Key Learning Outcomes for Clinical Pharmacology and Therapeutics Education in Europe: A Modified Delphi Study.

Harmonizing clinical pharmacology and therapeutics (CPT) education in Europe is necessary to ensure that the prescribing competency of future doctors is of a uniform high standard. As there are currently no uniform requirements, our aim was to achieve consensus on key learning outcomes for undergraduate CPT education in Europe. We used a modified Delphi method consisting of three questionnaire rounds and a panel meeting. A total of 129 experts from 27 European countries were asked to rate 307 learning outcomes. In all, 92 experts (71%) completed all three questionnaire rounds, and 33 experts (26%) attended the meeting. 232 learning outcomes from the original list, 15 newly suggested and 5 rephrased outcomes were included. These 252 learning outcomes should be included in undergraduate CPT curricula to ensure that European graduates are able to prescribe safely and effectively. We provide a blueprint of a European core curriculum describing when and how the learning outcomes might be acquired

Οι μακροπρόθεσμες ψυχοκοινωνικές επιπτώσεις της πανδημίας Covid 19 στο σχολικό περιβάλλον της Πρωτοβάθμιας Εκπαίδευσης

Η πανδημία του κορονοϊού που εμφανίστηκε στην Κίνα στα τέλη του 2019 και στην Ελλάδα το 2020 ανάγκασε τις κυβερνήσεις να λάβουν μέτρα κοινωνικής αποστασιοποίησης, μεταξύ των οποίων ήταν η τηλεκπαίδευση. Στην Ελλάδα για ένα αξιόλογο χρονικό διάστημα, όλες οι βαθμίδες εκπαίδευσης λειτουργούσαν εξ αποστάσεως, μέσω σύγχρονης και ασύγχρονης τηλεκπαίδευσης. Ο σκοπός της παρούσας εργασίας είναι να αναδείξει τα χαρακτηριστικά της τηλεκπαίδευσης, τις δυσκολίες της και τις επιπτώσεις στους μαθητές. Στα πλαίσια της εργασίας διεξήχθη ποσοτική έρευνα με σκοπό να διερευνηθούν κυρίως οι μακροπρόθεσμες επιπτώσεις της πανδημίας Covid 19 στον ψυχολογικό και κοινωνικό τομέα όσον αφορά το σχολικό περιβάλλον της Πρωτοβάθμιας Εκπαίδευσης. Η έρευνα πραγματοποιήθηκε με τη χρήση δύο δομημένων διαδικτυακών ερωτηματολογίων στα οποία συμμετείχαν 80 μαθητές Δημοτικού σχολείου και 80 εκπαιδευτικοί Πρωτοβάθμιας Εκπαίδευσης. Τα δεδομένα της έρευνας επεξεργάστηκαν με το στατιστικό πακέτο SPSS. Τα αποτελέσματα της έρευνας έδειξαν ότι τα βασικά προβλήματα της εξ αποστάσεως διδασκαλίας για τους μαθητές ήταν το περιβάλλον εργασίας τους, το οποίο ήταν ακατάλληλο και θορυβώδες. Οι μαθητές εξέφρασαν την άποψη ότι προτιμούν την δια ζώσης διδασκαλία και ανέφεραν δυσκολίες επικοινωνίας στην τηλεκπαίδευση. Κατά τη διάρκεια του εγκλεισμού περνούσαν πολλές ώρες στην οθόνη, αλλά και με τους γονείς τους. Οι εκπαιδευτικοί διέγνωσαν άγχος στους μαθητές και στους ίδιους κατά την περίοδο της καραντίνας ενώ παράλληλα ανέφεραν ότι οι μαθητές είχαν δυσκολίες συγκέντρωσης στο εξ αποστάσεως μάθημα. Επιπλέον, εξέφρασαν την άποψη ότι η αποχή από τις τάξεις είχε αρνητικές επιπτώσεις σε ψυχολογικό και κοινωνικό επίπεδο, αλλά και σε επίπεδο σχολικών δεξιοτήτων στους μαθητές. Σε ότι αφορά τη συγκέντρωση και τη συμμετοχή, οι μαθητές φάνηκε ότι επανήλθαν σε καλό βαθμό μετά το τέλος της τηλεκπαίδευσης, αλλά υστερούν σε κάποιο βαθμό στο μαθησιακό κομμάτι. Οι εκπαιδευτικοί ανέφεραν ότι η εξ αποστάσεως εκπαίδευση δεν ήταν αποτελεσματική, και υπολείπεται σε μεγάλο βαθμό της δια ζώσης εκπαίδευσης.The Covid-19 pandemic that emerged in China in late 2019 and in Greece in 2020 forced governments to adopt social distancing measures, among which was distance education. In Greece for a considerable period of time, all levels of education operated remotely, through synchronous and asynchronous distance learning. The purpose of this dissertation is to highlight the characteristics of distance education, its difficulties and the effects on students. As part of the work, quantitative research was conducted in order to investigate the long-term effects of the Covid 19 pandemic in the psychological and social field regarding the school environment of Primary Education. The research was carried out using two structured online questionnaires with the participation of 80 primary school students and 80 primary school teachers. The survey data were processed with the SPSS statistical package. The results of the research showed that the main problems of distance learning for the students were their working environment, which was not suitable and with noise problems. Students expressed the opinion that they prefer face-to-face teaching and expressed communication difficulties in distance learning. During the incarceration they spent many hours on computer screen and video games, but also with their parents. The teachers highlighted stress on the students and themselves during the quarantine period and that the students had difficulty concentrating in the distance course. They expressed the opinion that long distance learning had negative effects on the psychological and social level, but also on the school skills level of the students. In terms of concentration and participation, the students recovered to a good degree after the end of distance learning, but they lag behind to some extent in the learning part. Educators reported that distance education was not effective, and fell far short of face to face education

CT Findings of Pulmonary Involvement in Antiphospholipid Syndrome

Aims: Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by vascular thrombosis. Pulmonary changes regarding interstitium and airways have not been described in APS. Our aim was to determine the prevalence of nonthrombotic pulmonary CT manifestations in patients with APS. Study Design: Prospective study. Place and Duration of Study: Department of Pneumonology, First Department of Internal Medicine, Department of Cardiology, Department of Radiology Medicine, between June 2009 and May 2011. Methodology: Ten patients who met criteria for APS (5 primary and 5 secondary to systemic lupus erythematosus) were prospectively identified. All patients underwent chest high-resolution computed tomography (HRCT) and functional assessment including spirometry and 6-minute walking distance. Patients were free of respiratory symptoms. HRCT scans were evaluated for presence of air-trapping, subpleural reticular pattern, centrilobular nodules of ground-glass opacity, cysts, emphysema, atelectasis, consolidation and pleural effusion. Extent of air-trapping was estimated based on a HRCT scoring system. Results: All patients exhibited radiological and functional pattern compatible with smallairway disease, irrespective of smoking status. HRCT findings were negatively correlated with reduced levels of maximum midexepiratory flow (MMEF) 25/75%pred (r=-0.936, p<0.0001). Subpleural basal reticular pattern consistent with fibrosis was seen in 3 patients. Thin-walled cysts and upper-lobe hazy micronodular pattern were detected in 4 patients. Conclusion: CT findings of patients with APS may include air-trapping, subpleural reticular pattern, centrilobular nodules of ground-glass opacity and lung cysts irrespective of smoking history and SLE coexistence. HRCT and functional assessment may be valuable tools in evaluating APS patients

Autophagy Mediates the Delivery of Thrombogenic Tissue Factor to Neutrophil Extracellular Traps in Human Sepsis

Background: Sepsis is associated with systemic inflammatory responses and induction of coagulation system. Neutrophil extracellular traps (NETs) constitute an antimicrobial mechanism, recently implicated in thrombosis via platelet entrapment and aggregation. Methodology/Principal Findings: In this study, we demonstrate for the first time the localization of thrombogenic tissue factor (TF) in NETs released by neutrophils derived from patients with gram-negative sepsis and normal neutrophils treated with either serum from septic patients or inflammatory mediators involved in the pathogenesis of sepsis. Localization of TF in acidified autophagosomes was observed during this process, as indicated by positive LC3B and LysoTracker staining. Moreover, phosphatidylinositol 3-kinase inhibition with 3-MA or inhibition of endosomal acidification with bafilomycin A1 hindered the release of TF-bearing NETs. TF present in NETs induced thrombin generation in culture supernatants, which further resulted in protease activated receptor-1 signaling. Conclusions/Significance: This study demonstrates the involvement of autophagic machinery in the extracellular delivery of TF in NETs and the subsequent activation of coagulation cascade, providing evidence for the implication of this process in coagulopathy and inflammatory response in sepsis. © 2012 Kambas et al

Neutrophil extracellular traps regulate IL-1 beta-mediated inflammation in familial Mediterranean fever

Objective Inflammatory attacks of familial Mediterranean fever (FMF) are characterised by circulation and influx of high number of polymorphonuclear neutrophils (PMN) in the affected sites and profound therapeutic effect of IL-1 beta inhibitors. We investigated the role of neutrophil extracellular traps (NET) in the pathogenesis of FMF, and their involvement in IL-1 beta production. Methods Blood samples were obtained from six FMF patients during remissions and from three patients during attacks. NET formation and NET components were studied by fluorescence techniques, immunobloting and MPO-DNA complex ELISA. Results PMNs from patients released NETs decorated with IL-1 beta during disease attacks. On the other hand, PMNs from patients during remission were resistant to inflammatory stimuli that induce NET release in PMNs from control subjects. Lower basal autophagy levels were identified in PMNs during remission, while induction of autophagy facilitated NET release, suggesting that autophagy is involved in the regulation of NET release. During the resolution of attacks, inhibition of NET formation by negative feedback mechanism was also observed. The anti-inflammatory agents, colchicine and DNAse I, inhibited IL-1 beta production in PMNs and IL-1 beta activity in NETs, respectively. Conclusions We suggest two additive events for triggering the FMF attack; the production of IL-1 beta by PMNs and its release through NETs. At the same time NETs, homeostatically, downregulate further NETosis, facilitating the resolution of attack. Compensatorly, lower basal autophagy of PMNs may protect from crises by attenuating the release of pro-inflammatory NETs

Autophagy Mediates the Delivery of Thrombogenic Tissue Factor to Neutrophil Extracellular Traps in Human Sepsis

<div><h3>Background</h3><p>Sepsis is associated with systemic inflammatory responses and induction of coagulation system. Neutrophil extracellular traps (NETs) constitute an antimicrobial mechanism, recently implicated in thrombosis <em>via</em> platelet entrapment and aggregation.</p> <h3>Methodology/Principal Findings</h3><p>In this study, we demonstrate for the first time the localization of thrombogenic tissue factor (TF) in NETs released by neutrophils derived from patients with gram-negative sepsis and normal neutrophils treated with either serum from septic patients or inflammatory mediators involved in the pathogenesis of sepsis. Localization of TF in acidified autophagosomes was observed during this process, as indicated by positive LC3B and LysoTracker staining. Moreover, phosphatidylinositol 3-kinase inhibition with 3-MA or inhibition of endosomal acidification with bafilomycin A1 hindered the release of TF-bearing NETs. TF present in NETs induced thrombin generation in culture supernatants, which further resulted in protease activated receptor-1 signaling.</p> <h3>Conclusions/Significance</h3><p>This study demonstrates the involvement of autophagic machinery in the extracellular delivery of TF in NETs and the subsequent activation of coagulation cascade, providing evidence for the implication of this process in coagulopathy and inflammatory response in sepsis.</p> </div

Platelet activation by NET-forming neutrophils.

<p>Expression of CD62P (white bar) and annexin V (grey bar) in (i) sepsis neutrophil, (ii) control neutrophils treated with sepsis serum or (iii) treated with <i>E. coli</i> (E.coli), or TNF-α, IL-1β and G-CSF alone (Cyto) or primed with cytokines before the addition of <i>E. coli</i> (Cyto/E. coli). Treatment with bafilomycin A1 or anti-TF mAb in neutrophil cultures or inhibition of PAR-1 signaling in platelets with FLLRN inhibited this effect. (iv) CD62P expression in control platelets stimulated with supernatants (S/N) from control neutrophils treated with sepsis serum and subsequently irradiated to undergo apoptosis, or not. Untreated platelets from control subjects (untreated), or incubated with cytokines (Cyto) or with supernatants from control neutrophils treated with normal serum were used as controls. Expression of CD62P and annexin V was assessed by flow cytometry and presented as mean fluorescent intensity (MFI). Data are representative of four independent experiments and presented as mean ± SD. (*<i>P</i><.05, ‡<i>P</i><.05 compared to control, ns  =  non significant).</p

HMGB1, but not MPO, is colocalized with LC3B in control neutrophils treated with sepsis serum.

<p>Control neutrophils were treated at different time points with sepsis serum and the colocalization of HMGB1 (A) and MPO (B) with LC3B-coated structures was assessed by confocal microscopy (z stack analysis, 0.3 µm per plane). (DNA labeled with DAPI; blue, anti-LC3B mAb; red, anti-HMGB1; green in A, anti-MPO; green in B) (original magnification 1000×). One out of three independent experiments is shown in A–B. Scale bar represents 5 µM. (C) Percentage of neutrophils indicating colocalization of LC3B with TF, HMGB1 or MPO. Quantification of percentage was performed on the count of 50 cells per sample. Data are representative of three independent experiments and presented as mean ± SD. (‡ <i>P</i><.05 compared to control, *<i>P</i><.05).</p