MAPK phosphatase-1 represents a novel antiinflammatory target of glucocorticoids in the human endothelium

Glucocorticoids are well-established anti- inflammatory drugs thought to mainly act by inhibition of proinflammatory transcription factors like NF-κB. In recent years, however, transcription factorindependent mechanisms of glucocorticoid action have been proposed, namely the influence on MAPK pathways. Here we identify MAPK phosphatase-1 (MKP-1) as a pivotal mediator of the anti-inflammatory action of glucocorticoids in the human endothelium. We applied dexamethasone (Dex) to TNF-α-activated human endothelial cells and used the adhesion molecule E-selectin as inflammatory read-out parameter. Dex is known to reduce the expression of E-selectin, which is largely regulated by NF-κB. Here, we communicate that Dex at low concentrations (1–100 nM) markedly attenuates E-selectin expression without affecting NF-κB. Importantly, Dex is able to increase the expression of MKP-1, which causes an inactivation of TNF-α-induced p38 MAPK and mediates inhibition of E-selectin expression. In endothelial MKP-1ˉ/ˉ cells differentiated from MKP-1ˉ/ˉ embryonic stem cells and in MKP-1-silenced human endothelial cells, Dex did not inhibit TNF-α-evoked E-selectin expression. Thus, our findings introduce MKP-1 as a novel and crucial mediator of the anti-inflammatory action of glucocorticoids at low concentrations in the human endothelium and highlight MKP-1 as an important and promising antiinflammatory drug target

CLAS App ML

This is a multi-language (ML) update of the CLAS App original design by Bridget Maher from the School of Medicine at University College Cork, Ireland. The current version has an improve counting mechanism and has been translated from English to Spanish, Catalan and German languages within the European project PATIENT (www.patient-project.eu). The CLAS App ML aims to train good written communication skills as they are essential to the practice of medicine and avoidance of medical error. The hospital discharge letter is probably the most important of all written communications between hospital and General Practitioner (Family Doctors). However, discharge letters vary greatly in quality, structure, cohesion, and ‘readability’. Most discharge letters are written by junior doctors and frequently omit important information. The School of Medicine at University College Cork developed a comprehensive check-list i-phone application to improve the quality of hospital discharge letters. The CLAS scale lists the key elements of a discharge letter - reason for admission, investigations, results, diagnosis, problem list, medications, management plan, name and contact details of doctor writing the letter etc. There are 4 pages of items, divided into various sections. Either a section heading or an individual item can be ticked. Most items score 1, but some items of particular importance, such as medication, score higher. Total CLAS score is 50. At the end, the user is shown his total score and can swipe to see a list of unchecked items. By using the CLAS application as a point-of-practice reference tool, doctors and medical students can improve their letter-writing skills, decrease the risk of medical error and improve patient safety. With the new version CLAS App ML we aim to provide a standard within Europe for the structure of hospital discharge letter. Therefore, the App has been translated to 3 new languages.This work has been partly funded by the Patient Project (with support from the European Commission. 527620-LLP-1-2012-1-NLERASMUS-FEXI, http://patient-project.eu/

Procedural function-based modelling of volumetric microstructures

We propose a new approach to modelling heterogeneous objects containing internal volumetric structures with size of details orders of magnitude smaller than the overall size of the object. The proposed function-based procedural representation provides compact, precise, and arbitrarily parameterised models of coherent microstructures, which can undergo blending, deformations, and other geometric operations, and can be directly rendered and fabricated without generating any auxiliary representations (such as polygonal meshes and voxel arrays). In particular, modelling of regular lattices and cellular microstructures as well as irregular porous media is discussed and illustrated. We also present a method to estimate parameters of the given model by fitting it to microstructure data obtained with magnetic resonance imaging and other measurements of natural and artificial objects. Examples of rendering and digital fabrication of microstructure models are presented

NF05-628 Helping Children Resolve Conflict \u3cem\u3eConflict Mediation Model\u3c/em\u3e

During conflict mediation children learn the skills necessary to reach peaceful resolutions. These skills involve communication, compromise, the ability to see how different aspects of a dispute are related and the ability to consider their own perspective as well as that of another person. Adults play an important role in the socialization of children. They help children develop social skills. This NebFact discusses how to teach children to resolve conflicts

NF05-628 Helping Children Resolve Conflict \u3cem\u3eConflict Mediation Model\u3c/em\u3e

During conflict mediation children learn the skills necessary to reach peaceful resolutions. These skills involve communication, compromise, the ability to see how different aspects of a dispute are related and the ability to consider their own perspective as well as that of another person. Adults play an important role in the socialization of children. They help children develop social skills. This NebFact discusses how to teach children to resolve conflicts

Rotigotine in Hemodialysis-Associated Restless Legs Syndrome : A Randomized Controlled Trial

Background: Restless legs syndrome (RLS) has been associated with insomnia, decreased quality of life, and increased morbidity and mortality in end-stage renal disease. This randomized controlled trial investigated effects of rotigotine in patients with RLS and end-stage renal disease. Study Design: Double-blind placebo-controlled study. Setting & Participants: Adults with moderate to severe RLS (International RLS Study Group Rating Scale [IRLS] >= 15) and Periodic Limb Movement Index (PLMI) >= 15 who were receiving thrice-weekly hemodialysis enrolled from sites in the United States and Europe. Intervention: Following randomization and titration ( Outcomes & Measurements: Primary efficacy outcome: reduction in PLMI, assessed by ratio of PLMI at end of maintenance to baseline. Secondary/other outcomes (P values exploratory) included mean changes from baseline in PLMI, IRLS, and Clinical Global Impression item 1 (CGI-1 [severity of illness]) score. Results: 30 patients were randomly assigned (rotigotine, 20; placebo, 10); 25 (15; 10) completed the study with evaluable data. Mean (SD) PLMI ratio (end of maintenance to baseline) was 0.7 +/- 0.4 for rotigotine and 1.3 +/- 0.7 for placebo (analysis of covariance treatment ratio, 0.44; 95% CI, 0.22 to 0.88; P = 0.02). Numerical improvements were observed with rotigotine versus placebo in IRLS and CGI-1 (least squares mean treatment differences of -6.08 [95% CI, -12.18 to 0.02; P = 0.05] and -0.81 [95% CI, -1.94 to 0.33; P = 0.2]). 10 of 15 rotigotine and 2 of 10 placebo patients were CGI-1 responders (>= 50% improvement). Hemodialysis did not affect unconjugated rotigotine concentrations. The most common adverse events (>= 2 patients) were nausea (rotigotine, 4 [20%]; placebo, 0); vomiting (3 [15%]; 0); diarrhea (1 [5%]; 2 [20%]); headache (2 [10%]; 0); dyspnea (2 [10%]; 0); and hypertension (2 [10%]; 0). Limitations: Small sample size and short duration. Conclusions: Rotigotine improved periodic limb movements and RLS symptoms in the short term among ESRD patients requiring hemodialysis in a small-scale study. No dose adjustments are necessary for hemodialysis patients. (C) 2016 by the National Kidney Foundation, Inc.Peer reviewe