Search for a Neutron Dark Decay in

Neutron dark decays have been suggested as a solution to the discrepancy between bottle and beam experiments, providing a dark matter candidate that can be searched for in halo nuclei. The free neutron in the final state following the decay of ^{6}He into ^{4}He+n+χ provides an exceptionally clean detection signature when combined with a high efficiency neutron detector. Using a high-intensity ^{6}He^{+} beam at Grand Accélérateur National d'Ions Lourds, a search for a coincident neutron signal resulted in an upper limit on a dark decay branching ratio of Br_{χ}≤4.0×10^{-10} (95% C.L.). Using the dark neutron decay model proposed originally by Fornal and Grinstein, we translate this into an upper bound on a dark neutron branching ratio of O(10^{-5}), improving over global constraints by one to several orders of magnitude depending on m_{χ}.

Exact Off Shell Sudakov Form Factor in N=4 Supersymmetric Yang-Mills Theory.

We consider the Sudakov form factor in planar N=4 supersymmetric Yang-Mills theory in the off shell kinematical regime, which can be achieved by considering the theory on its Coulomb branch. We demonstrate that for up to three loops both the infrared-divergent as well as the finite terms do exponentiate, with the coefficient accompanying log^{2}(m^{2}) determined by the octagon anomalous dimension Γ_{oct}. This behavior is in stark contrast to previous conjectural accounts in the literature. Together with the finite terms we observe that for up to three loops the logarithm of the Sudakov form factor is identical to twice the logarithm of the null octagon O_{0}, which was recently introduced within the context of integrability-based approaches to four point correlation functions with infinitely large R charges. The null octagon O_{0} is known in a closed form for all values of the 't Hooft coupling constant and kinematical parameters. We conjecture that the relation between O_{0} and the off shell Sudakov form factor will hold to all loop orders.

Antiallergic Effects of Technologically Processed Antibodies to MHC II.

The risk of developing anaphylactic reactions to medications introduces additional difficulties for effective pharmacotherapy. Using a model of systemic anaphylaxis in mice, we showed that preventive administration of a preparation containing technologically processed antibodies (TPA) to MHC II induces an anti-anaphylactic effect comparable to that of dexamethasone (when assessing the severity of systemic anaphylaxis 30 and 60 min after challenge injection of the model antigen ovalbumin). The revealed activity may be related to the ability of TPA to MHC II to regulate the antigen presentation system and shift the immune response towards the production of IgG instead of IgE typical of anaphylactic reaction.

Evaluation of the Effectiveness of Systemic Therapy of Spinal Cord Injury of Moderate Severity with Human Umbilical Cord Placental Blood Mononuclear Cells Using Indicators of Dispersion of Articular Angles in the Swimming Test.

Female Sprague-Dawley rats were used as models of moderate contusion spinal cord injury to evaluate the efficiency of single systemic (intravenous) infusion of human mononuclear cord blood cells for restoration of the motor function of hind limbs. The dynamics of recovery of hind limb motor function was assessed using a specially designed method based on calculation of selective dispersion and amplitude-dependent dispersion of hind limbs joint angles measured in the swimming test. The obtained data suggest that systemic application of human mononuclear cord blood cells significantly (p<0.05) promoted recovery of hind limb motor function in the animal models of contusion spinal cord injury of moderate severity in comparison with control animals (without cell therapy).

[Time perspective, sleep and wellbeing of the elderly during COVID-19 pandemic.]

The purpose of this study was to analyze the association between the time perspective and the psychophysiological state of the elderly during the pandemic COVID-19. 433 residents from 11 Russian cities aged 60,8±9,8 years (range - 50-94 years, women - 78,7%) took part in the study. During the online survey, each participant of the study provided personal data (place of residence, sex, age, height, and weight) and completed the Zimbardo Time Perspective Inventory, the Munich Chronotype Questionnaire, the Beck Depression Inventory and the Yale Food Addiction Scale. It was found that elderly people with a balanced time perspective had the lowest level of depression during the pandemic COVID-19 and less expressed sleep inertia at work days, while those with a past negative time perspective had the highest level of depression, high frequency of detection of food addiction and low sleep efficiency. The other types of time perspective (past positive, present hedonistic, present fatalistic and future) had intermediate values of indicators between these two extreme options. Thus, the conducted studies have shown that elderly people with a balanced time perspective showed the highest level of resistance to psychoemotional stress caused by the pandemic COVID-19.

A Method of Assessment of the Motor Function of Hind Limbs by Swim Test in Spinal Cord Injury Models.

In most studies, various load tests are used to assess the recovery of functions after spinal cord injury in animals. However, the existing methods of assessing the movement in animals are not sufficiently accurate and objective. We developed a new method for assessing motor activity of laboratory animals that allows objective and highly accurate evaluation of movements in animals with serious neurological disorders caused by spinal cord injury. The swimming test was used as the main load test. Motor activity of swimming animals was assessed by measuring angles relative to the axis of motion, and the degree of angle spread for each joint and limb was estimated using the dispersion parameters depending on the values of the angles of the joints and the dispersion depending on the amplitudes of the angles. In Sprague-Dawley rats, contusion of the spinal cord at the Th9 level was modeled. In the swimming test, healthy control animals showed stability of both variance indicators over 6 weeks. In rats with spinal cord injury, motor activity of the hind limbs tended to increase from the first to the third weeks and remained at this level from the third to sixth weeks. The results suggest that the proposed method can become a good analogue of modern methods for assessing motor activity.

Effect of Biocides on the Activity of Extracellular Enzymes Produced by Degrader Fungi from Technical Objects Used in Tropical Climates (Vietnam).

Activity of extracellular enzymes was assessed in 20 strains of microscopic fungi involved in biodegradation of technical objects exploited under tropical climate conditions (Vietnam). It was found that 19 strains possessed catalase activity, 18 strains had phenol oxidase activity, and eight strains had protease activity. The effect of industrial biocides on the activity of these enzymes was also assessed. The biocides Bior-1, Bioneutral A 10, and Bioneutral A 101 were shown to inhibit the enzymatic activity to various extent. All biocides inhibited extracellular catalase activity in most fungal strains studied. The inhibition of protease and phenol oxidase activity of same test strains was less pronounced. The response to biocides varied at the strain level; its characteristics could differ significantly even between strains of the same species. In several cases, it was observed that exposure to biocides resulted in an increase in enzyme activity.

[Identification of factors influencing the texture sensitivity of young healthy volunteers based on a model for distinguishing the hardness of an agar-gelatin gel].

Elucidating the causes of variability in food texture sensitivity is important for understanding the mechanisms underlying food choice and portion size, eating rates, and enjoyment of food. Since texture perception significantly affects eating behavior, it is assumed that ability to recognize food texture, in turn, may depend on eating behavior. The aim of the study was to elucidate the relationship between the ability to recognize the hardness of an agar-gelatin gel, on the one hand, and the nutritional value of the diet, the type of eating behavior and the level of hunger and satiety feelings, on the other hand. Material and methods. In 38 healthy residents of Syktyvkar (15 men, 23 women aged 21 to 31 years) food textural sensitivity was determined by pairwise comparison of the hardness of model agar-gelatin gels and the level of the feeling of stomach fullness at the time of testing. All participants completed a food diary, the Dutch Eating Behavior Questionnaire, the Yale Food Addiction Scale, and assessed the standard organoleptic and hedonic properties of commercial fruit jelly. Statistical processing of the data was performed using non-parametric statistics: the Mann-Whitney U-test, Fisher's exact test, and calculating the Spearman's correlation coefficient. Results. The ability to recognize the hardness of food gel was found to vary significantly among the participants. The percentage of correct answers given by participants with high food textural sensitivity (n=20) was equal to 92 and 82% when comparing agargelatin gels with hardness in the range of 40-300 and 800-1000 kPa, respectively. Participants with low food texture sensitivity (n=18) gave the correct answer in 74 and 31% of cases when tasting soft and hard gels, respectively. Participants with high and low sensitivity to food gel texture did not differ in the type of eating behavior, as well as in the average daily intake of energy, macronutrients and dietary fiber. Correlation analysis revealed a negative relationship (rs=-0.37, p=0.020) between the percentage of correct answers when determining the hardness of the agar-gelatin gel and the level of the stomach fullness among all participants (n=38). In the sensory evaluation of fruit jelly, it was found that the descriptor «hard¼ was chosen by 60 and 22% (p=0.025) of the participants from the groups with high and low textural sensitivity, respectively. Conclusion. The ability to discriminate the hardness of an agar-gelatin gel is higher in people with a low level of stomach fullness feeling. Sensitivity to the texture of food gel is not related to energy value and macronutrient content in the daily diet and does not depend on the type of eating behavior. Participants with high food textural sensitivity are more likely to use the characteristic "hard" when evaluating fruit jelly.

[Features of pathogenesis and COVID-19 course for the elderly and old age.]

The causative agents of coronavirus infection have long been considered the cause of benign respiratory diseases «common colds¼ until their pathogenic types appeared on the epidemic arena: SARS-CoV-1, MERS and finally, SARS-CoV-2. Diseases caused by the listed viruses characterized by moderate invasiveness and noticeable mortality compared to other respiratory viruses. The pathogenesis of these infections is based on a wide range of innate immunity dysfunctions, manifested in the direct suppression of anti-inflammatory functions and, on the contrary, the activation of pro-inflammatory functions, such as the assembly and activation of NLRP3 inflammasome, as well as the synthesis and secretion of pro-inflammatory cytokines and chemokines. Excessive secretion of pro-inflammatory factors is accompanied by a disturbance in the balance of cytokines, leading to the development of a cytokine storm. When the body manages to cope with these disorders, a stable adaptive immunity develops, which is a harmonious combination of cellular and humoral mechanisms of resistance. Particularly difficult COVID-19 occurs in elderly and senile people. It has been shown that the main tests for the risk of multiple organ failure and death in COVID-19 in this category of patients are concomitant diseases, lymphocytopenia, increased transferases, D-dimer and other metabolic disorders. It has been established that critically ill COVID-19 patients develop endothelial dysfunction, thrombotic microangiopathy, immunothrombosis and disseminated intravascular coagulation, which are the basis of multiple organ failure. Pneumonia, as a complication of COVID-19, accompanied by the development of acute respiratory respiratory syndrome, ultimately leads to pulmonary fibrosis, which is often fatal. There is no specific therapy for COVID-19. Recently, immunomodulatory drugs have been widely introduced in the treatment of this infection, including remdesivir, synthetic quinine derivatives and neutralize antibodies.

Comparison of the Efficiency of Systemic and Local Cell Therapy with Human Umbilical Cord Blood Mononuclear Cells in Rats with Severe Spinal Cord Injury.

Rat model of severe contusion spinal cord injury was used to study the effect of single intravenous and intraspinal injection of human umbilical cord blood mononuclear cells on the restoration of motor function of the hind limbs. Recovery of the motor function of the hind limbs was assessed using load tests and open-field test according to BBB scale. Cell injection via both routes significantly improved (p≤0.05) the recovery of the motor function of the hind limbs by 35-40% relative to the level of "self-recovery"; the effects of intravenous andintraspinal administration did not differ significantly.

[To the 100th anniversary from birth of professor lev moiseevich bedrin]. / K 100-letiyu so dnya rozhdeniya professora L'va Moiseevicha Bedrina.

Professor L.M. Bedrin - Head of the Department of Forensic Medicine and Law of the Yaroslavl Medical Institute for over 18 years. L.M. Bedrin was the first to develop a new scientific field - study of microcirculation in extreme conditions. L.M. Bedrin is the author of more than 130 scientific works, 100 articles, monographs. Under the supervision of L.M. Bedrin 1 doctoral and 10 master's theses were successfully defended.

Incoherent scattering from dielectric metasurfaces under the influence of electromagnetic eigenmodes.

Anomalous optical properties of microscopically inhomogeneous dielectric films placed on a thick metal sublayer are investigated. We study the reflection, scattering, and absorption of the coherent electromagnetic radiation as a function of the incidence angle. Computer simulations show the existence of the incidence angle of the laser beam when the scattering and absorption increase simultaneously for the s-polarization so that almost 60% of the incident light goes in the scattering channel. The critical angle corresponds to the excitation of Fabry-Perot mode. The effect makes it possible to manipulate the reflection from the metafilms.

Effects of CYP2D6 activity on the efficacy and safety of mirtazapine in patients with depressive disorders and comorbid alcohol use disorder.

The objective of the study was to investigate the effects of CYP2D6 activity on the efficacy and safety of mirtazapine in patients with depressive disorders and comorbid alcohol use disorder who received mirtazapine. The study included 109 Russian patients who received mirtazapine at a dose of 30.0 [15.0; 45.0] mg per day. Genotyping of CYP2D6*4 (1846G > A, rs3892097) was performed using real-time polymerase chain reaction with allele-specific hybridization. The activity of CYP2D6 was evaluated by determining the concentration of endogenous substrate of the enzyme and its urinary metabolite - pinoline to 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline ratio, using high-performance liquid chromatography - mass spectrometry. The statistically significant differences between the scores on the Hamilton Depression Rating Scale (HAMD) in patients with different genotypes were revealed by day 16: (GG) 5.0 [3.0; 6.0], (GA) 1.5 [1.0; 3.2] (p < 0.001), and for the The UKU Side Effects Rating Scale (UKU): (GG) 6.0 [6.0; 7.0], (GA) 8.5 [8.0; 10.0] (p < 0.001). The calculation of correlation coefficients between the differences in scale scores and metabolic rate showed the presence of statistically significant weak inverse correlation with the efficacy indicator evaluated by HAMD (r = -0.278, p < 0.05), but not by UKU (r = 0.274, p > 0.05). This study demonstrated that an increased CYP2D6 activity reduces the efficacy of treatment with mirtazapine.

Comparison of Biological Effects of γ-Radiation of Low and Ultra-High Dose Rate on Lymphocytes and Cultured Human Malignant Lymphoma Cells.

We studied the effect of low and high-dose rate photon radiation on activation of cell death by apoptosis and necrosis in malignant cell lines of lymphocytic origin Raji and Jurkat (human B and T-cell lymphomas) and normal human lymphocytes from healthy volunteers. It was shown that photon radiation with ultra-high dose rate induced significantly higher levels of "early" apoptosis and lower levels of necrosis compared to γ-radiation with dose rate used for radiation therapy.

Forced oscillations of the string under conditions of 'sonic vacuum'.

We present the results of analytical study of the significant regularities which are inherent to forced nonlinear oscillations of a string with uniformly distributed discrete masses, without its preliminary stretching. It was found recently that a corresponding autonomous system admits a series of nonlinear normal modes with a lot of possible intermodal resonances and that similar synchronized solutions can exist in the presence of a periodic external field also. The paper is devoted to theoretical explanation of numerical data relating to one of possible scenarios of intermodal interaction which was numerically revealed earlier. This is unidirectional energy flow from unstable nonlinear normal mode to nonlinear normal modes with higher wavenumbers under the conditions of sonic vacuum. The mechanism of such a scenario has not yet been clarified contrary to alternative mechanisms consisting in almost simultaneous energy flow to all nonlinear normal modes with breaking the above-mentioned conditions of sonic vacuum. We begin with a description of single-mode manifolds and then show that consideration of arbitrary double mode manifolds is sufficient for solution of the problem. Because of this, the two-modal equations of motion can be reduced to a linear equation which describes a perturbation of initially excited nonlinear normal mode of the forced system in the conditions of sonic vacuum. We have found analytical representation (in the parametric space) of the thresholds for all possible energy transfers corresponding to unidirectional energy flow from unstable nonlinear normal modes. The analytical results are in a good agreement with previous numerical calculations.This article is part of the theme issue 'Nonlinear energy transfer in dynamical and acoustical systems'.

The Role of Interleukin-33 in Pathogenesis of Bronchial Asthma. New Experimental Data.

Interleukin-33 (IL-33) belongs to the IL-1 cytokine family and plays an important role in modulating immune system by inducing Th2 immune response via the ST2 membrane receptor. Epithelial cells are the major producers of IL-33. However, IL-33 is also secreted by other cells, e.g., bone marrow cells, dendritic cells, macrophages, and mast cells. IL-33 targets a broad range of cell types bearing the ST2 surface receptor. Many ST2-positive cells, such as Th2 cells, mast cells, basophils, and eosinophils, are involved in the development of allergic bronchial asthma (BA). This suggests that IL-33 directly participates in BA pathogenesis. Currently, the role of IL-33 in pathogenesis of inflammatory disorders, including BA, has been extensively investigated using clinical samples collected from patients, as well as asthma animal models. In particular, numerous studies on blocking IL-33 and its receptor by monoclonal antibodies in asthma mouse model have been performed over the last several years; IL-33- and ST2-deficient transgenic mice have also been generated. In this review, we summarized and analyzed the data on the role of IL-33 in BA pathogenesis and the prospects for creating new treatments for BA.

Collagen Implant and Mononuclear Cells of Umbilical Blood Allow the Restore of Movements of Hind Limbs after Removing the Site of Spinal Cord.

Replacement of the removal site of the spinal cord on a collagen implant restores the motor function of the hind limbs in rats to the level of movements in the two joints for 8 weeks. After intravenous administration of mononuclear cells of human umbilical blood, recovery accelerated, significantly improved to the level of motion in the three joints, and there is a tendency to improve further recovery of movements.

[PERSONALIZED MEDICINE IN INTERNAL MEDICINE].

Personalized medicine - a new direction in medicine, which is based on the study of various biomarkers and the use of new methods of molecular analysis (primarily evaluating the activity of isoenzymes of cytochrome P450), allowing individualized approach to the selection of both the drugs and the selection of the dosing regimen for the purpose of maximize the effectiveness and safety of pharmacotherapy. This personalized medicine is to change the development and use of preventive and curative interventions. Genetic polymorphism isozymes of cytochrome P450 may determine the individual activity of a particular isozyme, and thus, to predict the clinical effectiveness, and in some cases, the risk of adverse reactions. The article is an example of the use of information on the activity of cytochrome P450 in clinical practice in matters of diagnosis, treatment and prevention of diseases. The scheme of the five best-known activity of isoenzymes of cytochrome P450 is shown.

[Technologies for Complex Intelligent Clinical Data Analysis].

UNLABELLED: The paper presents the system for intelligent analysis of clinical information. Authors describe methods implemented in the system for clinical information retrieval, intelligent diagnostics of chronic diseases, patient's features importance and for detection of hidden dependencies between features. Results of the experimental evaluation of these methods are also presented. BACKGROUND: Healthcare facilities generate a large flow of both structured and unstructured data which contain important information about patients. Test results are usually retained as structured data but some data is retained in the form of natural language texts (medical history, the results of physical examination, and the results of other examinations, such as ultrasound, ECG or X-ray studies). Many tasks arising in clinical practice can be automated applying methods for intelligent analysis of accumulated structured array and unstructured data that leads to improvement of the healthcare quality. AIMS: the creation of the complex system for intelligent data analysis in the multi-disciplinary pediatric center. MATERIALS AND METHODS: Authors propose methods for information extraction from clinical texts in Russian. The methods are carried out on the basis of deep linguistic analysis. They retrieve terms of diseases, symptoms, areas of the body and drugs. The methods can recognize additional attributes such as "negation" (indicates that the disease is absent), "no patient" (indicates that the disease refers to the patient's family member, but not to the patient), "severity of illness", disease course", "body region to which the disease refers". Authors use a set of hand-drawn templates and various techniques based on machine learning to retrieve information using a medical thesaurus. The extracted information is used to solve the problem of automatic diagnosis of chronic diseases. A machine learning method for classification of patients with similar nosology and the methodfor determining the most informative patients'features are also proposed. RESULTS: Authors have processed anonymized health records from the pediatric center to estimate the proposed methods. The results show the applicability of the information extracted from the texts for solving practical problems. The records ofpatients with allergic, glomerular and rheumatic diseases were used for experimental assessment of the method of automatic diagnostic. Authors have also determined the most appropriate machine learning methods for classification of patients for each group of diseases, as well as the most informative disease signs. It has been found that using additional information extracted from clinical texts, together with structured data helps to improve the quality of diagnosis of chronic diseases. Authors have also obtained pattern combinations of signs of diseases. CONCLUSIONS: The proposed methods have been implemented in the intelligent data processing system for a multidisciplinary pediatric center. The experimental results show the availability of the system to improve the quality of pediatric healthcare.

RNA INTERFERENCE: NEW APPROACH TO THE TREATMENT OF ALLERGIC ASTHMA (A REVIEW).

Asthma is among the most common chronic disorders of airways, which affects both children and adults. Asthma being a common disease among different segments of population, it has a high mortality rate and, in the absence of appropriate care, affects the quality of life and leads to economics losses. In a view of continuing growth in the incidence of asthma, it is important to find relevant biological targets for developing new approaches to astma therapy. Recent advances in molecular immunology, genetics, and bioinformatics allowed genes involved in the pathogenesis of asthma to be identified, which provided prerequisites for the development of new types of drugs that can regulate the activity of pathogenically significant genes. To date, a number of technologies for sequence-specific gene regulation (ASO, ribozymes, DNAzymes, EGS, DNA-decoys, U 1-adapters) are available, but RNA interference is the most promising approach in both terms of efficacy and financial cost. This review focuses on the generalization and analysis of experimental data regarding the use of RNA interference technology for the treatment of astma.