Izgubljeno zaupanje? Izkušnje učiteljev in učencev medšolanjem, ki ga je prekinila pandemija covida-19

This paper aims to help understand how relational trust between students and teachers embedded in the teaching-learning process unfolded during the emergency distance and flexible hybrid education in Serbia in 2020. It also identifies niches in student-teacher relationships that hold potential for repairing and building trust. For the student-teacher relationship to be trust-based and thus conducive to students’ learning and wellbeing, a consensus about role expectations must be achieved. As the Covid-19 crisis interrupted schooling and education, participants faced uncertainties and ambiguities in role enactment, and the cornerstones of relational trust were disrupted. In an effort to understand 1) the context in which trust was challenged, 2) the ways in which trust was disrupted, and 3) the opportunities for its restoration, we relied on a multi-genre dynamic storytelling approach to data collection and values analysis for data processing. A total of 136 students and 117 teachers from 22 schools wrote 581 narratives in three genres: stories, letters and requests. The analysis yielded 22 codes that allowed further understanding of how changes in structural and institutional conditions affected both students’ and teachers’ expectations of each other, and how incongruence of these expectations fed into feelings of helplessness for both students and teachers, disengagement from learning for students, and heavy workload and poor performance for teachers. In addition, the narratives account for positive outcomes when these expectations were met, and for opportunities for trust-building if students’ and teachers’ perspectives are brought to each other’s attention and negotiated locally. Finally, recommendations for restoring trust are given. (DIPF/Orig.

In vitro antiglioma action of indomethacin is mediated via AMP-activated protein kinase/mTOR complex 1 signalling pathway

We investigated the role of the intracellular energy-sensing AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway in the in vitro antiglioma effect of the cyclooxygenase (COX) inhibitor indomethacin. Indomethacin was more potent than COX inhibitors diclofenac, naproxen, and ketoprofen in reducing the viability of U251 human glioma cells. Antiglioma effect of the drug was associated with p21 increase and G2M cell cycle arrest, as well as with oxidative stress, mitochondrial depolarization, caspase activation, and the induction of apoptosis. Indomethacin increased the phosphorylation of AMPK and its targets Raptor and acetyl-CoA carboxylase (ACC), and reduced the phosphorylation of mTOR and mTOR complex 1 (mTORC1) substrates p70S6 kinase and PRAS40 (Ser183). AMPK knockdown by RNA interference, as well as the treatment with the mTORC1 activator leucine, prevented indomethacin-mediated mTORC1 inhibition and cytotoxic action, while AMPK activators metformin and AICAR mimicked the effects of the drug. AMPK activation by indomethacin correlated with intracellular ATP depletion and increase in AMP/ATP ratio, and was apparently independent of COX inhibition or the increase in intracellular calcium. Finally, the toxicity of indomethacin towards primary human glioma cells was associated with the activation of AMPK/Raptor/ACC and subsequent suppression of mTORC1/S6K. By demonstrating the involvement of AMPK/mTORC1 pathway in the antiglioma action of indomethacin, our results support its further exploration in glioma therapy.The International Journal of Biochemistry & Cell Biology (2017), 83: 84-9

Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo

BACKGROUND: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated. METHODS: ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy. RESULTS: Enrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are men and 75% are white; at baseline, the mean ± SD age was 60.3 ± 9.7 years, body mass index was 30.2 ± 5.7 kg/m(2), and duration of T2DM was 9.3 ± 8.2 years. The qualifying ACS was a myocardial infarction in 83% and unstable angina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events. CONCLUSION: ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk