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https://www.readbyqxmd.com/read/29109432/als-associated-mutations-in-matrin-3-alter-protein-protein-interactions-and-impede-mrna-nuclear-export
#1
Ashley Boehringer, Krystine Garcia-Mansfield, Gurkaran Singh, Nadine Bakkar, Patrick Pirrotte, Robert Bowser
Mutations in Matrin 3 have recently been linked to ALS, though the mechanism that induces disease in these patients is unknown. To define the protein interactome of wild-type and ALS-linked MATR3 mutations, we performed immunoprecipitation followed by mass spectrometry using NSC-34 cells expressing human wild-type or mutant Matrin 3. Gene ontology analysis identified a novel role for Matrin 3 in mRNA transport centered on proteins in the TRanscription and EXport (TREX) complex, known to function in mRNA biogenesis and nuclear export...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29089726/the-use-of-idarucizumab-for-dabigatran-reversal-in-clinical-practice-a-case-series
#2
Pavel Goriacko, Vicken Yaghdjian, Issam Koleilat, Mark Sinnett, Harshal Shukla
PURPOSE: To describe the use of idarucizumab (Praxbind, Boehringer Ingelheim) in routine clinical practice at a large urban academic medical center. SUMMARY: Seven total doses of idarucizumab were administered to six unique patients from October 31, 2015, to October 31, 2016. The reversal agent was used in conjunction with local bleeding control measures, blood product transfusions, and acid-suppressive therapy. In 86% of cases, idarucizumab administration resulted in a successful cessation of bleeding by clinical assessment...
November 2017: P & T: a Peer-reviewed Journal for Formulary Management
https://www.readbyqxmd.com/read/29083972/inhaled-corticosteroid-containing-treatment-escalation-and-outcomes-for-patients-with-asthma-in-a-u-s-health-care-organization
#3
Lindsay G S Bengtson, Yanni Yu, Weijia Wang, Feng Cao, Erin M Hulbert, Ryan Wolbeck, Caitlin A Elliott, Ami R Buikema
BACKGROUND: Asthma is a common disorder that affects approximately 8% of the U.S. POPULATION: Treatment guidelines indicate inhaled corticosteroids (ICS) as the mainstay treatment, yet poor asthma control is common among ICS-treated patients. Treatment escalation (ICS dose increase and other controller therapy add-ons) is used to manage symptoms. Real-world studies of postescalation outcomes may inform treatment decisions. OBJECTIVES: To (a) describe characteristics and treatment patterns among asthma patients who escalated treatment and (b) assess outcomes (exacerbations, uncontrolled asthma, and health care resource utilization [HCRU]) after escalation...
November 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/29079252/effect-of-an-intensified-multifactorial-intervention-on-cardiovascular-outcomes-and-mortality-in-type-2-diabetes-j-doit3-an-open-label-randomised-controlled-trial
#4
Kohjiro Ueki, Takayoshi Sasako, Yukiko Okazaki, Masayuki Kato, Sumie Okahata, Hisayuki Katsuyama, Mikiko Haraguchi, Ai Morita, Ken Ohashi, Kazuo Hara, Atsushi Morise, Kazuo Izumi, Naoki Ishizuka, Yasuo Ohashi, Mitsuhiko Noda, Takashi Kadowaki
BACKGROUND: Limited evidence suggests that multifactorial interventions for control of glucose, blood pressure, and lipids reduce macrovascular complications and mortality in patients with type 2 diabetes. However, safe and effective treatment targets for these risk factors have not been determined for such interventions. METHODS: In this multicentre, open-label, randomised, parallel-group trial, undertaken at 81 clinical sites in Japan, we randomly assigned (1:1) patients with type 2 diabetes aged 45-69 years with hypertension, dyslipidaemia, or both, and an HbA1c of 6·9% (52·0 mmol/mol) or higher, to receive conventional therapy for glucose, blood pressure, and lipid control (targets: HbA1c <6·9% [52·0 mmol/mol], blood pressure <130/80 mm Hg, LDL cholesterol <120 mg/dL [or 100 mg/dL in patients with a history of coronary artery disease]) or intensive therapy (HbA1c <6·2% [44·3 mmol/mol], blood pressure <120/75 mm Hg, LDL cholesterol <80 mg/dL [or 70 mg/dL in patients with a history of coronary artery disease])...
October 24, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/29063828/assessment-of-the-insecticidal-activity-of-afoxolaner-against-aedes-aegypti-in-dogs-treated-with-nexgard-%C3%A2
#5
Julian Liebenberg, Josephus Fourie, Wilfried Lebon, Diane Larsen, Lenaïg Halos, Frédéric Beugnet
Twelve healthy dogs were studied in this parallel group, blinded, randomised, and negative controlled efficacy study. On Day -1, the 12 dogs included were ranked within sex in descending order of individual pre-treatment (Day -5) fed mosquito counts and randomly allocated by blocks of two dogs to the untreated control group or the afoxolaner-treated group. NexGard(®) (Merial, now part of Boehringer Ingelheim Animal Health) was administered orally on Day 0 in accordance with the European label instructions...
2017: Parasite: Journal de la Société Française de Parasitologie
https://www.readbyqxmd.com/read/28943267/the-effect-of-physical-activity-on-mortality-and-cardiovascular-disease-in-130%C3%A2-000-people-from-17-high-income-middle-income-and-low-income-countries-the-pure-study
#6
Scott A Lear, Weihong Hu, Sumathy Rangarajan, Danijela Gasevic, Darryl Leong, Romaina Iqbal, Amparo Casanova, Sumathi Swaminathan, R M Anjana, Rajesh Kumar, Annika Rosengren, Li Wei, Wang Yang, Wang Chuangshi, Liu Huaxing, Sanjeev Nair, Rafael Diaz, Hany Swidon, Rajeev Gupta, Noushin Mohammadifard, Patricio Lopez-Jaramillo, Aytekin Oguz, Katarzyna Zatonska, Pamela Seron, Alvaro Avezum, Paul Poirier, Koon Teo, Salim Yusuf
BACKGROUND: Physical activity has a protective effect against cardiovascular disease (CVD) in high-income countries, where physical activity is mainly recreational, but it is not known if this is also observed in lower-income countries, where physical activity is mainly non-recreational. We examined whether different amounts and types of physical activity are associated with lower mortality and CVD in countries at different economic levels. METHODS: In this prospective cohort study, we recruited participants from 17 countries (Canada, Sweden, United Arab Emirates, Argentina, Brazil, Chile, Poland, Turkey, Malaysia, South Africa, China, Colombia, Iran, Bangladesh, India, Pakistan, and Zimbabwe)...
September 21, 2017: Lancet
https://www.readbyqxmd.com/read/28905245/identification-of-polymorphic-forms-of-active-pharmaceutical-ingredient-in-low-concentration-dry-powder-formulations-by-synchrotron-x-ray-powder-diffraction
#7
Kenji Egusa, Fumiaki Okazaki, Joerg Schiewe, Ulrike Werthmann, Markus Wolkenhauer
BACKGROUND: The identification of different (pseudo) polymorphs of an active pharmaceutical ingredient in dry powder formulations is of importance during development and entire product lifecycle, e.g., quality control. Whereas determination of polymorphic differences of pure substances is rather easy, in dry powder formulations, it is generally difficult and the difficulties increase particularly, if the substance of interest is present only in low concentrations in the formulation. Such a formulation is Spiriva(®) inhalation powder (Boehringer Ingelheim), which contains only 0...
September 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28877027/tiotropium-in-early-stage-chronic-obstructive-pulmonary-disease
#8
RANDOMIZED CONTROLLED TRIAL
Yumin Zhou, Nan-Shan Zhong, Xiaochen Li, Shuyun Chen, Jinping Zheng, Dongxing Zhao, Weimin Yao, Rongchang Zhi, Liping Wei, Bingwen He, Xiangyan Zhang, Changli Yang, Ying Li, Fenglei Li, Juan Du, Jianping Gui, Bin Hu, Chunxue Bai, Ping Huang, Gang Chen, Yongjian Xu, Changzheng Wang, Biao Liang, Yinhuan Li, Guoping Hu, Hui Tan, Xianwei Ye, Xitao Ma, Yan Chen, Xiwei Hu, Jia Tian, Xiaodan Zhu, Zhe Shi, Xiufang Du, Minjing Li, Shengming Liu, Ronghuan Yu, Jianping Zhao, Qianli Ma, Canmao Xie, Xiongbin Li, Tao Chen, Yingxiang Lin, Lizhen Zeng, Changxiu Ye, Weishu Ye, Xiangwen Luo, Lingshan Zeng, Shuqing Yu, Wei-Jie Guan, Pixin Ran
BACKGROUND: Patients with mild or moderate chronic obstructive pulmonary disease (COPD) rarely receive medications, because they have few symptoms. We hypothesized that long-term use of tiotropium would improve lung function and ameliorate the decline in lung function in patients with mild or moderate COPD. METHODS: In a multicenter, randomized, double-blind, placebo-controlled trial that was conducted in China, we randomly assigned 841 patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 (mild) or 2 (moderate) severity to receive a once-daily inhaled dose (18 μg) of tiotropium (419 patients) or matching placebo (422) for 2 years...
September 7, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28865211/evaluation-of-in-feed-larch-sawdust-anti-inflammatory-effect-in-sows
#9
E D Tzika, P D Tassis, V G Papatsiros, E M Pferschy-Wenzig, A Siochu, R Bauer, C Alexopoulos, S C Kyriakis, C Franz
The study aimed to investigate the possible anti-inflammatory activity of larch sawdust as feed supplement in lactating sows' diet and its possible effect on the prevalence of Postpartum Dysgalactia Syndrome under field conditions. In a Greek farrow-to-finish pig farm, fifteen sows were randomly and equally allocated to a negative control group (NC group), a positive control group (PC group), and a treatment group (LT group). The animals of the first two groups received 99% basic diet and 1% corn starch, while LT group animals received 99% basic diet and 1% larch sawdust...
March 1, 2017: Polish Journal of Veterinary Sciences
https://www.readbyqxmd.com/read/28859942/a-multifaceted-intervention-to-improve-treatment-with-oral-anticoagulants-in-atrial-fibrillation-impact-af-an-international-cluster-randomised-trial
#10
Dragos Vinereanu, Renato D Lopes, M Cecilia Bahit, Denis Xavier, Jie Jiang, Hussein R Al-Khalidi, Wensheng He, Ying Xian, Andrea O Ciobanu, Deepak Y Kamath, Kathleen A Fox, Meena P Rao, Sean D Pokorney, Otavio Berwanger, Carlos Tajer, Pedro G M de Barros E Silva, Mayme L Roettig, Yong Huo, Christopher B Granger
BACKGROUND: Oral anticoagulation is underused in patients with atrial fibrillation. We assessed the impact of a multifaceted educational intervention, versus usual care, on oral anticoagulant use in patients with atrial fibrillation. METHODS: This study was a two-arm, prospective, international, cluster-randomised, controlled trial. Patients were included who had atrial fibrillation and an indication for oral anticoagulation. Clusters were randomised (1:1) to receive a quality improvement educational intervention (intervention group) or usual care (control group)...
August 25, 2017: Lancet
https://www.readbyqxmd.com/read/28844193/dual-antithrombotic-therapy-with-dabigatran-after-pci-in-atrial-fibrillation
#11
RANDOMIZED CONTROLLED TRIAL
Christopher P Cannon, Deepak L Bhatt, Jonas Oldgren, Gregory Y H Lip, Stephen G Ellis, Takeshi Kimura, Michael Maeng, Bela Merkely, Uwe Zeymer, Savion Gropper, Matias Nordaby, Eva Kleine, Ruth Harper, Jenny Manassie, James L Januzzi, Jurrien M Ten Berg, P Gabriel Steg, Stefan H Hohnloser
BACKGROUND: Triple antithrombotic therapy with warfarin plus two antiplatelet agents is the standard of care after percutaneous coronary intervention (PCI) for patients with atrial fibrillation, but this therapy is associated with a high risk of bleeding. METHODS: In this multicenter trial, we randomly assigned 2725 patients with atrial fibrillation who had undergone PCI to triple therapy with warfarin plus a P2Y12 inhibitor (clopidogrel or ticagrelor) and aspirin (for 1 to 3 months) (triple-therapy group) or dual therapy with dabigatran (110 mg or 150 mg twice daily) plus a P2Y12 inhibitor (clopidogrel or ticagrelor) and no aspirin (110-mg and 150-mg dual-therapy groups)...
October 19, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28819835/efficacy-and-safety-of-linagliptin-in-2681-asian-patients-stratified-by-age-obesity-and-renal-function-a-pooled-analysis-of-randomized-clinical-trials
#12
Guang Ning, Tushar Bandgar, Uwe Hehnke, Jisoo Lee, Juliana C N Chan
INTRODUCTION: Asian patients with type 2 diabetes (T2D) are younger, leaner, and more likely to develop renal dysfunction than White populations. In this multiethnic analysis of data from phase 3 trials, we investigated the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in Asians stratified by these subphenotypes. METHODS: Data from randomized, double-blind, placebo-controlled trials evaluating linagliptin (as monotherapy, add-on therapy to metformin ± sulfonylurea, combined with pioglitazone or added to insulin) were pooled with efficacy data from 11 randomized trials of at least 24 weeks and safety data from 15 trials of various durations...
September 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28801654/perceptions-of-asthma-control-in-the-united-kingdom-a-cross-sectional-study-comparing-patient-and-healthcare-professionals-perceptions-of-asthma-control-with-validated-act-scores
#13
Andrew Menzies-Gow, Gavin Chiu
Perceptions of asthma control often vary between patients and physicians. This cross-sectional survey provided UK-specific data on actual and perceived asthma control in patients (18-75 years) attending routine asthma reviews in primary, secondary and tertiary settings. Differences between healthcare professionals' (HCP) and patients' perceptions of asthma control were evaluated via an online questionnaire and compared to a control-the validated asthma control test (ACT)-which patients completed. Treated patients (at least a short acting ß-agonist) with a documented diagnosis of asthma were enroled and consented within a month of their last appointment...
August 11, 2017: NPJ Primary Care Respiratory Medicine
https://www.readbyqxmd.com/read/28792217/kinase-crystal-miner-a-powerful-approach-to-repurposing-3d-hinge-binding-fragments-and-its-application-to-finding-novel-bruton-tyrosine-kinase-inhibitors
#14
Prasenjit Mukherjee, Jörg Bentzien, Todd Bosanac, Wang Mao, Michael Burke, Ingo Muegge
Protein kinases represent an important target class for drug discovery because of their role in signaling pathways involved in disease areas such as oncology and immunology. A key element of many ATP-competitive kinase inhibitors is their hinge-binding motif. Here, we describe Kinase Crystal Miner (KCM)-a new approach developed at Boehringer Ingelheim (BI) that harvests the existing crystallographic information on kinase-inhibitor co-crystal structures from internal and external databases. About 1000 unique three-dimensional kinase inhibitor hinge binding motifs have been extracted from structures covering more than 180 different protein kinases...
September 25, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28772332/-expert-knowledge-and-supporting-advice-for-the-clinical-use-of-nintedanib-in-patients-with-idiopathic-pulmonary-fibrosis
#15
J Behr, A Günther, M Kreuter, D Koschel, A Prasse, M Pfeifer, U Costabel
In October 2016, a group of German IPF experts were invited by Boehringer Ingelheim to meet in Frankfurt with the aim, (a) to discuss relevant aspects of the management and treatment of idiopathic pulmonary fibrosis (IPF) using nintedanib; and, (b) to provide supportive advice for daily clinical practice with nintedanib. The resulting information compiled in this document is confined to practical issues regarding the use of nintedanib in patients with IPF. Where different therapeutic options were available, the choice of IPF medication was not discussed and the experts alluded to current guidelines for the diagnosis and treatment of IPF...
September 2017: Pneumologie
https://www.readbyqxmd.com/read/28752507/intravenous-alteplase-for-acute-ischemic-stroke-in-taiwan-can-we-expand-the-national-health-insurance-s-reimbursement-criteria
#16
Cheng-Yang Hsieh
lization of intravenous thrombolysis with alteplase was very low in Taiwanese patients with acute ischemic stroke(1). One of the reasons is the strict reimbursement guideline made by the Bureau of National Health Insurance (NHI) in 2004(2). In this issue of the Acta Neurologica Taiwanica, Yu-Hsiang Su and co-authors(3) retrospectively evaluated outcomes of their thrombolysed stroke patients who were "mismatched" between updated clinical practice guideline and NHI reimbursement criteria. They concluded that the outcomes of patients treated according to guidelines were comparable between the reimbursement and non-reimbursement groups...
March 15, 2017: Acta Neurologica Taiwanica
https://www.readbyqxmd.com/read/28693366/idarucizumab-for-dabigatran-reversal-full-cohort-analysis
#17
MULTICENTER STUDY
Charles V Pollack, Paul A Reilly, Joanne van Ryn, John W Eikelboom, Stephan Glund, Richard A Bernstein, Robert Dubiel, Menno V Huisman, Elaine M Hylek, Chak-Wah Kam, Pieter W Kamphuisen, Jörg Kreuzer, Jerrold H Levy, Gordon Royle, Frank W Sellke, Joachim Stangier, Thorsten Steiner, Peter Verhamme, Bushi Wang, Laura Young, Jeffrey I Weitz
BACKGROUND: Idarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran. METHODS: We performed a multicenter, prospective, open-label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding (group A) or were about to undergo an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the diluted thrombin time or ecarin clotting time...
August 3, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28683309/the-complete-structure-of-the-mycobacterium-smegmatis-70s-ribosome
#18
Jendrik Hentschel, Chloe Burnside, Ingrid Mignot, Marc Leibundgut, Daniel Boehringer, Nenad Ban
The ribosome carries out the synthesis of proteins in every living cell. It consequently represents a frontline target in anti-microbial therapy. Tuberculosis ranks among the leading causes of death worldwide, due in large part to the combination of difficult-to-treat latency and antibiotic resistance. Here, we present the 3.3-Å cryo-EM structure of the 70S ribosome of Mycobacterium smegmatis, a close relative to the human pathogen Mycobacterium tuberculosis. The structure reveals two additional ribosomal proteins and localizes them to the vicinity of drug-target sites in both the catalytic center and the decoding site of the ribosome...
July 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28680960/efficacy-and-safety-results-of-the-afatinib-expanded-access-program
#19
Edward S Kim, Balazs Halmos, Ingrid F Kohut, Taral Patel, Regan D Rostorfer, Alexander I Spira, Agnieszka Cseh, John McKay, Gudrun Wallenstein, Kathryn F Mileham
INTRODUCTION: Afatinib is an oral, irreversible ErbB family blocker approved for first-line treatment of metastatic epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). The expanded access program (EAP) allowed early access to afatinib and provided additional data on its safety, tolerability, and efficacy. METHODS: The afatinib EAP was an open-label, multicenter, single-arm program in the United States that treated and followed patients with locally advanced or metastatic NSCLC harboring EGFR mutations...
2017: Oncology and Therapy
https://www.readbyqxmd.com/read/28668987/a-case-of-fatal-idiosyncratic-reaction-to-the-designer-drug-3-4-methylenedioxypyrovalerone-mdpv-and-review-of-the-literature
#20
Brigitte Desharnais, Yann Dazé, Laura M Huppertz, Pascal Mireault, Cameron D Skinner
The stimulant designer drug 3,4-methylenedioxypyrovalerone (MDPV) was first synthesized by Boehringer Ingelheim in 1969 and introduced on the black market in 2006. Only a small number of fatal intoxication cases have been reported in the literature, all with significant blood MDPV concentrations. In this report, we describe one fatality attributed to an idiosyncratic reaction to MDPV. The victim displayed agitation, violent behavior and delirium followed by cardiac arrest. Hyperthermia was observed at the hospital...
July 1, 2017: Forensic Science, Medicine, and Pathology
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