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From the point of view of the mechanisms for the implementation of pathogenetic links in the development of steroid-induced osteoporosis considered in the paper, the increased risk of the oxidative stress in osteoblasts, as well as the development of the vessels endothelial dysfunction of the microcirculatory bloodstream in the bone tissue, are of particular interest. They lead to the impaired bone tissue trophism and progression of osteoporosis.The aim of the study was research of the osteoprotective effects of a 3-hydroxypyridine derivatives composition on the model of steroid-induced osteoporosis.Materials and methods. To model osteoporosis pathology, the animals (male Wistar rats) were injected with methylprednisolone (MP) at the dose of 5 mg/kg (intraperitoneally) every 5th day for 5 weeks. Аs a non-selective blocker of NO synthase, L-NAME was used at the dose of 25 mg/kg (intraperitoneally). Derivatives of 3-hydroxypyridine (hereinafter referred to as composition No. 1) were administrated at the dose of 50 mg/kg (per os) In all experimental groups, the level of microcirculation and the bone mineral density, as well as the analysis of histomorphological and biochemical samples, were assessed.Results. The study results showed that composition No. 1 (50 mg/kg) has an osteoprotective activity, effectively prevents a decrease in the level of the regional bone tissue microcirculation and in the development of an endothelial dysfunction. That makes it possible to increase the bone mineral density and to slow down the thinning of bone trabeculae. In addition, composition No. 1 (50 mg/kg) reduces the production of reactive oxygen species and increases the NO bioavailability.Conclusion. The data obtained indicate that the studied composition of 3-hydroxypyridine derivatives is considered a promising compound for the prevention and treatment of steroid-induced osteoporosis.

Purpose. To study the diagnostic value of cascade family screening and the spectrum of genetic variants in patients with familial and sporadic DCM, assess clinical outcomes and comparative analysis of 5-year event-free survival.Materials and methods. The study included 156 unrelated patients with verified DCM. All patients (aged 46 [34; 57] years; 125 (80%) male; LVEF 31 [24; 38]%; LV EDD 68 [61; 74] mm; follow-up period - 77 [59; 108] months) a complex of clinical and instrumental studies (ECG, ECHO, HM, MRI), cascade family screening with genetic testing (NGS+Sanger) and segregation analysis were performed.Results. Criteria for familial DCM were identified in 73 (46.8%) probands. The genetic cause of DCM was identified in 47 (64,4%) familial cases, while for sporadic form DCM pathogenic variants were detected in 19 (22,9%) patients. The dominant mutations were truncating variants in the titin gene (10,9%) and variants in the lamin A/C (LMNA) gene - 8,33%. As a result of the evaluation of cumulative event-free survival (Kaplan-Meier curves), LMNA carriers showed the poor 5-year prognosis for ventricular tachyarrhythmic events (x2=39.9; p=0,0001) and composite adverse outcomes (x2=12.1; p=0.001). Probands who had a familial DCM (log rang x2=38.5; p=0,0001) showed the worst prognosis and low cumulative survival when compared with patients of the sporadic DCM.Conclusion. Cascade clinical family screening and genetic testing in the DCM cohort increased the level of diagnosis of familial DCM from 4.5% to 46.8%. Associations of LMNA mutations with life-threatening tachyarrhythmias are defined as prognostically significant, that confirms the important role of genetic stratification of arrhythmic risk.

A phenetic analysis of the honey bee population of the Toratau Geopark (Russia) was performed. Over 1,000 worker and drone bee samples were collected from 250 colonies in 59 apiaries on the territory of the Toratau Geopark (Gafuriysky, Ishimbaysky, Meleuzovsky, and Sterlitamaksky districts of the Republic of Bashkortostan). Six phenes in worker bees and four phenes in drone bees were recognized. The phenes E, 1R, 2R, and 3R in workers and Is, I, and O-gray in drones were predominant in the honey bee population of the Toratau Geopark, which were associated with subspecies of the C-lineage. These phenes can be used as indicators of introgressive hybridization in the local dark European honey bee population. The phenes allow for quick evaluation of certain honey bee colonies hybridization states.

Background and Aim: Prolonged stress causes deleterious effects on both the organism and its microbiota. In this study, we examined the effects of exposure to variable frequency ultrasound (US) on the gut microbiota-liver-brain axis of mice. Materials and Methods: This study was conducted on 20 mature clinically healthy sexually naive C57BL/6J male mice (42–45 days old). Group 1 (Normal) consisted of healthy intact mice (n = 10). Group 2 (Stress) consisted of mice subjected to US-induced stress (n = 10) for 20 days with alternating frequencies (20–45 kHz). Stool samples were collected on days 0, 10, and 20, and the corresponding DNA was later subjected to 16SrRNA sequencing. After mice were sacrificed on day 21, the leukocyte count, blood serum biochemical parameters, and liver and brain antioxidant status were measured. Behavioral testing was performed on days 17, 18, and 19. Results: Ultrasound lead to higher stress and anxiety levels; increase in creatinine by 8.29% and gamma-glutamyltransferase activity by 5 times, a decrease in alkaline phosphatase activity by 38.23%, increase of de Ritis coefficient by 21.34%; increased liver and brain superoxide dismutase level by 20.8% and 21.5%, respectively; the stress-related changes in the gut microbiota composition – Bacteroidaceae and Firmicutes. Conclusion: Subjecting mice to 20 days of US-induced stress leads to systemic disorders due to oxidative stress and a decrease in the diversity of the gut microbiota. Keywords: antioxidant system, bacterial metabolites, gut microbiota, ultrasound-induced stress.

A comparative analysis of the technological processes of machining a part from a stamped workpiece using universal equipment and a CNC milling machining center is considered. Route technological processes have been developed. A diagram of a special fixture for machining on a CNC milling center Tongtai TMV-1050QII is presented. Comparative analysis of labor input is made.

The most frequent sources of microbial flora inside the eye are the ocular surface, foci of para-ocular infection of the patient. In vitreous samples from eyes with endophthalmitis microorganisms are revealed that are the saprophytic flora of the ocular surface. It is mainly represented by staphylococci, from which epidermal staphylococcus prevails quantitatively. Immunodeficiency states, diabetes mellitus, terminal liver and kidney diseases increase the risk of endophthalmitis development. Eradication of opportunistic pathogenic flora in the source loci, sanation of para-ocular infection, correction of somatic pathology by profile specialists is more relevant for endophthalmitis prevention. The problem of growing antibiotic resistance should also be considered. Thus, when selecting patients for surgery, one should be guided by the data on antibiotic resistance of the identified flora, pay attention to the presence of para-ocular infection and the systemic somatic status of the patient. This will provide a better vector for the development of recommendations for optimal prophylaxis.

Granulocyte-macrophage colony stimulating factor (GM-CSF) is a myelopoietic growth factor that exerts pleiotropic effect not only on the differentiation of immature progenitor cells into polymorphonuclear neutrophils, monocytes/macrophages and dendritic cells, but also controls the functioning of differentiated cells. GM-CSF is currently being investigated in clinical trials as an immunomodulator and adjuvant. However, a wide range of biological activities and, sometimes, paradoxical effects of this cytokine require more thorough studies of its action, in order to predict its efficacy under different conditions of immunotherapy. In this work, we have studied the effect of recombinant human GM-CSF on metabolic activity of mouse peritoneal exudate cells in primary cell cultures. Metabolic (redox) activity of the cells was assessed by their ability to reduce nitroblue tetrazolium (NBT) in the course of MF- and Fc-dependent phagocytosis triggered by addition of opsonized zymosan, or sheep erythrocytes to the culture medium. We have shown the dose-dependent stimulatory effect of GM-CSF on the oxidative metabolism of phagocytic peritoneal macrophages and neutrophils. Upon culturing the pepton-elicited cells at wide range of GM-CSF concentrations (5 to 40,000 ng/mL) for 2 and 24 hours, a more pronounced effect of the substance was observed for neutrophils. The GM-CSF preparation caused a significant increase (by 13-17%) in the redox activity of neutrophils induced by opsonized zymosan that persisted at a low dose range, and was retained after 24 hours. The stimulatory effect of GM-CSF on macrophages with NBT index increase by 16% was observed in the short-term cultures. In general, the elicited cells of both types showed a more pronounced response to lower concentrations of GM-CSF (5-125 ng/mL), and weaker effect at higher doses of the preparation. A similar dependence was found when studying the resident macrophages. Culturing of resident cells with GM-CSF at the doses of 5,000 to 40,000 ng/mL for 24 hours caused a significantly increased redox activity of the cells induced by zymosan, or sheep erythrocytes (by 33-52%). In both cases, the maximal response was detected at a dose of 5,000 ng/mL and decreased with increasing dose. The stimulatory effect of GM-CSF upon resident macrophages was more pronounced as compared to elicited cells, which was characterized by the prolonged period of cell activation (up to 24 hours of culture). The data obtained are of interest, in view of prospective usage of GM-CSF as a component of immunomodulatory and adjuvant therapy for various infectious diseases.

Purpose: Carrying out complex experimental studies of cyclic crack resistance of molten steel which is used for load-bearing parts of freight wagon running systems with kinetic diagram building for fatigue failure. Methods: Method of mechanical testing of molten steel samples under cyclic loading conditions was applied, the method makes it possible to obtain quantitative estimates of stuff ability to resist fatigue failure on the stage of fatigue crack development (testing on cyclic crack resistance). To study the surface of fatigue failure, relief micrographic analysis was used. To study molten steel elemental composition and the mechanisms of fatigue crack development, X-ray micro-spectral analysis was used on fatigue failure various stages. Results: The results of the research of cyclic crack resistance of 20 GL molten steel, which is used for load-bearing parts of freight cars, are presented. Fatigue failure kinetic diagram has been built, detailed micrographic analysis of fatigue failure surface has been carried out and elemental composition of non-metallic inclusions has been studied. Practical significance: Based on the research results, it is possible to assess the performance of 20 GL steel with cracks and to predict survivability. The results obtained make it possible to improve the methods of resource projection of molten bearing parts for freight wagon running systems in order to increase their operational reliability. The research results are used by enterprises - manufacturers of molten parts to control technology stability and to improve product quality.

In 1957 there occurred a technological disaster in the Southern Urals in the form of a nuclear accident at the Mayak chemical plant in Ozersk, Soviet Union. The accident led to the resettlement of two historical centres of the first wave of the Russian colonization of the region, as the villages along the Techa river were declared restricted areas during the cleaning of the radiation trail, and their residents were resettled. As a result, the original culture of the villages was lost. The inspiration for our research is Alexey Mityunin, a local historian, enthusiast, and public activist, who collected a martyrology of the disappeared Ural villages. This paper presents the results of field expeditions to Brodokalmak carried out in 2014–2017 by students of the Miass Branch of Chelyabinsk State University, Russia. Brodokalmak is the village where the people resettled from contaminated lands Zamanikha, Boevka, and Muslyumovo live or lived.

Objective. To assess the time-related changes in the titer of virus neutralizing antibodies to SARS-CoV-2 in patients with HIV infection within 6 months after experienced COVID-19, and to identify factors associated with the intensity and duration of the natural humoral immune response.Materials and Methods. А prospective study was performed in 102 HIV-infected patients who had COVID-19 without previous vaccination, the titer of virus neutralizing antibodies to SARS-CoV-2 was identified by microneutralization assay using the standard method, the follow-up period was 6 months. Patients were enrolled in St. Petersburg from October 2020 to January 2022. The possible impact of clinical and laboratory characteristics of HIV infection and the severity of COVID-19 on antibody titer was assessed.Results and discussion. А high antibody titer (>1:160) was detected at 1 month in 15 patients (14.7%), at 3 months — in 5 of 44 patients; at 6 months — in 3 of 26 patients. There was a statistically significant positive correlation of the titer at 1 month with an undetectable HIV viral load and the Cd4+lymphocytes count in the blood. Cases of a late increase in antibody titer (after 3 and 6 months) were registered without COVID-19 re-infection along with improvement of the immune status on antiretroviral therapy.Conclusion. А low incidence of effective humoral immune response 1 month after COVID-19 infection was demonstrated in HIV-infected patients without vaccination against SARS-CoV-2. Single cases of delay in antibody titer increase with an immune status improvement were observed.

Background. The most effective way to prevent infectious diseases is vaccination. Adjuvants contribute to the optimization of the immune response of vaccines. Double-stranded ribonucleic acids (dsRNAs) from natural sources are promising, but insufficiently studied adjuvants. The aim of the work was to study the adjuvant activity of dsRNA obtained from the killer strain of Saccharomyces cerevisiae using two models of induction of a specific immune response. Materials and methods. In the experiments, the substance of the drug Ridostin containing dsRNA, 21.72% (produced by Institute of Medical Biotechnology of the State Research Center of Virology and Biotechnology Vector), was used. A specific immune response was modeled using ovalbumin (OVA) or the substance of the EpiVacCorona vaccine (EVC). The experiments were carried out in 200 female BALB/c mice. Mice of the experimental groups were injected twice with antigen and adjuvant together with a 28-day interval, mice of the comparison group with antigen only. On the 10th day after the second immunization, blood samples were collected to determine the level of specific antibodies using enzyme immunoassay. The results were evaluated by calculation of the average geometric titers of specific antibodies against OVA or EVC. Results. OVA or EVC administered twice induced the specific antibodies in mice in dose-dependent titers. The combined administration of antigen and dsRNA increased the strength of the immune response. The highest stimulating effect of dsRNA was observed in the dose of 100 g/mouse administered into mice immunized with OVA (1 g/mouse) or in the dose of 50 g/mouse in mice immunized with EVC substance (0.25 of a human dose per mouse). Conclusion. The data obtained indicate that the substance of dsRNA exerts adjuvant properties, which gives reason to consider dsRNA as a promising adjuvant for peptide vaccines.

Rational layout of nets and enhancement of solid-phase wire joints is shown to lead to the growth of the interlayer strength and effective thermal conductivity through the porous net materials thickness, and also to the anisotropy reduction in the sheet plane. It is established that the highest possible interlayer strength of blanks is achieved by the preliminary chemical etch of nets, increase of vacuum level, optimization of temperature and strain rate under solid-phase joint conditions. Manufacturing conditions of sheet porous net materials with high interlayer strength by diffusion welding and net roll welding in vacuum-treated envelopes are found. Manufacturing procedures of argon-arc welding and electron-beam welding for liners of vaporizer-exchangers and stamp-welded filters for the liquid purification of mechanical impurities are elaborated.

Currently, the disease caused by the new coronavirus (COVID-19) and the possibility of co-infection with SARS-CoV-2 and other pathogens in the current epidemic situation continues to be of particular interest. The review, based on the analysis of literature and own materials, outlines the features of the relationship between SARS-CoV-2 and pathogens of acute respiratory viral infections (ARVI). Particular attention is paid to the combined course of COVID-19 and influenza, a comparative characteristic of the severity of the clinical picture. An assessment of the epidemic situation against the backdrop of the COVID-19 pandemic in foreign countries and the Russian Federation (RF) revealed the presence of the phenomenon of SARS-CoV-2 interference with other viral respiratory agents, based on the facts of a sharp suppression of the circulation of influenza viruses, respiratory syncytial virus (RSV) and other ARVI pathogens during the period of active spread of pandemic coronavirus. The main epidemiological indicators of the course of coronavirus infection were compared and the contribution of various pathogens to the etiology of acute respiratory viral infections during the development of the second wave of COVID-19 in the RF was assessed. It was noted that the decrease in the number of new cases by 11.4 and deaths by 2.1 times due to COVID-19 at 6 and 13 weeks in 2022 occurred with unchanged laboratory detection of the influenza virus (0.8%) and an increase in the frequency detection of pathogens of other SARS. The results of observations showed that against the background of a decrease in the incidence of COVID-19, there was no increase in the proportion of diagnosed cases of infections caused by other pathogens, especially influenza. The results obtained confirm the need to ensure effective epidemiological surveillance and additional application of pathogen identification methods for monitoring various ARVI, which can significantly affect the approach to differential diagnosis, patient management tactics and the decision on appropriate preventive measures.

Interferon inducers are of interest as the first line of defense against viral infections, including influenza. Double-stranded ribonucleic acid (dsRNA) for intranasal administration has been developed, the excipients and drug components were selected at the Institute of Medical Biotechnology, a branch of the State Research Center of Virology and Biotechnology «Vector». This work presents the results of the study on antiviral activity and pharmacological safety of a new form of dsRNA. The antiviral activity of the preparation was studied in BALB/c mice infected with influenza A/Aichi/2/68 (H3N2) or Bishkek/01/2009 (H1N1pdm09) viruses. A safety study was performed with a single administration of intranasal dsRNA into white outbred ICR mice. The study showed that the administration of therapeutic and prophylactic regimen of intranasal dsRNA at a dose of 2.5 mg/kg increases the survival and average life expectancy of mice infected with the mentioned strains of influenza virus. The protective effect of the preparation in mice infected with a lethal dose of Bishkek/01/2009 virus was comparable to the effect of Tamiflu. The absence of toxic effects of intranasal dsRNA at a pharmacological dose in laboratory mice, the functional state of their physiological systems, as well as main types of metabolism, established in the experiments, lead to a conclusion concerning pharmacological safety of the preparation and the prospects for further work to complete pharmaceutical development of a new antiviral drug.

The aim of the work is to evaluate the hemostimulating activity of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) conjugates with alendronic acid (ALN) in the model of cytostatic myelosuppression and the dynamics of rhGM-CSF accumulation as a part of the conjugate in the bone tissue and bone marrow of mice.Materials and methods. The conjugates obtained by a solid-phase synthesis using 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide or periodate oxidation, were used. A hemostimulating activity was evaluated in a model of a cytostatic myelosuppression induced by the administration of cyclophosphamide to CBA/Calac mice. RhGM-CSF preparations were injected subcutaneously for 4-5 days at the dose of 90 µg/kg. After the injections cycle had been completed, the total leukocyte and segmented neutrophil counts were carried out in the blood samples, and the total karyocyte count was carried out in the bone marrow samples.The tissue distribution of rhGM-CSF preparations was assessed in outbred CD-1 mice after a single intravenous administration at the effective dose. The content of rhGM-CSF in blood, femoral tissue and bone marrow was determined by enzyme immunoassay.Results. RhGM-CSF conjugates with ALN have been shown to retain the ability of the original protein to increase the number of leukocytes, segmented blood neutrophils, and bone marrow karyocytes under the action of conjugates. The stimulation of the neutrophil production used to be observed at earlier times than in the case of rhGM-CSF. The increase in the total number of bone marrow cells after the introduction of all three conjugates was more pronounced compared to the original protein (by 34%). The increased hemostimulatory effect of the AEG conjugate was accompanied by a more intense accumulation of rhGM-CSF in the bone tissue and bone marrow of mice. The rhGM-CSF introduced into the conjugate was detected in the bone tissue for 24 h and it circulated in the bloodstream for a longer time compared to the original protein.Conclusion. The data obtained make it possible to conclude that further work on the development of effective hemostimulating drugs based on rhGM-CSF conjugates with ALN, is promising.

The purpose of the present work was to evaluate population immunity to influenza and molecular genetic analysis of influenza viruses detected in the Russian Federation over 2020-2022. In this study, 1344 samples of blood serum collected prior to the 2021-2022 flu season in Siberian, Southern, Far Eastern, Volga and Ural Federal Districts were studied. Seropositivity to the A/Victoria/2570/2019 vaccine strain (H1N1) pdm09 was detected in 25% to 31% of samples from the four federal districts, and in 8% of samples from the Far Eastern Federal District. Seropositivity to the A/Cambodia/e0826360/2020 strain (H3N2) was detected in 24% to 37% of the samples. The lowest population immunity was revealed to the influenza B/Washington/02/2019 vaccine strain (Victoria lineage), with < 10% of serum samples reactive to the studied strain. Since March 2020, the worldwide turnover of all seasonal respiratory viruses has sharply decreased, except of rhinoviruses. From March 2020 to June 2021, we have identified six B/Victoria influenza viruses from sporadic cases of influenza. From June 2021 to the end February 2022, the State Research Center “Vector” received 901 samples positive for influenza A(H3N2) virus RNA, two specimens positive for A(H1N1) pdm09 virus RNA, and 17 samples positive for influenza B. All studied A(H3N2) viruses belonged to the 3C.2a1b.2a2 subclade (Bangladesh group). The two verified A(H1N1) pdm09 influenza viruses belonged to the 6B.1A.5a clade. All studied influenza B viruses were assigned to the B/Victoria genetic lineage, and to 1A.3a2 subclade. The genomes of all identified viruses did not contain mutations of the NA gene responsible for drug resistance to neuraminidase inhibitors, or mutations in РA gene responsible for baloxavir resistance. All viruses tested by fluorescence assay were sensitive to oseltamivir and zanamivir. The worldwide frequency of influenza isolates resistant to antineuraminidase drugs does not exceed 1-2% of cases. Hence, oseltamivir and zanamivir provide effective treatment for seasonal influenza.

Currently, vaccination is one of the most efficient ways to control and prevent influenza infection. Vaccine production largely relies on the results of laboratory assays, including hemagglutination inhibition and microneutralization assays, which are time-consuming and laborious. Viruses can escape from the immune response that results in the need to revise and update vaccines biannually. The hemagglutination inhibition assay can measure how effectively antibodies against a reference strain bind and block an antigen of the test strain. Various computer-aided models have been developed to optimize candidate vaccine strain selection. A general problem in modeling of antigenic evolution is the representation of genetic sequences for input into the research model. Our motivation stems from the well-known problem of encoding genetic information for modeling antigenic evolution. This paper introduces a two-fold encoding approach based on reduced amino acid alphabet and amino acid index databases called AAindex. We propose to apply a simplified amino acid alphabet in modeling of antigenic evolution. A simplified alphabet, also called a sub-alphabet or reduced amino acid alphabet, implies to use the 20 amino acids being clustered and divided into amino acid groups. The proposed encoding allows to redefine mutations termed for amino acid groups located in reduced alphabets. We investigated 40 reduced amino acid sets and their performance in modeling antigenic evolution. The experimental results indicate that the proposed reduced amino acid alphabets can achieve the performance of the standard alphabet in its accuracy. Moreover, these alphabets provide deeper insight into various aspects of the relationship between mutation and antigenic variation. By checking identified high-impact sites in the Influenza Research Database, we found that not only antigenic sites have a significant influence on antigenicity, but also other amino acids located in close proximity. The results indicate that all selected non-antigenic sites are related to immune responses. According to the Influenza Research Database, these have been experimentally determined to be T-cell epitopes, B-cell epitopes, and MHC-binding epitopes of different classes. This highlighted a caveat: while simulating antigenic evolution, the model should consider not only the genetic information on antigenic sites, but also that of neighboring positions, as they may indirectly impact antigenicity. Additionally, our findings indicate that structural and charge characteristics are the most beneficial in modeling antigenic evolution, which is in agreement with previous studies.

Ribonucleic acids (RNA), in particular, double-stranded RNAs, due to their ability to modulate innate immune responses, are of undoubted interest in view of their usage as vaccine adjuvants. However, despite the fact that dsRNA preparations have been known for a long time, the issues of cellular interactions and orientation of immune response upon their exposure have not yet been properly studied. The aim of this work was to evaluate the in vitro response of mouse splenocytes to dsRNA exposure in cell cultures, and after drug administration in vivo. The studies were carried out in female Balb/c mice. Activation status of various splenocyte populations after treatment with yeast dsRNA and reference substance (PolyI:PolyC) was assessed by means of flow cytometry by expression of CD69 and CD86 activation markers on CD19+B lymphocytes and CD11c+ dendritic cells (DC). During in vitro studies, the splenocytes were incubated in DMEM medium containing 10% fetal calf serum for 22 hours following addition of the yeast dsRNA preparations, or PolyI:PolyC (2.5 μg/mL) preparation. Single-stranded high-polymer RNA (hpRNA), which is a component of the substance, was used as an additional control at the dose of 16 μg/mL. Our study has shown that the activating effect of dsRNA and PolyI:PolyC on expression of CD86 and CD69 markers upon the cells of the entire pool of splenocytes, B lymphocytes and DC. Highly polymeric RNA increased the total number of CD86+ cells in the population without changing the expression level of these markers upon B lymphocytes and DCs. When performing the in vivo studies, yeast dsRNA substance was administered intravenously into mice at a dose of 2.5 mg/kg, and hpRNA was used at a dose of 16 mg/kg. The number of CD69+ and CD86+ splenocytes was assessed 4 hours after drug administration. The highest stimulating effect of dsRNA was registered with CD69 expression marker: significantly increased numbers of CD69+ cells were registered for B lymphocytes and the entire cell population. The stimulation of CD86 co-receptor expression on B lymphocytes was less pronounced, but statistically significant. The ability of single-stranded and double-stranded RNAs to cause significant increase in CD86+ cell numbers was demonstrated among dendritic cell population. The results of the study made it possible to evaluate the effect of dsRNA on the immune cell function, with respect of their interaction, maturation, and migration. This approach may be useful for developing optimal strategies for selection and screening of new nucleic acid-based adjuvants.

Danon disease (DD), a rare X-linked genetic illness with a poor prognosis, is caused by a mutation in the lysosome-associated membrane protein 2 gene (LAMP2). Three main clinical features of this pathology are cardiomyopathy, skeletal myopathy, and mental retardation. Most Danon disease mutations create premature stop codons resulting in the decrease or absence of LAMP2 protein. The present case reports the frameshift variant c.190_191delАС in the LAMP2 in the family with sudden cardiac death history and three members with cardiomyopathy. The presenting phenotype in a female proband with c.190_191delАС was isolated dilated cardiomyopathy in her thirties whereas in two males, DD presented as hypertrophic cardiomyopathy and mild skeletal myopathy since childhood. To examine the contribution of X-inactivation to cardiomyopathy onset we estimated the X-inactivation status in the heart tissue of the affected female. We observed the random pattern (66:34) with the proportion of cardiomyocytes expressing healthy LAMP2 allele reduced to 34%. Deletion c.190_191delАС has led to a complete loss of function LAMP2 due to a single copy of this gene in males. In a woman, cardiomyopathy developed because of both the LAMP2 mutation and a decrease in the expression of a healthy allele in the heart. Based on the strong association of truncating LAMP2 mutations with DD and phenotypes in affected members, the variant c.190_191delАС was classified as pathogenic.

Background. There are a great number publications presenting results of various types of optical and ultrasound biometry before and after scleral buckling (SB).Patients and methods. Biometry was performed for 22 eyes of 22 patients before and after surgical treatment of rhegmatogenous retinal detachment. We used 4 types of optical (IOLMaster 500, IOLMaster 700, Lenstar LS 900 and REVO SOCT Copernicus) and 2 types of ultrasound biometry (A- and B-scan).Results. According to the all biometry data, there was an increase in the axial lens (AL) (the maximum value of eye elongation according to IOLMaster 500 data was 0.84 ± 0.69 mm, p = 0.000), swallowing of the anterior chamber depth (ACD) in regard to IOLMaster 700 (0,48 ± 0,32 mm, p = 0.000) and lens thickness (LT) augmentation (according to A-scan data the largest thickening was 0.17 ± 0.59 mm, p = 0.064).Conclusions. The anatomy of the eye reliably changes after SB implantation due to increase in the AL, ACD swallowing and an LT augmentation, that makes changes in IOL power calculation with modern formulas during combined surgery. Lenstar LS 900 is the preferred method of biometry when planning simultaneously lens exchange with SB procedure.

While the energizing effect of light has been known since the early years of light therapy, its reliable detection using objective measures is still not well-established. This review aims to ascertain the immediate energizing effect of light and determine its best indicators. Sixty-four articles published before July 2022 were included in the review. The articles described 72 (sub-)studies performed in healthy individuals. Fourteen measures were analyzed. The analysis showed that light causes an energizing effect that can be best documented by measuring core (rectal) body temperature: the proportion of the studies revealing increasing, unchanging, and decreasing rectal temperature was 13/6/1. The second most suitable indicator was heart rate (10/22/1), which showed concordant changes with rectal temperature (a trend, seven mutual studies). There is no evidence from the reviewed articles that oxygen consumption, skin conductance, blood pressure, heart rate variability, non-rectal inner temperature (combined digestive, tympanic, and oral), skin temperature, or cortisol levels can provide light effect detection. Four other measures were found to be unsuitable as well but with less certainty due to the low number of studies (≤3): skin blood flow, noradrenaline, salivary alpha-amylase, and thyroid-stimulating hormone levels. On the other hand, light exposure had a noticeable effect on sympathetic nerve activity measured using microneurography; however, this measure can be accepted as a marker only tentatively as it was employed in a single study. The analysis took into account three factors—study limitation in design/analysis, use of light in day- or nighttime, and relative brightness of the light stimulus—that were found to significantly influence some of the analyzed variables. The review indicates that the energizing effect of light in humans can be reliably detected using rectal temperature and heart rate.

Background. The ongoing pandemic of the novel coronavirus infection (COVID-19) draws attention to the significance of molecular and genetic monitoring of the SARS-CoV-2 spread among the population of the Russian Federation. The aim of the study was to analyze the dynamics of circulation of SARS-CoV-2 genetic variants in Russia.Materials and methods. The analysis of the circulation dynamics for SARS-CoV-2 genetic variants in Russia was carried out, covering the period from 28/12/2020 to 26/6/2022. The analysis included the data from Rospotrebnadzor Report No. 970 "Information about Infectious Diseases in Individuals with Suspected Novel Coronavirus Infection" and the Virus Genome Aggregator of Russia (VGARus). The presence of SARS-CoV-2 RNA was confirmed by the real-time reverse transcription polymerase chain reaction. The primer panels developed at the Central Research Institute of Epidemiology were used for amplification of genomic fragments and the subsequent sequencing.Results and discussion. Using the Russian VGARus platform developed by the Central Research Institute of Epidemiology, we received the data on mutational variability of SARS-CoV-2. By monitoring the circulation of SARS-CoV-2 genetic variants in Russia from 28/12/2020 to 26/6/2022, we found that Delta and Omicron genetic variants prevailed at different stages of the epidemic.Conclusion. The data of molecular and genetic studies are an essential component of epidemiological surveillance, being critically important for making executive decisions aimed at prevention of further spread of SARS-CoV-2 and laying the groundwork for creating new vaccines.

The global probiotics industry has been undergoing major changes in recent years. Approaches to finding and creating new probiotics, as well as a paradigm of their use in food, medicine, and pharmacology are changing. The catalyst proved to be the increasing popularity and availability of omics technologies, in particular, metagenomic studies of human and animal microbiomes. However, the efficiency and safety of drugs based on probiotic strains, as well as their marketing rates, largely depend on the levels of legal and technical regulation in the field. The present review discusses the aspects of legal regulation in Russia, the European Union and the United States, along with the advantages and disadvantages of probiotics and postbiotics. A consensus is emerging that postbiotics have a number of advantages over classical live probiotic cultures. The review also focuses on the lactobacilli family, which includes the largest number of probiotic strains studied so far and still holds a leading position among probiotics. On the legislative front, Russia is often ahead of its time with adopting such laws as the Federal Law No. 492-FZ on biosecurity, which defined the concept of human and animal microbiota and set forth legislative guidelines for its preservation. The new field of research referred to as microbiome nutrigenomics aims to achieve this goal.

The classical Poisson functor associates to every infinite measure preserving dynamical system $(X,\mu,T)$ a probability preserving dynamical system $(X^*,\mu^*,T_*)$ called the Poisson suspension of $T$. In this paper we generalize this construction: a subgroup Aut$_2(X,\mu)$ of $\mu$-nonsingular transformations $T$ of $X$ is specified as the largest subgroup for which $T_*$ is $\mu^*$-nonsingular. Topological structure of this subgroup is studied. We show that a generic element in Aut$_2(X,\mu)$ is ergodic and of Krieger type III$_1$. Let $G$ be a locally compact Polish group and let $A:G\to\text{Aut}_2(X,\mu)$ be a $G$-action. We investigate dynamical properties of the Poisson suspension $A_*$ of $A$ in terms of an affine representation of $G$ associated naturally with $A$. It is shown that $G$ has property (T) if and only if each nonsingular Poisson $G$-action admits an absolutely continuous invariant probability. If $G$ does not have property $(T)$ then for each generating probability $\kappa$ on $G$ and $t>0$, a nonsingular Poisson $G$-action is constructed whose Furstenberg $\kappa$-entropy is $t$., Comment: Little corrections. Subsection 8.1 is completely rewritten

Background The Global Influenza Hospital Surveillance Network (GIHSN) was established in 2012 to conduct coordinated worldwide influenza surveillance. Here we describe underlying comorbidities, symptoms, and outcomes in hospitalized patients with influenza. Methods Between November/2018 and October/2019, GIHSN included 19 sites in 18 countries using a standardized surveillance protocol. Influenza infection was laboratory-confirmed with RT-PCR. A multivariate logistic regression model was utilized to analyze the extent to which various risk factors predict severe outcomes. Results Of 16,022 enrolled patients, 21,9% had laboratory-confirmed influenza; 49.2% of influenza cases were A/H1N1pdm09. Fever and cough were the most common symptoms, though they decreased with age (p Conclusions Both virus and host factors contributed to influenza burden. We identified age differences in comorbidities, presenting symptoms, and adverse clinical outcomes among those hospitalized with influenza, and benefit from influenza vaccination in protecting against adverse clinical outcomes. The GIHSN provides an ongoing platform for global understanding of hospitalized influenza illness.

Objectives The clinical use of soluble transferrin receptor (sTfR) as an iron status indicator is hindered by a lack of assay standardization and common reference ranges and decision thresholds. In 2009, the WHO and National Institute for Biological Standards and Controls (NIBSC) released a sTfR reference material (RM), 07/202, for assay standardization; however, a comprehensive, formal commutability study was not conducted. Methods This study evaluated the commutability of WHO 07/202 sTfR RM and human serum pools and the impacts of their use as common calibrators. Commutability was assessed for six different measurement procedures (MPs). Serum pools were prepared according to updated CLSI C37-A procedures (C37) or non-C37 procedures. The study design and analyses were based on Parts 2 and 3 of the 2018 IFCC Commutability in Metrological Traceability Working Group’s Recommendations for Commutability Assessment. WHO 07/202 and serum pools were used for instrument/assay and mathematical recalibration, respectively, to determine if their use decreases inter-assay measurement variability for clinical samples. Results The WHO 07/202 RM dilutions were commutable for all 6 MPs assessed and, when used for instrument calibration, decreased inter-assay variability from 208 to 55.7 %. Non-C37 and C37 serum pools were commutable for all 6 MPs assessed and decreased inter-assay variability from 208 to 13.8 % and 4.6 %, respectively, when used for mathematical recalibration. Conclusions All materials evaluated, when used as common calibrators, substantially decreased inter-assay sTfR measurement variability. MP calibration to non-C37 and C37 serum pools may reduce the sTfR IMPBR to a greater extent than WHO 07/202 RM.

XLSX file - 30K, IC50 concentrations and CD22 expression levels for cell lines.

Antibody–drug conjugates (ADC), potent cytotoxic drugs linked to antibodies via chemical linkers, allow specific targeting of drugs to neoplastic cells. We have used this technology to develop the ADC DCDT2980S that targets CD22, an antigen with expression limited to B cells and the vast majority of non-Hodgkin lymphomas (NHL). DCDT2980S consists of a humanized anti-CD22 monoclonal IgG1 antibody with a potent microtubule-disrupting agent, monomethyl auristatin E (MMAE), linked to the reduced cysteines of the antibody via a protease cleavable linker, maleimidocaproyl-valine-citrulline-p-aminobenzoyloxycarbonyl (MC-vc-PAB). We describe the efficacy, safety, and pharmacokinetics of DCDT2980S in animal models to assess its potential as a therapeutic for the treatment of B-cell malignancies. We did not find a strong correlation between in vitro or in vivo efficacy and CD22 surface expression, nor a correlation of sensitivity to free drug and in vitro potency. We show that DCDT2980S was capable of inducing complete tumor regression in xenograft mouse models of NHL and can be more effective than rituximab plus combination chemotherapy at drug exposures that were well tolerated in cynomolgus monkeys. These results suggest that DCDT2980S has an efficacy, safety, and pharmacokinetics profile that support potential treatment of NHL. Mol Cancer Ther; 12(7); 1255–65. ©2013 AACR.

PDF file - 61K, Supplemental Figure 1. Human, cynomolgus monkey, and rat PBMCs were isolated from whole blood in accordance with BD Vacutainer CPT protocol. Mouse PBMCs were isolated from whole blood by ACK lysis buffer treatment to lyse red blood cells followed by centrifucation to recover PBMCs. Human antibodies were labeled in accordance with the protocol with Zenon Alexa Fluor 647 Human IgG Labeling Kit. Mean fluorescent intensity (MFI) was calculated from the CD20‑positive B cells (human and cynomolgus monkey), CD45RA‑positive B cells (rat), or CD45R‑positive B cells (mouse).

Introduction: Inflammatory mediators play a major role in pathogenesis of acute pancreatitis with TNF (tumor necro­sis factor) as the most important one. Development of effective combined therapy could help to decrease tissue damage, improve results and, finally, diminish the mortality rate in this severe pathology. Materials and methods: All the studies were performed on 120 female white Wistar rats, weighing 250±25g. Acute pancreatitis reproduced by an intracanalicular injection of bile salts compound. Results and discussion: The data obtained in the course of the study on the pronounced pancreatoprotective effect of infliximab are explained by its key role in the onset of the systemic inflammatory response, and, therefore, with the blockade of tumor necrosis factor alpha in the early stages, there is no pronounced secondary damage to the pancreas, which is reflected in a significant decrease in edema from 4.87±0.03 in the model up to 2.75±0.04, and as a conse­quence, an improvement in the blood supply of the acinar tissue from 182.38±15.92 PU up to 287.92±14.64 PU, which is expressed in a decrease in the zones of necrosis and in a decrease in mortality and, finally, efficiency coefficient from 13480.000 to 4283.348. A selective blocker of cysteinyl leukotrienes has a less pronounced protective reaction against damage to pancreatocytes, but to a much greater extent than octreotide. That is expressed by changes in the efficiency coefficient to the level of 8621.18 in montelukast group and 12767.30 in octreotide group, respectively. On the other hand, the effect of the use of infliximab does not surpass that of montelukast, and their combined use has a pronounced additive effect, which is proved by the efficiency coefficient at the level of 2390.33. This reaction is explained by the fact that TNF alpha-mediated pathway of activation of leukotriene biosynthesis is the main, but not the only one. Conclusion: The combined anti-mediator therapy provides a great opportunity to improve the standard therapy of acute pancreatitis.

The purpose of the research was to scientifically substantiate the conceptual approaches to the development of normative document on drinking water quality in order to prevent morbidity and mortality in martial law during armed aggression in Ukraine and other emergencies. Materials and methods: descriptive, sanitary-chemical, normative-search, comparative analysis, expert assessments have been used. The paper analyzes the results of observations of efficiency and monitoring of water quality from water supply stations of Ukraine before and after the war, and compare assessment of the main provisions of regulations on drinking water quality of some countries, including those used in emergencies. Results. The research established that in wartime centralized drinking water supply companies are burdened by problems due to unguaranteed quality of source water, lack of stable conditions for the technological process of water treatment, operation or destruction of water treatment plants and networks etc. Current standards in Ukraine( DSanPiN 2.2.4-171-10 "Hygienic requirements for drinking water intended for human consumption") during martial law require significant changes: supplementation of safety and quality indicators due to the new risks of drinking water pollution; exclusion of certain safety and quality indicators at the expense of non-priority ones; establishment of temporary hygienic standards for tap water and water dispensing points and the procedure for their use; adjusting the frequency of production control of potable water; implementation preventive measures to reduce morbidity and mortality. Today the project of “DSanPiN "Safety indicators and some particular indicators of potable water quality during martial law and emergencies of another nature" (hereinafter - DSanPiN) has been scientifically substantiated and developed. According to the draft of this document, the quality of drinking water in terms of epidemic and radiation safety must meet the requirements of DSanPiN 2.2.4-171; in terms of physicochemical - see requirements of DSanPiN. The requirements of DSanPiN after their state registration will be applied during martial law and during emergencies of other nature in a particular area for a specified period as short as possible by the relevant regional or local commission for technogeneous environmental safety and emergencies. Conclusions. It is established that during the military emergency situation in Ukraine the current DSanPiN 2.2.4-171-10 "Hygienic requirements for potable water intended for human consumption" require significant changes in order to: supplement safety indicators due to the emergence of new risks of drinking water pollution; exclude certain indicators of safety and quality due to non-priority; establish temporary hygienic standards for potable tap water and bottling points in personal containers of consumers and the procedure for their use; adjust the frequency of production control of potable water quality; implement other preventive measures to reduce morbidity and mortality.. Nowadays the draft DSanPiN "Safety indicators and some indicators of potable water quality in martial law and emergencies of other nature" is scientifically substantiated and developed, and it was submitted to the Ministry of Justice of Ukraine for state registration.