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Cody Caba, Hyder Ali Khan, Janeen Auld, Ryo Ushioda, Kazutaka Araki, Kazuhiro Nagata, Bulent Mutus
Despite its study since the 1960's, very little is known about the post-translational regulation of the multiple catalytic activities performed by protein disulfide isomerase (PDI), the primary protein folding catalyst of the cell. This work identifies a functional role for the highly conserved CxxC-flanking residues Lys57 and Lys401 of human PDI in vitro . Mutagenesis studies have revealed these residues as modulating the oxidoreductase activity of PDI in a pH-dependent manner. Non-conservative amino acid substitutions resulted in enzyme variants upwards of 7-fold less efficient...
2018: Frontiers in Molecular Biosciences
Lining Ju, James D McFadyen, Saheb Al-Daher, Imala Alwis, Yunfeng Chen, Lotte L Tønnesen, Sophie Maiocchi, Brianna Coulter, Anna C Calkin, Eric I Felner, Neale Cohen, Yuping Yuan, Simone M Schoenwaelder, Mark E Cooper, Cheng Zhu, Shaun P Jackson
Diabetes is associated with an exaggerated platelet thrombotic response at sites of vascular injury. Biomechanical forces regulate platelet activation, although the impact of diabetes on this process remains ill-defined. Using a biomembrane force probe (BFP), we demonstrate that compressive force activates integrin αIIb β3 on discoid diabetic platelets, increasing its association rate with immobilized fibrinogen. This compressive force-induced integrin activation is calcium and PI 3-kinase dependent, resulting in enhanced integrin affinity maturation and exaggerated shear-dependent platelet adhesion...
March 14, 2018: Nature Communications
Johann Bartko, Christian Schoergenhofer, Michael Schwameis, Patricia Wadowski, Jacek Kubica, Bernd Jilma, Eva-Luise Hobl
Aspirin is a cornerstone in the anti-platelet therapy of acute coronary syndromes. Co-administration of morphine may potentially influence the intestinal absorption, pharmacokinetics and pharmacodynamics as seen with P2Y12-inhibitors. In this trial, healthy volunteers were randomized to receive morphine (5 mg, iv bolus injection) at one of 7 different time points before, after or with aspirin (162 mg, po) in a double-blind, placebo controlled fashion. After a 14-day washout, subjects received placebo instead of morphine...
March 14, 2018: Journal of Pharmacology and Experimental Therapeutics
Sonia S Anand, Francois Caron, John W Eikelboom, Jackie Bosch, Leanne Dyal, Victor Aboyans, Maria Teresa Abola, Kelley R H Branch, Katalin Keltai, Deepak L Bhatt, Peter Verhamme, Keith A A Fox, Nancy Cook-Bruns, Vivian Lanius, Stuart J Connolly, Salim Yusuf
BACKGROUND: Patients with lower extremity peripheral artery disease (PAD) are at increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). There is limited information on the prognosis of patients who suffer MALE. OBJECTIVES: Among participants with lower extremity PAD, we investigated: 1) if hospitalizations, MACE, amputations, and deaths are higher after first episode of MALE compared with PAD patients who do not experience MALE and 2) the impact of treatment with low dose rivaroxaban and aspirin compared to aspirin alone on the incidence of MALE, peripheral vascular interventions, and all peripheral vascular outcomes over a median follow-up of 21 months...
March 7, 2018: Journal of the American College of Cardiology
Fred Stephen Sarfo, Osei Sarfo-Kantanka, Sheila Adamu, Vida Obese, Jennifer Voeks, Raelle Tagge, Vipin Sethi, Bruce Ovbiagele
BACKGROUND: There is an unprecedented rise in the prevalence of stroke in sub-Saharan Africa (SSA). Secondary prevention guidelines recommend that antihypertensive, statin and antiplatelet therapy be initiated promptly after ischemic stroke and adhered to in a persistent fashion to achieve optimal vascular-risk reduction. However, these goals are seldom realized in routine clinical care settings in SSA due to logistical challenges. We seek to assess whether a polypill containing fixed doses of three antihypertensive agents, a statin and antiplatelet therapy taken once daily per os for 12 months among recent stroke survivors would result in carotid intimal thickness regression compared with usual care (UC)...
March 14, 2018: Trials
T Jayaraman, M S Wong, N Mustaffa, Y Y Lee
No abstract text is available yet for this article.
December 2017: Journal of the Royal College of Physicians of Edinburgh
Matthew Gaskins, Martin Dittmann, Lisa Eisert, Ricardo Niklas Werner, Corinna Dressler, Christoph Löser, Alexander Nast
BACKGROUND: A survey in 2012 revealed marked heterogeneity in the management of antithrombotic agents in dermatologic surgery in Germany. An evidence-based guideline on this topic was published for the first time in 2014. METHODS: Using the same study sample, we conducted an anonymous survey on the management of antithrombotic agents and familiarity with the guideline. We reported the results as relative frequencies and compared them with those from 2012. RESULTS: We analyzed a total of 208 questionnaires (response rate: 36...
March 2018: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
M Y Tan, D Wright, A Syngelaki, R Akolekar, S Cicero, D Janga, M Singh, E Greco, A Wright, K Maclagan, L C Poon, K H Nicolaides
OBJECTIVE: To test the hypothesis that the performance of first-trimester screening for pre-eclampsia (PE) by a method that uses Bayes' theorem to combine maternal factors with biomarkers is superior to that defined by current National Institute for Health and Care Excellence (NICE) guidelines. METHODS: This was a prospective multicenter study (screening program for pre-eclampsia (SPREE)) in seven National Health Service maternity hospitals in England, of women recruited between April and December 2016...
March 14, 2018: Ultrasound in Obstetrics & Gynecology
Linda E Flinterman, Karin Hek, Joke C Korevaar, Liset van Dijk
Governments have several options to reduce the increasing costs of health care, including restrictions for the reimbursement of medicines. Next to the intended effect of reduced costs for medicines, reimbursement restriction can have unintended effects such as patients refraining from their treatment which may lead to health problems and increased use of health care. An example of a reimbursement restriction is the one for proton pump inhibitors (PPIs) that became effective in the Netherlands in January 2012...
2018: Frontiers in Public Health
Valerio De Stefano, Alessandra Carobbio, Vincenzo Di Lazzaro, Paola Guglielmelli, Alessandra Iurlo, Maria Chiara Finazzi, Elisa Rumi, Francisco Cervantes, Elena Maria Elli, Maria Luigia Randi, Martin Griesshammer, Francesca Palandri, Massimiliano Bonifacio, Juan-Carlos Hernandez-Boluda, Rossella Cacciola, Palova Miroslava, Giuseppe Carli, Eloise Beggiato, Martin H Ellis, Caterina Musolino, Gianluca Gaidano, Davide Rapezzi, Alessia Tieghi, Francesca Lunghi, Giuseppe Gaetano Loscocco, Daniele Cattaneo, Agostino Cortelezzi, Silvia Betti, Elena Rossi, Guido Finazzi, Bruno Censori, Mario Cazzola, Marta Bellini, Eduardo Arellano-Rodrigo, Irene Bertozzi, Parvis Sadjadian, Nicola Vianelli, Luigi Scaffidi, Montse Gomez, Emma Cacciola, Alessandro M Vannucchi, Tiziano Barbui
We analyzed 597 patients with myeloproliferative neoplasms (MPN) who presented transient ischemic attacks (TIA, n = 270) or ischemic stroke (IS, n = 327). Treatment included aspirin, oral anticoagulants, and cytoreductive drugs. The composite incidence of recurrent TIA and IS, acute myocardial infarction (AMI), and cardiovascular (CV) death was 4.21 and 19.2%, respectively at one and five years after the index event, an estimate unexpectedly lower than reported in the general population. Patients tended to replicate the first clinical manifestation (hazard ratio, HR: 2...
February 28, 2018: Blood Cancer Journal
Lamiae Grimaldi-Bensouda, Nicolas Danchin, Jean Dallongeville, Bruno Falissard, Alain Furber, Yves Cottin, Laurent Bonello, Olivier Morel, Florence Leclercq, Etienne Puymirat, Fahmi Ghanem, Nicolas Delarche, Jacques Benichou, Lucien Abenhaim
OBJECTIVE: To compare ticagrelor and prasugrel with clopidogrel for recurrent fatal and non-fatal myocardial infarction (reMI) in real-life conditions. METHODS: Case-referent study using the Pharmacoepidemiological General Research eXtension (PGRx)-acute coronary syndrome (ACS) registry. Cases were patients with reMI from a cohort with index ACS or external to the cohort (same sites). Referents from the cohort, without recurrent event, were matched on index ACS type and date, age and sex with reMI cases...
March 13, 2018: Heart: Official Journal of the British Cardiac Society
Giuseppe Brescia, Daniela Parrino, Lorenzo Nicolè, Claudia Zanotti, Cristiano Lanza, Umberto Barion, Filippo Marino, Gino Marioni
PURPOSE: The term aspirin-exacerbated respiratory disease (AERD) refers to a combination of asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), and acute respiratory tract reactions to nonsteroidal anti-inflammatory drugs. AERD has now been included among the CRSwNP endotypes, and is considered one of the most aggressive in terms of disease recurrence. Cortactin is a multi-domain protein with a part in several cellular mechanisms involving actin assembly and cytoskeleton arrangement...
March 5, 2018: American Journal of Otolaryngology
Yan Qiao, Tingting Yang, Yong Gan, Wenzhen Li, Chao Wang, Yanhong Gong, Zuxun Lu
BACKGROUND: Epidemiological studies have clarified the potential associations between regular aspirin use and cancers. However, it remains controversial on whether aspirin use decreases the risk of cancers risks. Therefore, we conducted an updated meta-analysis to assess the associations between aspirin use and cancers. METHODS: The PubMed, Embase, and Web of Science databases were systematically searched up to March 2017 to identify relevant studies. Relative risks (RRs) with 95% confidence intervals (CIs) were used to assess the strength of associations...
March 13, 2018: BMC Cancer
Jeehoon Kang, Jung-Kyu Han, Youngkeun Ahn, Shung Chull Chae, Young Jo Kim, In-Ho Chae, Seung-Ho Hur, In-Whan Seong, Jei-Keon Chae, Myeong Chan Cho, Ki-Bae Seung, Myung Ho Jeong, Han-Mo Yang, Kyung Woo Park, Hyun-Jae Kang, Bon-Kwon Koo, Hyo-Soo Kim
Third-generation P2Y12 inhibitors (prasugrel, ticagrelor) are recommended in acute myocardial infarction (AMI). We aimed to evaluate the efficacy and safety of third-generation P2Y12 inhibitors in East Asian AMI patients. From the Korean AMI Registry, 9,355 patients who received dual antiplatelet agent (aspirin with clopidogrel [AC], 6,444 [70.5%] patients; aspirin with prasugrel [AP], 1,100 [11.8%] patients; or aspirin with ticagrelor [AT], 1,811 [19.4%] patients) were analysed. In-hospital endpoints were all-cause mortality or bleeding events during admission and 1-year endpoints were major adverse cardiac and cerebrovascular events (MACCE) and major bleeding events...
March 2018: Thrombosis and Haemostasis
Jacek Staszewski, Renata Piusińska-Macoch, Ewa Skrobowska, Bogdan Brodacki, Katarzyna Macek, Adam Stępień
BACKGROUND: The clinical significance of aspirin resistance (AR) in patients with symptomatic cerebrovascular disease is not well known. The aim of this single-center, prospective study was to examine the prevalence, risk factors and prognostic significance of AR in patients with different clinical manifestations of cerebral small vessel disease (CSVD) over 24-month follow-up. METHODS: We studied 104 patients with MRI confirmed CSVD, including those with recent lacunar stroke (LS, n=49), vascular parkinsonism (VaP, n=16) and dementia (VaD, n=39)...
January 2018: Annals of Clinical and Laboratory Science
Stefan James
No abstract text is available yet for this article.
March 13, 2018: Circulation
Anirban Basu, David Meltzer
BACKGROUND: In value of information (VOI) calculations, such as the expected value of perfect information (EVPI), partial perfect information (EVPPI), sample information (EVSI) or implementation (EVIM), the maximum expected value criterion defines the decision making criterion for the adoption of decisions for treatments. However, because decision makers are often risk averse, the uncertainty that accompanies a decision problem may influence adoption decisions. METHODS: VOI estimates were studied based on 2 alternate decision making criteria: 1) maximum expected value and 2) 95% credible intervals...
March 1, 2018: Medical Decision Making: An International Journal of the Society for Medical Decision Making
Diren Arsoy, Nicholas J Giori, Steven T Woolson
BACKGROUND: The use of chemoprophylaxis to prevent thromboembolic disease after primary THA and TKA can be associated with postoperative bleeding complications. Mechanical prophylaxis has been studied as an alternative to chemoprophylaxis with greater safety in patients undergoing THA, but no data have been published comparing the safety of chemoprophylaxis versus mechanical methods for patients undergoing TKA. The risk of readmission resulting from bleeding and venous thromboembolism (VTE) has also not been determined for patients undergoing THA or TKA when treated with low-molecular-weight heparin (LMWH) alone compared with mechanical prophylaxis plus aspirin (ASA)...
February 2018: Clinical Orthopaedics and related Research
Wahid Bouida, Kaouthar Beltaief, Houda Baccouche, Mouna Sassi, Zohra Dridi, Imen Trabelsi, Kamel Laaouiti, Taher Chakroun, Ilhem Hellara, Riadh Boukef, Nabil Sakly, Mohsen Hassine, Faouzi Added, Rabie Razgallah, Fadhel Najjar, Semir Nouira
AIMS: Ramadan fasting (RF) may affect aspirin resistance. We conducted this study in patients with cardiovascular risk (CVR) factors to assess the effect of RF on aspirin resistance and explore whether type 2 diabetes mellitus (DM) would influence this effect. METHODS: A total of 177 stable patients with ≥2 CVR factors were recruited. All patients observed RF and were taking aspirin. Physical exam and standard biological tests including glycaemia and serum lipids data were performed before Ramadan (Pre-R), at the last week of Ramadan (R) and four weeks after the end of Ramadan (Post-R)...
2018: PloS One
Justin M Cloutier, Clarence Khoo, Brett Hiebert, Anthony Wassef, Colette M Seifer
OBJECTIVES: The objectives of this study were to evaluate the effectiveness of a physician notification system for atrial fibrillation (AF) detected on cardiac devices, and to assess predictors of anticoagulation in patients with device-detected AF. METHODS: In 2013, a physician notification system for AF detected on a patient's CIED [including pacemakers, implantable cardioverter defibrillators (ICD) or cardiac resynchronization therapy (CRT) devices] was implemented, with a recommendation to consider oral anticoagulation in high-risk patients...
April 2018: Therapeutic Advances in Cardiovascular Disease
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