[Diagnosis of fragility and age resilience from a dynamical systems perspective.]

The concepts of fragility and resilience are often used together to describe elderly people with reduced physical activity. While fragility, which develops with the aging of the body, is a biological syndrome of a decrease in the stressors response resulting from cumulative regression in many physiological systems, and age related a comprehensive assessment of the ability resistance to stress. In this regard, it is important to develop systems and scales for the identification groups of risk among the elderly. The complexity of the solution lies in the fact that the study of fragility and physical resilience is interdisciplinary, primarily related to the health and increase in the active life of older people. The review describes theories based on the mechanisms of physiological aging, among them the theory of a decrease in the ability to stress, in which stress-related to diseases. The cycles of the development of fragility and a decrease in physiological reserves are considered, and, as a consequence, a change in reactivity to stress, which leads to the development and progression of diseases. The article presents data on homeostatic dysregulation in the accumulation of cumulative deficiency and related changes in heart rate variability, which allows early diagnosis of stressors in the elderly. These data will be useful for the development and implementation of preventive measures aimed at improving the quality of life and resistance to stress factors in elderly and senile people.

[Questionnaire of the Ryzhikh National Medical Research Centre for Coloproctology is a new tool for assessing chronic pelvic pain and pelvic organ dysfunction]. / Oprosnik NMITs koloproktologii imeni A.N. Ryzhikh ­ novyi instrument otsenki khronicheskoi tazovoi boli i narusheniya funktsii tazovykh organov.

The article presents the work of a multidisciplinary team of experts from various fields of medicine to optimize the «Questionnaire for assessing chronic pelvic pain and pelvic organ dysfunction (QCPPD) of the Ryzhikh National Medical Research Centre for Coloproctology¼ for use in clinical practice. The survey of respondents was conducted from June 28 to September 28, 2021. As a result of this survey, by repeatedly making edits and clarifications during communication with respondents, the final version was obtained, which allows assessing the patient's subjective sensations by the nature and localization of pelvic pain, sensitivity disorders and pelvic organ function. The main objective of this Questionnaire is to differentiate patients with neurogenic pain from a huge number of patients with chronic pelvic pain. This aspect will allow a more targeted approach to the diagnosis and pathogenetically justified treatment of patients, including after appropriate instrumental examinations. The work of a multidisciplinary team implies a higher degree of objectification and terminological accuracy of the Questionnaire under discussion. The presented version of the «Questionnaire for assessing chronic pelvic pain and pelvic organ dysfunction (QCPPD) of the Ryzhikh National Medical Research Centre for Coloproctology¼ will be primarily used in coloproctological patients with pelvic pain problems and anal incontinence and obstructive defecation. Further studies will be directed to the clinical evaluation of the results of the work carried out.

[Age-related resilience as a manifestation of neurovegetative regulation of organism's functions.]

The concept of human resilience was created to search for new approaches to improving the well-being of middle-aged, elderly and old people. Resilience is based on the physiological mechanisms of maintaining homeostasis and the ability of organs and tissues to regenerate. Identifying the correlation between environmental factors and the level of reactivity of the body is an important aspect in assessing viability. It contributes to an increase in human life expectancy. Age-related resilience is based on neurophysiological mechanisms of protective processes at different levels, including neural networks and epigenetic mechanisms regulating the expression of MANF, TIMP-2, adropin, irisin, CCL2, CCLR2, ß2M genes. The study of medical, psychological, and social indicators of resilience will contribute to the development of new approaches to the correction of age-related pathology.

Genome Features of Probiotic Bifidobacteria Determining Their Strain-Specific Properties.

The aim of the study was to analyze the genome features of the probiotic strains Bifidobacterium longum 379, Bifidobacterium bifidum 1, and Bifidobacterium bifidum 791 and study their antiviral activity. Materials and Methods: Whole genome sequencing of three strains of bifidobacteria was performed on the MiSeq platform (Illumina Inc., USA). The genomes were annotated using the Prokka v. 1.11 utility and RAST genomic server. The individual genetic determinants were searched using the ResFinder 3.2, PathogenFinder, PlasmidFinder, RAST, and Bagel 4 software. The antiviral activity of the strains against influenza A viruses was studied using MDCK cells (Madin-Darby canine kidney cells), the epidemic strain of influenza A/Lipetsk/1V/2018 (H1N1 pdm09) (EPI_ISL_332798), the highly pathogenic avian influenza virus A/common gull/Saratov/1676/2018 (H5N6) strain (EPI_ISL_336925), and neutral red vital dye. Results: The genomes of all studied strains contained determinants responsible for utilization of carbohydrates of plant origin; the genes of key enzymes for the synthesis of tryptophan and folic acid are present in the genomes of B. longum 379 and B. bifidum 791. A feature of the B. bifidum 791 genome is the presence of determinants responsible for the synthesis of thermostable type I bacteriocins - flavucin and lasso peptide. The B. bifidum 791 strain was found to show pronounced antiviral activity against both the strains of influenza A, the supernatant of which suppressed viral replication in vitro up to a dilution of 1:8, and the cells inhibited viral reproduction up to a concentration of 6·106 CFU/ml. Conclusion: The analysis of complete genomes of B. longum 379, B. bifidum 1, and B. bifidum 791 showed features that determine their strain-specific properties, the findings on which were previously made empirically based on indirect signs. In the genomes of B. longum 379 and B. bifidum 791 strains, in contrast to B. bifidum 1 strain, key enzymes for the synthesis of tryptophan and folic acid were found. These substances have an impact on the human body in many ways, including having a thymoleptic effect (reducing emotional stress, irritability, anxiety, eliminating lethargy, apathy, melancholy, anxiety) and regulating cognitive activity. The presence of determinants responsible for the synthesis of thermostable type I bacteriocins in the genome of B. bifidum 791 strain determines its pronounced antiviral activity.

Comparison of Fragments in Human Hemostatic Proteins That Mimics Fragments in Proteins of A/H1N1 Viruses and Coronaviruses.

Objective: To compare the repertoire of proteins of the human hemostatic system and fragments mimicking these proteins in the proteins of influenza A/H1N1 viruses and coronaviruses. Material and methods. Influenza viruses A/H1N1 (A/Brevig Mission/1/18), A/St. Petersburg /RII04/2016 (H1N1)pdm09, coronaviruses SARS-CoV and SARS-CoV-2 (strain Wuhan-Hu-1) were used for comparative computer analysis. The sources of the primary structures of proteins of the analyzed viruses and 41 proteins of the human hemostatic system were publicly available Internet databases, respectively, www.ncbi.nlm.nih.gov and www.nextprot.org. The search for homologous sequences in the structure of viral proteins and hemostatic proteins was carried out by comparing fragments of 12 amino acids in length, taking as related those that showed identity at ≥8 positions. Results. Comparative analysis of the repertoire of cellular proteins of the hemostatic system and fragments mimicking these proteins in the structure of proteins of viruses A/H1N1 1918, A(H1N1)pdm09 isolated in 2016, SARS-CoV and SARS-CoV-2, showed a significant difference between SARS-CoV-2 and analyzed viruses. In the protein structure of the SARS-CoV-2 virus, mimicry was revealed for almost all analyzed hemostasis proteins. As for the comparison of viruses A/H1N1 1918, A(H1N1)pdm09 2016 and SARS-CoV, the influenza virus A/H1N1 1918 and SARS-CoV are the closest in the repertoire of hemostatic proteins. Conclusion. Obtained bioinformatic analysis data can serve as a basis for further study of the role of homologous fragments in the regulation of hemostasis of the host organism.

[Modulation of endothelial factors activity in human endothelial cells in influenza A(H1N1)pdm09 virus infection].

INTRODUCTION: Influenza A virus infection can lead to endothelial dysfunction (ED), including apoptosis of endothelial cells and modulation of endothelial factor activities. Affected biochemical factors may include those playing important roles in vascular homeostasis. However, the effect of this pathogen on the expression pattern of key endothelial factors is still unknown.The aim of this work was to study the expression of endothelial nitric oxide synthase (eNOS) and plasminogen activator inhibitor-1 (PAI-1, serpin E1) in the EA.hy926 endothelial cells. RESEARCH OBJECTIVES: to assess expression of eNOS and PAI-1 in endothelial cells infected with influenza virus A(H1N1)pdm09, and to identify homologous fragments in structure of viral proteins and endothelial factors. MATERIAL AND METHODS: Cells were infected with influenza virus A/St. Petersburg/48/16 (H1N1)pdm09 and analyzed in dynamics in 6, 12, 18, 24, 48, and 72 hrs post infection (hpi). Detection of endothelial factors expression levels was performed by immunocytochemical method (ICC) using antibodies for eNOS and PAI-1 while quantitative assessment of expression levels was carried out by program Nis-Elements F3.2 («Nikon¼, Japan). The search for homologous sequences between viral proteins and eNOS and PAI-1 was performed by computer comparison. Sequences were analyzed as fragments 12 amino acid residues (aar) in length. RESULTS AND DISCUSSION: eNOS expression in infected cells had decreased to 7.9% by 6 hpi (control was taken as 100%) to 3.3% at 72 hpi. PAI-1 expression varied significantly over the course of the experiment: by 6 hpi it had decreased to 49.6%, and to 43.2% by 12 hpi. Later PAI-1 levels were: 116.3% (18 hpi); 18.9% (24 hpi); 23.5% (48 hpi), and 35% (72 hpi). CONCLUSION: These results indicate that influenza A infection of endothelial cells causes a significant decrease in eNOS expression, while modulating PAI-1 one. The described phenomenon can be used in the further development of directions of pathogenetic therapy of vascular complications of infection caused by this pathogen.

[Epigenetic regulation of adaptogenesis by pathology and aging.]

The organism adaptive possibilities by pathology and aging are discussed in account of the epigenetic. The organism adaptation to inner and external factors is carried out by organism unite humoral protective system, inclusive hypothalamus-hypophysis-pineal and hypothalamus-hypophysis-thymus axises. AEDG, AEDP, EDR, KED, EW, KE short peptides are the epigenetic regulators of gene expression and protein synthesis, which can be involve to the adaptation by stress and in the activation of hypothalamus-hypophysis-pineal and hypothalamus-hypophysis-thymus axises. These short peptides regulate the synthesis of proteins of heat shock, stress-protective proteins, cytocines, fibrinolysis and hemostasis factors and can participate in primary and tardive epigenetic regulation of adaptive response by stress, pathology and aging. The early functional diagnostic of element disturbances of organism unite humoral protective system by age-associative pathology can be usefull for the detection of deficient synchronization of epigenetic mechanisms, by wich the depletion and decrease of organism reserve possibilities occurs. The use of peptide can grade the adaptive syndrome manifestation by the stress and age pathology.

Pharmacological disinhibition enhances paced breathing following complete spinal cord injury in rats.

Respiratory dysfunction is one of the most devastating and life-threatening deficits that occurs following cervical spinal cord injury (SCI). Assisted breathing with mechanical ventilators is a necessary part of care for many cervical injured individuals, but it is also associated with increased risk of secondary complications such as infection, muscle atrophy and maladaptive plasticity. Pre-clinical studies with epidural stimulation (EDS) have identified it as an alternative/additional method to support adequate lung ventilation without mechanical assistance. The full potential of EDS, however, may be limited by spinal inhibitory mechanisms within the injured spinal cord. The goal of the present work is to assess the potential improvement for EDS in combination with pharmacological disinhibition of spinal circuits following complete high cervical SCI. All experiments were performed in decerebrate, unanesthetized, non-paralyzed (n = 13) and paralyzed (n = 8) adult Sprague-Dawley rats 6 h following a complete C1 transection. The combination of high-frequency EDS (HF-EDS) at the C4 spinal segment with intrathecal delivery of GABA and glycine receptors antagonists (GABAzine and strychnine, respectively) resulted in significantly increased phrenic motor output, tidal volume and amplitude of diaphragm electrical activity compared to HF-EDS alone. Thus, it appears that spinal fast inhibitory mechanisms limit phrenic motor output and present a new neuropharmacological target to improve paced breathing in individuals with cervical SCI.

[Modeling influenza virus infection in mature Wistar rats].

It has now been established that blood vessels are target for influenza, but the mechanism by which the influenza virus affects the cardiovascular system is unknown. The aim - adaptation of influenza virus A/St. Petersburg/48/16 H1N1(pdm09) to mature Wistar rats, as these animals are the main experimental model for studying the pathology of the cardiovascular system. MATERIAL AND METHODS: Passage of influenza A virus (IAV) in embryonated chicken eggs, intranasal inoculation of rats with virus-containing material s, production of pulmonary homogenate, determination of IAV titer in embryonated chicken eggs, detection of histological changes in lung and pulmonary vessels. RESULTS: The article presents the results of the adaptation of influenza virus A/St. Petersburg/48/16 H1N1(pdm09) to mature Wistar rats. The infectious titer of the virus in the homogenates of infected rats lungs at the last stage of adaptation was 7.0 lg EID50/ml. Histological studies revealed pronounced changes in the respiratory tract (spasm of bronchioles, submucosal edema, desquamation of ciliated epithelium of bronchioles) and pulmonary vessels (spasm, desquamation and swelling of endotheliocytes, dissociation and swelling of the elastic membrane and media). In order to identify IAV in blood vessels and lung tissues, an immunohistochemical study was performed using monoclonal antibodies to NP antigen of IAV. CONCLUSION: The data obtained allow us to conclude that the strain of influenza virus A/St. Petersburg/48/16 H1N1(pdm09) was adapted to mature Wistar rats maintaining virulent properties. The infectious titer of the virus at the last stage of adaptation was 7.0 lg EID50/ml. IAV identification is confirmed by immunohistochemical examination.

PT-symmetric periodic structures with the modulation of the Kerr nonlinearity.

We study the PT-symmetric periodic layered structure with the modulated Kerr nonlinearity. We demonstrate that such systems can be transformed from the full to the broken PT symmetry or in the opposite direction. These transitions in the periodic structure with a finite length may be observed indirectly with the help of the dependence of the transmitted wave intensity on the incident wave intensity. Furthermore, the bistability properties depend on a gain and loss value and the choice of an input surface. The reduction of a feedback between counterpropagating waves is the main impact of the complex PT-symmetric refractive index variation on a bistability curve.

Isolation and characterization of H5Nx highly pathogenic avian influenza viruses of clade 2.3.4.4 in Russia.

In 2016-2017, several subtypes of the highly pathogenic avian influenza (HPAI) virus were isolated on the territory of Russia. In the autumn of 2016, during the avian influenza virus surveillance in the territory of the Kamchatka region of Russia the HPAI A(H5N5) influenza virus was isolated. Then, during 2016-2017, multiple outbreaks among wild birds and poultry caused by HPAI A(H5N8) avian influenza virus were recorded in European part of Russia. At the end of 2017, an outbreak among poultry caused by HPAI A(H5N2) influenza virus was recorded in the European part of Russia. Phylogenetic analysis of HA of the A(H5N5), A(H5N8), A(H5N2) showed the strains belong to the clade 2.3.4.4 b. All isolated strains were antigenically closely related to candidate vaccine viruses of clade 2.3.4.4 and showed high virulence in mice. Genetic analysis revealed presence of genetic markers potentially related to high virulence in mice in all studied viruses.

[Donor age affects on the «behavior¼ and the sensibility bone marrow cells in on copper ion of the primary culture].

The changes of bone marrow cells (BMC) number in the primary culture from 0 to 96 hours, the pattern (the distribution of cells) of cells morphotypes and «lifespan¼ (the time of cell life after isolation) of myelocytes, metamyelocytes, band and segmented neutrophils, isolated of the young (3 months) and old (20months) animals, were investigated. The number of the BMC obtained from intact old animals increased faster in primary culture, than from young animals. The Cu induced fibrosis had different influence on the rate of BMC culture growth of old and young animals. The adding of 4 mM and 8 mM CuSO4x5H2O in the BMC culture of young and old animals resulted in a dose-dependent inhibition of growth rate of young animal cells. If copper ions were added into the culture of BMC of old animals, the decreased of the BMC number was described less than for cells of young animals. The adding of 8 mM CuSO4x5H2O inhibited proliferation less, than the adding of 4 mM CuSO4x5H2O. The Cu-induced liver fibrosis had accelerated the BMC rate death of both old and young animals. However, this effect was more pronounced in young animals. It is suggested, that during the ontogenesis the BMC undergo such epigenetic changes, which change functional properties.

[ANALYSIS OF POPULATION IMMUNITYAGAINST INFLUENZA PRIOR TO 2014 AND 2015 EPIDEMIC SEASONS].

AIM: Control for the population herd immunity against seasonal influenza viruses as well as for emergence of antibodies against influenza with pandemic potential in human blood sera. MATERIALS AND METHODS: HAI reaction against vaccine and epidemic influenza viruses as well as HPAI viruses A/rook/Chany/32/2015 (H5N1) (clade 2.3.2. lc.) andA/Anhui/01/2013 (H7N9). RESULTS: Among all the sera samples collected in the autumn of 2014 and 2015, none had reacted in HAI against A(H5N 1) and A(H7N9) antigens even at 1:10 dilution. Among samples collected in autumn 2014, 41% were positive to A/California/07/09(H1Nlpdm9) virus, 36% - A/Texas/50/2012 (H3N2), 40% - B/Brisbane/60/2008 (Vict.lin.) and 47% reacted in HAI against the B/Massachusetts/2/2012 (Yam.lin.) strain. 22% of all the samples had a titer of at least 40 against all the antigens and only 10% in HAI had a titer of 40 or more against all the vaccine strains. Among the samples collected in autumn 2015, the number of seropositive against A/California/07/09(HlNlpdmO9) varied from 31% in the Urals FD to 46% in the Southern FD. The amount of seropositive against A/Switzerland/9715293/13 (H3N2) strain was at the level of 4 - 13% in all the FDs except Urals, where this parameter was slightly above 30%. The amount of seropositive against vaccine influenza B viruses varied from 23 to 76%. Only 2% of sera had titers in HAI of 40 or above against all the vaccine strains, 29% of all the samples were seronegative. CONCLUSION: Population immunity in Russia against influenza A(H3N2) is at a very low level, thus socially significant consequences of influenza epidemics in many aspects will depend on the vaccination campaign of autumn 2016.

[SURGICAL TREATMENT OF AN ACUTE MESENTERIAL ISCHEMIA].

Experience of surgical treatment of 143 patients, suffering an acute mesenterial ischemia, was summarized. Isolated intestinal resection was performed in 41 patients (lethality 65.9%), intestinal resection with the mesenterial vessels thrombembolectomy--in 9 (lethality 33.3%). After performance of the combined intervention postoperative lethality was in two times lower, than after isolated intestinal resection.

Highly pathogenic influenza H5N1 virus of clade 2.3.2.1c in Western Siberia.

In the spring of 2015, avian influenza virus surveillance in Western Siberia resulted in isolation of several influenza H5N1 virus strains. The strains were isolated from several wild bird species. Investigation of biological features of those strains demonstrated their high pathogenicity for mammals. Phylogenetic analysis of the HA gene showed that the strains belong to clade 2.3.2.1c.

[Dynamics of spatial synchronization of epileptiform discharges in the rat neocortex].

Epileptiform potentials after the application of GABA A receptor antagonist first appeared in a local part of the cortex of anesthetized rats, and then with a small time lag appeared in other areas of the cortex. Externally, it looked like spreading. Potentials originally appeared at any point of recording, and then appeared (propagated) both in the rostral-caudal direction (forward) and reciprocally. The quantitative evaluation of this phenomenon showed that there are three periods of the epileptiform potential spreading. During the initial period, the epileptiform potentials appeared and spread relatively equally in rostrocaudal direction and backwards. In period 2 dominated potentials shift in rostrocaudal direction. After application of a sodium channel blocker epileptic activity significantly decreased. Frequency of initial appearance of potentials in the caudal areas increased. Propagation of the activity in one or another direction was observed. Obtained in this study quantitative characteristics of the initiation and spreading of epileptic activity suggest that in the cortex may exist independent generators, and distribution of the epileptiform potentials and the nature of this distribution implies that this process is based on direct and reciprocal functional connection of neurons.

Molecular characterization and phylogenetics of a reassortant H13N8 influenza virus isolated from gulls in Mongolia.

Double reassortant H13N8 influenza A virus was isolated from gull in Mongolia. The basic virological characteristics were studied. Complete genome sequence analysis indicated the complicated evolutionary history. The PA gene belongs to classical Avian-like lineage and more likely originated from non-gull avian virus pool. Data confirm the state of extensive geographic mosaicism in AIV from gulls in the Northern Hemisphere.

[Application of the method of one-day learning in a Morris water maze to analyse the effects of sleep deprivation on memory trace recall 24 hours later, after learning].

The proposed model of a one-day spatial learning is of interest in research of how sleep influences the hippocamp-dependent memory consolidation. We have studied the influence of a one-day total sleep deprivation on spatial memory consolidation in hooded rats after a one-day learning in the Morris water maze according to Feldman et al. [2010] protocol. According to it rats had to find a submerged platform that was alternatively marked by a flag or completely invisible to an animal. In a previous study [Dorokhov et al., 2011] we have used another one-day learning protocol [Frick et al., 2000] and Wistar rats and have demonstrated a large interindividual variance in learning parameters and sleep deprivation effects on memory consolidation. In this study we confirm previously acquired results on negative impact of sleep deprivation on spatial memory consolidation. To demonstrate the effects of sleep deprivation on the results of one-day learning we are using for the first time an evaluation of the time spent by an animal in the area of the platform placement and corresponding areas in the other quadrants of the water maze.

[Synchronization and propagation of electrical potentials in neural networks of the brain cortex].

On the basis of the published data the scheme is proposed which explains the spread and synhronization of oscillatory activity in cortex. The main property of the neocortex is the existence of vertically oriented functional columns. Within and between the neuronal columns exist a feedforward and feedback morphological and functional connections. At the certain conditions inside the single module temporal windows are created using inhibitory process, and a synchronized activity can be generated of variable frequency (oscillations). The activity in the columns is enhanced by the synchronous involvement of great amount of neurons which is expressed in the form of local field potentials of high amplitude. Further the information about arisen in a single generator activity is transmitted through direct links to the nearby generator or to the group of such generators. In the nearby generator the activity increases and is transferred to the next generator. At the same time the signal is transmitted through feedback to the primary generator, and the activity is terminated until the next cycle will be initiated and so on along the cortex. The most important notion is that in the transfer of activity from one generator to another is involved a small number of elements. The major part of recorded oscillations of different frequency or epileptiform discharges, is not transmitted via the brain, but is generated in each module according to the characteristics transferred to it. The generation of epileptiform spikes occurs in cases when balance of inhibition determined by GABA A and GABA B receptors is disturbed.

Ecology of influenza virus in wild bird populations in Central Asia.

The study provides the results of avian influenza virus surveillance in Central Asia during 2003-2009. We have analyzed 2604 samples from wild birds. These samples were collected in Kazakhstan (279), Mongolia (650), and Russia (1675). Isolated viruses from samples collected in Mongolia (13 isolates) and in Russia (4 isolates) were described. Virological analysis has shown that six isolates belong to the H3N6 subtype and five isolates belong to the H4N6 subtype. Two H1N1 influenza viruses, one H10N7 virus, two H3N8 viruses, and an H13N8 virus that is new for Central Asia have been also isolated. Samples were taken from birds of six orders, including several species preferring water and semiaquatic biotopes, one species preferring dry plain regions, and one more species that can inhabit both dry and water biotopes.