Sinteza 2-(1H-indol-3-il)acetil-N-(supstituiranih fenil)hidrazinkarbotioamida i srodnih heterocikličkih spojeva te procjena njihovog antikonvulzivnog djelovanja i toksičnosti

A series of new 5-(1H-indol-3-yl)methyl-4-(substituted aryl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones (4a-g), 5-(1H-indol-3-yl)methyl-N-(substituted aryl)-1,3,4-oxadiazol-2-amines (5a-g) and 5-(1H-indol-3-yl)methyl-N-(substituted aryl)-1,3,4-thiadiazol-2-amines (6a-g) were prepared by treating 2-(1H-indol-3-yl)acetyl-N-(substituted phenyl)hydrazine carbothioamides (3a-g) with suitable reagents. All the newly synthesized compounds were screened for their anticonvulsant activity in the MES model and were compared with the standard drugs phenytoin sodium and carbamazepine. Out of the twenty-one compounds studied, 4b, 4e, 4f, 5b, 5d, 5g, 6b, 6d and 6e showed comparable MES activity to phenytoin and carbamazepine after 0.5 h. Compound 5b showed to be more potent than carbamazepine after 4 h. Compounds 4a, 4c, 4d, 5a, 5c, 5e, 5f, 6f and 6g showed lower neurotoxicity than phenytoin.Reakcijom 2-(1H-indol-3-il)acetil-N-(supstituiranih fenil)hidrazinkarbotioamida (3a-g) s odgovarajućim reaktantom sintetizirana je serija novih 5-(1H-indol-3-il)metil-4-(supstituiranih aril)-2,4-dihidro-3H-1,2,4-triazol-3-tiona (4a-g), 5-(1H-indol-3-yl)metil-N-(supstituiranih aril)-1,3,4-oksadiazol-2-amina (5a-g) i 5-(1H-indol-3-il)metil-N-(supstituiranih aril)-1,3,4-tiadiazol-2-amina (6a-g). Ispitano je antikonvulzivno djelovanje sintetiziranih spojeva na MES modelu i uspoređeno s djelovanjem fenitoin natrija i karbamazepina. Spojevi 4b, 4e, 4f, 5b, 5d, 5g, 6b, 6d i 6e pokazali su MES djelovanje usporedivo s djelovanjem fenitoina i karbamazepina nakon 0,5 h, dok je spoj 5b nakon 4 sata imao snažnije djelovanje od karbamazepina. Osim toga, spojevi 4a, 4c, 4d, 5a, 5c, 5e, 5f, 6f i 6g su manje neurotoksični od fenitoina

Predicating from an early age: edusemiotics and the potential of children’s preconceptions

This paper aims to explain how semiotics and constructivism can collaborate in an educational epistemology by developing a joint approach to prescientific conceptions. Empirical data and findings of constructivist research are interpreted in the light of Peirce’s semiotics. Peirce’s semiotics is an anti-psychologistic logic (CP 2.252; CP 4.551; W 8:15; Pietarinen in Signs of logic, Springer, Dordrecht, 2006; Stjernfelt in Diagrammatology. An investigation on the borderlines of phenomenology, ontology and semiotics, Springer, Dordrecht, 2007) and relational logic. Constructivism was traditionally developed within psychology and sociology and, therefore, some incompatibilities can be expected between these two schools. While acknowledging the differences, we explain that constructivism and semiotics share the assumption of realism that knowledge can only be developed upon knowledge and, therefore, an epistemological collaboration is possible. The semiotic analysis performed confirms the constructivist results and provides a further insight into the teacher-student relation. Like the constructivist approach, Peirce’s doctrine of agapism infers that the personal dimension of teaching must not be ignored. Thus, we argue for the importance of genuine sympathy in teaching attitudes. More broadly, the article also contributes to the development of postmodern humanities. At the end of the modern age, the humanities are passing through a critical period of transformation. There is a growing interest in semiotics and semiotic philosophy in many areas of the humanities. Such a case, on which we draw, is the development of a theoretical semiotic approach to education, namely edusemiotics (Stables and Semetsky, Pedagogy and edusemiotics: theoretical challenge/practical opportunities, Sense Publishers, Rotterdam, 2015)

High platelet reactivity in patients with acute coronary syndromes undergoing percutaneous coronary intervention: Randomised controlled trial comparing prasugrel and clopidogrel

Background: Prasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes. Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e. poor responders, is limited. Objectives: To determine the effects of prasugrel loading on platelet function in patients on clopidogrel and high platelet reactivity undergoing percutaneous coronary intervention for acute coronary syndrome (ACS). Patients: Patients with ACS on clopidogrel who were scheduled for PCI found to have a platelet reactivity ≥40 AUC with the Multiplate Analyzer, i.e. “poor responders” were randomised to prasugrel (60 mg loading and 10 mg maintenance dose) or clopidogrel (600 mg reloading and 150 mg maintenance dose). The primary outcome measure was proportion of patients with platelet reactivity <40 AUC 4 hours after loading with study medication, and also at one hour (secondary outcome). 44 patients were enrolled and the study was terminated early as clopidogrel use decreased sharply due to introduction of newer P2Y12 inhibitors. Results: At 4 hours after study medication 100% of patients treated with prasugrel compared to 91% of those treated with clopidogrel had platelet reactivity <40 AUC (p = 0.49), while at 1 hour the proportions were 95% and 64% respectively (p = 0.02). Mean platelet reactivity at 4 and 1 hours after study medication in prasugrel and clopidogrel groups respectively were 12 versus 22 (p = 0.005) and 19 versus 34 (p = 0.01) respectively. Conclusions: Routine platelet function testing identifies patients with high residual platelet reactivity (“poor responders”) on clopidogrel. A strategy of prasugrel rather than clopidogrel reloading results in earlier and more sustained suppression of platelet reactivity. Future trials need to identify if this translates into clinical benefit

Alcohol dose in septal ablation for hypertrophic obstructive cardiomyopathy

Background: The aim of this study was to evaluate short- and long-term outcomes related to dose of alcohol administered during alcohol septal ablation (ASA) in patients with hypertrophic obstructive cardiomyopathy (HOCM). Current guidelines recommend using 1–3 mL of alcohol administered in the target septal perforator artery, but this recommendation is based more on practical experience of interventionalists rather than on systematic evidence. Methods: We included 1448 patients and used propensity score to match patients who received a low-dose (1.0–1.9 mL) versus a high-dose (2.0–3.8 mL) of alcohol during ASA. Results: The matched cohort analysis comprised 770 patients (n = 385 in both groups). There was a similar occurrence of 30-day post-procedural adverse events (13% vs. 12%; p = 0.59), and similar all-cause mortality rates (0.8% vs. 0.5%; p = 1) in the low-dose group and the high-dose group, respectively. In the long-term follow-up (5.4 ± 4.5 years), a total of 110 (14%) patients died representing 2.58 deaths and 2.64 deaths per 100 patient-years in the low dose and the high dose group (logrank, p = 0.92), respectively. There were no significant differences in the long-term dyspnea and left ventricular outflow gradient between the two groups. Patients treated with a low-dose of alcohol underwent more subsequent septal reduction procedures (logrank, p = 0.04). Conclusions: Matched HOCM patients undergoing ASA with a low-dose (1.0–1.9 mL) or a high-dose (2.0–3.8 mL) of alcohol had similar short- and long-term outcomes. A higher rate of repeated septal reduction procedures was observed in the group treated with a low-dose of alcohol. © 2021 The Author

Use of Portfolios for Assessment in Design and Technology Education

This chapter explores the use of portfolios in assessment, starting with a general overview of the nature of assessment portfolios, then moving on to their use within technology education for developing and assessing capability. I start by considering their early use in public examinations in England and reasons why they were introduced. From this I explore issues presented by using portfolios, their potential and their problems. I draw on a range of research and development projects, mainly from within technology education, then present a case study of portfolio development from research at Goldsmiths, University of London, and use this as a basis for exemplifying the potential of digital portfolios. Finally, I provide hopeful but cautious guidance, drawing from the success stories, the findings, and the concerns raised through the chapter