Половые отличия пула свободных аминокислот-нейромедиаторов у крыс Крушинского-Молодкиной

The study of the role of neurotransmitter systems in the pathogenesis of epilepsy is one of the priorities of epileptology. New data on the functions of free neurotransmitter-like amino acid in the central nervous system are of the greatest importance and determine the prospects for the development of novel effective anticonvulsants. It is widely believed in clinical medicine that epilepsy has distinct gender characteristics. The aim of this study was to investigate the gender peculiarities in the content of neurotransmitter amino acids in the brain of Krushinsky-Molodkina (KM) rats, which were used as model organisms for the study of genetically induced audiogenic epilepsy. The content of Asp, Glu, GABA, Gly, and Tau of the medulla oblongata, hippocampus and cerebral cortex were determined using high-performance liquid chromatography (HPLC) in intact KM rats, KM rats exposed to a series of epileptiform seizures, and Wistar rats (control group). Both the Wistar and KM rats had gender distinctions in the distribution of free amino acids among the investigated brain parts. The audiogenic epilepsy was characterized by smoothing gender differences as well as differences between the concentrations of free amino acids in the cortex and medulla oblongata, specific for Wistar rats. The changes observed in male rats after the set of seizures included the increase in GABA concentration and a decrease in the Gly level in all investigated brain parts, as well as the decrease of the Tau content in the cortex and hippocampus. At the same time, the Glu content in cortex increased, while the Asp level decreased. After 6 days of audiogenic stimulations the female KM rats demonstrated the increase in the Glu level in all investigated brain parts, the increase in Gly and Asp levels in hippocampus, and no changes in the GABA content. Thus, after the set of epileptiform seizures the KM rats achieved a new steady state of the studied amino acids pool, which differed in males and females. In this case, gender differences significantly changed after the seizures. © 2020 Russian Academy of Medical Sciences. All rights reserved.The work was performed within the framework of the state task of the IIF UB RAS (Registration number AAAA-A18-118020590108-7)

Skyrmion Hall Effect Revealed by Direct Time-Resolved X-Ray Microscopy

Magnetic skyrmions are highly promising candidates for future spintronic applications such as skyrmion racetrack memories and logic devices. They exhibit exotic and complex dynamics governed by topology and are less influenced by defects, such as edge roughness, than conventionally used domain walls. In particular, their finite topological charge leads to a predicted "skyrmion Hall effect", in which current-driven skyrmions acquire a transverse velocity component analogous to charged particles in the conventional Hall effect. Here, we present nanoscale pump-probe imaging that for the first time reveals the real-time dynamics of skyrmions driven by current-induced spin orbit torque (SOT). We find that skyrmions move at a well-defined angle {\Theta}_{SH} that can exceed 30{\deg} with respect to the current flow, but in contrast to theoretical expectations, {\Theta}_{SH} increases linearly with velocity up to at least 100 m/s. We explain our observation based on internal mode excitations in combination with a field-like SOT, showing that one must go beyond the usual rigid skyrmion description to unravel the dynamics.Comment: pdf document arxiv_v1.1. 24 pages (incl. 9 figures and supplementary information

Взаимосвязь динамики сывороточных концентраций интерлейкина-1β, интерлейкина-6 и интерлейкина-10 с клиническими данными в остром периоде ишемического инсульта в зависимости от стратегии реперфузионной терапии

Aim. To study the relationship between the dynamics of serum concentrations of interleukin-1β, interleukin-6 and interleukin-10 with clinical data in the acute period of ischemic stroke, and the strategy of reperfusion therapy.Materials and methods. In 28 patients with acute ischemic stroke, half of whom underwent intravenous thrombolysis, the concentration of interleukin-1β, interleukin-6 and interleukin-10 was assessed at admission, on the 3rd and 10th day of the disease.Results. The concentration of interleukin-1β and interleukin-6 decreases during the acute period of stroke. The concentration of interleukin-10 remains unchanged for the first 10 days since the development of stroke. When thrombolysis is performed, there is a more significant decrease in interleukin-1β concentration in the hyperacute period of stroke, whereas in patients without reperfusion there is a decrease in interleukin-6 concentration from 1 to 10 days. The concentration of cytokines is associated with age, lipid spectrum, severity of carotid atherosclerosis, myocardial hypertrophy and injection fraction of the heart. Only in the subgroup of thrombolysis, correlations of cytokine concentrations with systolic blood pressure at admission, hemoglobin concentration, total cholesterol and high-density lipoproteins, hematocrit, degree of stenosis of the contralateral carotid artery, injection fraction and the number of antihypertensive drugs prescribed in the hospital were recorded. The concentration of interleukin-6 at day 10 is associated with the severity of stroke at admission, and the level of IL-10 on day 3 of the disease, with the mobility of patients at discharge.Conclusions. In the hyperacute period of stroke, there is a decrease in the pro-inflammatory activity of blood serum, more pronounced in patients undergoing systemic thrombolysis. Concentrations of interleukin1β, interleukin-6 and interleukin-10 are associated with a wide range of parameters characterizing the cardiovascular and functional status, and the pattern of these associations differs depending on the reperfusion therapy strategy. Цель. Изучить взаимосвязь динамики сывороточных концентраций интерлейкина-1β, интерлейкина-6 и интерлейкина-10 с клиническими данными в остром периоде ишемического инсульта в зависимости от стратегии реперфузионной терапии.Материалы и методы. В исследование включены 28 пациентов в возрасте от 47 до 87 (64 ± 13) лет, в том числе 21 мужчина и 7 женщин. У всех пациентов в остром периоде ишемического инсульта, 14 из которых проводилась внутривенная тромболитическая терапия, оценена концентрация интерлейкина-1β, интерлейкина-6 и интерлейкина-10 при поступлении, на 3-и и 10-е сут заболевания. Результаты. Концентрация интерлейкина-1β и интерлейкина-6 снижается в течение острейшего периода инсульта. Концентрация интерлейкина-10 остается неизменной на протяжении первых 10 сут с момента развития мозговой катастрофы. При проведении тромболизиса отмечается более значимое снижение концентрации интерлейкина-1β в острейшем периоде инсульта, тогда как у пациентов без реперфузии наблюдается снижение концентрации интерлейкина-6 с 1-го по 10-е сут заболевания. Концентрация цитокинов ассоциирована с возрастом, параметрами липидного спектра, выраженностью каротидного атеросклероза, гипертрофией миокарда и насосной функцией сердца. Лишь в подгруппе тромболизиса зафиксированы корреляции концентрации цитокинов с величиной систолического артериального давления при поступлении, концентрацией гемоглобина, общего холестерина и липопротеинов высокой плотности, гематокритом, степенью стенозирования контралатеральной сонной артерии, фракцией выброса сердца и количеством антигипертензивных препаратов, назначенных в стационаре. Концентрация интерлейкина-6 на 10-е сут связана с тяжестью инсульта при поступлении в стационар, а уровень интерлейкина-10 на 3-и сут заболевания − с мобильностью пациентов при выписке.Выводы. В острейшем периоде инсульта происходит снижение провоспалительной активности сыворотки крови, более выраженное у пациентов, которым проведен системный тромболизис. Концентрация интерлейкина-1β, интерлейкина-6 и интерлейкина-10 ассоциирована с широким спектром параметров, характеризующих сердечно-сосудистый и функциональный статус, причем паттерн данных ассоциаций отличается в зависимости от стратегии реперфузионной терапии

Хронические нарушения сознания: клинические рекомендации Общероссийской общественной организации «Федерация анестезиологов и реаниматологов»

Хронические нарушения сознания (ХНС) представляют собой синдромы тяжелого поражения центральной нервной системы, приводящие к длительной грубой инвалидизации и требующие значительных усилий по лечению и реабилитации, которые ложатся на медицинские учреждения и на плечи близких пациентов. ХНС развиваются у пациентов после комы и характеризуются наличием бодрствования при полном или практически полном отсутствии признаков осознанного поведения. К ХНС относятся вегетативное состояние (ВС) и состояние минимального сознания (СМС). Также для описания начальных стадий этих состояний используется термин «продленное нарушение сознания» (ПНС). Отдельно выделяют выход из СМС — состояние, которое формируется по мере восстановления когнитивных функций. Диагностика ХНС основывается на многократном структурированном клиническом осмотре с применением специализированных шкал при условии исключения обратимых причин нарушения сознания. Лечение пациентов с ХНС включает в себя поддержание жизненно важных функций, обеспечение оптимального питания и борьбу с типичными осложнениями и сопутствующими состояниями (пролежни, спастичность, боль, пароксизмальная симпатическая гиперактивность и др.). У пациентов с ХНС должна проводиться реабилитация с участием мультидисциплинарной реабилитационной команды в объеме, который определяется проблемами и возможностями конкретного пациента. Наиболее эффективной реабилитация является при условии ее раннего начала. На данный момент однозначных доказательств эффективности каких-либо специфических методов, направленных на восстановление сознания, не получено; изучается ряд соответствующих фармакологических и нефармакологических вмешательств, обязательным условием применения которых является максимально возможная коррекция соматических проблем пациента. Важную роль в ведении пациентов с ХНС играет вовлечение близких пациента, которые, в свою очередь, нуждаются в получении объективной практической информации о состоянии своего родственника и о направлениях реабилитации, а также в психологической помощи

X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes

X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4−/− mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases

Clinical features of post-COVID-19 period. Results of the international register “Dynamic analysis of comorbidities in SARS-CoV-2 survivors (AKTIV SARS-CoV-2)”. Data from 6-month follow-up

Aim. To study the clinical course specifics of coronavirus disease 2019 (COVID-19) and comorbid conditions in COVID-19 survivors 3, 6, 12 months after recovery in the Eurasian region according to the AKTIV register. Material and methods.The AKTIV register was created at the initiative of the Eurasian Association of Therapists. The AKTIV register is divided into 2 parts: AKTIV 1 and AKTIV 2. The AKTIV 1 register currently includes 6300 patients, while in AKTIV 2 — 2770. Patients diagnosed with COVID-19 receiving in- and outpatient treatment have been anonymously included on the registry. The following 7 countries participated in the register: Russian Federation, Republic of Armenia, Republic of Belarus, Republic of Kazakhstan, Kyrgyz Republic, Republic of Moldova, Republic of Uzbekistan. This closed multicenter register with two nonoverlapping branches (in- and outpatient branch) provides 6 visits: 3 in-person visits during the acute period and 3 telephone calls after 3, 6, 12 months. Subject recruitment lasted from June 29, 2020 to October 29, 2020. Register will end on October 29, 2022. A total of 9 fragmentary analyzes of the registry data are planned. This fragment of the study presents the results of the post-hospitalization period in COVID-19 survivors after 3 and 6 months. Results. According to the AKTIV register, patients after COVID-19 are characterized by long-term persistent symptoms and frequent seeking for unscheduled medical care, including rehospitalizations. The most common causes of unplanned medical care are uncontrolled hypertension (HTN) and chronic coronary artery disease (CAD) and/or decompensated type 2 diabetes (T2D). During 3- and 6-month follow-up after hospitalization, 5,6% and 6,4% of patients were diagnosed with other diseases, which were more often presented by HTN, T2D, and CAD. The mortality rate of patients in the post-hospitalization period was 1,9% in the first 3 months and 0,2% for 4-6 months. The highest mortality rate was observed in the first 3 months in the group of patients with class II-IV heart failure, as well as in patients with cardiovascular diseases and cancer. In the pattern of death causes in the post-hospitalization period, following cardiovascular causes prevailed (31,8%): acute coronary syndrome, stroke, acute heart failure. Conclusion. According to the AKTIV register, the health status of patients after COVID-19 in a serious challenge for healthcare system, which requires planning adequate health system capacity to provide care to patients with COVID-19 in both acute and post-hospitalization period