In Search of Suspended Judgment

This project is about exploring the process of suspending judgment, and the ways it can be facilitated. The author approaches the subject from different perspectives: through personal practice of suspending judgment and observing one’s own process; through collaboration with professionals from different areas looking for ways of integrating different non-cognitive approaches into a process of Creative Problem Solving (CPS) facilitation; and through exploring practical ways of facilitating suspending judgment with a pilot group. Rather than aiming at achieving concrete results, the project represents the beginning of the journey of exploration. Its main conclusion is that developing the ability to suspend judgment forms an integral part of a personal development process

In Search of Suspended Judgment

This project is about exploring the process of suspending judgment, and the ways it can be facilitated. The author approaches the subject from different perspectives: through personal practice of suspending judgment and observing one’s own process; through collaboration with professionals from different areas looking for ways of integrating different non-cognitive approaches into a process of Creative Problem Solving (CPS) facilitation; and through exploring practical ways of facilitating suspending judgment with a pilot group. Rather than aiming at achieving concrete results, the project represents the beginning of the journey of exploration. Its main conclusion is that developing the ability to suspend judgment forms an integral part of a personal development process

Personalization of Art Students' Training in the Context of the Transition to the Digital Economy

Today, one of the main resources for the effective functioning of many political, sociocultural, and communication processes is transition to the digital economy and digital reality in general. Informatization, computerization, automation naturally integrate into the artistic culture and transform it into a digital one. As a result, changes in the professional field of art definitely require changes in both the content, methodology and technological base of art education in the context of transition to digital economy. At the same time, digital technologies are a factor in the modernization of the higher education system, and its tool. There is an objective need to individualize and personalize educational technologies. In turn, digitalization creates the foundations by which these processes can be implemented. The article specifies pedagogical conditions for personalization of art students' training: activating self-education and self-development mechanisms through the creation of individual educational routes; enriching the informational educational and methodological base to maintain an individual format for studying the content of artistic culture; adopting a personal position of an adviser and a facilitator by the university teacher, which contributes to the design, stimulation and reflection of the personal and competent development of art students. The reliability of conclusions made within this theoretical study is confirmed by the positive results of experimental work

To the 110 anniversary since the birth of professor E.A.Vasyukova

110 years ago was born famous scientist, talented teacher and doctor, organizer of public health, honoured worker of science of RSFSR, doctor of medicine, professor Ekaterina Alekseevna Vasyukova. Ekaterina Alekseevna had long and difficult career path - from research assistant to the director of the All-Russian Institute of Experimental Endocrinology(now Endocrinology Research Centre), was head of it for 10 years, a long time was head of the Department of Endocrinology at the Central Institute of Advanced Medical Ministry of Health (now the Academy of Postgraduate Education). She had more than 200 publications, including 14 monographs, collections and algorithms in endocrinology. Under her leadershipthere were defended 16 doctoral and 63 master's theses. The main areas of her research were the methods of diagnostics and treatment of diabetes, Cushing's disease, thyroid diseases, abnormalities of reproductive growth. In 1971 she had identified the current trends in the nativeclinical endocrinology, which were the relationship between the central nervous system and the endocrine glands; immunopathology in endocrinology; study of the prevalence and prevention of diabetes. EkaterinaAlekseevnawassensitive person, a great clinician, a professional teacher. She had great authority and respect among the medical community of our country and abroad

Genotype-phenotype correlations in SCN8A-related disorders reveal prognostic and therapeutic implications

We report detailed functional analyses and genotype-phenotype correlations in 392 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel Nav1.6, with the aim of describing clinical phenotypes related to functional effects. Six different clinical subgroups were identified: Group 1, benign familial infantile epilepsy (n = 15, normal cognition, treatable seizures); Group 2, intermediate epilepsy (n = 33, mild intellectual disability, partially pharmaco-responsive); Group 3, developmental and epileptic encephalopathy (n = 177, severe intellectual disability, majority pharmaco-resistant); Group 4, generalized epilepsy (n = 20, mild to moderate intellectual disability, frequently with absence seizures); Group 5, unclassifiable epilepsy (n = 127); and Group 6, neurodevelopmental disorder without epilepsy (n = 20, mild to moderate intellectual disability). Those in Groups 1-3 presented with focal or multifocal seizures (median age of onset: 4 months) and focal epileptiform discharges, whereas the onset of seizures in patients with generalized epilepsy was later (median: 42 months) with generalized epileptiform discharges. We performed functional studies expressing missense variants in ND7/23 neuroblastoma cells and primary neuronal cultures using recombinant tetrodotoxin-insensitive human Nav1.6 channels and whole-cell patch-clamping. Two variants causing developmental and epileptic encephalopathy showed a strong gain-of-function (hyperpolarizing shift of steady-state activation, strongly increased neuronal firing rate) and one variant causing benign familial infantile epilepsy or intermediate epilepsy showed a mild gain-of-function (defective fast inactivation, less increased firing). In contrast, all three variants causing generalized epilepsy induced a loss-of-function (reduced current amplitudes, depolarizing shift of steady-state activation, reduced neuronal firing). Functional effects were known for 170 individuals. All 136 individuals carrying a functionally tested gain-of-function variant had either focal (n = 97, Groups 1-3) or unclassifiable (n = 39) epilepsy, whereas 34 individuals with a loss-of-function variant had either generalized (n = 14), no (n = 11) or unclassifiable (n = 6) epilepsy; only three had developmental and epileptic encephalopathy. Computational modelling in the gain-of-function group revealed a significant correlation between the severity of the electrophysiological and clinical phenotypes. Gain-of-function variant carriers responded significantly better to sodium channel blockers than to other anti-seizure medications, and the same applied for all individuals in Groups 1-3. In conclusion, our data reveal clear genotype-phenotype correlations between age at seizure onset, type of epilepsy and gain- or loss-of-function effects of SCN8A variants. Generalized epilepsy with absence seizures is the main epilepsy phenotype of loss-of-function variant carriers and the extent of the electrophysiological dysfunction of the gain-of-function variants is a main determinant of the severity of the clinical phenotype in focal epilepsies. Our pharmacological data indicate that sodium channel blockers present a treatment option in SCN8A-related focal epilepsy with onset in the first year of life

Genotype-phenotype correlations in SCN8A-related disorders reveal prognostic and therapeutic implications

We report detailed functional analyses and genotype-phenotype correlations in 433 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel NaV1.6. Five different clinical subgroups could be identified: 1) Benign familial infantile epilepsy (BFIE) (n=17, normal cognition, treatable seizures), 2) intermediate epilepsy (n=36, mild ID, partially pharmacoresponsive), 3) developmental and epileptic encephalopathy (DEE, n=191, severe ID, majority pharmacoresistant), 4) generalized epilepsy (n=21, mild to moderate ID, frequently with absence seizures), and 5) affected individuals without epilepsy (n=25, mild to moderate ID). Groups 1-3 presented with early-onset (median: four months) focal or multifocal seizures and epileptic discharges, whereas the onset of seizures in group 4 was later (median: 39 months) with generalized epileptic discharges. The epilepsy was not classifiable in 143 individuals. We performed functional studies expressing missense variants in ND7/23 neuroblastoma cells and primary neuronal cultures using recombinant tetrodotoxin insensitive human NaV1.6 channels and whole-cell patch clamping. Two variants causing DEE showed a strong gain-of-function (GOF, hyperpolarising shift of steady-state activation, strongly increased neuronal firing rate), and one variant causing BFIE or intermediate epilepsy showed a mild GOF (defective fast inactivation, less increased firing). In contrast, all three variants causing generalized epilepsy induced a loss-of-function (LOF, reduced current amplitudes, depolarising shift of steady-state activation, reduced neuronal firing). Including previous studies, functional effects were known for 165 individuals. All 133 individuals carrying GOF variants had either focal (76, groups 1-3), or unclassifiable epilepsy (37), whereas 32 with LOF variants had either generalized (14), no (11) or unclassifiable (5) epilepsy; only two had DEE. Computational modeling in the GOF group revealed a significant correlation between the severity of the electrophysiological and clinical phenotypes. GOF variant carriers responded significantly better to sodium channel blockers (SCBs) than to other anti-seizure medications, and the same applied for all individuals of groups 1-3.In conclusion, our data reveal clear genotype-phenotype correlations between age at seizure onset, type of epilepsy and gain- or loss-of-function effects of SCN8A variants. Generalized epilepsy with absence seizures is the main epilepsy phenotype of LOF variant carriers and the extent of the electrophysiological dysfunction of the GOF variants is a main determinant of the severity of the clinical phenotype in focal epilepsies. Our pharmacological data indicate that SCBs present a therapeutic treatment option in early onset SCN8A-related focal epilepsy

Genotype-phenotype correlations in SCN8A-related disorders reveal prognostic and therapeutic implications

We report detailed functional analyses and genotype-phenotype correlations in 392 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel Na(v)1.6, with the aim of describing clinical phenotypes related to functional effects. Six different clinical subgroups were identified: Group 1, benign familial infantile epilepsy (n = 15, normal cognition, treatable seizures); Group 2, intermediate epilepsy (n = 33, mild intellectual disability, partially pharmaco-responsive); Group 3, developmental and epileptic encephalopathy (n = 177, severe intellectual disability, majority pharmaco-resistant); Group 4, generalized epilepsy (n = 20, mild to moderate intellectual disability, frequently with absence seizures); Group 5, unclassifiable epilepsy (n = 127); and Group 6, neurodevelopmental disorder without epilepsy (n = 20, mild to moderate intellectual disability). Those in Groups 1-3 presented with focal or multifocal seizures (median age of onset: 4 months) and focal epileptiform discharges, whereas the onset of seizures in patients with generalized epilepsy was later (median: 42 months) with generalized epileptiform discharges. We performed functional studies expressing missense variants in ND7/23 neuroblastoma cells and primary neuronal cultures using recombinant tetrodotoxin-insensitive human Na(v)1.6 channels and whole-cell patch-clamping. Two variants causing developmental and epileptic encephalopathy showed a strong gain-of-function (hyperpolarizing shift of steady-state activation, strongly increased neuronal firing rate) and one variant causing benign familial infantile epilepsy or intermediate epilepsy showed a mild gain-of-function (defective fast inactivation, less increased firing). In contrast, all three variants causing generalized epilepsy induced a loss-of-function (reduced current amplitudes, depolarizing shift of steady-state activation, reduced neuronal firing). Functional effects were known for 170 individuals. All 136 individuals carrying a functionally tested gain-of-function variant had either focal (n = 97, Groups 1-3) or unclassifiable (n = 39) epilepsy, whereas 34 individuals with a loss-of-function variant had either generalized (n = 14), no (n = 11) or unclassifiable (n = 6) epilepsy; only three had developmental and epileptic encephalopathy. Computational modelling in the gain-of-function group revealed a significant correlation between the severity of the electrophysiological and clinical phenotypes. Gain-of-function variant carriers responded significantly better to sodium channel blockers than to other anti-seizure medications, and the same applied for all individuals in Groups 1-3. In conclusion, our data reveal clear genotype-phenotype correlations between age at seizure onset, type of epilepsy and gain- or loss-of-function effects of SCN8A variants. Generalized epilepsy with absence seizures is the main epilepsy phenotype of loss-of-function variant carriers and the extent of the electrophysiological dysfunction of the gain-of-function variants is a main determinant of the severity of the clinical phenotype in focal epilepsies. Our pharmacological data indicate that sodium channel blockers present a treatment option in SCN8A-related focal epilepsy with onset in the first year of life