The neuronal correlates of mirror illusion in children with spastic hemiparesis: a study with functional magnetic resonance imaging.

To investigate the neuronal activation pattern underlying the effects of mirror illusion in children/adolescents with normal motor development and in children/adolescents with hemiparesis and preserved contralateral corticospinal organisation. The type of cortical reorganisation was classified according to results of transcranial magnetic stimulation. Only subjects with congenital lesions and physiological contralateral cortical reorganisation were included. Functional magnetic resonance imaging was performed to investigate neuronal activation patterns with and without a mirror box. Each test consisted of a unimanual and a bimanual motor task. Seven children/adolescents with congenital hemiparesis (10-20 years old, three boys and four girls) and seven healthy subjects (8-17 years old, four boys and three girls) participated in this study. In the bimanual experiment, children with hemiparesis showed a significant effect of the mirror illusion (p<0.001 at voxel level, family-wise error corrected at cluster level) in the dorsolateral prefrontal cortex and anterior cingulate cortex of the affected and unaffected hemispheres, respectively. No significant effects of the mirror illusion were observed in unimanual experiments and in healthy participants. Mirror illusion in children/adolescents with hemiparesis leads to activation of brain areas involved in visual conflict detection and cognitive control to resolve this conflict. This effect is observed only in bimanual training. We consider that for mirror therapy in children and adolescents with hemiparesis a bimanual approach is more suitable than a unimanual approach

Дистанционное образование в условиях пандемии: новые вызовы российскому высшему образованию

COVID-19 was the catalyst for many processes that were actively developing in the previous period, including the further introduction of distance education in Russian higher educational institutions. Russian higher education has faced new challenges due to the total transition to distance learning in the face of the pandemic. In March–May 2020, a sociological study was conducted in a number of universities in Yekaterinburg, Chelyabinsk, Moscow. The research purpose was to identify the main challenges universities faced during the pandemic and the prospects for the further development of distance education in Russian higher education. The study used the qualitative and quantitative strategies: a questionnaire survey of students (N=500) from different fields of study (social, humanitarian, technical, economic ones) who received distance learning experience during the pandemic; in-depth interviews with teachers of Russian universities (N=20), frame analysis of students’ cases on their daily practices in online educational interaction (N=42). The study made it possible to identify the challenges faced by Russian higher education in the total transition to distance education in a pandemic: the need to adapt students and teachers to work online (80% of respondents’ answers); decline in the quality of education (62.7% of respondents’ answers); changing the role of a teacher in the educational process (68% of the respondents’ answers); digital divide in the digital culture of the younger and older generation of teachers (67% of respondents’ answers); etc. A number of contradictions were recorded in the further implementation of distance education in Russian higher education. Considering that the policy towards digitalization in Russia has now been declared a priority, higher education cannot remain aloof from technological progress. Besides, the further introduction of distance learning should take place with overcoming the challenges and contradictions faced by Russian higher education during the pandemic, while maintaining the national achievements of Russian higher education, acquired over its long history. © 2020 LLC Ecological Help. All rights reserved

THE EVOLUTION OF MODELLING PRACTICES ON CANADA’S PARLIAMENT HILL: AN ANALYSIS OF THREE SIGNIFICANT HERITAGE BUILDING INFORMATION MODELS (HBIM)

In this paper, we explore the evolution of modelling practices used to develop three significant Heritage Building Information Models (HBIM) on Canada’s Parliament Hill National Historic Site – West Block, Centre Block, and The Library of Parliament. The unique scope, objective, and timeline for each model required an in-depth analysis to select the appropriate classification for Level of Detail (LOD) and Level of Accuracy (LOA). With each project, the refinement of modelling practices and workflows evolved, culminating in one of our most complex and challenging projects – the Library of Parliament BIM. The purpose of this paper is to share ideas and lessons learned for the intricate challenges that emerge when using LOD and LOA classifications including trade-offs between model performance, tolerances, and anticipated BIM use. In addition, we will evaluate how these decisions effected managing the digitization, data processing, data synthesis, and visualisation of the models

Follow-up assessment of high-risk newborns in Switzerland

Target population High-risk newborns in the context of these guidelines are children who were born very preterm (before 32 weeks gestational age) or children who developed a ypoxic ischaemic encephalopathy (Sarnat grade 2–3) during the first hours of life

A novel inhibitor of fatty acid synthase shows activity against HER2+ breast cancer xenografts and is active in anti-HER2 drug-resistant cell lines

Introduction: Inhibiting the enzyme Fatty Acid Synthase (FASN) leads to apoptosis of breast carcinoma cells, and this is linked to human epidermal growth factor receptor 2 (HER2) signaling pathways in models of simultaneous expression of FASN and HER2. Methods: In a xenograft model of breast carcinoma cells that are FASN+ and HER2+, we have characterised the anticancer activity and the toxicity profile of G28UCM, the lead compound of a novel family of synthetic FASN inhibitors. In vitro, we analysed the cellular and molecular interactions of combining G28UCM with anti-HER drugs. Finally, we tested the cytotoxic ability of G28UCM on breast cancer cells resistant to trastuzumab or lapatinib, that we developed in our laboratory. Results: In vivo, G28UCM reduced the size of 5 out of 14 established xenografts. In the responding tumours, we observed inhibition of FASN activity, cleavage of poly-ADPribose polymerase (PARP) and a decrease of p-HER2, p- protein kinase B (AKT) and p-ERK1/2, which were not observed in the nonresponding tumours. In the G28UCM-treated animals, no significant toxicities occurred, and weight loss was not observed. In vitro, G28UCM showed marked synergistic interactions with trastuzumab, lapatinib, erlotinib or gefitinib (but not with cetuximab), which correlated with increases in apoptosis and with decreases in the activation of HER2, extracellular signal-regulated kinase (ERK)1/2 and AKT. In trastuzumab-resistant and in lapatinib-resistant breast cancer cells, in which trastuzumab and lapatinib were not effective, G28UCM retained the anticancer activity observed in the parental cells. Conclusions: G28UCM inhibits fatty acid synthase (FASN) activity and the growth of breast carcinoma xenografts in vivo, and is active in cells with acquired resistance to anti-HER2 drugs, which make it a candidate for further pre-clinical development

Different fatty acid metabolism effects of (−)-epigallocatechin-3-gallate and C75 in adenocarcinoma lung cancer

Background Fatty acid synthase (FASN) is overexpressed and hyperactivated in several human carcinomas, including lung cancer. We characterize and compare the anti-cancer effects of the FASN inhibitors C75 and (−)-epigallocatechin-3-gallate (EGCG) in a lung cancer model. Methods We evaluated in vitro the effects of C75 and EGCG on fatty acid metabolism (FASN and CPT enzymes), cellular proliferation, apoptosis and cell signaling (EGFR, ERK1/2, AKT and mTOR) in human A549 lung carcinoma cells. In vivo, we evaluated their anti-tumour activity and their effect on body weight in a mice model of human adenocarcinoma xenograft. Results C75 and EGCG had comparable effects in blocking FASN activity (96,9% and 89,3% of inhibition, respectively). In contrast, EGCG had either no significant effect in CPT activity, the rate-limiting enzyme of fatty acid β-oxidation, while C75 stimulated CPT up to 130%. Treating lung cancer cells with EGCG or C75 induced apoptosis and affected EGFR-signaling. While EGCG abolished p-EGFR, p-AKT, p-ERK1/2 and p-mTOR, C75 was less active in decreasing the levels of EGFR and p-AKT. In vivo, EGCG and C75 blocked the growth of lung cancer xenografts but C75 treatment, not EGCG, caused a marked animal weight loss. Conclusions In lung cancer, inhibition of FASN using EGCG can be achieved without parallel stimulation of fatty acid oxidation and this effect is related mainly to EGFR signaling pathway. EGCG reduce the growth of adenocarcinoma human lung cancer xenografts without inducing body weight loss. Taken together, EGCG may be a candidate for future pre-clinical development