[Possibilities of optimizing therapy in COVID-19 survivors with focal epilepsy]. / Vozmozhnosti optimizatsii terapii u patsientov s fokal'noi epilepsiei, perenesshikh COVID-19.

OBJECTIVE: To study the effect of phenosanoic acid therapy on the frequency of seizures, asthenia and quality of life of adult patients with focal epilepsy who had a new coronavirus infection caused by SARS-CoV-2. MATERIAL AND METHODS: The data of 20 patients with focal epilepsy who suffered COVID-19 and received therapy with phenosanic acid (Dibufelon) were studied. The frequency of epileptic seizures, the severity of asthenia and the quality of life were evaluated according to clinical scales. RESULTS: Significant decrease in the frequency of bilateral tonic-clonic seizures and focal seizures with loss of consciousness was recorded. There was a significant improvement in the quality of life. There was no significant dynamics of asthenia against the background of taking the drug phenosanic acid in patients. CONCLUSION: The preparation of phenosanic acid can be an effective means of add-on therapy in patients with epilepsy who have undergone COVID-19.

Determination of the Prevalence of Postcovid Syndrome and Assessment of the Effectiveness of the Drug Cortexin in the Treatment of Neurological Disorders in Patients with Postcovid Syndrome. Results of the CORTEX Multicenter Clinical and Epidemiological Observational Program.

Objectives. To study the prevalence and clinical manifestations of postcovid syndrome (PCS) in out-patients and to assess the efficacy of treatment with the drug Cortexin at doses of 10 and 20 mg i.m. for 10 days. Materials and methods. A total of 979 patients with PCS from regions of the Russian Federation, Azerbaijan, Kyrgyzstan, and Kazakhstan were studied; mean age was 54.6 ± 4.5 years; duration of COVID-19 was from one month upwards. Investigations involved three visits. The first was on the day of consultation (assessment of complaints, analysis of scale indicators, prescription of drug Cortexin at a dose of 10 or 20 mg i.m. for 10 days). The second visit (telephone consultation) was on day 10-14. The third visit was on day 30 of out-patient treatment. Assessment of patients' status used an asthenia assessment scale (MFI-20), a brief mental state assessment scale (MMSE), the Schulte test, and the Subjective Treatment Quality Assessment Scale. Results. The proportion of patients with PCS was up to 30% of all neurological admissions. The commonest manifestations were: fatigue, general weakness, decreased memory and concentration of attention, vertigo, sleep impairment, irritability, and aggression; less frequent were breathlessness, pain, increased sweating, anosmia, hyposmia, dysgeusia, paresthesia, hair loss, degradation of vision, tachycardia, allergic reactions, menstrual cycle impairments, erectile dysfunction, panic attacks, suicidal ideation, depression and refusal to eat meat. Conclusions: No associations were found between clinical symptomatology and the severity of COVID-19, the volume of lung tissue affected, or different periods of postcovid syndrome. Cortexin was found to be effective at doses of 10 and 20 mg for correcting the cognitive and asthenic manifestations of PCS. Cortexin was found to have anti-anxiety, antidepressant, and anxiolytic effects, which were more marked at the 20-mg dose.

[Determination of the prevalence of postcovid syndrome and assessment of the effectiveness of the drug Cortexin in the treatment of neurological disorders in patients with postcovid syndrome. Results of the multicenter clinical and epidemiological observational program CORTEX]. / Opredelenie rasprostranennosti postkovidnogo sindroma i otsenka effektivnosti preparata Korteksin v terapii nevrologicheskikh narushenii u patsientov s postkovidnym sindromom. Rezul'taty mnogotsentrovoi nablyudatel'noi programmy KORTEKS.

OBJECTIVE: To study the prevalence of clinical manifestations of postcoid syndrome in patients at an outpatient neurological appointment, to evaluate the effectiveness of therapy regimens using Cortexin at doses of 10 mg and 20 mg IM for 10 days. MATERIALS AND METHODS: 674 neurologists from all regions of the Russian Federation, Azerbaijan, Kyrgyzstan and Kazakhstan took part in the study. A total of 979 COVID-19 patients were recruited. The average age is 54.6±0.45 years. The duration of the transferred SARS-CoV-2 days and from 1 month or more 12. 3 visits were carried out: 1 on the day of treatment (assessment of complaints, analysis of scale indicators, prescription of the drug Cortexin in doses of 10-20 mg/m for 10 days). 2 (telephone survey) visit for 10-14 days, 3 visit - for 30 days at the reception. The condition was assessed using the Asthenia Assessment Scale (MFI-20), the Brief Mental Status Assessment Scale (MMSE questionnaire), the Schulte test, and the Subjective Treatment Quality Assessment Scale. RESULTS: The daily proportion of patients with complaints after a previous coronavirus infection was 30% in the total structure of neurological admission. The most common complaints: fatigue, general weakness, decreased memory and concentration, dizziness, sleep disturbance, irritability, aggression, shortness of breath, pain syndromes, excessive sweating, anosmia, hyposmia, perverted taste of paresthesia, hair loss, blurred vision, unstable blood pressure, tachycardia, allergic reactions, menstrual irregularities, erectile dysfunction, apathy, panic attacks, suicidal thoughts, depression, refusal to eat meat. CONCLUSION: There was no significant correlation of clinical symptoms with the severity of COVID-19, the percentage of lung tissue damage, and different periods of postcovid syndrome. The clinical efficacy of the drug Cortexin in dosages of 10 and 20 mg for the correction of cognitive and asthenic disorders has been proven. Revealed anti-anxiety, antidepressant and anxiolytic activity of Cortexin is more pronounced when using a dosage of 20 mg.

Diagnostic value of microbiome biomarkers of the periodonite microbiome in patients with the association of chronic periodontitis and diabetes mellitus type 2.

The place of high-tech methods of molecular biology in clinical laboratory diagnostics of various diseases and the development of a system of biomarkers as an important component of diagnostic research is currently attracting the closest attention of the scientific community. In this paper, an attempt is made to use high-tech metagenomic analysis to solve problems that arise due to the high frequency of association of periodontal diseases with systemic pathology, in particular, with type 2 diabetes mellitus. The aim of the study was to determine the taxonomic and metabolic features of the microbiome of periodontal tissues in periodontal diseases associated with type 2 diabetes mellitus, as a model of the ratio of local and systemic effects of periodontal pathogenic bacteria. The study included 16S shotgun sequencing of bacterial DNA as part of biological material from periodontal pockets/dentoalveolar furrows of 46 people - 15 patients with chronic periodontitis associated with type 2 diabetes mellitus, 15 patients with chronic periodontitis unrelated to systemic pathology, as well as 16 healthy people in the control group, followed by bioinformatic processing of the data obtained. The obtained data allowed us to establish the taxonomic features of the periodontal microbiome in the association of chronic periodontitis with type 2 diabetes mellitus, which included the predominance of representatives of the families Prevotellaceae and Spirochaetaceae in its composition. The features of metabolic processes in periodontal tissues with the participation of the microbiome were also revealed, which consisted in an increase in the exchange of cysteine and methionine against the background of a decrease in the metabolism of pyrimidine, methane, sphingolipids, and the synthesis of fatty acids, which are of diagnostic value in assessing the condition of patients with type 2 diabetes mellitus.

[Acupuncture in the prevention and treatment of stroke: a review of foreign studies]. / Akupunktura v profilaktike i lechenii insul'ta: obzor zarubezhnykh issledovanii.

Acupuncture has been recommended by the World Health Organization (WHO) as an alternative and complementary method for treating stroke and a way to increase the effectiveness of rehabilitation. The data available in the literature suggest that acupuncture has a beneficial effect on the status of patients with stroke. The mechanism of action of acupuncture for stroke includes the following components: 1) stimulation of neurogenesis and cell proliferation in the CNS; 2) regulation of cerebral blood flow; 3) antiapoptosis; 4) regulation of neurotransmitters; 5) improvement of the neuronal synaptic function, stimulation of long-term potentiation; 6) stimulation of neuroplasticity; and 7) decrease in blood-brain barrier permeability. Acupuncture has been proven to have a positive impact on the restoration of stroke-related dysfunctions, such as motor disorders, spasticity, cognitive impairment, and dysphagia. The most commonly used acupuncture points for the treatment of motor disorders are GV20, GB20, LI4, ST36, SP6, LI11, GB39, and motor scalp area; those for the treatment of cognitive dysfunction are GV20 and EX-HN-1, and those for the treatment of dysphagia are GV20, GV16, and CV23. A review of the literature indicates that studies of the clinical potential of acupuncture in the treatment of complications and the prevention of stroke are insufficient. It is assumed that the international community's recent interest in acupuncture methods used in the treatment of stroke will lead to the emergence of new studies and publications.

[The methodology of complex social hygienic investigation of various groups of population and families (In memoriam of professor O. V. Grinina)].

The article expounds main principal positions of professor O. V. Grinina scientific educational methodological school of social hygienic investigations of health of population and family. The methodological analysis of scientific works of professor O. V. Grinina and her disciples was implemented to demonstrate key positions and results of studies constituting scientific school of program methodological basics of complex social hygienic studies of population health, health care and conditions of life of families. The purpose of publication is to characterize indications of the school of complex social hygienic investigations of priority population groups and families. These issues are covered by thematic fundamental works substantiating patterns of formation and estimation of health of families, program methodological issues of complex medical social studies of family and its individual members, availability of large group за disciples developing priority issues of investigation of population health at the level of family and organization of medical care based on the principles of per family observations, general (family) medical practice. The results are demonstrated and patterns are established containing in implemented complex social hygienic per family studies of various population groups, women, children and families in 1970s-1990s. The methodological significance of valid family-focused technologies in new social economic conditions of development of society and health care and principles of curative preventive activities in conditions of mandatory medical insurance are demonstrated. The professor O. V. Grinina substantiated and developed program of medical social characteristic of family. its sections and methodology of long-term continuous monitoring of family. She also determined characteristics of health of family as a group patient, principles of work of out-patient physicians with families directly at the polyclinic district.

[Clinical and molecular-genetic characteristics of X-linked spinal-bulbar amyotrophy (Kennedy's disease) in the Sakha Republic (Yakutia)]. / Klinicheskaia i molekuliarno-geneticheskaia kharakteristika Kh-stseplennoi spinal'no-bul'barnoi amiotrofii Kennedi v Respublike Sakha (Iakutiia).

AIM: To perform a clinical-genealogical and molecular genetic analysis of X-linked spinal-bulbar amyotrophy (Kennedy's disease) in the Sakha Republic (Yakutia). MATERIAL AND METHODS: Six patients, aged from 30 to 60 years, from 4 unrelated Yakut families registered in the Republican genetics registry of hereditary and congenital abnormalities of the Sakha Republic were studied. The average age of onset was 45.1±4.4 years. A clinical-genealogical and molecular genetic methods were used. RESULTS AND CONCLUSION: The prevalence of spinal-bulbar amyotrophy Kennedy in the Republic of Sakha (Yakutia) is 1.3 per 100 thousand, among Yakut men is 2.8 per 100 thousand. Clinical manifestations of the disease in the patients included in the study were similar to those described previously in the literature. Patients underwent molecular genetic diagnosis in exon 1 of the androgen receptor (AR) gene. All of them carried the allele with more than 38 CAG repeats. There was an inverse correlation between the age at disease onset and the number of CAG-repeats. A method of DNA diagnosis of Kennedy's disease with visualization on an agarose gel has been introduced in genetic testing.

[Latent autoimmune diabetes of adults (LADA): The informative value of autoantibodies]. / Latentnyi autoimmunnyi diabet vzroslykh: informativnost' autoantitel.

AIM: To investigate the prevalence of autoantibodies (autoAbs) associated with the development of type 1 diabetes mellitus (T1DM) in latent autoimmune diabetes of adults (LADA) in the Russian Federation. SUBJECTS AND METHODS: A total of 96 patients (46 women and 50 men) with LADA were examined. All the patients underwent an immunological examination including the determination of autoAbs, such as glutamic acid decarboxylase autoAbs (GADA), islet antigen-2 auto-Abs (IA-2A), islet cell cytoplasmic auto-Abs (ICA), zinc transporter 8 auto-Abs (ZnT8A), and insulin auto-Abs (IAA). RESULTS: GADAs were found in 61.5% of the examinees. ICAs were detected in 24%, IA-2As were observed in 57.3%. AutoAbs were more frequently observed in combination than alone. IAAs were least commonly seen in 8.3% and only in combinations. ZnT8As were found in 52.1% of the examinees and they were present alone in 5.2%. CONCLUSION: The antibodies that are most frequently observed in LADA are GADAs, IA-2As and ZnT8As. It is insufficient to identify only GADAs, as the latter are found in only 61.5% of the patients. IA-2As and ZnT8As, which are present in 57.3% and 52.1% of the patients, respectively, should also be used in the diagnosis of LADA. ICAs are much less commonly seen and along with IAAs may be additional markers for LADA.

[WORK-REST CYCLE OF COSMONAUTS IN MISSIONS 22/23-39/40 OF THE INTERNATIONAL SPACE STATION].

Analyzed were the results of in-flight monitoring of the work-rest cycle (WRC) of Russian crewmembers during 17 instances of the International space station crew rotation in the period of 2010-2014. Weakly crew health reports of the MCC-M medical group were reviewed as well as documented overworks, sleep shifts and consequent health complaints as testimonies of WRC intensity level. Hard work schedule characterized 69% of the flight weeks. The contributing factors were extravehicular activities, dock and undock operations with transport vehicles and redock operations with orbital modules, joint work with space shuttle crews, preparations for landing, off-nominal events, cargo transfer, procedures from the Task List and requested by the MCC-M. Facts stated by the analysis give grounds to believe that distribution of equally extra and planned works over days and weeks in 2013-2014 was more uniform as compared with 2010-2012. This seems to somewhat obviate "critical" workload levels on the days of particularly important operations.

[Genetic Variability and Structure of SNP Haplotypes in the DMPK Gene in Yakuts and Other Ethnic Groups of Northern Eurasia in Relation to Myotonic Dystrophy].

The genetic variability of the DMPK locus has been studied in relation to six SNP markers (rs2070736, rs572634, rs1799894, rs527221, rs915915, and rs10415988) in Yakuts with myotonic dystrophy (MD) in the Yakut population and in populations of northern Eurasia. Significant differences were observed in the allele frequencies between patients and a population sample of Yakuts for three SNP loci (rs915915, rs1799894, and rs10415988) associated with a high chance of disease manifestation. The odds ratios (OR) of MD development in representatives of the Yakut population for these three loci were 2.59 (95% CI, p = 0,004), 4.99 (95% CI, p = 0.000), and 3.15 (95% CI, p = 0.01), respectively. Haplotype TTTCTC, which is associated with MD, and haplotype GTCCTT, which was observed only in Yakut MD patients (never in MD patients of non-Yakut origin), were revealed. A low level of variability in the locus of DMRK gene in Yakuts (H(e) = 0.283) compared with other examined populations was noted. An analysis of pairwise genetic relationships between populations revealed their significant differentiation for all the examined loci. In addition, a low level of differentiation in territorial groups of Yakut populations (F(ST) = 0.79%), which was related to the high subdivision of the northern Eurasian population (F(ST) = 11.83%), was observed.

[Heart rate and energy expenditure during extravehicular activity in different time of day].

The article discusses the comparative heart rate (HR) characteristics associated with day and night extravehicular activities (EVA). HR was commonly higher in the night but not in the daytime. Presumably, the reason is psychological and physiological challenges of the night work on the background of natural performance decrement. These circumstances could lead to elevation of psychic tension and, consequently, increase of heartbeats to a greater extent as compared with daytime EVA. According to the correlation analysis data, the pattern of HR relation to physical loads evaluated by energy expenditure in the daytime was other than at night, i.e. it was positive unlike the nighttime correlation. We cannot exclude it that in the daytime increase in cardiac output (CO) in response to physical work was largely due to increase in HR, whereas it was stroke volume that dominated during night work; at least, it could support CO fully in the periods of low loading.

Effects of subchronic exposure to atrazine on zebrafish (Danio rerio).

The aim of this study was to investigate the effects of subchronic exposure to atrazine on fish growth and the development of histopathological changes in selected organs (gill, kidney, liver) in Danio rerio. Juvenile growth tests were performed on D. rerio according to OECD method No. 215. For 28 days, fish at an initial age of 30 days were exposed to the environmental atrazine concentration commonly detected in Czech rivers (0.3 microg/L) and a range of sublethal concentrations of atrazine (3.0, 30.0 and 90.0 microg/L). The results showed decreasing growth rates and morphological changes in the liver (dystrophic lesions of hepatocytes) at 90.0 microg/L of atrazine. The environmental concentration of atrazine in Czech rivers did not have any effect on fish growth and development of histopathological changes in D. rerio. The value of NOEC was 30.0 microg/L and the value of LOEC was 90.0 microg/L.

[Topics of cosmonauts' work and rest management on board the International Space Station].

Intensity of the rest and work cycle (WRC) of the ISS cosmonauts was examined in terms of overplanning, as well as frequency of sleep shifting and incidence of crew overstrain evidenced from the weekly reports of MCC-M medical operators. Level of WRC intensity in the recent ISS missions was compared with the WRC chronicles of early missions made by three crewmembers including one cosmonaut, and subsequent missions by six crewmembers including 2 or 3 cosmonauts. Though weak, a trend toward a WRC reduction in the period of 2010-2011 was achieved through a more realistic task planning for an average cosmonaut.

[Results of operator's work during space flight (experiment "pilot") under different work-and-rest cycles].

The correlation between operator's job quality and crew work-rest cycle (WRC) aboard the International space station was studied. The experiment involved 10 Russian members of ISS missions 17-24 at the age of 35 to 51 yrs. Mission duration varied from 163 to 200 days, averaging 180 days. Each cosmonaut carried out several "pilot" test sessions. The number of sessions per mission ranged from 4 to 6. The procedure consisted of simulating manual operation of transport vehicle Soyuz on the stages of hang-up, berthing and docking with the ISS. Objective job quality parameters were accuracy of the Soyuz and ISS relative motion control and time for completion which actually characterized work rate. WRC intensity was judged by the data of monitoring at the Moscow Mission Control Center. The results lend support to the dependence of operator's efficiency on WRC. In operators aimed at the highest accuracy this dependence manifested itself in work rate parameters; work accuracy but not rate was more WRC-dependent in operators aimed at doing their job fast. In other words, WRC intensity impacted mostly those job qualities that operator considered to be of secondary importance.

[Quality of operator's performance and associated physiological reactions in relation to stress-tolerance].

The purpose was to study operator's stress-resistance by correlating the results of work with its physiological effects associated with the sympathetic system reactions. Hard- and software Neurolab-200M was used to test 10 subjects in two experiments with different stressful conditions. Work efficiency was assessed by time for completion and accuracy of the "Manometers test" challenging the ability to perceive information and to take decision under severe time limitation. Heart rate per a minute, systolic and diastolic blood pressure were measured immediately before and during the test. According to the results of the experiments, two subjects demonstrated low stress-resistance when doing the operator's tests. Comparison of the physiological data of these and the rest subjects showed good agreement with the hypothesis that weak stress-resistance, unlike the strong one, is associated with less pronounced stress-induced sympathetic reactions.

[General condition evaluations by members of ISS missions 1 to 15].

Traditionally crew questioning about general wellbeing is a part of their psychic monitoring. Information provided during compasses at the Earth's request is included in the neuropsychic section of the weekly crew health report prepared by the medical support group at the Moscow Mission Control Center. Purpose of the work was to analyze the structure content of comments on well-being made by the members of ISS-1-15 crews as well as emotionality of these comments excited by heavy work-rest schedule and length of space duties. Most often well-being evaluations were positive varying within the range from non-committal "all right" and reserved "It's OK" to exaggerated "terrific" "great" "fine"and "perfect"which were more common to astronauts than cosmonauts. Cosmonauts' comments had the seal of personality It was recognized that the demanding work/rest schedule had little impact on the comments and that they did not change with time during 24-wk missions.

[Evaluation of operator's quality using test "Manometers" implemented with the use of hard- and software Neurolab-2000M].

Purpose of the work was to correlate the quality parameters (speed and accuracy) of test Manometers implementation with the use of hard- and software Neurolab-2000M. The operator's quality parameters were latent reaction time (LRT) as a speed criterion, number of errors as an accuracy criterion, and speed and accuracy dependent time of task presentation (TP). The parameters were related by evaluation of statistical significance of calculated linear correlation coefficients Correlations between TP and LRT as well as between LRT and the number of errors were neither unique nor significant. On the opposite, TP and the number of errors were in direct correlation on the level of proximity and high statistical significance. These results suggest that, like the number of errors, TP can serve as a criterion of test completion accuracy. Regarding LRT, the parameter is not suitable for evaluation of accuracy of the Manometers test completion.

[Job quality evaluation with regard to individual stress tolerance of operators].

Male test-subjects (n = 8, 25 to 36 years of age) were kept awake and working for 67 hrs. in an anechoic room. Every 1-2 hours the test-subjects performed eye-tracking of rhythmic light points with an abrupt and unexpected change of frequency. The task was to strike the key the moment the frequency was noticed to have changed. One test session took 10 to 15 minutes; depending on test duration, the number of frequency change could be from 38 up to 59-60. The moments of frequency change and keystroke were registered. Latent reaction time was determined (LRT). Individual LRT values and variations (SD) were evaluated. A statistically significant correlation between individual LRT values and variations was established, i.e. high SD corresponded to high LRT values and visa versa. Thus the worst test results were associated with high LRT values and variations, whereas, on the contrary, the best test results were characterized by low LRT values and variations. Data of the investigation are subject to analysis with regard to their relation to operator's stress tolerance; possible neurophysiological mechanisms of this relation are discussed.

[The correlation between the heart contraction rate and the operator's stress-resistance].

There is factual confirmation of the correlation between operator's stress-resistance and heart rate (HR). HR data alone without assessment of the job quality in a group of operators were enough to rank the operators by their resistance to stress. However, there are several requirements to be met. To begin with, operators should experience a weak or moderate mental stress that will modify HR. Secondly, other sympathetic influences should be reduced to a minimum, as they may mask the emotion-driven effects (motor activity, elevated tone of posture muscles, meals). With this in view, HR measurements are advisable during night sleep to escape, in addition, the endogenous sympathetic activation associated with ergotrophic metabolism. In the day time, HR should be measured after 10 to 15 minutes in recumbent position.