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Aim of investigation. To evaluate expediency of testing for carbohydrate-deficient transferrin for diagnostics of alcohol intoxication.Material and methods. For 1996-2007 overall 978 patients with liver cirrhosis (LC) were investigated, including 531 patients with alcoholic LC, 189 patients with HBV-related LC and 258 patients with HCV-related LC. One hundred and three patients taking alcohol (as two subgroups) were tested for carbohydrate-deficient transferrin – a marker of chronic alcohol intoxication. In 56 patients (54,4%) asialoglycoside transferrin was studied, in 47 (45,6%) – all spectrum of sialoglycoside transferrin deficiency: a-, mono-, bi- and three- sialotransferrin deficiency.Results. Growth of alcohol consumption by population in the country resulted in increase of number of patients with alcohol-induced LC. It account for 3,5 times more deaths (78,0%), than all viral LC. Results of these investigations demonstrated, that at testing only for asialotransferrin positive result was obtained only in 3 (5,4%) patients admitted to the hospital with severe manifestations of acute alcoholic hepatitis. At assessment of integral deficiency of transferrin, changes have been found in 36 (76,6%) patients. It confirms high diagnostic capacity of this method in testing for chronic alcohol intoxication.Conclusion. In the last decade the number of patients with alcohol-induced LC with lethal outcome essentially exceeded number of patients, died of viral LC. Assessment of integral deficiency of transferrin is highly informative method of diagnostics of chronic alcohol intoxication.

The article reveals the essence and content of the concepts of "moral stability", "moral instability", "variability", forms, methods, and means of formation of moral stability in adolescents. Moral stability is not an innate quality of personality, it is formed by means of purposeful educational work. The core of formation of moral stability in adolescents is internalization, i.e. the transformation of moral requirements of society, moral principles into internal attitudes, personal beliefs of each student. The educational process is based on the principles of science, historicism, humanity, the relationship of socio-cultural and educational values, taking into account the age and individual characteristics of students. The article presents a generalized experience of Chuvashia schools in the formation of moral stability in adolescents (secondary schools No. 10, 40, 53, 62 Cheboksary, Secondary school No. 2 Alatyr, secondary school No. 3 Kanash). The study revealed a number of pedagogical conditions that make it possible to successfully form moral stability in adolescents.

Thermo-vortices (bright spots, blobs, swirls) in cosmic fluids (planetary atmospheres, or even black hole accretion disks) are sometimes observed as clustered into quasi-symmetrical quasi-stationary groups but conceptualized in models as autonomous items. We demonstrate—using the (analytical) Sharp Boundaries Evolution Method and a generic model of a thermo-vorticial field in a rotating “thin” fluid layer in a spacetime that may be curved or flat—that these thermo-vortices may be not independent but represent interlinked parts of a single, coherent, multi-petal macro-structure. This alternative conceptualization may influence the designs of numerical models and image-reconstruction methods.

Abstract Structural transformations of metal-organic frameworks (MOFs) go through a complex energy landscape with multiple intermediate states. Although the transformations allow controlling the functional properties of the MOFs, an imbalance between MOF flexibility and rigidity sets a fundamental barrier to achieving fast and multiple transformations. Here, we study the stimuli-responsive structural transformation in a 2D MOF assembled from paddle-wheel secondary building units joined by a semi-flexible organic ligand with 1,2,4-triazole and carboxylate groups with a rigid adamantane cage between them. The structure results in a distinctive combination of MOF flexibility and rigidity, thus, facilitating a continuous transformation driven by laser light. We reveal the laser-induced anisotropic thermal expansion nature of such transformation, initiating optical changes of the 2D MOF. The latter is utilized for fast and highly repeatable optical modulation of over 10,000 cycles. The endurance of such a 2D MOF-based optical modulator during 1 year of storage at ambient conditions paves the way to design tunable and robust MOFs for diverse applications.

Background. Symptomatic uncomplicated diverticular colon disease (SNDCD) is a common condition that significantly affects the quality of life of patients. One of the main therapeutic targets in SNDCD is the microbiota. Aim. To evaluate the efficacy and safety of microbiocenosis-based therapy (prebiotic Mucofalk + metabiotic Zakofalk) in relieving symptoms of SNDCD and maintaining asymptomatic remission. Materials and methods. The study included 60 patients with clinically apparent SNDCD. For 3 months, they were treated with Mukofalk and Zakofalk and then followed up for another 3 months. Parameters such as treatment efficacy, satisfaction and compliance were evaluated, as well as change of short-chain fatty acids in feces using gas-liquid chromatography was measured. Results. A statistically significant improvement of all assessed symptoms (abdominal pain, constipation, diarrhea, flatulence, tenesmus) was observed after 3 months of therapy. Relapse of abdominal pain and bowel movement disorders (constipation) after completion of therapy were observed in 7 (11.6%) subjects. The compliance study showed that more than 80% of the required number of sachets/tablets was taken by more than 80% of patients. At the end of follow-up, 49 (81.7%) patients rated their outcomes as "excellent" and 11 (18.3%) as "good". During treatment, there was a significant tendency to increase the absolute content of butyric acid in feces. Conclusion. Microbiocenosis-based therapy with the prebiotic Mukofalk and the metabiotic Zakofalk is effective and safe for treating SNDCD and preventing the recurrence of symptoms and disease complications. The therapy is associated with excellent and good satisfaction and a high compliance to treatment. Therapy with Mukofalk and Zakofalk resulted in the normalization of the intestinal microbiota.

Aim. To analyze long-term consequences of the new coronavirus infection and rehabilitation prospective of microbiocenosis-oriented therapy in patients with functional bowel disorders. Materials and methods. The study enrolled 100 consecutive patients with various types of functional bowel disorders with recurrence of symptoms after the new coronavirus infection. The severity of abdominal pain was evaluated in points, and bowel movement disorders were assessed using the Bristol stool scale. A questionnaire was used as part of an in-depth clinical examination for COVID-19 survivors to identify the clinical symptoms typical for the post-COVID syndrome. The Hospital Anxiety and Depression Scale was used to identify and assess the severity of depression and anxiety, and the Asthenic State Scale was used to diagnose the asthenia. Results. All patients in the study subjectively linked the recurrence of bowel disorders with the new coronavirus infection. The most common bowel disorder was irritable bowel syndrome with diarrhea. A distinctive feature of exacerbations of intestinal symptoms in the post-COVID period is their association with depression/anxiety and asthenic states. The addition of Zakofalk® metaprebiotic to the treatment regimen was associated with significant regression of abdominal pain and normalization of bowel movement, an improvement of asthenia, anxiety, and depression. Conclusion. The addition of Zakofalk® to treatment regimens for exacerbations of functional bowel disorders after the new coronavirus infection significantly improves the effectiveness of therapy.

A novel supramolecular complex C44H71Cl2N26O22 (CB[6]@Pipa·2HCl) of the “host-guest” type has been synthesized. It is based on cucurbit[6]uril (CB[6]) with dihydrochloride 1,4-bis(2-hydroxyethyl)piperazine (Pipa·2HCl) localized within the portals of the macrocycle. Based on 1H NMR and X-ray crystallography, the host–guest ratio in the complex under the specified conditions was determined to be 1:1. Further evidence of complex formation was observed through IR spectroscopy, where a shift in the absorption band of carbonyl vibrational frequencies of cucurbit[6]uril by 36 cm−1 towards the longer wavelength region was detected in CB[6]@Pipa·2HCl compared to the original CB[6]. TGA/DSC analysis results indicated an increase in thermal stability by 55 °C for the obtained CB[6]@Pipa·2HCl complex compared to the initial 1,4-bis(2-hydroxyethyl)piperazine dihydrochloride. The structure of the synthesized CB[6]@Pipa·2HCl complex was confirmed using single-crystal XRD.

INTRODUCTION. To expand the range of the pantohematogen based drugs usage, to develop indications for their use in variousforms and methods, scientific research is necessary and appropriate on evaluation of the effectiveness of the antler drugs use for therehabilitation of patients with post-coronavirus syndrome, which is detected in most patients after the coronavirus infection COVID-19and is characterized by various changes in metabolism and hemostasis, autonomic nervous system, external respiration, indicators ofcentral and peripheral hemodynamics, reduced exercise tolerance, quality of life and working capacity of patients.AIM. To scientifically establish and develop of a comprehensive program of COVID-rehabilitation of patients with the use ofpantohematogen at the sanatorium-resort stage.MATERIAL AND METHODS. We conducted randomized study in parallel groups. The study included women aged 39 to 65 years(mean age 53.9±1.18 years) – 30 patients. The rehabilitation program of the patients who had pneumonia associated with COVID-19novel coronary virus infection was evaluated 3-4 months after the disease. The study group was additionally prescribed 1 capsule ofpantohematogen, three times a day with meals, for 10-12 days (dietary supplements with increased iron content). The comparisongroup received the same rehabilitation program, but without the use of pantohematogen.RESULTS AND DISCUSSION. According to the severity of post-COVID pneumonia, 66.6% were diagnosed with pneumonia of moderateseverity and 33.4% with mild severity. Mild degree of dyspnea was revealed in 63.3% of patients, physical asthenia was diagnosed in70% of patients. The use of pantohematogen showed an advantage in terms of a more significant decrease in the level of physicalasthenia, a decrease in dyspnea during physical exertion, a decrease in the frequency of autonomic disorders, an improvement in thepsycho-emotional status, and a more significant decrease in reactive anxiety in these patients. In order to prolong the effectivenessof the post-COVID rehabilitation program for patients, it is advisable to continue taking pantohematogen in outpatient or homeconditions for 2 weeks, 1 capsule three times a day.CONCLUSION. For the first time the possibility and expediency of using pantogematogen with additional iron content to increasethe efficiency of the health center rehabilitation program has been studied and proved; it can be used in patients with post-COVID conditions for normalization of functional disorders, vegetative-status and normalization of psycho-emotional status in allorganizational forms of sanatorium-resort organizations, as well as at home.

Abstract The dynamics when a hot many-body quantum system is brought into instantaneous contact with a cold many-body quantum system can be understood as a combination of early time quantum correlation (von Neumann entropy) gain and late time energy relaxation. We show that at the shortest timescales there is an energy increase in each system linked to the entropy gain, even though equilibrium thermodynamics does not apply. This energy increase is of quantum origin and results from the collective binding energy between the two systems. Counter-intuitively, this implies that also the hotter of the two systems generically experiences an initial energy increase when brought into contact with the other colder system. In the limit where the energy relaxation overwhelms the (quantum) correlation build-up, classical energy dynamics emerges where the energy in the hot system decreases immediately upon contact with a cooler system. We use both strongly correlated SYK systems and weakly correlated mixed field Ising chains to exhibit these characteristics, and comment on its implications for both black hole evaporation and quantum thermodynamics.

Multiple myeloma (MM) is the second most common hematological malignancy, which remains incurable despite recent advances in treatment strategies. Like other forms of cancer, MM is characterized by genomic instability, caused by defects in DNA repair. Along with mutations in DNA repair genes and genotoxic drugs used to treat MM, non-canonical secondary DNA structures (four-stranded G-quadruplex structures) can affect accumulation of somatic mutations and chromosomal abnormalities in the tumor cells of MM patients. Here, we tested the hypothesis that G-quadruplex structures may influence the distribution of somatic mutations in the tumor cells of MM patients. We sequenced exomes of normal and tumor cells of 11 MM patients and analyzed the data for the presence of G4 context around points of somatic mutations. To identify molecular mechanisms that could affect mutational profile of tumors, we also analyzed mutational signatures in tumor cells as well as germline mutations for the presence of specific SNPs in DNA repair genes or in genes regulating G-quadruplex unwinding. In several patients, we found that sites of somatic mutations are frequently located in regions with G4 context. This pattern correlated with specific germline variants found in these patients. We discuss the possible implications of these variants for mutation accumulation and specificity in MM and propose that the extent of G4 context enrichment around somatic mutation sites may be a novel metric characterizing mutational processes in tumors.

The rational design of composites based on graphene/metal oxides is one of the pillars for advancing their application in various practical fields, particularly gas sensing. In this study, a uniform distribution of ZnO nanoparticles (NPs) through the graphene layer was achieved, taking advantage of amine functionalization. The beneficial effect of amine groups on the arrangement of ZnO NPs and the efficiency of their immobilization was revealed by core-level spectroscopy, pointing out strong ionic bonding between the aminated graphene (AmG) and ZnO. The stability of the resulting Am-ZnO nanocomposite was confirmed by demonstrating that its morphology remains unchanged even after prolonged heating up to 350 °C, as observed by electron microscopy. On-chip multisensor arrays composed of both AmG and Am-ZnO were fabricated and thoroughly tested, showing almost tenfold enhancement of the chemiresistive response upon decorating the AmG layer with ZnO nanoparticles, due to the formation of p-n heterojunctions. Operating at room temperature, the fabricated multisensor chips exhibited high robustness and a detection limit of 3.6 ppm and 5.1 ppm for ammonia and ethanol, respectively. Precise identification of the studied analytes was achieved by employing the pattern recognition technique based on linear discriminant analysis to process the acquired multisensor response.

SARS-CoV-2 has accumulated many mutations since its emergence in late 2019. Nucleotide substitutions leading to amino acid replacements constitute the primary material for natural selection. Insertions, deletions, and substitutions appear to be critical for coronavirus’s macro- and microevolution. Understanding the molecular mechanisms of mutations in the mutational hotspots (positions, loci with recurrent mutations, and nucleotide context) is important for disentangling roles of mutagenesis and selection. In the SARS-CoV-2 genome, deletions and insertions are frequently associated with repetitive sequences, whereas C>U substitutions are often surrounded by nucleotides resembling the APOBEC mutable motifs. We describe various approaches to mutation spectra analyses, including the context features of RNAs that are likely to be involved in the generation of recurrent mutations. We also discuss the interplay between mutations and natural selection as a complex evolutionary trend. The substantial variability and complexity of pipelines for the reconstruction of mutations and the huge number of genomic sequences are major problems for the analyses of mutations in the SARS-CoV-2 genome. As a solution, we advocate for the development of a centralized database of predicted mutations, which needs to be updated on a regular basis.

Background. The article reflects the clinical significance of the early diagnosis of toxic hepatitis in patients who have undergone a new coronavirus infection with the determination of clinical and laboratory predictors of the response to therapy. A dynamic analysis of the effectiveness of toxic hepatitis therapy in patients of three experimental groups and a control group is presented. Aim. The aim of the present study is to increase the effectiveness of the treatment of toxic hepatitis in patients who have undergone COVID-19. Materials and methods. On the basis of the newly created infection centers of the Central Clinical Hospital RZhD-Medicine and Vishnevsky 3-rd Central Military Clinical Hospital 996 patients with COVID-19, who had clinical and laboratory signs of toxic liver damage (cytolytic and/or cholestatic syndromes) against the background of COVID-19 therapy. Results. On the 14th day from the start of therapy in group 3, there was a significant decrease in the clinical manifestations of jaundice in 163 (72.8%) patients, on the 21st day of treatment, this symptom was stopped in all patients. In groups 1 and 2, the decrease in clinical manifestations of jaundice was significantly lower 122 (55.2%) and 134 (58.8%); p0.05. At the end of therapy, no manifestations of jaundice were observed in all experimental groups, while in the control group, symptom reduction was achieved only in 47 (14.5%) patients. Conclusion. The use of drugs with hepatoprotective effect in the form of monotherapy in groups 1 (UDCA) and 2 (ademethionine) showed a low therapeutic effect with positive dynamics of clinical and laboratory indicators of toxic hepatitis activity. The use of combined treatment in group 3 (UDCA and ademethionine) demonstrated the maximum therapeutic effect, pronounced positive dynamics in the form of normalization of clinical and laboratory indicators of toxic hepatitis activity.

In recent years, interest in the search for new potential molecular biomarkers to assess the effectiveness of the training process in elite sports, various pathologies caused by overload, and abuse of prohibited substances has reached an unprecedented level. MicroRNAs that regulate the processes of metabolism, differentiation, proliferation, and apoptosis of cells at the post-transcriptional level are the most valuable candidates for use in this regard. They are found in all biological fluids of the human body, are stable during long-term storage and resistant to changes in environmental conditions. It is known that changes in the miRNA expression profile are closely associated with physical activity, as well as with the administration of recombinant hormones, erythropoiesis-stimulating agents, and other substances and methods that improve sports performance, which are prohibited by the World Anti-Doping Agency (WADA).Objective: In this study, plasma samples from athletes involved in endurance sports (race walking) and non-athletic volunteers were analyzed using a hypoxia signaling pathway panel to identify hypoxia candidate markers.Materials and methods: Expression profiles of plasma circulating miRNAs were assessed by reverse transcription followed by real-time quantitative polymerase chain reaction (RT Q-PCR). The obtained data were subjected to statistical processing using the CFX Manager Software v3.1 program.Results: Three potential microRNA markers were identified: hsa-miR-210-3p, hsa-miR-320a and hsa-miR-935 (increased in athletes by 61.6 times, 51.8 and 41.0 times, respectively) — of physiological response to the training, load, which may be associated with the emergence of hypoxia during endurance training.Conclusion: We have obtained preliminary data on differences in the expression profiles of circulating miRNAs in healthy non-athletic volunteers and professional athletes in the out-of-competition period. In the future, it is planned to expand the sample of studied blood plasma samples and compare the expression profiles of circulating microRNAs in athletes in competition and out-of-competition periods, as well as to compare the expression profiles of circulating microRNAs during aerobic and anaerobic loads. In addition, it is of interest to analyze changes in the expression levels of circulating miRNAs when using hypoxia mimetics applied to improve sports performance.

Purpose. Comparative assessment of the dynamics of visual performance (VP) of a patient with visually intense work with binocular cataract after various technologies of cataract phacoemulsification (PEC).Methods. There were 300 patients with binocular cataract under our observation. Patients were divided into three equals in number (n = 100), age (from 38 to 66 years, mean age 55.8 ± 1.3 years), gender (78 % — men; 22 % — women), refractive values of the group who underwent PEС using the following technologies: delayed sequential bilateral cataract surgery (DSBCS), immediate sequential bilateral cataract surgery according to the traditional (trISBCS) and developed algorithms (maISBCS). Examination of the state of vision of patients in all groups was performed before and 3 months after surgery according to clinical (BCVA in terms of the difference between the first and second eye) and the following ophthalmo-ergonomic indicators, which were assessed using special computer programs: “Visual productivity”, “Glazomer”, “Visual search”.Results. Differences between the clinical outcomes of the first and second eyes with maISBCS and DSBCS are practically insignificant (UDVA within 0.02 rel. units), after trISBCS they are statistically significant (by 0.08–0.09 rel. units, p < 0.05). After the operation, a pronounced (p < 0.001) increase in VP was noted in all groups. At the same time, there were differences between the groups of patients who underwent maISBCS and trISBCS, manifested by a decrease in VP in the trISBCS group according to the “Visual Search” and “Eye Meter” tests, by 16.1–22.1 % (p < 0.05).Conclusion. The postoperative level of VR achieved during maISBCS and and DSBCS is almost identical. It has been determined that with an increase in the level of complexity of the ophthalmo-ergonomic tests presented (“signal-response”; “selection of a signal from several — response”; “selection of a signal in conditions of time pressure”), there is a corresponding increase in the difference in the level of SR between groups of patients who were maISBCS and trISBCS, were performed (by 1.5 %, p > 0.05; 16.1 %, p < 0.05; and 22.1 %, p < 0.05, respectively), which may be associated with the occurrence of postoperative anisometropia.

The discovery of the CRISPR/Cas9 microbial adaptive immune system has revolutionized the field of genetics, by greatly enhancing the capacity for genome editing. CRISPR/Cas9-based editing starts with DNA breaks (or other lesions) predominantly at target sites and, unfortunately, at off-target genome sites. DNA repair systems differing in accuracy participate in establishing desired genetic changes but also introduce unwanted mutations, that may lead to hereditary, oncological, and other diseases. New approaches to alleviate the risks associated with genome editing include attenuating the off-target activity of editing complex through the use of modified forms of Cas9 nuclease and single guide RNA (sgRNA), improving delivery methods for sgRNA/Cas9 complex, and directing DNA lesions caused by the sgRNA/Cas9 to non-mutagenic repair pathways. Here, we have described CRISPR/Cas9 as a new powerful mutagenic factor, discussed its mutagenic properties, and reviewed factors influencing the mutagenic activity of CRISPR/Cas9.

This work presents the synthesis of a new compound, 1-[aryl-(diphenylphosphono)methyl]-3,4,6-trimethylglycolurils, via the interaction of benzaldehyde and its mononitro- and monohydroxyderivatives with 1,3,4-trimethylglycoluril and triphenylphosphite. By varying the reaction conditions and the catalysts, the obtained product yields ranged from satisfactory to good. The diastereomers formed during the reaction were separated by semipreparative HPLC on the C18 stationary phase. The isolated diastereomers were characterized by 1H, 13C, and 31P NMR, and the structures of the diastereomers were confirmed using a single-crystal X-ray crystal structure analysis and quantum chemical calculations.

TThe most important factor limiting sports performance is insufficient fluid intake by athletes and dehydration of the body, while a significant decrease in performance and sports endurance begins with a dehydration level of 2 % and above.Objective: to study the effectiveness and safety of rehydration of the body of athletes­skiers of children and youth using isotonic drinks «Izonok» and «Izonok+».Materials and methods: the main group (n = 12, 16.2 ± 1.4 years) took isotonic drinks for 30 days to compensate for fluid losses, the comparison group (n = 8, 15.7 ± 1.1 years) — drinking water. Bioimpedance body composition analysis was carried out on a KM-AR-01-”Diamant” device (RF, St.Petersburg), and central hemodynamic analysis was carried out on a «SIMONA 111» (LLC “Okulyus 2000”, RF). The content of secretory immunoglobulin A (sIgA) and lysozyme in saliva samples of athletes was carried out by the enzyme immunoassay on an ANTHOS 2010 analyzer (Austria). Statistical data processing was carried out using the Statistica 6.0 software package from Stat Soft @ Ink USA.Results: The intake of an isotonic drink is accompanied by the stimulation of the production of secretory immunoglobulin (sIgA) and lysozyme compared to the consumption of drinking water. The total volume of fluid and the volume of extracellular fluid tended to increase; the volume of intracellular fluid remained practically unchanged; the amount of total water when taking isotonic increased.Conclusion: The investigated isotonic drinks “Izonok” and “Izonok+” are effective sports drinks for maintaining optimal water-salt balance and local immunity

Purpose. Development of the final version of the “quality of life” (QoL) questionnaire for a patient after cataract phacoemulsification (PEC) based on an expert assessment by ophthalmologists.Methods. According to the results of the previously completed stage of work, 35 possible complaints of the patient were identified. The study was performed with the participation of 47 expert ophthalmologists with professional experience from 7 to 35 years (average 19.2 ± 1.4 years), including experience in performing PE from 1 to 24 years (average 11.9 ± 1. 7 years). Each of the experts performed three main tasks: analysis of the primary version of the questionnaire for adding and (or) correcting questions; assessment of the relevance of each of the questions from the standpoint of the degree of influence on the patient’s QoL (0 points — the question is not relevant; 10 points — the question is very relevant); assessment of the “severity” of the complaint in terms of the frequency of occurrence (in the range from 10 points — the occurrence of a symptom does not determine the severity of the disease, to 0 points — the occurrence of a symptom determines the highest severity of the disease). At the same time, the following scaling procedure was used: “Practically no problems” (occur during 0–4 % of the patient’s total active time), “Mild problems” (5–24 %), “Moderate problems” (25–49 %), “Severe problems” (50–95 %), “Absolute problems” (96–100 %). “Virtually no problems” was indicated as 10 points.Results. As part of the solution of the first task, the number of questions was increased from 35 to 52. Mathematical analysis of the results of the second task was carried out on the basis of calculating the basic parameters of descriptive statistics for all 52 questions — the arithmetic mean (as a “weight” coefficient of the question) and standard deviation (as indicator of consistency of the position of the respondents). Subsequently, the “ejection” of insignificant questions was performed (according to the Pareto method with 80 % of the “pool” of questions with the maximum contribution to relevance), as well as the clinical association of similar questions and the assessment of statistical validation (feasibility) of such an association.Conclusion. An expert assessment of ophthalmologists confirmed the validity of using the “social model” of health based on the development of “domains” of the international classification of functioning when developing the QoL questionnaire after FEC. The final version of the «FEC-22» questionnaire fully complies with the content validity requirements.

Purpose. Scientific substantiation of methodological approaches to the development of a “quality of life” (QoL) questionnaire after cataract phacoemulsification (PEC) in patients with visually stressful work (VLT), based on a “medico-social” health model.Methods. The study was carried out on the basis of methodological standards for the development of new tools for assessing symptoms in clinical medicine developed by specialists from the International Center for the Study of Quality of Life (St. Petersburg). This article presents the first stage of development aimed at the formation of a preliminary version of the questionnaire. The initial volume of questions (complaints) of the patient was carried out in the following areas: individual interviews (according to the standard developed methodology) with 50 patients with ZNT; analysis of proven methods for studying QOL in cataracts (“NEI-VFQ”, “Cataract Symptom Scale”, “Catquest-9SF”, etc.); analysis of proven methods for studying QoL in keratorefractive surgery and asthenopic conditions in patients with RNT; analysis of the classification structure of the International Classification of Functioning (ICF) from the standpoint of the development of characteristic “domains”.Results. The data obtained indicate that a total of 35 patient complaints were identified (7 — “visual”; 6 — “professional”; 16 — “functional”; 4 — “household”; 4 — “medical and psychological”). The fundamental difference between the development of the methodology for assessing the patient’s QoL after performing PE is the use of a “social model” of health, which confirms the leading (46 % of all complaints) place for “functional” manifestations of the patient’s subjective status, based on specific “domains” of the ICF. Along with this, the practical application of the basic provisions of the ICF involves scaling the severity of the patient’s complaints in the context of the ratio of the duration of the complaint to the total active time of the patient with a gradation: “Mild problems” (5–24 %); “Moderate problems” (25–49 %); “Severe problems” (50–95 %); “Absolute problems” (96–100 %).Conclusion. The results of the first stage of the development of the patient’s QoL questionnaire after the FEC testify to the compliance with clinical standards in terms of content validity, since the questions, scales and general content reflect the significance for the patient and important parameters from a clinical and functional point of view. A distinctive feature and scientific novelty of the questionnaire is the use of a “social model” of health based on the development of “domains” of the international classification of functioning, as well as optimization of the procedure for scaling patient responses.

High-Q optical microresonators are particularly efficient practical tools of modern applied optics and photonics. Using them, one inevitably faces the problem of thermal effects. Accurate determination of effective thermal parameters of high-Q microresonators (effective thermal relaxation rate and optical absorption rate) is of particular importance for developing microresonator-based devices. Our investigation looks into diverse methodologies to estimate these effective parameters for such systems, ultimately revealing a divergence between the commonly employed simplified model, the direct numerical approach, and classical analytical formulas. We introduce a novel approach to calculate effective parameters based on the decomposition of the thermal field into microresonator thermal modes, which inherently considers the intricate geometry and material anisotropy inherent in microresonators, as well as the influence of external conditions. The method for the accurate determination of the effective thermal parameters of the microresonator for corresponding thermal modes is developed. As a result of applying this method, we modified the classical approach for the simulation of thermal effects in optical microresonators for better agreement with the numerical simulations. By accounting for the complexities of microresonator shapes, material properties, and external factors, our proposed method contributes to a more accurate understanding of thermal dynamics and enhances the predictive capabilities of simulations for these systems. We demonstrated the application of this method on the example of integrated microring resonators, but it can be used to analyze thermal effects in other microresonator platforms.

It is known that partitioning a society into groups with subsequent averaging in each group decreases the Gini coefficient. The resulting Lorenz function is piecewise linear. This study deals with a natural question: by how much the Gini coefficient could decrease when passing to a piecewise linear Lorenz function? Obtained results are quite illustrative (since they are expressed in terms of the geometric parameters of the polygon Lorenz curve, such as the lengths of its segments and the angles between successive segments) upper bound estimates for the maximum possible change in the Gini coefficient with a restriction on the group shares, or on the difference between the averaged values of the attribute for consecutive groups. It is shown that there exist Lorenz curves with the Gini coefficient arbitrarily close to one, and at the same time with the Gini coefficient of the averaged society arbitrarily close to zero.

In the modern world, a doctor of any specialty knows about a relatively new direction in the treatment of severe and previously untreatable diseases - stem cell (SC) transplantation. A scientific discussion around this is an actively developing direction. At present time laboratory studies of the cell therapy have gone beyond the limits of the experiment and began to actively find their application in practical medicine, which gives rise to scientific, ethical, legal and legislative problems. Thousands of laboratory experiments and clinical studies are carried out around the world, hundreds of stem cell culture laboratories and clinics are opened that use cell transplantation for the treatment of a wide range of diseases. The world governments start introduce SC transplantation into the medical system. The classical dogma that CNS cells are unable to regenerate has been challenged in recent decades by studies demonstrating new mechanisms of stem cell migration in the brain in trauma models. One of the most popular and promising areas for using cell therapy is treatment of nervous system diseases. Today, the actual problem for society is the cost of treating the consequences of moderate and severe traumatic brain injury, due to the wide prevalence (30-40% of all types of traumas), high disability rate in the working-age population and the global trend increase number of TBI cases by constant development of the technogenic environment. The review provides information on the history of development, legal, bioethical aspects, the prospects for the use of SC in the treatment of TBI.

Spontaneous or induced DNA lesions can result in stable gene mutations and chromosomal aberrations due to their inaccurate repair, ultimately resulting in phenotype changes. Some DNA lesions per se may interfere with transcription, leading to temporary phenocopies of mutations. The direct impact of primary DNA lesions on phenotype before their removal by repair is not well understood. To address this question, we used the alpha-test, which allows for detecting various genetic events leading to temporary or hereditary changes in mating type α→a in heterothallic strains of yeast Saccharomyces cerevisiae. Here, we compared yeast strains carrying mutations in DNA repair genes, mismatch repair (pms1), base excision repair (ogg1), and homologous recombination repair (rad52), as well as mutagens causing specific DNA lesions (UV light and camptothecin). We found that double-strand breaks and UV-induced lesions have a stronger effect on the phenotype than mismatches and 8-oxoguanine. Moreover, the loss of the entire chromosome III leads to an immediate mating type switch α→a and does not prevent hybridization. We also evaluated the ability of primary DNA lesions to persist through the cell cycle by assessing the frequency of UV-induced inherited and non-inherited genetic changes in asynchronous cultures of a wild-type (wt) strain and in a cdc28-4 mutant arrested in the G1 phase. Our findings suggest that the phenotypic manifestation of primary DNA lesions depends on their type and the stage of the cell cycle in which it occurred.

11H-Indeno[1,2-b]quinoxalin-11-one oxime (IQ-1) and tryptanthrin-6-oxime are potent c-Jun N-terminal kinase 3 (JNK-3) inhibitors demonstrating neuroprotective, anti-inflammatory and anti-arthritic activity. However, the stereochemical configuration of the oxime carbon–nitrogen double bond (E- or Z-) in these compounds was so far unknown. In this contribution, we report the results of the determination of the double bond configuration in the solid state by single crystal X-ray diffraction and in solution by 1D and 2D NMR techniques and DFT calculations. It was found that both in the solid state and in solution, IQ-1 adopts the E-configuration stabilized by intermolecular hydrogen bonds, in contrast to previously assumed Z-configuration that could be stabilized only by an intramolecular hydrogen bond.

Supramolecular 3D Zn(II) coordination polymer {[Zn(bim)(bdc)]⋅0.8DMF⋅0.4EtOH⋅0.1H2O }n (Zn-MOF), constructed from Zn2+ ions, bis(imidazol-1-yl)methane (bim) and terephthalate (bdc2−) anions, was synthesized and structurally characterized. Zn-MOF crystallizes in the tetragonal crystal system, space group P42/n. Each Zn(II) ion coordinates two neutral bim molecules in a bridging bidentate coordination mode via nitrogen atoms at position 3 of the imidazole rings and two bdc2− anions, with monodentate coordination of the carboxylate group for one of them and bidentate coordination for another. Zn(II) cations are in a distorted square pyramidal ZnN2O3 coordination environment. Metal cations are alternately linked by the bim and bdc2− ligands, forming a two-dimensional layered structure along the crystallographic plane ab. As a result of layer interpenetration, a supramolecular 3D network is formed. Zn-MOF demonstrated blue (aquamarine) emission with a maximum at 430 nm upon excitation at 325 nm. The luminescence lifetime of 6 ns is characteristic for ligand-centered fluorescence. The luminescent sensing properties of Zn-MOF in ethanol suspension toward inorganic cations and anions were evaluated and an emission quenching response was observed for Fe3+ and chromate/dichromate ions. Photoinduced electron transfer from Zn-MOF to Fe3+ was elucidated as a possible quenching mechanism on the basis of DFT calculations.

Aim. Analysis of the effectiveness of therapy for non-alcoholic fatty liver disease (NAFLD) with severe asthenic syndrome. Materials and methods. In the period from 2017 to 2019, on the basis of the gastroenterology center of the Vishnevsky 3-rd Central Military Clinical Hospital, 247 patients with NAFLD, including those at the stage of steatohepatitis, and severe asthenic syndrome were examined and treated. The main group included 124 patients, the control group 123 patients. All patients underwent complex laboratory and instrumental diagnostics and neuropsychological research using the subjective asthenia assessment scale (MFI-20). In both groups, domestic drugs were included in the therapy regimen: from the 1st to the 10th day, Heptrong solution 3 ml intramuscularly in the morning; from the 1st to the 60th day UDCA 250 mg orally, 3 capsules at bedtime, Omega-3 forte 1000 mg, 2 capsules in the morning with meals. In group I patients received additionally from the 1st to the 10th day intravenous drip Cytoflavin 10 ml + 0.9% NaCl solution 200 ml; pentoxifylline solution 5 ml + 0.9% NaCl solution 200 ml. Then, from the 11th to the 60th day, Cytoflavin inside, 2 tablets 2 times a day. Pentoxifylline inside 400 mg 1 tablet 3 times a day. All patients underwent neuropsychological examination using the subjective asthenia rating scale (MFI-20). Results. The effectiveness of treatment in patients of both groups was assessed by clinical, laboratory data and neuropsychological studies. In the main group, a significant reduction in asthenic syndrome was achieved against the background of diagnosed NAFLD compared with the control group. Conclusion. The early inclusion of patients with NAFLD and severe asthenic syndrome in the treatment regimen, in addition to the basic therapy of Cytoflavin, achieved a significantly high therapeutic effect in the form of normalization of the main clinical, laboratory and instrumental parameters, as well as a significant reduction in the manifestations of asthenia.

Background. The novel coronavirus infection COVID-19 can be manifested by damage to the organs of the gastrointestinal tract (GIT). Damage to the gastrointestinal tract by the SARS-CoV-2 virus leads to a violation of the microbial-tissue complex of the mucous membrane of the digestive tract. A common gastroenterological manifestation of COVID-19 is diarrhea. Aim. Study of the clinical features of gastroenterological disorders and the possibility of optimizing the treatment of diarrheal syndrome in patients with COVID-19 with a mild form of viral infection. Materials and methods. The observation group consisted of 230 patients with mild COVID-19: K-group (n=115) with respiratory symptoms, I group (n=115) with gastrointestinal manifestations in combination and without signs of respiratory damage. In order to compare the effectiveness of treatment of diarrheal syndrome, patients of group I are randomized into 2 subgroups: Ia (n=58) prebiotic treatment (Zacofalk) and Ib (n=57) enterosorbents. Results. The development of gastrointestinal symptoms with SARS-CoV-2 infection is significantly more often noted in comorbid patients (67%). Gastrointestinal symptoms were dominated by diarrhea (93.9%) and flatulence (76.5%), in 1/3 of patients they were the first manifestos of infection. It was established that in 98.4% of patients of group I (against 42.6% of the K-group) signs of infectious intoxication were detected. In patients with gastrointestinal lesions, an elongation of the febrile period by 91.5 days was noted, a later (6 days) verification of the viral etiology of the disease. It was found that in patients of group I, the regression of clinical symptoms, the duration of viral disease, the dynamics of antibody formation, the prognosis for the development of IBS-like disorders in the post-infectious period depended on the treatment. In patients taking (Zacofalk), these indicators were significantly better. Conclusion. In mild cases, to reduce the severity of viral intestinal damage, for effective relief of intestinal symptoms, to reduce the risk of IBS-like symptoms, it is advisable to prescribe (Zacofalk) in an initial dose of 3 tablets per day.

Purpose: to study the clinical and functional state of the visual analyzer of patients after surgery for the epiretinal membrane (ERM) from the standpoint of the relevance of postoperative rehabilitation.Patients and methods. There were 158 patients under observation (158 eyes, main group, MG), among whom 66 % were men, 34 % were women aged 45–74 years (the average age of patients was 62.4 ± 1.5 years) with a diagnosis of ERM. At the same time, the leading form of ERM was idiopathic (122 patients, 77.2 %). As a control group (CG), were examined 32 patients of equal age and gender, who did not have visual organ pathology. In order to remove ERM, all patients underwent subtotal posterior vitrectomy with intraoperative administration of antioxidants, in particular glutathione contained in a balanced salt solution “BSS-PLUS” (Bausch + Lomb, USA). A comprehensive examination of the clinical and functional state of the visual analyzer was performed one month after surgery.Results. The data obtained indicate that almost all the studied parameters revealed a significant deterioration in the MG compared to the CG with a fairly good anatomical effect (the thickness of the central retinal zone after the operation was 287.1 ± 11.6 μm). In particular, a decrease in the subjective indicator “Quality of life” (by 53.1 %), as well as a deterioration in the objective indicators of the critical frequency of flicker fusion, the magnitude of the electrical lability of the retina and the threshold of electrical sensitivity of the retina (by 36.2; 38.2 and 45, 5 % respectively).Conclusions. A fairly good anatomical effect of vitreoretinal surgical intervention for ERM is accompanied (one month after the operation) by a significant decrease in the functional state of the visual analyzer. In order to restore vision more quickly, it seems advisable to conduct early postoperative rehabilitation (based on the complex use of physiotherapeutic effects and combined drug therapy) aimed at correcting functional disorders of the retina, which will lead to a decrease in the severity of characteristic complaints and an increase in the “Quality of life” of the patient.

The facile synthesis of biografted 2D derivatives complemented by a nuanced understanding of their properties are keystones for advancements in biosensing technologies. Herein, we thoroughly examine the feasibility of aminated graphene as a platform for the covalent conjugation of monoclonal antibodies towards human IgG immunoglobulins. Applying core-level spectroscopy methods, namely X-ray photoelectron and absorption spectroscopies, we delve into the chemistry and its effect on the electronic structure of the aminated graphene prior to and after the immobilization of monoclonal antibodies. Furthermore, the alterations in the morphology of the graphene layers upon the applied derivatization protocols are assessed by electron microscopy techniques. Chemiresistive biosensors composed of the aerosol-deposited layers of the aminated graphene with the conjugated antibodies are fabricated and tested, demonstrating a selective response towards IgM immunoglobulins with a limit of detection as low as 10 pg/mL. Taken together, these findings advance and outline graphene derivatives’ application in biosensing as well as hint at the features of the alterations of graphene morphology and physics upon its functionalization and further covalent grafting by biomolecules.

Baker’s yeast, S. cerevisiae, is an excellent model organism exploited for molecular genetic studies of the mechanisms of genome stability in eukaryotes. Genetic peculiarities of commonly used yeast strains impact the processes of DNA replication, repair, and recombination (RRR). We compared the genomic DNA sequence variation of the five strains that are intensively used for RRR studies. We used yeast next-generation sequencing data to detect the extent and significance of variation in 183 RRR genes. We present a detailed analysis of the differences that were found even in closely related strains. Polymorphisms of common yeast strains should be considered when interpreting the outcomes of genome stability studies, especially in cases of discrepancies between laboratories describing the same phenomena.

Subungual melanoma is a rare malignant tumor, little known to practitioners. Its location makes diagnosis difficult and requires differentiation with conditions such as onychomycosis, panaritium, hematoma, etc. Unsymptomatic onset brings more problems, the error level during visual examination even among experienced oncologists reaches 25–40%, and the average life expectancy of patients with fully manifested melanoma is limited to 3–4 years.So we present a clinical case to emphasize the need for oncological alertness during an outpatient examination of the subungual lesions. A 32-year-old woman came to the reception complaining of a non-healing bleeding, relatively painless wound of the left little toe. The condition was associated with trauma, for about a month she treated the wound herself, “cauterizing” it with antiseptics.After outpatient treatment of a granulating wound, the material was sent for histological diagnosis, which showed the presence of pigmentless melanoma in the stage of active growth. The woman was urgently hospitalized in the oncology department, where 5th finger exarticulation and inguinal-iliac lymphadenectomy were performed successfully. After this, the condition remained stable, but 14 months later there was a formation in the area of the postoperative scar. A study of a new surgical material confirmed the recurrence of malignant melanoma with Clark invasion level 2.In our opinion, outpatient surgeons should not delay histological examination for all ulcerative and granulomatous lesions of the feet, which will improve the differential diagnosis.

Erythropoietin (EPO) has multiple nonerythropoietic functions, including immune modulation, but EPO’s effects in transplantation remain incompletely understood. We tested the mechanisms linking EPO administration to prolongation of murine heterotopic heart transplantation using WT and conditional EPO receptor–knockout (EPOR-knockout) mice as recipients. In WT controls, peritransplant administration of EPO synergized with CTLA4-Ig to prolong allograft survival (P < 0.001), reduce frequencies of donor-reactive effector CD8+ T cells in the spleen (P < 0.001) and in the graft (P < 0.05), and increase frequencies and total numbers of donor-reactive Tregs (P < 0.01 for each) versus CTLA4-Ig alone. Studies performed in conditional EPOR-knockout recipients showed that each of these differences required EPOR expression in myeloid cells but not in T cells. Analysis of mRNA isolated from spleen monocytes showed that EPO/EPOR ligation upregulated macrophage-expressed, antiinflammatory, regulatory, and pro-efferocytosis genes and downregulated selected proinflammatory genes. Taken together, the data support the conclusion that EPO promotes Treg-dependent murine cardiac allograft survival by crucially altering the phenotype and function of macrophages. Coupled with our previous documentation that EPO promotes Treg expansion in humans, the data support the need for testing the addition of EPO to costimulatory blockade-containing immunosuppression regimens in an effort to prolong human transplant survival.

A general model of the origin and evolution of chaotic wave processes in electrochemically active neuronal media based on the proposed method of matrix decomposition of operators of nonlinear systems has been developed. The mathematical models of Hodgkin – Huxley and FitzHugh – Nagumo of an electrochemically active neuronal media are considered. The necessary conditions for self-organization of chaotic self-oscillations in the FitzHugh – Nagumo model are determined. Computer modeling based on the matrix decomposition of chaotic wave processes in electrochemically active neuronal media has shown the interaction of higher-order nonlinear processes leading to stabilization (to a finite value) of the amplitude of the chaotic wave process. Mathematically, this is expressed in the synchronous “counteraction” of nonlinear processes of even and odd orders in the general vector-matrix model of an electrochemically active neuronal media being in a chaotic mode. It is noted that the state of hard self-excitation of nonlinear oscillations in an electrochemically active neuronal media leads to the appearance of a chaotic attractor in the state space. At the same time, the proposed vector-matrix model made it possible to find more general conditions for the appearance and evolution of chaotic wave processes in comparison with the initial Landau turbulence model and, as a result, to explain the occurrence of consistent nonlinear phenomena in an electrochemically active neuronal media.

Striving to achieve the goals of the training process with the irrational use of physical activity can lead to a decrease in the adaptive and reserve capabilities of the athlete. The development of changes in the endocrine, cardiovascular and central nervous systems may result in the development of overtraining syndrome. There is no unified approach to the definition, diagnosis, treatment and prevention of overtraining syndrome in the literature up to the present day. The endocrine aspects of the development of the overtraining syndrome are not sufficiently studied. In particular, there is no clear understanding of the degree of involvement of various hormonal mechanisms in its pathogenesis and ideas about the possibilities of using hormone levels to diagnose this condition. The purpose of this publication is to summarize and systematize the available concepts regarding the endocrine aspects of the overtraining syndrome.

Despite significant progress in the understanding of galactic nucleosynthesis and its influence on the solar system neighborhood, challenges remain in the understanding of enrichment of the solar system itself. Based on the detailed review of multi-disciplinary literature, we propose a scenario that an event of nucleogenesis—not nucleosynthesis (from lower nucleon numbers A to higher A) but nuclear-fission (from higher A to lower A)—occurred in the inner part of the solar system at one of the stages of its evolution. We propose a feasible mechanism of implementation of such event. The occurrence of such event could help explain the puzzles in yet-unresolved isotopic abundances, certain meteoritic anomalies, as well as peculiarities in the solar system’s composition and planetary structure. We also discuss experimental data and available results from existing models (in several relevant sub-fields) that provide support and/or appear consistent with the hypothesis.

The recent image of our galaxy’s supermassive black hole Sgr A* derived from the 7 April 2017 data of the Event Horizon Telescope Collaboration shows multiple hot spots in its accretion disk. Using the analytical framework, we demonstrate that the observed hot spots may not be disjoint elements but causally linked components (“petals”) of one rotating quasi-stationary macro-structure formed in the thermo-vorticial field within the accretion disk.

A new metal–organic framework based on cadmium(II) cations, di(p-carboxyphenyl)sulphone and 4,7-di(imidazol-1-yl)-2,1,3-benzothiadiazole was prepared, and its crystal structure was determined using single-crystal XRD analysis. MOF demonstrated bright luminescence with a maximum near 500 nm and quantum yield reaching 20%. In addition, this MOF demonstrated sensing properties towards antibiotics and a toxic natural polyphenol gossypol through effective luminescence quenching in an ethanol suspension. The determined detection limit for gossypol was among the lowest reported so far (0.65 µM), and did not significantly change in the interference experiments with cottonseed oil as background, indicating the possibility of using this MOF as a sensor for the detection and determination of gossypol in real-life samples.

TNF ligation of TNF receptor 1 (TNFR1) promotes either inflammation and cell survival by (a) inhibiting RIPK1’s death-signaling function and activating NF-κB or (b) causing RIPK1 to associate with the death-inducing signaling complex to initiate apoptosis or necroptosis. The cellular source of TNF that results in RIPK1-dependent cell death remains unclear. To address this, we employed in vitro systems and murine models of T cell–dependent transplant or tumor rejection in which target cell susceptibility to RIPK1-dependent cell death could be genetically altered. We show that TNF released by T cells is necessary and sufficient to activate RIPK1-dependent cell death in target cells and thereby mediate target cell cytolysis independently of T cell frequency. Activation of the RIPK1-dependent cell death program in target cells by T cell–derived TNF accelerates murine cardiac allograft rejection and synergizes with anti-PD1 administration to destroy checkpoint blockade–resistant murine melanoma. Together, the findings uncover a distinct immunological role for TNF released by cytotoxic effector T cells following cognate interactions with their antigenic targets. Manipulating T cell TNF and/or target cell susceptibility to RIPK1-dependent cell death can be exploited to either mitigate or augment T cell–dependent destruction of allografts and malignancies to improve outcomes.

The molecular structure of bis(pyrazol-1-yl)methane-4,4′-dicarboxylic acid (H2bpmdc) was determined by single crystal X-Ray diffraction analysis. The compound crystallizes in a monoclinic crystal system; the unit cell contains four formula units. The molecules of H2bpmdc are linked into zig-zag chains by intermolecular carboxyl–carboxyl hydrogen bonds. Other types of supramolecular interactions, namely, CH···N and CH···O short contacts, CH–π interactions and carbonyl–carbonyl interactions were detected in the crystal structure.