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https://www.readbyqxmd.com/read/28635653/virtual-screening-against-phosphoglycerate-kinase-1-in-quest-of-novel-apoptosis-inhibitors
#1
Jie Xia, Bo Feng, Qianhang Shao, Yuhe Yuan, Xiang Simon Wang, Naihong Chen, Song Wu
Inhibition of apoptosis is a potential therapy to treat human diseases such as neurodegenerative disorders (e.g., Parkinson's disease), stroke, and sepsis. Due to the lack of druggable targets, it remains a major challenge to discover apoptosis inhibitors. The recent repositioning of a marketed drug (i.e., terazosin) as an anti-apoptotic agent uncovered a novel target (i.e., human phosphoglycerate kinase 1 (hPgk1)). In this study, we developed a virtual screening (VS) pipeline based on the X-ray structure of Pgk1/terazosin complex and applied it to a screening campaign for potential anti-apoptotic agents...
June 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28635374/sepsis-favors-high-on-clopidogrel-platelet-reactivity
#2
Karolina Akinosoglou, Angelos Perperis, Spyridoula Theodoraki, Dimitrios Alexopoulos, Charalambos Gogos
High-on-treatment platelet reactivity (HPR) is associated with ischemic events in patients on antiplatelet therapy with a history of cardiovascular disease. On the other hand, recent data have associated sepsis with adverse cardiovascular events in patients admitted with bacteremia or respiratory infection. We aimed to assess P2Y12-mediated platelet reactivity (PR) during sepsis and recovery in patients under clopidogrel. This was a prospective observational study. Incoming patients presenting with signs/symptoms of sepsis already on a maintenance dose of clopidogrel of 75 mg qd for cardiovascular events were included in this study...
June 21, 2017: Platelets
https://www.readbyqxmd.com/read/28635339/methods-for-estimating-costs-in-patients-with-hyperlipidemia-experiencing-their-first-cardiovascular-event-in-the-united-kingdom
#3
Mark D Danese, Michelle Gleeson, Robert I Griffiths, David Catterick, Lucie Kutikova
AIMS: Methods for integrating external costs into clinical databases are not well-characterized. The purpose of this research was to describe and implement methods for estimating the cost of hospitalizations, prescriptions, and general practitioner and specialist visits used to manage hyperlipidemia patients experiencing cardiovascular (CV) events in the United Kingdom (UK). METHODS: This study was a retrospective cohort study using the Clinical Practice Research Datalink and Hospital Episode Statistics data...
June 21, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28635328/dietary-implications-for-patients-receiving-long-term-oral-anticoagulation-therapy-for-treatment-and-prevention-of-thromboembolic-disease
#4
Emmanouela Kampouraki, Farhad Kamali
The effectiveness of oral anticoagulation therapy with warfarin (a vitamin K antagonist) in the treatment of thromboembolic disease, including stroke prophylaxis in patients with atrial fibrillation is well recognised. However, warfarin has a narrow therapeutic window and an unpredictable anticoagulation response, which make it difficult to achieve and maintain optimal anticoagulation. Various dietary factors, including sudden changes in eating patterns, can significantly alter anticoagulation control, thereby potentially exposing patients to the risk of bleeding or thromboembolic complications...
June 21, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28634421/the-role-of-von-willebrand-factor-in-vascular-inflammation-from-pathogenesis-to-targeted-therapy
#5
REVIEW
Felice Gragnano, Simona Sperlongano, Enrica Golia, Francesco Natale, Renatomaria Bianchi, Mario Crisci, Fabio Fimiani, Ivana Pariggiano, Vincenzo Diana, Andreina Carbone, Arturo Cesaro, Claudia Concilio, Giuseppe Limongelli, Mariagiovanna Russo, Paolo Calabrò
Beyond its role in hemostasis, von Willebrand factor (VWF) is an emerging mediator of vascular inflammation. Recent studies highlight the involvement of VWF and its regulator, ADAMTS13, in mechanisms that underlie vascular inflammation and immunothrombosis, like leukocyte rolling, adhesion, and extravasation; vascular permeability; ischemia/reperfusion injury; complements activation; and NETosis. The VWF/ADAMTS13 axis is implicated in the pathogenesis of atherosclerosis, promoting plaque formation and inflammation through macrophage and neutrophil recruitment in inflamed lesions...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28634365/different-levels-of-blood-pressure-different-benefit-from-dual-antiplatelet-therapy-in-minor-stroke-or-tia-patients
#6
Jie Xu, Yongli Tao, Hao Li, Hongqiu Gu, Xuewei Xie, Xia Meng, Yuming Xu, Yilong Wang, Yongjun Wang
The study aimed to evaluate whether the benefits of dual antiplatelet therapy would be influenced by blood pressure (BP) levels, among acute minor stroke or transient ischemic attack (TIA). In CHANCE (Clopidogrel in High-Risk Patients with Acute Nondisabling cerebrovascular Events) trail, Patients were stratified by systolic BP (SBP) and diastolic BP (DBP) level measured on admission, respectively, using the supine position BP within 24 hours after symptoms onset. The primary efficacy outcome was stroke recurrence, bleeding was the safety outcome...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634314/-a-case-of-moyamoya-disease-associated-with-sapho-syndrome
#7
Nobutaka Horie, Mayuko Baba, Ken Kawada, Yuuki Matsunaga, Eisaku Sadakata, Yoichi Morofuji, Tsuyoshi Izumo, Minoru Morikawa, Takeo Anda, Takayuki Matsuo
Moyamoya disease is a unique occlusive disease of the internal carotid artery(ICA)with moyamoya vessels that can lead to transient ischemic attacks and hemorrhagic stroke. When other inherited or acquired disorders and conditions occur in conjunction with moyamoya disease, the syndrome is known as quasi-moyamoya disease. We report the case of a 34-year-old woman with a past history of SAPHO(Synovitis-Acne-Pustulosis-Hyperostosis-Osteomyelitis)syndrome, who presented with arm weakness and headache. Magnetic resonance angiography revealed severe terminal stenosis of the left ICA with moyamoya vessels, and she was diagnosed as moyamoya disease associated with SAPHO syndrome...
June 2017: No Shinkei Geka. Neurological Surgery
https://www.readbyqxmd.com/read/28634198/the-effect-of-sustained-virological-response-on-the-risk-of-extrahepatic-manifestations-of-hepatitis-c-virus-infection
#8
Parag Mahale, Eric A Engels, Ruosha Li, Harrys A Torres, Lu-Yu Hwang, Eric L Brown, Jennifer R Kramer
BACKGROUND AND AIM: Chronic HCV infection is associated with several extrahepatic manifestations (EHMs). Data on the effect of sustained virological response (SVR) on the risk of EHMs are limited. METHODS: We conducted a retrospective cohort study using data of patients from the US Veterans Affairs HCV Clinical Case Registry who had a positive HCV RNA test (10/1999-08/2009). Patients receiving interferon-based antiviral therapy (AVT) were identified. SVR was defined as negative HCV RNA at least 12 weeks after end of AVT...
June 20, 2017: Gut
https://www.readbyqxmd.com/read/28634003/spasticity-video-challenge-a-look-at-methods-for-addressing-difficult-cases
#9
Katharine E Alter, Mark Gormley, Atul T Patel
As seen in this CME online activity (available at http://courses.elseviercme.com/spasticity/662e), treatment of patients with spasticity due to upper motor neuron syndromes, including traumatic brain injury, stroke, and cerebral palsy, is multifaceted, involving chemodenervation, systemic medications, surgical therapy, rehabilitation efforts, and home care. Optimal care begins with the recognition that each patient's impairments are unique and must be assessed carefully to determine the impact of muscle overactivity, loss of dexterity, and weakness on passive and active function in the context of the patients' goals...
June 17, 2017: PM & R: the Journal of Injury, Function, and Rehabilitation
https://www.readbyqxmd.com/read/28632508/combined-dextroamphetamine-and-transcranial-direct-current-stimulation-in-poststroke-aphasia
#10
Zafer Keser, Michelle Weber Dehgan, Shaparak Shadravan, Nuray Yozbatiran, Lynn M Maher, Gerard E Francisco
There is a growing need for various effective adjunctive treatment options for speech recovery after stroke. A pharmacological agent combined with noninvasive brain stimulation has not been previously reported for poststroke aphasia recovery. In this "proof of concept" study, we aimed to test the safety of a combined intervention consisting of dextroamphetamine, transcranial direct current stimulation, and speech and language therapy in subjects with nonfluent aphasia. Ten subjects with chronic nonfluent aphasia underwent two experiments where they received dextroamphetamine or placebo along with transcranial direct current stimulation and speech and language therapy on two separate days...
June 20, 2017: American Journal of Physical Medicine & Rehabilitation
https://www.readbyqxmd.com/read/28631762/-safety-and-tolerability-of-oral-hypoglycemic-therapies-in-type-2-diabetes-mellitus-patients-at-high-cardiovascular-risk
#11
Giuseppe Ambrosio, Gaetano M De Ferrari, Massimo Federici, Pasquale Perrone Filardi
Oral hypoglycemic drugs for type 2 diabetes aim at preventing the metabolic effects of hyperglycemia and cardiovascular (CV) events. The evidence of the possible CV risk related to the prescription of some antidiabetic drugs prompted regulatory agencies to require safety studies. This review provides an updated analysis of CV safety profiles for antidiabetic drugs used for the treatment of patients with high CV risk.The most recent studies analyze different aspects of CV morbidity, such as ischemic events, heart failure and arrhythmia, and their interactions with hyperglycemia...
June 2017: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/28630234/multiparametric-model-for-penumbral-flow-prediction-in-acute-stroke
#12
Michelle Livne, Tabea Kossen, Vince I Madai, Olivier Zaro-Weber, Walter Moeller-Hartmann, Kim Mouridsen, Wolf-Dieter Heiss, Jan Sobesky
BACKGROUND AND PURPOSE: Identification of salvageable penumbra tissue by dynamic susceptibility contrast magnetic resonance imaging is a valuable tool for acute stroke patient stratification for treatment. However, prior studies have not attempted to combine the different perfusion maps into a predictive model. In this study, we established a multiparametric perfusion imaging model and cross-validated it using positron emission tomography perfusion for detection of penumbral flow. METHODS: In a retrospective analysis of 17 subacute stroke patients with consecutive magnetic resonance imaging and H2O15 positron emission tomography scans, perfusion maps of cerebral blood flow, cerebral blood volume, mean transit time, time-to-maximum, and time-to-peak were constructed and combined using a generalized linear model (GLM)...
June 19, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28630232/long-noncoding-rna-h19-promotes-neuroinflammation-in-ischemic-stroke-by-driving-histone-deacetylase-1-dependent-m1-microglial-polarization
#13
Jue Wang, Haiping Zhao, Zhibin Fan, Guangwen Li, Qingfeng Ma, Zhen Tao, Rongliang Wang, Juan Feng, Yumin Luo
BACKGROUND AND PURPOSE: Long noncoding RNA H19 is repressed after birth, but can be induced by hypoxia. We aim to investigate the impact on and underlying mechanism of H19 induction after ischemic stroke. METHODS: Circulating H19 levels in stroke patients and mice subjected to middle cerebral artery occlusion were assessed using real-time polymerase chain reaction. H19 siRNA and histone deacetylase 1 (HDAC1) plasmid were used to knock down H19 and overexpress HDAC1, respectively...
June 19, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28629806/prevalence-of-bleeding-complications-following-ultrasound-guided-botulinum-toxin-injections-in-patiens-on-anticoagulation-or-antiplatelet-therapy
#14
Jeffrey Lavallee, Regan Royer, Geoffrey Smith
BACKGROUND: Patients on anticoagulation or antiplatelet therapy may be at higher risk of bleeding complications following intramuscular chemodenervation injections. Musculoskeletal ultrasound may be able to reduce the risk of bleeding complications by providing real time visualization of vascular structures and post-injection monitoring. Limited data exist addressing risk of bleeding complications following ultrasound-guided botulinum neurotoxin intramuscular chemodenervation procedures in the setting of anticoagulation or antiplatelet therapy...
June 16, 2017: PM & R: the Journal of Injury, Function, and Rehabilitation
https://www.readbyqxmd.com/read/28629575/outcome-of-patients-with-proximal-vessel-occlusion-of-the-anterior-circulation-and-dwi-pwi-mismatch-is-time-dependent
#15
Sibu Mundiyanapurath, Sascha Diatschuk, Sarah Loebel, Johannes Pfaff, Mirko Pham, Markus Alfred Möhlenbruch, Wolfgang Wick, Martin Bendszus, Peter A Ringleb, Alexander Radbruch
BACKGROUND AND PURPOSE: Patients with ischemic stroke and large vessel occlusion are assumed to benefit from endovascular therapy (ET) independent of the symptom onset-to-treatment time (OTT) if they present with a mismatch of diffusion- and perfusion-weighted imaging (DWI-PWI mismatch). We aimed at studying the influence of OTT on clinical outcome in these patients. METHODS: Retrospective database review in a tertiary care university hospital. All patients presented with proximal vessel occlusion of the anterior circulation and DWI-PWI mismatch...
June 2017: European Journal of Radiology
https://www.readbyqxmd.com/read/28629510/screening-strategies-for-atrial-fibrillation-a-systematic-review-and-cost-effectiveness-analysis
#16
Nicky J Welton, Alexandra McAleenan, Howard Hz Thom, Philippa Davies, Will Hollingworth, Julian Pt Higgins, George Okoli, Jonathan Ac Sterne, Gene Feder, Diane Eaton, Aroon Hingorani, Christopher Fawsitt, Trudie Lobban, Peter Bryden, Alison Richards, Reecha Sofat
BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia that increases the risk of thromboembolic events. Anticoagulation therapy to prevent AF-related stroke has been shown to be cost-effective. A national screening programme for AF may prevent AF-related events, but would involve a substantial investment of NHS resources. OBJECTIVES: To conduct a systematic review of the diagnostic test accuracy (DTA) of screening tests for AF, update a systematic review of comparative studies evaluating screening strategies for AF, develop an economic model to compare the cost-effectiveness of different screening strategies and review observational studies of AF screening to provide inputs to the model...
May 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28629235/atrial-fibrillation-as-a-complication-of-ibrutinib-therapy-clinical-features-and-challenges-of-management
#17
Bronwyn C Thorp, Xavier Badoux
Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor finding increasingly widespread use in non-Hodgkin lymphoma. Evidence of an increased risk of atrial fibrillation (AF) emerged in Phase III studies with a median incidence of approximately 6%. The mechanism remains unknown, but inhibition of a cardioprotective pathway has been proposed. Ibrutinib induces a platelet function defect, increasing the bleeding risk of anticoagulation for AF stroke prophylaxis. Multiple potential drug interactions are an added complication...
June 20, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28628946/structural-plasticity-of-the-ventral-stream-and-aphasia-recovery
#18
Emilie T McKinnon, Julius Fridriksson, G Russell Glenn, Jens H Jensen, Joseph A Helpern, Alexandra Basilakos, Christopher Rorden, Andy Y Shih, M Vittoria Spampinato, Leonardo Bonilha
Re-strengthening of the residual language network is likely crucial for speech recovery in post-stroke aphasia. Eight participants with chronic aphasia received intensive speech therapy for three weeks, with standardized naming tests and brain MRIs before and after therapy. Kurtosis-based diffusion tensor tractography was used to measure mean kurtosis (MK) along a segment of the inferior longitudinal fasciculus (ILF). Therapy related reduction in the number of semantic but not phonemic errors was associated with strengthening (renormalization) of ILF MK (r=-0...
June 19, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28628597/integrating-health-promotion-into-physical-therapy-practice-to-improve-brain-health-and-prevent-alzheimer-disease
#19
Ellen McGough, Neva Kirk-Sanchez, Teresa Liu-Ambrose
BACKGROUND AND PURPOSE: Alzheimer disease is the most common cause of dementia, and brain pathology appears years before symptoms are evident. Primary prevention through health promotion can incorporate lifestyle improvement across the lifespan. Risk factor assessment and identifying markers of disease might also trigger preventive measures needed for high-risk individuals and groups. SUMMARY OF KEY POINTS: Many potential risk factors are modifiable through exercise, and may be responsive to early intervention strategies to reduce the downward slope toward disability...
July 2017: Journal of Neurologic Physical Therapy: JNPT
https://www.readbyqxmd.com/read/28628594/telehealth-wearable-sensors-and-the-internet-will-they-improve-stroke-outcomes-through-increased-intensity-of-therapy-motivation-and-adherence-to-rehabilitation-programs
#20
Jane H Burridge, Alan Chong W Lee, Ruth Turk, Maria Stokes, Jill Whitall, Ravi Vaidyanathan, Phil Clatworthy, Ann-Marie Hughes, Claire Meagher, Enrico Franco, Lucy Yardley
BACKGROUND AND PURPOSE: Stroke, predominantly a condition of older age, is a major cause of acquired disability in the global population and puts an increasing burden on health care resources. Clear evidence for the importance of intensity of therapy in optimizing functional outcomes is found in animal models, supported by neuroimaging and behavioral research, and strengthened by recent meta-analyses from multiple clinical trials. However, providing intensive therapy using conventional treatment paradigms is expensive and sometimes not feasible because of social and environmental factors...
July 2017: Journal of Neurologic Physical Therapy: JNPT
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