approach for the assessment of consequences of chemically dispersed oil, followed by a high hydrostatic pressure challenge. This work was conducted on a model fish: juvenile Dicentrarchus labrax. Seabass were exposed for 48 h to dispersant alone (nominal concentration (NC) = 4 mg L(-1)), mechanically dispersed oil (NC = 80 mg L(-1)), two chemically dispersed types of oil (NC = 50 and 80 mg L(-1) with a dispersant/oil ratio of 1/20), or kept in clean seawater...
November 16, 2016: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/27837387/vitamin-d3-loading-is-superior-to-conventional-supplementation-after-weight-loss-surgery-in-vitamin-d-deficient-morbidly-obese-patients-a-double-blind-randomized-placebo-controlled-trial
#12
Maria Luger, Renate Kruschitz, Christian Kienbacher, Stefan Traussnigg, Felix B Langer, Gerhard Prager, Karin Schindler, Enikö Kallay, Friedrich Hoppichler, Michael Trauner, Michael Krebs, Rodrig Marculescu, Bernhard Ludvik
BACKGROUND: Bariatric patients often suffer from vitamin D deficiency (VDD), and both, morbid obesity and VDD, are related to non-alcoholic fatty liver disease. However, limited data are available regarding best strategies for treating VDD, particularly, in bariatric patients undergoing omega-loop gastric bypass (OLGB). Therefore, we examined the efficacy and safety of a forced vitamin D dosing regimen and intervention effects in liver fibrotic patients. METHODS: In this double-blind, randomized, placebo-controlled trial, 50 vitamin D-deficient patients undergoing OLGB were randomly assigned to receive, in the first month postoperatively, oral vitamin D3 (≤3 doses of 100,000 IU; intervention group) or placebo as loading dose (control group) with subsequent maintenance dose (3420 IU/day) in both groups until 6-month visit...
November 12, 2016: Obesity Surgery
https://www.readbyqxmd.com/read/27832979/zika-virus-induced-itching-rash-in-a-returning-traveller-from-brazil
#13
Luzia Veletzky, Daniela Knafl, Christopher Schuster, Stephan W Aberle, Karin Stiasny, Michael Ramharter, Heimo Lagler
No abstract text is available yet for this article.
November 7, 2016: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/27829303/psychometric-validation-of-the-electronic-chronic-pain-questions-ecpq-in-a-primary-care-setting
#14
Karin S Coyne, Brooke M Currie, Sean Donevan, Marina Brodsky, Michael J Asmus, Daniel W Krichbaum, Joseph C Cappelleri, Rozelle Hegeman-Dingle, Alesia Sadosky, Samuel Z Whipple, Claire Burbridge, Elie Mulhem, J Bruce Hillenberg
OBJECTIVE: Collecting data that helps evaluate different types of pain may improve physicians' decision-making with regard to treatment selection and on-going monitoring of patients. To date, no chronic pain assessments have been widely implemented in primary care. The aim of this study was to psychometrically validate the electronic Chronic Pain Questions (eCPQ) in a primary care setting. RESEARCH DESIGN AND METHODS: All men and women ≥18 years arriving at two similar primary care clinics in southeastern Michigan were invited to participate...
November 10, 2016: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/27823689/safety-and-efficacy-of-the-0-h-3-h-protocol-for-rapid-rule-out-of-myocardial-infarction
#15
Karin Wildi, Berit Nelles, Raphael Twerenbold, Maria Rubini Giménez, Tobias Reichlin, Hélène Singeisen, Sophie Druey, Philip Haaf, Zaid Sabti, Petra Hillinger, Cedric Jaeger, Isabel Campodarve, Philip Kreutzinger, Christian Puelacher, Zoraida Moreno Weidmann, Mathias Gugala, Gilles Pretre, Stephanie Doerflinger, Max Wagener, Fabio Stallone, Michael Freese, Claudia Stelzig, Katharina Rentsch, Stefano Bassetti, Roland Bingisser, Stefan Osswald, Christian Mueller
BACKGROUND: The early and accurate diagnosis of acute myocardial infarction (AMI) is an important medical and economic challenge. We aimed to prospectively evaluate the performance of the new European Society of Cardiology rapid 0-hour/3-hour (0 h/3 h) rule out protocol for AMI. METHODS: We enrolled 2,727 consecutive patients presenting with suspected AMI without persistent ST-segment elevation to the emergency department in a prospective international multicenter study...
November 2016: American Heart Journal
https://www.readbyqxmd.com/read/27821696/molecular-evidence-of-malaria-and-zoonotic-diseases-among-rapid-diagnostic-test-negative-febrile-patients-in-low-transmission-season-mali
#16
Mahamoudou Touré, Pelle T Petersen, Sidy N'd Bathily, Daouda Sanogo, Christian W Wang, Karin L Schiøler, Flemming Konradsen, Seydou Doumbia, Michael Alifrangis
From November to December 2012 in Sélingué-Mali, blood samples from 88 febrile patients who tested negative by malaria Paracheck (®) rapid diagnostic tests (RDTs) were used to assess the presence of sub-RDT Plasmodium falciparum as well as Borrelia, Coxiella burnetii, and Babesia applying molecular tools. Plasmodium sp. was present among 57 (60.2%) of the 88 malaria RDT-negative patients, whereas the prevalence of Borrelia, C. burnetii, and Babesia were 3.4% (N = 3), 1.1% (N = 1), and 0.0%, respectively...
November 7, 2016: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/27814993/evaluation-of-the-interaction-between-lrrk2-and-park16-loci-in-determining-risk-of-parkinson-s-disease-analysis-of-a-large-multicenter-study
#17
Lisa Wang, Michael G Heckman, Jan O Aasly, Grazia Annesi, Maria Bozi, Sun Ju Chung, Carl Clarke, David Crosiers, Gertrud Eckstein, Gaetan Garraux, Georgios M Hadjigeorgiou, Nobu Hattori, Beom Jeon, Yun J Kim, Masato Kubo, Suzanne Lesage, Juei Jueng Lin, Timothy Lynch, Peter Lichtner, George D Mellick, Vincent Mok, Karin E Morrison, Aldo Quattrone, Wataru Satake, Peter A Silburn, Leonidas Stefanis, Joanne D Stockton, Eng King Tan, Tatsushi Toda, Alexis Brice, Christine Van Broeckhoven, Ryan J Uitti, Karin Wirdefeldt, Zbigniew Wszolek, Georgia Xiromerisiou, Demetrius M Maraganore, Thomas Gasser, Rejko Krüger, Matthew J Farrer, Owen A Ross, Manu Sharma
A recent study MacLeod et al. has shown that an interaction between variants at the LRRK2 and PARK16 loci influences risk of development of Parkinson's disease (PD). Our study examines the proposed interaction between LRRK2 and PARK16 variants in modifying PD risk using a large multicenter series of PD patients (7715) and controls (8261) from sites participating in the Genetic Epidemiology of Parkinson's Disease Consortium. Our data does not support a strong direct interaction between LRRK2 and PARK16 variants; however, given the role of retromer and lysosomal pathways in PD, further studies are warranted...
October 6, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/27814504/inflammation-improves-glucose-homeostasis-through-ikk%C3%AE-xbp1s-interaction
#18
Junli Liu, Dorina Ibi, Koji Taniguchi, Jaemin Lee, Hilde Herrema, Bedia Akosman, Patrick Mucka, Mario Andres Salazar Hernandez, Muhemmet Fatih Uyar, Sang Won Park, Michael Karin, Umut Ozcan
It is widely believed that inflammation associated with obesity has an important role in the development of type 2 diabetes. IκB kinase beta (IKKβ) is a crucial kinase that responds to inflammatory stimuli such as tumor necrosis factor α (TNF-α) by initiating a variety of intracellular signaling cascades and is considered to be a key element in the inflammation-mediated development of insulin resistance. We show here, contrary to expectation, that IKKβ-mediated inflammation is a positive regulator of hepatic glucose homeostasis...
November 3, 2016: Cell
https://www.readbyqxmd.com/read/27808515/the-discovery-of-ruzasvir-mk-8408-a-potent-pan-genotype-hcv-ns5a-inhibitor-with-optimized-activity-against-common-resistance-associated-polymorphisms
#19
Ling Tong, Wensheng Yu, Lei Chen, Oleg Selyutin, Michael P Dwyer, Anilkumar Gopinadhan Nair, Robert Mazzola, Jae-Hun Kim, Deyou Sha, Jingjun Yin, Rebecca Tamra Ruck, Ian W Davies, Bin Hu, Bin Zhong, Jinglai Hao, Tao Ji, Shuai Zan, Rong Liu, Sony Agrawal, Ellen Xia, Stephanie Curry, Patricia Mcmonagle, Karin Bystol, Frederick Lahser, Donna Carr, Laura Rokosz, Paul Ingravallo, Shiying Chen, Kung-I Feng, Mark Cartwright, Ernest Asante-Appiah, Joseph A Kozlowski
We describe the research that led to the discovery of compound 40 (ruzasvir, MK-8408), a pan-genotypic HCV nonstructural protein 5A (NS5A) inhibitor with a "flat" GT1 mutant profile. This NS5A inhibitor contains a unique tetracyclic indole core, while maintaining the imidazole-proline-valine Moc motifs of our previous NS5A inhibitors. Compound 40 is currently in early clinical trials and is under evaluation as part of an all-oral DAA regimen for the treatment of chronic HCV infection..
November 3, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27806243/benefits-and-risks-of-antiretroviral-therapy-for-perinatal-hiv-prevention
#20
Mary G Fowler, Min Qin, Susan A Fiscus, Judith S Currier, Patricia M Flynn, Tsungai Chipato, James McIntyre, Devasena Gnanashanmugam, George K Siberry, Anne S Coletti, Taha E Taha, Karin L Klingman, Francis E Martinson, Maxensia Owor, Avy Violari, Dhayendre Moodley, Gerhard B Theron, Ramesh Bhosale, Raziya Bobat, Benjamin H Chi, Renate Strehlau, Pendo Mlay, Amy J Loftis, Renee Browning, Terence Fenton, Lynette Purdue, Michael Basar, David E Shapiro, Lynne M Mofenson
Background Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking. Methods We randomly assigned HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter to zidovudine and single-dose nevirapine plus a 1-to-2-week postpartum "tail" of tenofovir and emtricitabine (zidovudine alone); zidovudine, lamivudine, and lopinavir-ritonavir (zidovudine-based ART); or tenofovir, emtricitabine, and lopinavir-ritonavir (tenofovir-based ART)...
November 3, 2016: New England Journal of Medicine
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