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Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection in young children and the second leading cause of infant death worldwide. While global circulation has been extensively studied for respiratory viruses such as seasonal influenza, and more recently also in great detail for SARS-CoV-2, a lack of global multi-annual sampling of complete RSV genomes limits our understanding of RSV molecular epidemiology. Here, we capitalise on the genomic surveillance by the INFORM-RSV study and apply phylodynamic approaches to uncover how selection and neutral epidemiological processes shape RSV diversity. Using complete viral genome sequences, we show similar patterns of site-specific diversifying selection among RSVA and RSVB and recover the imprint of non-neutral epidemic processes on their genealogies. Using a phylogeographic approach, we provide evidence for air travel governing the global patterns of RSVA and RSVB spread, which results in a considerable degree of phylogenetic mixing across countries. Our findings highlight the potential of systematic global RSV genomic surveillance for transforming our understanding of global RSV spread.

Abstract Currently A(H5Nx) avian influenza viruses are globally widespread and continue to evolve. Since their emergence in 2020 novel highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b reassortant viruses have become predominant in the world and caused multiple infections in mammals. It was shown that some of A(H5N1) viruses mostly isolated from mammals contain an E627K mutation in the PB2 protein which can lead to adaptation of influenza viruses to mammalian cells. In 2023 in Russia we have isolated two highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b viruses from birds one of which contained an E627K mutation in the PB2 protein. This virus had increased virulence in mice. Limited airborne transmission of the virus with the PB2-E627K mutation was observed between ferrets, in which infectious virus was detected in the nasal washings of the three of the twelve recipient ferrets, and clinical symptoms of the disease were observed in one case. Both viruses showed dominant binding to avian-type sialoside receptors, which was most likely the reason for the limited transmissibility. Thus, this study indicates a possible limited increase in the pandemic potential of A(H5N1) 2.3.4.4b viruses and highlights the importance of continuous avian influenza surveillance for pandemic preparedness and response.

Vitamin D3 transporter (DBP) is a multifunctional protein. Site-specific deglycosylation results in its conversion to group-specific component protein-derived macrophage activating factor (GcMAF), which is capable of activating macrophages. It has been shown that depending on precursor conversion conditions, the resulting GcMAF activates mouse peritoneal macrophages towards synthesis of either pro- (IL-1β, TNF-α—M1 phenotype) or anti-inflammatory (TGF-β, IL-10—M2 phenotype) cytokines. The condition for the transition of the direction of the inflammatory response of macrophages when exposed to GcMAF is the initial glycosylated state of the population of DBP molecules and the associated effective deglycosylation of DBP by β-galactosidase. In vivo experiments with GcMAF exhibiting anti-inflammatory properties on models of induced arthritis in mice and cystitis in rats indicate a significant anti-inflammatory effect of the macrophage activator. The feasibility of unidirectional induction of anti-inflammatory properties of macrophages allows creation of combined therapeutic platforms where M2 macrophages are among the key therapeutic components.

Background. Polysaccharides are known to possess adjuvant properties, they are biodegradable, safe, and are of low-labor production. In this regard, the development of polysaccharide-based adjuvants is an urgent task.The aim. To develop a method for obtaining mannans from the cell walls of Saccharomyces cerevisiae yeast and to study their adjuvant properties using subunit vaccine model.Materials and methods. The preparation of mannans was obtained from the Saccharomyces cerevisiae yeast by enzymatic and alkaline hydrolysis. Its adjuvant properties were assessed in BALB/c mice immunized with the recombinant receptor-binding domain (RBD) of the SARS-CoV-2 (S) protein (Delta (B.1.617.2)). The titers of specific antibodies in the blood sera were determined by ELISA assays using the recombinant RBD (Wuhan-Hu-1 and Delta), and the recombinant (S) protein (Wuhan-Hu-1, Delta and Omicron) as antigens. The titers of virus-neutralizing antibodies were determined using virus-neutralization tests with the SARS-CoV-2 virus strains Wuhan – hCoV19/Australia/VIC01/2020 (Wuhan-Hu-1), Delta – hCoV-19/Russia/PSK-2804/2021 (Delta (B.1.617.2)), and Omicron 1 – hCoV-19/Russia/Moscow171619-031221/2021 (Omicron (B.1.1.529)).Results. The developed scheme allowed for obtaining up to 200 mg of mannans from 10 g of yeast cell debris. Double, with a two-week interval, immunization with RBD (50 μg) in combination with mannans (40 μg and 10 μg) induced the production of specific antibodies in titers from 1:2477330 to 1:188360. The titer of virus-neutralizing antibodies to the Delta – hCoV-19/Russia/PSK-2804/2021 was 1:485 (40 μg of mannans per mouse).Conclusions. We developed a scheme for obtaining a low-toxic preparation of mannans from the Saccharomyces cerevisiae yeast. The highest adjuvant activity was achieved when using mannans at the dose of 40 µg per mouse. Blood sera obtained from the immunized animals neutralized both homologous and heterologous SARS-CoV-2 strains.

Relevance. The improvement of the surveillance of evolution of influenza viruses and the refinement of the capacity of prognostics of their evolutionary tendencies would lead to the better understanding and control on influenza epidemics. Aim. Establish the etiological nature of influenza epidemics in 2020–2023 in Russia and the antigenic properties of influenza viruses of the types A and B which circulated on its territory in 2020–2023. Methods. Isolation of influenza viruses from PCR+-clinical materials (nazo-pharingeal swabs and post-mortem tissue samples) in the cell lines MDCK and MDCK-Siat1; antigenic analysis by means of the reaction of hemagglutination-inhibition (HI) and micro-neutralization (MN) with the cell-ELISA detection using the post-infectious ferret antisera and rat polyclonal antisera; antigenic cartography. Results and discussion. The season 2020–2021 – the 1st season of pandemic of COVID-19, was characterized by quasi-total disappearance of influenza viruses from human population on the territory of REussia, probably as a consequence of stringent sanitary-hygienic measures worldwide due to COVID-19 pandemic. In the next epidemic season we could observe the domination of influenza viruses A(H3N2) during all season with the slight growth of the proportion of influenza B in the second part of the season. We could not isolate influenza viruses A(H1N1)pdm09 in that season due to their low epidemic activity, and the majority of isolated strains were А(H3N2) viruses – 94,4% of the total number of isolates. Influenza Вvic consisted 28 % of all number of isolates. The season 2022-23, opposite to the previous one, was characterized by the domination of influenza viruses of the sub-type А(H1N1)pdm09 what made it different from the epidemic in Europe and North America, where the A(H3N2) were prevalent, particularly in the first half of the epidemic season. Later on, the situation in Europe has changed and, as in Russia, influenza B actively introduced in circulation. The proportion of isolation of influenza viruses A(H1N1) pdm09 in Russia was 69,2 %, of influenza A(H3N2) – 3,5 %, of influenza Вvic – 27,3 %. Activation of A(H1N1)pdm09 viruses was probably a result of emergence of drift-variants of this sub-type during the epidemics what was supported by the data of antigenic and genetic analyses. Thus in 2020 the first isolates of a genetic clade 6В.1А5а were discovered. They possessed the key substitution N156K in the antigenic site Sb of НА1. The results of genetic analysis have shown that among the A(H1N1)pdm09 viruses of the last season which belonged to the clade 6В.1А.5а.2а, a group of viruses carrying the substitutions P137S, K142R, D260E, T277A in HA1 could be found, which are also present in the new vaccine strain А/Victoria/4897/2022 (genetic sub-group 6В.1А.5а.2а.1). This virus was recommended for the next season 2023-2024 for the Northern Hemisphere. Concerning the antigenic properties, the viruses having such substitutions practically did not differ from the majority of strains A(H1N1)pdm09 in circulation during the last season. So influenza A(H1N1)pdm09 viruses, that circulated in Russia in 2022-2023 represented the antigenic cluster of A/Victoria/2570/2019-like strains. They were also similar to the strain A/Victoria/4897/2022, which was recommended by the WHO experts for the composition of vaccines for the season 2023–2024. The majority of viruses A(H3N2) have preserved the ability to agglutinate erythrocytes of mammals in the presence of 20 nM oseltamivir carboxylate, that is why we applied for their characterization the HI-test. The strains under study were very close to the strain A/Darwin/09/21, recommended by the WHO as the vaccine strain for the season 2022-2023. They belonged to the most wide-spread in the World genetic group 3С.2а1b.2a.2. All studied influenza B viruses belonged to the Victoria lineage and were B/Austria/1359417/2021-like. According to the phylogenetic analysis, all modern Victoria strains clustered into the sub-clade V1A.3a.2, coding the substitutions A127T, P144L и K203R in HA1. Inside this clade one can determine two genetic sub-groups: the 1st include viruses with the substitution in the HA1-protein D197E and the second – a group of viruses with the substitutions E128K, A154E, S208P in НА1. Strains of the Yamagata lineage were not registered on the territory of Russia since 2021, so the problem of their antigenic drift and possible return into circulation stays opened. The very low level of circulation of influenza viruses in 2020-2021 complicated the prognostics and selection of vaccine strains. According the results of HI- and MN-tests we could conclude that in 2021-2022 there was a partial consistency between the vaccine strain A/Cambodia/е0826360/20 (H3N2) and the strains in circulation which were more like to the reference strain A/ Darwin/9/21. We could also observe a mismatch of influenza viruses B in circulation and the vaccine variant B/Washington/02/19. As a result of the propagation of drift variants, the substitution of vaccine strains was made for the Northern Hemisphere for 2022/23. For the H3 component the strain A/Darwin/09/21 was introduced, and for Bvic component –B/Austria/1359417/21. Conclusion. In the period under consideration the relative homogeneity of population was observed inside each type and sub-type of influenza viruses and their fitness to the actual vaccine strains. However the selection of the strains – candidates for seasonal vaccines still remains a serious problem. Thus, in the season 2019-2020 one could observe a mismatch of the vaccine strain and the viruses in circulation in Russia for the component A(H3N2) and partial mismatch for the component B Victoria. In the season 2021-22 was evident a mismatch for Bvic and partial conformity for the component A(H3N2) and only in the last season 2022-23 we could confirm a complete fitness of the vaccine composition and the viruses in the circulation. The timely submission of data and samples to the WHO CCs promotes decision-making on the selection of strains and their introduction into influenza vaccines for the future epidemic season. The sustainability of the epidemiologic surveillance and the refinement of the methods of analysis of antigenic, genetic and other biological properties of circulating viruses would enhance the level of preparedness of healthcare system to the yearly influenza epidemics in the country.

Aim of the study: to compare the antitumor efficacy and immunogenicity of vaccines with the same antigens but different adjuvants: Ridostin Pro or Poly(I:C); to evaluate the effect of Ridostin Pro and Poly(I:C) on the cytokine profile of serum and the immunophenotype of mouse spleen cells. Material and Methods. To evaluate the antitumor efficacy of vaccines with different adjuvants, two transplantable tumor lines were used: melanoma B16-F10 and EG 7-OVA lymphoma (expressing ovalbumin) for C57BL/6 mice. Against melanoma B16-F10, vaccination with the peptide TRP2 180–188 with the studied adjuvants was performed in a mixed (preventive/therapeutic) and therapeutic regimens. Ovalbumin with adjuvants was vaccinated against EG 7 lymphoma in a therapeutic mode. The immunogenicity of vaccines with different adjuvants in mice without tumors was evaluated by the ELISPOT method. In this case, the peptide TRP2 180–188 and the protein ovalbumin also served as antigens. The cytokine profile of blood serum and changes in the immunophenotype of mouse spleen cells after administration of Ridostin Pro or Poly(I:C) were studied using flow cytometry. Results. In the B16-F10 model, vaccination in a mixed mode protected mice from tumor formation, and the mice lived for more than 100 days. For B16-F10 and EG 7, vaccination in the therapeutic mode led only to inhibition of tumor growth. Ridostin Pro and Poly(I:C) showed a similar ability to develop specific immunity to the peptide TRP2 and ovalbumin. Ridostin Pro increased cytokine levels in the blood serum of mice more strongly than Poly(I:C). Both drugs caused similar changes in the immunophenotype of spleen cells, but Ridostin Pro increased the number of CD 69+ T cells more strongly than Poly(I:C). Conclusion. The comparison of two drugs as adjuvants for antitumor vaccines showed that the domestic drug Ridostin Pro did not inferior in effectiveness to Poly(I:C) on mouse models. In this regard, Ridostin Pro can be considered as a promising adjuvant for antitumor vaccines and deserves further study.

To increase the effectiveness and immunogenicity of modern vaccines, especially subunit ones, it is required to use adjuvants. Polysaccharides, due to their safety and biocompatibility, are desirable candidates for the creation of vaccine adjuvants. The aim of our study was to develop a method for obtaining beta-Glucans from the yeast Saccharomyces cerevisiae cell wall, and evaluate their adjuvant properties. The high purity and non-toxicity of the resulting preparation was achieved by using enzyme complexes of cellulase and protease in combination with ultrasound (22 kHz) at the purification stage. The developed scheme allows for the yield of beta-Glucans up to 2 g from 100 g of the biomass of wet cells. The adjuvant properties of beta-Glucans were studied in 50 male BALB/c mice, weighing 16–18 g. Immunization was performed twice, with a 14-day interval, intramuscularly, 200 μl per animal. The recombinant receptor-binding domain (RBD) of the surface S protein of the SARS-CoV-2 virus (Wuhan-Hu-1 and B.1.617.2 (Delta)) was used as an antigen, at a dose of 50 μg per animal. A positive control group was administered with the antigen combined with aluminum hydroxide. As a negative control, mice injected with the saline solution were used. The titers of specific antibodies in the blood sera were determined by ELISA assays. RBD (Wuhan-Hu-1 and Delta), and S protein (Wuhan-Hu-1, Delta and Omicron) were used as antigens. The titers of virus-neutralizing antibodies were measured in neutralization tests using SARS-CoV-2 virus strains Wuhan-Hu-1, Delta (B.1.617.2) and Omicron (B.1.1.529). The results of the study have shown that beta-Glucans have the ability to enhance the production of specific and virus-neutralizing antibodies in mice immunized with RBD. The titers of specific and virus neutralizing antibodies are comparable to their levels in the group immunized with RBD and Al(OH)₃. It has been found in the experiments in white outbred ICR mice that the preparation belongs to practically non-toxic substances. Therefore, it can be concluded that the use of beta-Glucans could become a preferable alternative to the conventional adjuvants based on aluminum salts, being biocompatible, biodegradable and non-toxic substances of low labor-intensive production.

Introduction. The traditional surveillance system for influenza and ARVI provides a general description of epidemics, but does not provide information on the age-related characteristics of the etiology and clinical peculiarities of severe acute respiratory diseases (SARI) in hospitalized patients. Aim. To monitor the etiology of SARI in hospitalized children and adults, assessing the impact of the COVID-19 pandemic on this process. Materials and methods. Standardized clinical and laboratory monitoring of SARI among 18,458 hospitalized patients was carried out in hospitals in three cities of Russia with weekly PCR detection of 11 types of pathogens. Results. According to the investigation of hospitalized patients with SARI for the period from 2018 to 2023, the viral etiology of respiratory diseases was deciphered in 58.3% of cases. Weekly monitoring showed a change in the etiological mosaic of SARI pathogens during the SARS-CoV-2 pandemic with a sharp decrease in the frequency of detection of influenza and respiratory syncytial virus (RSV) during the 2020–2021 season against the background of a significant increase of metapneumovirus and rhinovirus infections in children. During the 2022-2023 season an increase in the proportion of RSV infection in children under 6 years of age (up to 36.2%) was noted against the background of a significant decrease in the frequency of SARS-CoV-2. In the intensive care units (ICU), RSV infection was most often in children during the post-pandemic period (up to 30.1–53.6% of positive cases, p 0.001); in adults, SARS-CoV-2 was mostly detected (76,5–100% of cases, p 0.001). Conclusion. Hospital surveillance data significantly complements the epidemiological information obtained in the traditional surveillance system. Monitoring of infections has shown a continuously changing etiological infrastructure of SARI, with the disappearance of influenza and RSV during the COVID-19 pandemic and their return to circulation in the post-pandemic period.

Abstract Gulf War Illness (GWI) describes a series of symptoms suffered by veterans of the Gulf war, consisting of cognitive, neurological and gastrointestinal dysfunctions. Two chemicals associated with GWI are the insecticide permethrin (PER) and the nerve gas prophylactic pyridostigmine-bromide (PB). In this study we assessed the effects of PER and PB exposure on the pathology and subsequent alcohol (EtOH)-induced liver injury, and the influence of a macrophage depletor, PLX3397, on EtOH-induced liver damage in PER/PB-treated mice. Male C57BL/6 mice were injected daily with vehicle or PER/PB for 10 days, followed by 4 months recovery, then treatment with PLX3397 and a chronic-plus-single-binge EtOH challenge for 10 days. PER/PB exposure resulted in the protracted increase in liver transaminases in the serum and induced chronic low-level microvesicular steatosis and inflammation in GWI vs Naïve mice up to 4 months after cessation of exposure. Furthermore, prior exposure to PER/PB also resulted in exacerbated response to EtOH-induced liver injury, with enhanced steatosis, ductular reaction and fibrosis. The enhanced EtOH-induced liver damage in GWI-mice was attenuated by strategies designed to deplete macrophages in the liver. Taken together, these data suggest that exposure to GWI-related chemicals may alter the liver’s response to subsequent ethanol exposure.

The year 2023 saw a challenging epizootiological and epidemiological situation regarding highly pathogenic avian influenza. The virus affected 150 bird species and dozens of mammal species. More than 650 outbreaks were reported in poultry across 29 countries, resulting in the death or destruction of approximately 19 million specimens. There was a high incidence of the influenza among wild birds (approximately 3,000 outbreaks in 65 countries) and mammals (more than 16,000 cases). The majority of outbreaks in wild birds, poultry and mammals were caused by influenza A(H5N1) clade 2.3.4.4b viruses. Many countries in Europe, Asia, Africa, North and South America experienced the outbreaks throughout the year. For the first time, a polar bear death from A(H5N1) virus was documented. Moreover, molecular markers of virus adaptation to mammals were found in PB2 proteins of 50 % of influenza A(H5N1) viruses that caused the death of animals. During the year 2023, human infections with highly pathogenic avian influenza A(H5N1) viruses were reported in Cambodia, Chile, China, and the UK. In addition, human infections with A(H3N8), A(H5N6), A(H9N2) and A(H10N5) viruses were reported in China. In Russia in 2023, outbreaks among wild birds and poultry were registered in 25 regions, as well as an outbreak among fur seals in the Sakhalin Region. The stated outbreaks were caused by highly virulent influenza A(H5N1) clade 2.3.4.4b. Hemagglutinin sequences of all Russian viruses analyzed in this study in 2023 were genetically close to the WHO candidate vaccine strains A/Astrakhan/3212/2020 (H5N8), A/chicken/ Ghana/AVL-763_21VIR7050-39/2021 (H5N1) and A/American Wigeon/South Carolina/22-000345-001/2021 (H5N1). All studied A(H5N1) viruses were antigenically similar to the A/Astrakhan/3212/2020 vaccine strain.

Introduction: Elevated intraocular pressure (IOP) has been identified as a major risk factor for the progression of primary open-angle glaucoma (POAG). However, the continued progression of POAG in some patients, despite the successful IOP reduction, indicates that IOP-independent mechanisms contribute to the development of optical neuropathy. Thus, it is relevant to further determine the molecular mechanisms of retinal ganglion cells (RGCs) death in order to develop therapeutic approaches independent of IOP in order to stop the progression of the disease. The aim: to research the correction possibility of experimental POAG induced by intracameral (i.c.) administration of hyaluronic acid using 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyltaurinate. Materials and Methods: The study of the correction of neuroretinal changes on a model of POAG was carried out on Wistar rats. In order to correct POAG, 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyltaurinate (EHMP-NAT) was used at doses of 27.5 mg/kg intramuscularly (i.m.) and 0.5 mg/kg instillationally. Further, the effectiveness of the combination of timolol eye drops with i.m. EHMP-NAT was studied. The effectiveness of the studied agents was evaluated on the 67th day of the experiment using ophthalmoscopic semi-quantitative assessment of the fundus condition, ocular tonometry, estimation of oxidative stress markers and markers involved in retinal apoptosis pathway using enzyme-linked immunosorbent assay (ELISA). Results: On the model of POAG, it was shown that 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyltaurinate with the laboratory code EHMP-NAT has a pronounced neuro-, retinoprotective action based on the data of ophthalmoscopy, semi-quantitative assessment of the fundus condition, ocular tonometry, estimation of oxidative stress markers (GSH, CAT, SOD) and markers involved in retinal apoptosis (BAX, BCL-2, Caspase-3). On the 67th day of the experiment, the results of a comprehensive analysis revealed that the combination of EHMP-NAT 27.5 mg/kg i.m. + timolol 0.04 mg/kg instillationally has a more pronounced protective effect than EHMP-NAT 27.5 mg/kg i.m. in monotherapy in the POAG model. Conclusion: The data obtained indicate the need for the combined use of drugs with a hypotensive effect to normalize IOP with neuroretinoprotective agents in the correction of POAG.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by heterogeneous cognitive, behavioral and communication impairments. Disruption of the gut-brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, we developed a Bayesian differential ranking algorithm to identify ASD-associated molecular and taxa profiles across 10 cross-sectional microbiome datasets and 15 other datasets, including dietary patterns, metabolomics, cytokine profiles and human brain gene expression profiles. We found a functional architecture along the GBA that correlates with heterogeneity of ASD phenotypes, and it is characterized by ASD-associated amino acid, carbohydrate and lipid profiles predominantly encoded by microbial species in the genera Prevotella, Bifidobacterium, Desulfovibrio and Bacteroides and correlates with brain gene expression changes, restrictive dietary patterns and pro-inflammatory cytokine profiles. The functional architecture revealed in age-matched and sex-matched cohorts is not present in sibling-matched cohorts. We also show a strong association between temporal changes in microbiome composition and ASD phenotypes. In summary, we propose a framework to leverage multi-omic datasets from well-defined cohorts and investigate how the GBA influences ASD.

Conditionally pathogenic conjunctival microflora is the most frequent cause of endophthalmitis after cataract phacoemulsification (“PEC”).The purpose. To evaluate the sterility of the surgical field and anterior chamber fluid (ACF) during elective (PEC).Materials and methods. 75 eyes were examined. Patients in the group I underwent standard treatment of the surgical field, in the group IA — the standard technique was supplemented with mechanical delimitation of the upper eyelid margin, in group II additional treatment of the surgical field with povidone iodine after blepharostat installation was performed. Microbiological material was collected preoperatively from three loci (conjunctival cavity, eyelid free margin, lacrimal ducts) and at different stages of surgery from the conjunctival cavity (after standard treatment, after blepharostat placement, after additional treatment). In addition, anterior chamber fluid (ACF) was examined — also during surgery. Microorganisms were identified by the MALDI­-TOF method, sensitivity was determined by the disc­diffusion method.Results. S. epidermidis prevails among all microorganisms. The percentage of the surgical field contamination by S.epidermidis after blepharostat setting was 33,33 %, 26 % and 40 % in the I, IA, II groups respectively; after additional treatment 6,6 % in the II group; in the ACF it was found in 23,33 %, 13 % and 0 % in the I, IA, II groups respectively.Conclusion. The additional treatment of the surgical field is the most effective technique to reduce the contamination of the conjunctival cavity by S.epidermidis after placing a blepharostat and the only one in the study to ensure its absence in the ACF. Standard treatments with and without mechanical delineation are less effective and do not prevent the contamination of the ACF.

The aim of the work was to study the influence of the researcher on the muscle strength assessment in animals in the experiment by comparing the results of the automated “inverted grid” test and its classical variant.Materials and methods. Male lines (Bla/J, n=20; FUS(1-359), n=20; Tau P301S+/+, n=20) and their background controls (C57BL/6J, n=20; CD1, n=20) were selected for the study. The dynamics of changes in the muscle deficit of the animals was evaluated in the automated and classical variant of the “inverted grid” test.Results. According to the results of the muscle strength assessment of mice with an edited genome of lines FUS(1-359)+/-, Tau P301S+/+, B6.ADysfprmd/GeneJ, using the “inverted grid” test in the classical variant and the automated one, it was found that statistically significant differences were not obtained in comparison with the results obtained by the classical variant of the test. The standard error of the mean increases by 23–39% in the classical test compared to the automated one. It was shown that the standard error of the mean in the classical variant of the test in Tau P301S+/+ mice was 6.24; 5.94; 5.88; 7.38 at 4 age points; in FUS(1-359)+/- mice, 4.49; 6.8; 6.98 and 4.1; B6.ADysfprmd/GeneJ mice, 7.66; 7.58; 8.3 and 7.92, respectively.Conclusion. Thus, the value of the standard error of the results study mean of the changes dynamics in the muscle strength when using the automated variant of the “inverted grid” test was reduced in comparison with the results of the classical variant of the test. The results of the study show that the automation of generally recognized behavioral tests is able to increase the accuracy of the obtained data reducing the influence of a human factor on the manipulation.

Purpose: to evaluate the features and outcomes of penetrating keratoplasty in combined opto-reconstructive surgery for combat eye injury and its complications.Patients and methods. The study enrolled 17 eyes (16 men) aged 34.00 ± 12.51 years, divided into 2 groups: I — with inflammatory diseases of the anterior segment, complicated combat eye injury (4 eyes), II — with open eye injury (OGI, 13 eyes). Patients underwent examination to reveal and localize damaged intraocular structures and intraocular foreign bodies (IOFB), determine the prognosis of visual functions, as well as impression cytology. In all cases penetrating keratoplasty was performed, as well as complex of vitreoretinal surgery if it was needed. In the postoperative period, visual acuity, the timing of epithelialization, and graft transparency were assessed. Period of observation was 4,5 ± 2,1 months.Results. Group I had severe keratouveitis, when intraocular structures were intact also as electrophysiological parameters. The presence of mucosal cells was determined in 50 % of cases. The number of surgery was 2.00 ± 0.82. Graft epithelialization was completed in 38.99 ± 35.43 days. Postoperatively all grafts had transparent retention and complete epithelialization, also as had high visual acuity (0.25 ± 0.10) was noted. Group II had damaged several intraocular structures and varying electrophysiological parameters. The epithelial phenotype was corneal all over. The average number of surgical treatments was 3.00 ± 1.48. The time of graft epithelialization was significantly less — 17.66 ± 8.69 days (p = 0.014). Corrected visual acuity ranged from zero (30.77 %) to 0.3 (0.08 ± 0.11) and was significantly less than in group I (p = 0.018). The parameters that correlated low visual acuity were aphakia, the level of electrical sensitivity, the number of surgical interventions, and the age of patients.Conclusions. Penetrating keratoplasty functional results prognosis is better in group with infectious complications of combat eye injury with reduced cornea transparency than in patient with open globe injury. Besides light perception and conducting structures (retina, optical nerve) lesion, optico-reconstructive surgery in open globe injury often leads to single-chamber formation in silicone filled eye, which significantly worsens the functional prognosis of treatment.

Abstract Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection in young children and the second leading cause of infant death worldwide. While global circulation has been extensively studied for respiratory viruses such as seasonal influenza, and more recently also in great detail for SARS-CoV-2, a lack of global multi-annual sampling of complete RSV genomes limits our understanding of RSV molecular epidemiology. Here, we capitalise on the genomic surveillance by the INFORM-RSV study and apply phylodynamic approaches to uncover how selection and neutral epidemiological processes shape RSV diversity. Using complete viral genome sequences, we show similar patterns of site-specific diversifying selection among RSVA and RSVB and recover the imprint of non-neutral epidemic processes on their genealogies. Using a phylogeographic approach, we provide evidence for air travel governing the global patterns of RSVA and RSVB spread, which results in a considerable degree of phylogenetic mixing across countries. Our findings highlight the potential of systematic global RSV genomic surveillance for transforming our understanding of global RSV spread.

Abstract This is the protocol for a Campbell systematic review. The objectives are as follows: Our proposed systematic review and meta‐analysis will integrate the evidence available from all sources to answer the following questions: (1) to what extent can information, behavioral and monetary interventions reduce energy consumption of households in residential buildings? (average treatment effect of interventions) (2) what is the relative effectiveness of interventions? (account for heterogeneity in treatment effects across and within studies) (3) how effective are combinations of different interventions?

The COVID-19 pandemic has uncovered the high genetic variability of the SARS-CoV-2 virus and its ability to evade the immune responses that were induced by earlier viral variants. Only a few monoclonal antibodies that have been reported to date are capable of neutralizing a broad spectrum of SARS-CoV-2 variants. Here, we report the isolation of a new broadly neutralizing human monoclonal antibody, iC1. The antibody was identified through sorting the SARS-CoV-1 RBD-stained individual B cells that were isolated from the blood of a vaccinated donor following a breakthrough infection. In vitro, iC1 potently neutralizes pseudoviruses expressing a wide range of SARS-CoV-2 Spike variants, including those of the XBB sublineage. In an hACE2-transgenic mouse model, iC1 provided effective protection against the Wuhan strain of the virus as well as the BA.5 and XBB.1.5 variants. Therefore, iC1 can be considered as a potential component of the broadly neutralizing antibody cocktails resisting the SARS-CoV-2 mutation escape.

According to the World Health Organization (WHO), antibiotic resistance is currently one of the most serious threats to human health, food security, and development. Tuberculosis (TB) remains one of the deadliest bacterial diseases. The primary challenge in treating tuberculosis infection is the emergence of strains with multidrug resistance (MDR) to 4-9 drugs. The emergence of bacterial strains with MDR is a consequence of patients’ insufficient adherence to treatment, interrupted therapy, improperly prescribed courses of chemotherapy, and, according to recent data, the accumulation of antibiotics in the environment, which can activate the natural drug resistance system in bacteria. The consequences of MDR to antibiotics include prolonged hospitalizations, increased medical expenses, and mortality. Therefore, the task is to develop new effective antibacterial agents with novel mechanisms to reduce the emergence of bacterial resistance. In this study, we investigated the mechanisms of action of new promising antimycobacterial derivatives of quinoxalin-1,4-dioxide on the model organism Mycobacterium smegmatis .

The review provides brief historical information on the highly pathogenic influenza A (H5) and presents data on massive outbreaks caused by this subtype. It includes historical background, data on outbreaks, and the formation of potentially pandemic viruses. The abstract also highlights the current state of the problem, such as the spread of H5 influenza in new territories and its ability to infect mammals and humans. The issues of vaccination for poultry and the challenges of implementing it globally are addressed. Furthermore, the risks of further spread of the virus and the emergence of pandemic strains are being discussed.

Agricultural and industrial activities are increasing pollution of water bodies with low doses of xenobiotics that have detrimental effects on aquaculture. The aim of this work was to determine the possibility of using Levilactobacillus brevis 47f culture in fish aquaculture under the influence of low doses of xenobiotics as an adaptogen. An increase in the survival of Danio rerio individuals exposed to the xenobiotic bisphenol A solution and fed with the L. brevis 47f was shown compared to control groups and, at the same time, the cytokine profile in the intestinal tissues of Danio rerio was also investigated. Analysis of differential gene expression of the L. brevis 47f grown under the action of high concentrations of bisphenol A showed changes in mRNA levels of a number of genes, including genes of various transport proteins, genes involved in fatty acid synthesis, genes of transcriptional regulators, genes of the arabinose operon, and the oppA gene. The identification of L. brevis 47f proteins from polyacrylamide gel by mass spectrometry revealed L-arabinose isomerase, Clp chaperone subunit, ATP synthase subunits, pentose phosphate pathway and glycolysis enzyme proteins, which are likely part of the L. brevis 47f strain’s anti-stress response, but probably do not affect its adaptogenic activity toward Danio rerio.