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The article is devoted to the problems of implementation of the WHO Global Polio Eradication Initiative. The influence of the features of poliovirus infection and poliovirus vaccines on the course of the program, its successes and difficulties is considered, the issue of possibility of eradication this infection is discussed.

Abstract Human-Computer Interaction (HCI) is a multidisciplinary field focused on designing and utilizing computer technology, underlining the interaction interface between computers and humans. HCI aims to generate systems that allow consumers to relate to computers effectively, efficiently, and pleasantly. Multiple Spoken Language Identification (SLI) for HCI (MSLI for HCI) denotes the ability of a computer system to recognize and distinguish various spoken languages to enable more complete and handy interactions among consumers and technology. SLI utilizing deep learning (DL) involves using artificial neural networks (ANNs), a subset of DL models, to automatically detect and recognize the language spoken in an audio signal. DL techniques, particularly neural networks (NNs), have succeeded in various pattern detection tasks, including speech and language processing. This paper develops a novel Coot Optimizer Algorithm with a DL-Driven Multiple SLI and Detection (COADL-MSLID) technique for HCI applications. The COADL-MSLID approach aims to detect multiple spoken languages from the input audio regardless of gender, speaking style, and age. In the COADL-MSLID technique, the audio files are transformed into spectrogram images as a primary step. Besides, the COADL-MSLID technique employs the SqueezeNet model to produce feature vectors, and the COA is applied to the hyperparameter range of the SqueezeNet method. The COADL-MSLID technique exploits the SLID process’s convolutional autoencoder (CAE) model. To underline the importance of the COADL-MSLID technique, a series of experiments were conducted on the benchmark dataset. The experimentation validation of the COADL-MSLID technique exhibits a greater accuracy result of 98.33% over other techniques.

Background. Determining the impact of the sympatho-adrenal system on the morpho-functional state of the heart in acute coronary syndrome is a relevant task today. On the other hand, an important objective is to study the dynamics of changes in the heart’s functional processes under the influence of biologically active substances as alternative treatments for heart muscle tissue, aiming to accelerate reparative regeneration of the myocardium after epinephrine-induced damage. Purpose – the study focuses on the dynamics of ultrasound indicators of the heart under conditions of acute experimental myocardial damage induced by high doses of adrenaline, influenced by extracts from cryopreserved heart fragments of piglets. Materials and Methods. The study was conducted on 35 outbred white rats, weighing 380–410 g and aged 15 months. Toxic myocardial damage was modeled by subcutaneously injecting epinephrine hydrotartrate in the interscapular region at a dose of 0.5 mg/100 g of body weight. Piglet heart extracts were administered intraperitoneally at a dose of 50 µg of peptides per 100 g of body weight. Sonographic examination of the heart was performed using a «Sonomed 500» ultrasound echotomoscope («Poly-Spectrum», Ukraine) in B- and M-modes with a linear transducer 7.5L38 operating at a frequency of 7.5 MHz. Results. During the period of a fully developed inflammatory process (day 7), there was a disruption of systolic myocardial function associated with volume overload, as evidenced by an increase in end-systolic volume and, consequently, a 16% decrease in ejection fraction in the control group from the norm. Daily administration of the extract had a positive inotropic and chronotropic effect, as indicated on day 7 by a 17.7 and 18.5% increase in stroke volume and cardiac output, respectively, compared to the control group. The ejection fraction, as a comprehensive indicator of the heart’s functional capacity, was 59.5% in the group receiving the extract, which was statistically significantly higher than the corresponding indicator in untreated animals. The administration of the extract facilitated a more complete recovery of volume-speed characteristics and indicators of left ventricular myocardial contractile function by day 28 after epinephrine-induced damage, during the period of the resolution of the active inflammatory process and adaptation of the heart muscle to new hemodynamic conditions. The end-systolic and end-diastolic volumes, as well as calculated indicators of left ventricular systolic function – stroke volume, cardiac output, and ejection fraction – on day 28 did not statistically differ from the corresponding indicators in intact animals. Conclusions. It was established that the administration of piglet heart extract exerts a positive inotropic and chronotropic effect on day 7 and promotes a more complete recovery of the volume-speed characteristics of the left ventricular myocardium by day 28 after epinephrine-induced damage.

The efficacy and safety of levilimab (LVL) in patients with active rheumatoid arthritis (RA) has been confirmed in controlled clinical trials. This article presents the results of a preliminary analysis of a non-interventional observational study of LVL in RA patients. Objective: to evaluate the efficacy and safety of LVL in the treatment of patients with RA in real-world clinical practice. Materials and methods. The HELIOS study is a retrospective-prospective, multicenter, non-interventional study of retention rate of LVL therapy and the safety of LVL in patients with RA in real-world clinical practice. Patients received medical care, including LVL, according to routine clinical practice for the treatment of RA and Russian instructions for medical use of the drug. This article presents the results of an analysis of the efficacy and safety of LVL after 12 and 24 weeks of treatment. Efficacy was assessed using the DAS28-CRP/ESR, SDAI, CDAI and patient assessment of pain, fatigue and morning stiffness according to VAS (0–100 mm). Results and discussion. 524 patients from 42 medical centers in the Russian Federation were enrolled in the study from June 2022 to November 2023. The majority of patients were female (83.2 %) and the mean age of patients was 53 years. A statistically significant decrease in DAS28-CRP/ESR, SDAI, CDAI, patient assessment of pain, fatigue and morning stiffness (VAS) was observed after 12 and 24 weeks of treatment, regardless of previous treatment with biologics or Jak inhibitors (JAKi). LVL was well tolerated by patients, the most frequently reported adverse events were infections, changes in peripheral blood and laboratory abnormalities characteristic of treatment with IL-6R inhibitors. Conclusion. In real-world clinical practice, LVL has been shown to be highly effective and well tolerated in patients with RA when prescribed as the first biologic disease-modifying antirheaumatic drus (bDMARD) and after switching from other bDMARDs or JAKi.

Summary: Background: While many patients seem to recover from SARS-CoV-2 infections, many patients report experiencing SARS-CoV-2 symptoms for weeks or months after their acute COVID-19 ends, even developing new symptoms weeks after infection. These long-term effects are called post-acute sequelae of SARS-CoV-2 (PASC) or, more commonly, Long COVID. The overall prevalence of Long COVID is currently unknown, and tools are needed to help identify patients at risk for developing long COVID. Methods: A working group of the Rapid Acceleration of Diagnostics-radical (RADx-rad) program, comprised of individuals from various NIH institutes and centers, in collaboration with REsearching COVID to Enhance Recovery (RECOVER) developed and organized the Long COVID Computational Challenge (L3C), a community challenge aimed at incentivizing the broader scientific community to develop interpretable and accurate methods for identifying patients at risk of developing Long COVID. From August 2022 to December 2022, participants developed Long COVID risk prediction algorithms using the National COVID Cohort Collaborative (N3C) data enclave, a harmonized data repository from over 75 healthcare institutions from across the United States (U.S.). Findings: Over the course of the challenge, 74 teams designed and built 35 Long COVID prediction models using the N3C data enclave. The top 10 teams all scored above a 0.80 Area Under the Receiver Operator Curve (AUROC) with the highest scoring model achieving a mean AUROC of 0.895. Included in the top submission was a visualization dashboard that built timelines for each patient, updating the risk of a patient developing Long COVID in response to clinical events. Interpretation: As a result of L3C, federal reviewers identified multiple machine learning models that can be used to identify patients at risk for developing Long COVID. Many of the teams used approaches in their submissions which can be applied to future clinical prediction questions. Funding: Research reported in this RADx® Rad publication was supported by the National Institutes of Health. Timothy Bergquist, Johanna Loomba, and Emily Pfaff were supported by Axle Subcontract: NCATS-STSS-P00438.

SCIENTIFIC RELEVANCE. Pseudomonas aeruginosa is one of the main causative agents of focal and diffuse suppurative inflammations in immunocompromised individuals. The multiple antimicrobial resistance of Р. aeruginosa has created an urgent need to develop effective preventive vaccines against this bacterium and to enhance their protective properties by selecting adjuvants. A promising strategy is to use flagellin, a P. aeruginosa flagellum component inducing the innate immune system through interaction with toll-like receptor 5 (TLR5) and activating the T-cell immune response, as a component or adjuvant in vaccine development.AIM. This study aimed to produce recombinant flagellin C (FliC) of P. aeruginosa and investigate its immunogenicity, adjuvanticity, and protective properties.MATERIALS AND METHODS. The fliC nucleotide sequence was obtained by PCR on template DNA of P. aeruginosa PA-103 and was inserted into the pQE-30 plasmid for subsequent expression in Escherichia coli M15. Recombinant FliC purification involved two stages: isolation of inclusion bodies and their dissolution in buffers containing urea and guanidine hydrochloride. Mice were immunised by two intraperitoneal injections with a two-week interval. The immunisation used purified recombinant FliC at a dose of 50 μg per animal and its combination with the Klebsiella pneumoniae surface antigen in a 1:1 ratio. Serum samples from immunised mice were tested for specific antibodies to recombinant FliC by enzyme-linked immunosorbent assay (ELISA). The protective properties of FliC were assessed by intraperitoneal challenge of mice with cultures of P. aeruginosa PA-103 and K. pneumoniae 204.RESULTS. The authors obtained the producing strain, generated recombinant FliC, and purified the protein to a 97.6% purity. The analysis of serum samples from immunised mice by ELISA and the protection assessment in challenge experiments showed that the purified recombinant FliC protein had immunogenic properties. Furthermore, the experimental challenge of FliC-immunised mice with P. aeruginosa confirmed that recombinant FliC had protective properties, as evidenced by the protection index of 3.0. Recombinant FliC exhibited adjuvant properties, as demonstrated by the effectiveness index of 6.1 observed in the experimental challenge of mice immunised with the combination of recombinant FliC and the surface antigen of K. pneumoniae.CONCLUSIONS. The purified recombinant FliC protein of P. aeruginosa demonstrated protective activity in mice challenged with P. aeruginosa and adjuvant properties when combined with the K. pneumoniae surface antigen, increasing the immunogenicity of the latter. The use of recombinant FliC holds promise for the creation of a candidate vaccine against P. aeruginosa infection.

Abstract Extrapulmonary tuberculosis with a renal involvement can be a manifestation of a disseminated infection that requires therapeutic intervention, particularly with a decrease in efficacy of conventional regimens. In the present study, we investigated the therapeutic potency of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in the complex anti-tuberculosis treatment (ATT). A rabbit model of renal tuberculosis (rTB) was constructed by injecting of the standard strain Mycobacterium tuberculosis H37Rv into the cortical layer of the kidney parenchyma. Isolated rabbit MSC-EVs were intravenously administered once as an addition to standard ATT (isoniazid, pyrazinamide, and ethambutol). The therapeutic efficacy was assessed by analyzing changes of blood biochemical biomarkers and levels of anti- and pro-inflammatory cytokines as well as by renal computed tomography with subsequent histological and morphometric examination. The therapeutic effect of therapy with MSC-EVs was shown by ELISA method that confirmed a statistically significant increase of the anti-inflammatory and decrease of pro-inflammatory cytokines as compared to conventional treatment. In addition, there is a positive trend in increase of ALP level, animal weigh, and normalization of ADA activity that can indicate an improvement of kidney state. A significant reduction of the area of specific and interstitial inflammation indicated positive affect of MSC-EVs that suggests a shorter duration of ATT. The number of MSC-EVs proteins (as identified by mass-spectometry analysis) with anti-microbial, anti-inflammatory and immunoregulatory functions reduced the level of the inflammatory response and the severity of kidney damage (further proved by morphometric analysis). In conclusion, MSC-EVs can be a promising tool for the complex treatment of various infectious diseases, in particularly rTB.

The article presents the results of the three-year use of netakimab (NTK) in patients with ankylosing spondylitis (AS) as part of the phase III BCD-085-5/ASTERA study.Objective: to evaluate the long-term efficacy and safety of NTK over a three-year period in patients with active AS.Material and methods. BCD-085-5/ASTERA – double-blind, multicenter, randomized phase III clinical trial that enrolled patients with active AS (BASDAI ≥4) and a back pain intensity ≥4 on a numeric rating scale with inefficacy or intolerance of non-steroidal anti-inflammatory drugs or biologic drugs. A total of 228 patients were randomized in a 1:1 ratio and assigned to either the NTK group or the placebo/NTK group. Starting at week 16, patients who did not achieve ASAS20 (20% improvement according to ASAS criteria) received NTK 120 mg once every 2 weeks in an open-label regimen. Patients who achieved ASAS20 response at week 52 in the NTK group and week 68 in the placebo/NTK group continued to receive NTK (120 mg every 2 weeks) until week 156 in the NTK group and until week 172 in the placebo/NTK group.Results and discussion. Over the course of three years of NTK use, most patients experienced a sustained decline in AS activity (according to ASDAS-CRP, BASDAI) with sustained response (ASAS20/40, ASAS5/6) to therapy. Most adverse events reported were mild to moderate. 36.7% of patients had adverse events, which were mainly laboratory abnormalities, blood and lymphatic system abnormalities and infectious complications.Conclusion. The clinical effect of NTK was maintained in most patients with AS over a three-year period, with no significant loss of response. NTK was well tolerated and the safety profile remained favorable.

Abstract Oropharyngeal cancer, a subset of head and neck cancer, is increasingly recognized as a unique clinical entity primarily influenced by high-risk human papillomavirus (HPV) infections, particularly HPV-16. This review delves into the viral life cycle of HPV-16 and its interactions with host cells, with a specific focus on the crucial roles played by the viral oncoproteins E6 and E7. These oncoproteins drive cellular proliferation by targeting critical tumor suppressor proteins like p53 and Rb, resulting in uncontrolled cell growth and genomic instability. Furthermore, the significance of epigenetic modifications induced by HPV-16 and their implications is important for cancer progression. This comprehensive review provides valuable insights into the intricate molecular landscape of HPV-induced oropharyngeal cancer, shedding light on the development of targeted therapies and preventive strategies for this emerging global health concern. Video Abstract

Scientific relevance. A promising option for dysbiosis correction is the use of metabiotics, products based on metabolites of probiotic microorganisms. During fermentation, Bacillus subtilis bacteria (strains 3H and 1719) produce metabolites that exhibit probiotic properties in vitro. These observations in vitro motivate an in vivo investigation of B. subtilis metabolite effects on colonic mucosal microbiota in mice in experimentally induced dysbiosis and an assessment of the potential of B. subtilis metabolites as metabiotics.Aim. The authors aimed to compare the probiotic activity of B. subtilis 3H and B. subtilis 1719 metabolites and a commercial metabiotic in antibiotic-induced dysbiosis in mice.Materials and methods. The authors induced experimental dysbiosis in BALB/c mice weighing 18–20 g by intraperitoneal injection of gentamicin. For subsequent correction, the test groups received sorbent-bound B. subtilis metabolites, and the comparison group received a commercial metabiotic containing B. subtilis metabolites (VKPM B-2335(3)3) via intragastric injection for 21 days. The quantitative and qualitative analysis of colonic mucosal microbiota included microbial culturing and colony identification by MALDI-TOF mass spectrometry.Results. Antibiotic-induced colonic dysbiosis in mice manifested itself as a decrease in the dominant microbiota and an increase in opportunistic pathogens. After 7 days of metabolite administration, the Lactobacillus population returned to normal in all treatment groups. The mice that received B. subtilis 3H metabolites showed the best results: their Lactobacillus spp. composition corresponded to that of intact animals. The content of Lac+ Escherichia coli returned to 100% in all treatment groups. After 21 days of metabolite administration, the authors observed the elimination of bacteria (Rodentibacter spp., Aerococcus spp.) and fungi (Trichosporon spp., Kazachstania spp.) in the B. subtilis 3H group; Trichosporon spp. (no effect on Kazachstania spp.) in the B. subtilis 1719 group; and Enterococcus spp., Kazachstania spp., and Trichosporon spp. (no effect on Rodentibacter spp. and Aerococcus spp.) in the commercial metabiotic group.Conclusions. Metabolites of B. subtilis strains 3H and 1719 help to restore the diversity and abundance of colonic microbiota in antibiotic-induced dysbiosis. The differences observed in microbiota re-establishment in the treatment groups indicate that there is interstrain variability in the probiotic activity of B. subtilis metabolites.

Understanding the molecular mechanisms of atherosclerotic vascular lesions formation is necessary both for assessing the risks of cardiovascular diseases and for finding approaches to their therapy. The task remains relevant, despite the large number of studies carried out, because there are differences in the factors of genetic predisposition to atherosclerosis and its complications between different ethno-territorial groups. The aim of this study was to search for genetic variants of pattern recognition receptors associated with lipid metabolism disorders that can lead to the development of coronary atherosclerosis (CA).Material and methods. Analysis of exons and adjacent splicing sites of pattern recognition receptors genes in patients with CA (30 men), and then genotyping of a population sample from Novosibirsk (n = 1441) by real-time PCR for selected rs113706342 of the TLR1 gene and analysis of associations of its carriage with lipid metabolism were performed.Results and discussion. The frequency of the minor allele rs113706342 C of the TLR1 gene in the sample of residents of Novosibirsk was 0.0114 ± 0.0062, the carriage of this variant was associated with an increased level of low-density lipoprotein cholesterol in both women and men (p = 0.009 and p = 0.019, respectively). Women carriers of the minor allele C for rs113706342 also had a statistically significant increase in total serum cholesterol (p = 0.013) compared with TT homozygotes. To test the role of this variant in the development of CA, genotyping of an extended sample of patients is required. In one of the patients with CA, a previously undescribed single nucleotide variant chr16:3614637 G/C was found, leading to the Leu101Val substitution in the NLRC3 gene; segregation analysis is required to assess its functional significance.Conclusions. The association of rs113706342 C of the TLR1 gene with lipid metabolism disorders in the Russian population is shown.

The widespread use of the oral poliovaccine from Sabin strains (tOPV) radically reduced poliomyelitis incidence worldwide. However, OPV became a source of neurovirulent vaccine-derived polioviruses (VDPVs). Currently, circulating type 2 VDPVs (cVDPV2) are the leading cause of poliomyelitis. The novel OPV type 2 vaccine (nOPV2), based on genetically modified Sabin strain with increased genetic stability and reduced risk of cVDPV formation, has been used to combat cVDPV2 outbreaks, including one in Tajikistan in 2021. In order to identify the importation of cVDPV2 and nOPV2-derivates, stool samples from 12,127 healthy migrant children under 5 years of age arriving from Tajikistan were examined in Russia (March 2021–April 2022). Viruses were isolated in cell culture and identified via intratype differentiation RT-PCR, VP1 and whole-genome sequencing. cVDPV2 isolates closely related with the Tajikistan one were isolated from two children, and nOPV2-derived viruses were detected in specimens from 106 children from 37 regions of Russia. The duration of nOPV2 excretion ranged from 24 to 124 days post-vaccination. nOPV2 isolates contained 27 mutations per genome (0.36%) on average, with no critical genetic changes, which confirms the genetic stability of nOPV2 during field use. The possibility of epidemiologically significant poliovirus introduction into polio-free countries has been confirmed. The screening of special populations, including migrants, is required to maintain epidemiological well-being.

Aim. To assess the role of obstructive sleep apnea and other cardiovascular (CV) risk factors in the development of the antihypertensive therapy (AHT) efficacy escape phenomenon in patients with arterial hypertension (AH). Materials and methods. The data of 75 patients with AH stage III, grades 13 were proceeded. All patients included in the study underwent night respiratory monitoring. After AHT prescription, blood pressure (BP) was monitored by three measurement methods (office, daily monitoring and self-control of blood pressure) initially, in 1, 3 and 6 months after the inclusion in order to confirm the initial therapy efficacy and to identify or exclude the escape phenomenon. Results. In 36.0% of patients, the escape phenomenon was diagnosed in 1 or 3 months of observation. When comparing the group with the escape phenomenon, an initially higher level of systolic BP was revealed according to office measurements, 24-hour monitoring and self-control BP monitoring (134.04.7 mmHg vs 126.08.5 mmHg; 129.02.3 mmHg vs 121.07.7 mmHg; 131.08.2 mmHg vs 121.56.2 mmHg resp.; р0,05). There were no differences in sleep apnea and CV risk factors between the groups. However in patients with a minimal SpO285% during sleep, there were a higher levels of office systolic BP both before the AHT prescription, and during its use (157.610.4 mmHg vs 152.48.1 mmHg resp., р0,05; 132.06.8 vs 127.18.9 mmHg resp.; р0,05), and mean 24-hour systolic BP (125.75.9 vs 121.68.2 mmHg resp.; р0,05) compared with patients with a minimum SpO285%. Conclusion. The higher BP level in patients with lover nocturnal hypoxemia does not allow us to exclude the delayed negative impact of obstructive sleep apnea, especially severe, on the BP profile in case of initially successful AH control.

Abstract Recently, mesenchymal stem/stromal cells (MSCs) therapy has become an emerging therapeutic modality for the treatment of inflammatory bowel disease (IBD), given their immunoregulatory and pro-survival attributes. MSCs alleviate dysregulated inflammatory responses through the secretion of a myriad of anti-inflammatory mediators, such as interleukin 10 (IL-10), transforming growth factor-β (TGFβ), prostaglandin E2 (PGE2), tumor necrosis factor-stimulated gene-6 (TSG-6), etc. Indeed, MSC treatment of IBD is largely carried out through local microcirculation construction, colonization and repair, and immunomodulation, thus alleviating diseases severity. The clinical therapeutic efficacy relies on to the marked secretion of various secretory molecules from viable MSCs via paracrine mechanisms that are required for gut immuno-microbiota regulation and the proliferation and differentiation of surrounding cells like intestinal epithelial cells (IECs) and intestinal stem cells (ISCs). For example, MSCs can induce IECs proliferation and upregulate the expression of tight junction (TJs)-associated protein, ensuring intestinal barrier integrity. Concerning the encouraging results derived from animal studies, various clinical trials are conducted or ongoing to address the safety and efficacy of MSCs administration in IBD patients. Although the safety and short-term efficacy of MSCs administration have been evinced, the long-term efficacy of MSCs transplantation has not yet been verified. Herein, we have emphasized the illumination of the therapeutic capacity of MSCs therapy, including naïve MSCs, preconditioned MSCs, and also MSCs-derived exosomes, to alleviate IBD severity in experimental models. Also, a brief overview of published clinical trials in IBD patients has been delivered.

The aim of this review was to provide extended information on current trends in the diagnosis of complicated diabetic foot syndrome (DFS), the most frequent and severe complication of diabetes mellitus, including hightech medical imaging methods and instrumental and laboratory predictors of the complicated course and risk of amputation in DFS.The article provides an analytical review of modern publications over the past 5 years on diagnosis and therapy. Pilot data on the use of high-tech medical imaging methods, assessment of skin microbiota and ulcers in DFS, molecular testing methods in terms of predicting the amputation risk and survival of patients with DFS, as well as the effectiveness of biosensing systems have been systematized, summarized, and subjected to analytical evaluation.The review provides an expert assessment of the capabilities of pathogen-specific molecular imaging using modern positron emission tomography (PET), single-photon emission computed tomography (SPECT), and highenergy radionuclides in bacterial infection to understand its pathogenesis, minimize diagnostic problems, improve antimicrobial treatment, and address fundamental and applied aspects of DFS. Literature data on the assessment of foot perfusion in diabetic patients with varying degrees of limb ischemia by hybrid technologies (SPECT / CT and PET / CT) and new modalities of magnetic resonance imaging (MRI) are also systematized, which contributes to new understanding of the response to revascularization, surgical shunting, and stimulation of angiogenesis within ischemic tissue, as well as potentially to healing of foot ulcers.The review is aimed at substantiating a multidisciplinary approach in DFS, selection, development, and implementation of innovative strategies for diagnostic modalities to identify diabetic foot pathologies, and choice of an adequate method for treating and monitoring the results of therapy in the context of personalized medicine.

The purpose of this work was to research the encapsulation of lactic acid bacteria (LAB) of the probiotic "Evitalia" in pectic gel particles (PGPs) formed on the basis of apple pectin and citrus pectin. Methods and Results: Commercial apple pectin (AP) AU701 (Herbstreith & Fox KG, Germany) and citrus pectin (CP) CU701 (Herbstreith & Fox KG, Germany) were used. Gel particles were prepared from 3% aqueous solutions of pectins in the presence of 0.34M CaCl2 by ionotropic gelation. The diameter and density of PGPs were determined using an optical microscope (ALTAMI, Russia). For encapsulation in PGPs, a complex of "Evitalia" dry probiotic microorganisms was used, which consists of freeze-dried strains of Lactococcus lactis, Streptococcus thermophilus, Lactobacillus acidophilus, Lactobacillus helveticus, and Propionibacterium freudenreichii ssp. shermanii. To accumulate cells of probiotic LAB, we used a modified MRS medium. An extrusion method was used to encapsulate probiotic cells in PGPs. In the study of probiotic-encapsulated PGPs, they were preliminarily destroyed by ultrasound in an HD2070 ultrasonic homogenizer (Sonopuls, Germany). The encapsulation efficiency of the formulation for the probiotic bacteria was determined according to the formula: Encapsulation efficiency (%) = Bacteria in the capsules (CFU/ml) / Bacteria in initial cell suspension (CFU/ml) × 100. "Evitalia" probiotic cells (PC) were grown on three different nutrient media: MRS medium, milk medium, and glucose-peptone medium. The largest number of LAB cells was formed when growing on MRS medium after 3 days of cultivation. In experiments on encapsulating bacterial cells, we used 3-day-old cultures of "Evitalia." The morphological and structural-mechanical characteristics of PGPs and particles loaded with the "Evitalia" LAB cells were studied. The degree of encapsulation of the probiotic LAB in PGPs was studied. More effectively, the LAB cells are encapsulated in PGPs formed from CP. The degree of loading of wet pectic particles from CP was 17.5%, and less for dry pectic particles based on CP (1.96%). Similar indicators for PGPs formed on the basis of AP were 5.6% and 0.33%, respectively. Conclusion: PGPs formed on the basis of AP and CP can serve as a matrix for encapsulating probiotic LAB.

Introduction. The prevalence of bacterial vaginosis (BV) in the population ranges from 12 to 80% and depends on the cohort of examined women. Of the total confirmed cases, 37-40% are pregnant women.Aim. To assess the effectiveness of the treatment of bacterial vaginosis (BV) in pregnant women.Materials and methods. The study included 43 women at 22 to 30 weeks' gestation, divided into two groups: the treatment group consisted of 30 pregnant women diagnosed with BV, the control group comprised 13 pregnant women with normal vaginal microbiocenosis. To determine the antimicrobial activity of vaginal epithelium, samples of vaginal discharge were examined. The treatment was carried out using clindamycin according to the following regimen: 100 mg intravaginally per day at bedtime for 3 days.Results. The study results showed that the highest activity of antimicrobial peptides (AMP) was found in the group of healthy pregnant women, which accounted for 79.1%. In pregnant women with BV, the level of antimicrobial activity significantly decreased as compared with the group of healthy pregnant women as the severity of the disease increased, amounting to 44.5% in women with mild BV, 36.4% in women with moderate BV and 33.6% in women with severe BV. The level of antimicrobial activity in the group of pregnant women with BV, who received treatment with clindamycin significantly increased by almost two times from the baseline values and amounted to 86.1% in women with mild BV, 78.5% in women with moderate BV and 76.9% in women with severe BV.Conclusion. The production of endogenous antibiotics, AMP, provides adequate protection against infectious agents. After a course of therapy with clindamycin 100 mg intravaginally at bedtime for 3 days, the AMP level normalized 2 weeks after treatment.

Introduction. Isthmic-cervical insufficiency (ICI) continues to be one of the main causes of miscarriage and premature birth (PB), contributing to the growth of reproductive losses and directly affecting the indicators of perinatal morbidity and mortality.Objective of the study – to study the features of the course of pregnancy, childbirth and perinatal outcomes in ICI, depending on the method of delivery.Material and methods. A retrospective analysis of birth histories (n = 144) with a diagnosis of Isthmic-cervical insufficiency was carried out, for the period from 2015 to 2020. 102 pregnant women who delivered through the natural birth canal (70.8%) made up group 1, and 42 women whose births ended with cesarean section (29.2%) made up group 2. The control groups included patients with a singleton uncomplicated pregnancy, which ended with an emergency delivery through the natural birth canal (group 3 – n = 96) and by caesarean section (group 4 – n = 58). Anamnestic data, peculiarities of the course of pregnancy, childbirth and perinatal outcomes were studied in detail. Statistical analysis was carried out using the programs Excel MS Office Professional and STATISTICA 7.0.Results and discussion. ICI is more common in repeat-bearing women with a male fetus (p < 0.001), with a burdened obstetric and gynecological history, concomitant extragenital pathology, over the age of 30 years. In PB, conservative management of the birth act prevails against the background of ICI (70.8%) (p < 0.001). The choice of delivery method in ICI determines the gestation period, fetal condition, the occurrence of urgent obstetric complications and premature rupture of fetal membranes. With ICI, the birth of children in a state of asphyxia prevails (p < 0.001). With operative delivery, the probability of diagnosing mild asphyxia (1.3 times) and respiratory distress syndrome (2 times) increases. With conservative management of childbirth against the background of ICI in newborns, the frequency of grade I cerebral ischemia increases significantly (by 5 times) (p < 0.001).Conclusion. The results of the study once again confirmed the significant importance of the ICI in the implementation of PB, which dictates the need for further study of this problem to improve the quality of care for pregnant women and improve perinatal outcomes.

The purpose of the present work was to obtain and study the properties of composite calcium-agar-pectic gel particles (CaAPGPs) obtained from aqueous solutions of agar (AA) and apple pectin (AP), from aqueous solutions of agar (AA) and pectin heracleuman (HS) in the presence of Ca2+ ions (0.34 M). The swelling of the obtained composite CaAPGPs in an artificial gastroenteric environment was also investigated. Methods and Results: We used commercial AP AU701 (AP, Herbstreith & Fox KG, Germany), HS isolated from the aerial part of the Sosnovskyi hogweed Heracleum sosnowskyi Manden, and food agar (AA). Spherical composite CaAPGPs were obtained from low-methyl esterified AP with a molecular weight of 406 kDa, pectin HS with a molecular weight >300 kDa, and food agar (AA) in the presence of Ca2+ ions (0.34 M) as a cross-linking agent by the method of ionotropic gelation. It was found that dry CaAPGPs based on AP (Ca-AA-AP) have a diameter of 1.16±0.14-1.23±0.05 mm, which was greater than the diameter of dry CaAPGPs based on HS (Ca-AA-HS) (0.95±0.12-1.16±0.05 mm). The density of dry CaAPGPs based on AP (Ca-AA-AP) with an increase in the concentration of AP in their composition from 1% to 2% increased by 1.7 times – from 0.37±0.07 mg/mm3 to 0.63±0.05 mg/mm3. Dry composite CaAPGPs based on HS (Ca-AA-HS) were denser. With an increase in the HS concentration in their composition from 1% to 2%, the degree of particle density increases by 2.2 – from 0.45±0.03 mg/mm3 to 0.97±0.19 mg/mm3. The swelling and degradation of the obtained dry composite CaAPGPs in an artificial gastroenteric environment were studied. It was found that CaAPGPs formed from 1% AP and 2% AA degraded almost immediately in SIF. Whereas, CaAPGPs formed from 2% AP and 1% or 2% AA completely degraded in SCF after 1 hour of incubation in it. CaAPGPs formed from 1% HS and 2% AA, and particles obtained from 2% HS and 1% AA, remained stable in SIF, and then completely degraded immediately upon entering in SCF. CaAPGPs, consisting of 2% HS and 2% AA, dissolve in SCF after 1 hour of incubation in it.

Background. Mantle cell lymphoma (MCL) is a rare and clinically aggressive lymphoma subtype. Current approaches have greatly improved patients outcomes, but relapse is inevitable. In phase IIIII clinical trials, ibrutinib has shown significant activity in patients with relapsed or refractory (R/R) MCL. Aim. To assess efficacy and toxicity of ibrutinib monotherapy in patients with R/R MCL in routine practice outside of clinical trials. Materials and methods. The study enrolled patients with confirmed R/R MCL who had received at least one line of previous chemotherapy. ECOG 24, cytopenia, infectious complications, hemorrhagic syndrome were not exclusion criteria. Patients received daily oral ibrutinib 560 mg until progression or unacceptable toxicity. Results. From May 2015 to September 2020 ibrutinib therapy was started in 106 patients with R/R MCL in 16 regions of Russia. The median age was 66 years; ECOG2 18%, blastoid variant (or Ki6740% or WBC50109/l) 43%. The median number of previous treatment lines was 2 (111). The ORR was 78.4% (CRR 27.4%). The median PFS was 13.6 months and OS 23.2 months. In the blastoid group the median PFS was 4.4 months vs 36.5 months in the alternative group (p0.001), the median OS 9.0 vs 41.0 (p=0.001). The median OS of patients after progression on ibrutinib was 3.2 months. The common complications are hemorrhages (63%), diarrhea (62%), myalgia and muscle cramps (60%), infections (31%), skin and nail toxicity 15%, arrhythmia 8%. None of recipients had to completely discontinue ibrutinib therapy due to complications. Conclusion. Ibrutinib is effective and well tolerated in routine practice of R/R MCL treatment and our results are consistent with international clinical trials. The favorable toxicity profile and the high response rate made it possible to prescribe ibrutinib in severe somatic status, cytopenia, and even in the presence of infectious complications.

Dyskeratosis congenita (DC) is a hereditary syndrome of bone marrow failure, which develops because of telomeres defects and combines with cancer predisposition. Its classical clinical features are skin pigmentation, nail dystrophy, oral leukoplakia (skin-mucosa triad). The goal is to describe the algorithm of diagnosis, clinical specificities of DC and specific treatment for cases of DC in one family. The present report includes descriptions of diagnosis and treatment of family members diagnosed for the first time as having a DC. The report shows an importance of all diagnostic stages: from a medical history and clinical picture to an application of modern high-tech diagnostic methods (flow-FISH, NGS). The report underlines an importance of diagnosis of all family members for excluding an asymptomatic form after a case of DC has been already detected in that family. A high frequency of a toxicity and secondary neoplasia makes it necessary to realize an individual approach at treatment of each patient with DC (the earliest start of androgen treatment, prompt decision of implementation of allogenic hematopoietic stem cell transplantation). The knowledge of pathogenesis, clinical features and principles of diagnosis and therapy of this disease is relevant to pediatricians and hematologists.

Chronic kidney disease (CKD) is characterized by high mortality from cardiovascular diseases, the development of which is facilitated by traditional risk factors (typical for the general population) and by nontraditional ones (specific to patients with CKD) as well. These factors include also uremic toxins, for which a causal relationship has been established with specific pathological processes in patients with CKD, comprising the development of vascular dysfunction and accelerated progression of atherosclerosis. Urea has long been considered not as a uremic toxin, but as a marker of metabolic imbalance or dialysis efficiency (Kt/V) in CKD patients. In recent years, more and more publications have appeared on the study of the toxic effects of urea with the development of toxic-uremic complications and the phenotype of premature aging, common in CKD. It was found that an increase in urea levels in uremic syndrome causes damage to the intestinal epithelial barrier with translocation of bacterial toxins into the bloodstream and the development of systemic inflammation, provokes apoptosis of vascular smooth muscle cells, as well as endothelial dysfunction, which directly contributes to the development of cardiovascular complications. The indirect effects of increased urea levels are associated with carbamylation reactions, when isocyanic acid (a product of urea catabolism) changes the structure and function of proteins in the body. Carbamylation of proteins in CKD patients is associated with the development of renal fibrosis, atherosclerosis and anemia. Thus, urea is now regarded as an important negative agent in the pathogenesis of complications in CKD. Studies on a low-protein diet with using ketoanalogues of essential amino acids to minimize the accumulation of urea and other uremic toxins demonstrate the clinical benefit of such an intervention in slowing the progression of CKD and the development of cardiovascular complications.

Abstract Over a century of scientific inquiry since the discovery of v-SRC but still no final judgement on SRC function. However, a significant body of work has defined Src family kinases as key players in tumor progression, invasion and metastasis in human cancer. With the ever-growing evidence supporting the role of epithelial-mesenchymal transition (EMT) in invasion and metastasis, so does our understanding of the role SFKs play in mediating these processes. Here we describe some key mechanisms through which Src family kinases play critical role in epithelial homeostasis and how their function is essential for the propagation of invasive signals. Video abstract

The purpose of the present work was to obtain and study the properties of composite calcium-pectic gel particles (CaPGPs) obtained from aqueous solutions of apple pectin (AP) in the concentration of 2% and pectin heracleuman (HS) in the concentration of 3% in the presence of Ca2+ ions (0.34 M). The swelling of the obtained CaPGPs in an artificial gastric environment was also investigated. Methods and Results: We used commercial AP AU701 (AP, Herbstreith & Fox KG, Germany) and HP isolated from the aerial part of the Sosnovskyi hogweed Heracleum sosnowskyi Manden. Composite CaPGPs were obtained from aqueous solutions of AP (2%) and HS (3%) in the presence of Ca2+ ions (0.34 M) by the method of ionotropic gelation. The diameter and density of CaPGPs were determined. Dry gel particles from 2% AP were larger (1.18±0.19 mm) than dry gel particles from 3% HS (1.04±0.07 mm) and dry composite gel particles (1.01±0.06 mm). However, dry composite gel particles and dry gel particles from HS were approximately 3 times denser than dry gel particles from AP. Composite CaPGPs swelled by 74.2% in simulated gastric fluid (SGF). The degree of swelling in SGF of CaPGPs formed from HS was 15.6% lower, and CaPGPs formed from AP –52.2%.

This review focuses on the causes and consequences of nutritional deficiencies in the pregnant woman’s diet, as well as on the possibilities of its supplementation. It has been shown that inadequate intake of vitamins and minerals during pregnancy is accompanied by a lack of nutrient supply to the fetus, which can cause growth retardation, low birth weight and other obstetric and perinatal complications.According to the analysed guidelines and recommendations, the body’s need for vitamins and minerals increases at least twice as much during pregnancy. Adverse effects of the environment, a number of gastrointestinal and liver diseases, chronic diseases, antibiotic therapy, etc. increase this need.However, adequate nutritional support of the fetus is the result of several steps. These include the frequency of maternal food intake, the availability of nutrients in the food and the ability of the placenta to transport substrates effectively to the fetus.The most recommended vitamin for consumption in pregnancy is folic acid, alone or in combination with other B vitamins, as its deficiency leads to birth defects in the child.The authors of this review have reviewed a number of large studies conducted over the past decade that recommend iron and folic acid for pregnant women, regardless of dietary intake, as they have proven beneficial effects on the course and outcome of pregnancy. Folic acid, according to current recommendations, must be prescribed to every pregnant woman in the form of 400 mcg tablets daily regardless of her diet. Other most important and necessary vitamins for pregnant women are: vitamins A, C, D, E, K, B1, B2, B6, B12, PP, pantothenic acid, biotin.

Abstract Sympatric coexistence of recently diverged species raises the question of barriers restricting the gene flow between them. Reproductive isolation may be implemented at several levels, and the weakening of some, e.g. premating, barriers may require the strengthening of the others, e.g. postcopulatory ones. We analysed mating patterns and shell size of mates in recently diverged closely related species of the subgenus Littorina Neritrema (Littorinidae, Caenogastropoda) in order to assess the role of premating reproductive barriers between them. We compared mating frequencies observed in the wild with those expected based on relative densities using partial canonical correspondence analysis. We introduced the fidelity index (FI) to estimate the relative accuracy of mating with conspecific females and precopulatory isolation index (IPC) to characterize the strength of premating barriers. The species under study, with the exception of L. arcana, clearly demonstrated preferential mating with conspecifics. According to FI and IPC, L. fabalis and L. compressa appeared reliably isolated from their closest relatives within Neritrema. Individuals of these two species tend to be smaller than those of the others, highlighting the importance of shell size changes in gastropod species divergence. L. arcana males were often found in pairs with L. saxatilis females, and no interspecific size differences were revealed in this sibling species pair. We discuss the lack of discriminative mate choice in the sympatric populations of L. arcana and L. saxatilis, and possible additional mechanisms restricting gene flow between them.

Aim.To study the effectiveness of prolonged use of PAP therapy (positive airway pressure therapy) in eliminating sleep respiratory disorders and associated cardiac conduction disturbances. Materials and methods.We included 21 patients who were examined at the Myasnikov Institute of Clinical Cardiology, National Medical Research Center of Cardiology, regarding cardiac rhythm and conduction disturbances, as well as obstructive sleep apnea and who have been on PAP therapy for more than 12 months. The average age was 66.5 [63.5; 73.2] years, body mass index 33.0 [30.2; 38.5] kg/m2, apnea-hypopnea index 65.0 [59.0; 86.3]/h. At the time of analysis, 15 patients continued to use PAP therapy (mean time of use: 6.0 years [4.7; 9.2]) and 6 patients refused long-term use of PAP therapy, mean time to use PAP therapy until failure amounted to 2.82.1 years. Results.PAP therapy lead to a persistent decrease in apnea-hypopnea index of 63.6/h to 3.7/h was (p=0.0002). 86% of patients met the criteria for adherence to PAP therapy (use 4 hours/night, more than 70% of nights). Initially, before the use of PAP therapy, all cardiac conduction disorders were during sleep and exceeded 3 seconds, with fluctuations from 3.1 to 10.6 seconds. PAP therapy appeared to be effective in all patients: no asystoles, duration of more than 3 seconds, were detected. Conclusion.In obstructive sleep apnea patients with concomitant nighttime cardiac conduction disturbances, the long-term use of PAP therapy is effective and with good adherence.

This article overviews and systemizes published data on the ways of implementing different methods of biofeedback, robotic devices, and brain-computer interfaces (BCI) for rehabilitation of children with cerebral palsy (CP).Aim. To survey implementation practices and clinical outcomes of rehabilitation technologies and possible neurophysiological mechanisms underlying their efficacy in patients with CP. We searched PubMed, Web of Science and eLIBRARY.ru databases for relevant publications using specified keywords.Results. The analysis of relevant literature has shown that robotic technologies and BCIs with biofeedback based on electroencephalography and electromyography parameters are rapidly developing and implemented for the rehabilitation of children with CP. The first evidence of effectiveness for such methods and approaches has been found. However, there is a lack of fully developed conventional standards for the use of such rehabilitation methods and protocols in children. Control groups comprising of children with CP are often absent in such studies. In many cases, the variations of neurophysiological and neurochemical parameters before and after a course of rehabilitation are not evaluated. Having such data would help clarify physiological mechanisms underlying effective rehabilitation of motor functions and then design more adequate rehabilitation procedures and medication protocols.

The purpose of this study was to investigate the relation between the presence of cervical dysplasia and HPV infection in women of the Republic of Sakha (Yakutia) (RS(Y)), to analyze cytological samples for detecting the presence of pathology and the degree of cervical dysplasia, and to detect the level of HPV infection, and establish the dependence of HPV-test positivity on the presence of dysplasia and the woman’s age. Methods and Results: Cytological material was taken from cervix uteri and cervical canal scraping from 100 patients aged between 22 and 60 years (mean age of 38.9±9.2 years). The sample from every patient was obtained by traditional cytology and liquid-based cytology (LBC) on the automated system CellPrep Plus (Korea). The results of LBC were interpreted under the terminology system of the Bethesda System (2015). HPV detection and typing (types 6, 11, 44, 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82) were performed by real-time PCR using commercial test systems according to their instructions. The analysis of cytological samples by the LBC method in women of RS(Y) revealed a high prevalence of NILM in the samples to compare with intraepithelial lesions of the cervix. Among intraepithelial lesions, LSIL was significantly more common. Positive HPV tests were observed in less than half of the cases. The vast majority of positive HPV tests were high–risk HPV types, and 16 and 51 types marked the most frequent. The positive tests for high–risk HPV types in women with NILM and intraepithelial lesions (LSIL, HSIL, ASCUS) were approximately equal. The frequency of positive tests for high–risk HPV types in women under 45 was higher than in women 46 years and older. Conclusion: The combined use of LBC and HPV testing for high–risk HPV infection improves the effectiveness of diagnostics by reducing the amount of uninformative material and allows detecting pathological changes at an earlier stage.

The review addresses the problem of kidney lesions in patients with cardiovascular and oncological diseases. In the context of the current spread of cardiovascular and oncological pathologies, a growing number of patients reveal comorbid and/or polymorbid renal dysfunctions. In confluence with cardiovascular disorders, kidney lesions are manifested in various types of the cardiorenal syndrome. In current knowledge, the heart and kidneys are highly interdependent and interact across several interfaces in a complex feedback system. The kidneys can both play a target role and back-influence cardiac functions and pathology. Evidently, the development of acute kidney lesions and / or chronic renal dysfunctions worsens the prognosis of the primary disease and elevates risks of developing acute cardiovascular disorders. Combined cardiovascular and oncological pathologies are nowadays more common. Numerous patients with malignant neoplasms develop renal pathologies due to tumour infiltration or exposure to tumour metabolites, as well as indirectly through the nephrotoxic effect of antitumour chemotherapy and/or radiation therapy. Many studies show that acute kidney lesions and/or chronic renal disorders contribute independently to the severity of cancer and mortality rate. In recent decades, the level of serum creatinine is used as a marker of acute kidney damage, which although harbours inherent weaknesses of being responsive to a spectrum of renal and extra-renal factors and having a delay of 48–72 h of elevation in the blood after exposure to the trigging factor. In this respect, the development of novel kidney-specific lesion biomarkers continues. Among such candidate agents is the kidney injury molecule KIM-1.

Relevance. Obstructive sleep apnea syndrome (OSAS) is an important medical and social problem due to its high prevalence and impact on quality of life. The relationship between OSAS and cardiovascular pathology has been proven by many studies, which confirms the necessity for early diagnosis of OSAS and its treatment for the prevention of fatal and non-fatal events. Aim: to study epidemiological and clinical profile of the patients referred by a cardiologist to a specialized sleep laboratory to verify the diagnosis of OSAS. Materials and methods. Object of study 527 patients aged 56.912.5 years who were hospitalized to the Myasnikov Clinical Cardiology Research Institute from 20162018 and had OSAS risk factors. Initially, complaints, medical history, anthropometric data were collected. As a screening survey, questionnaires were conducted using questionnaire scales. Verification of the diagnosis of OSAS and determination of the severity was carried out by cardiorespiratory or respiratory monitoring. Subsequently, 4 groups were formed depending on the presence and severity of OSAS. Results. The prevalence of OSAS among patients in a cardiology hospital referred to a verification study was 88.6%. A comparative analysis of the groups revealed a progressive increase in the values of anthropometric indicators with increasing severity of OSAS. No differences were found between the groups by gender and daytime sleepiness on the Karolinska Sleepiness Scale. The average score on the Epworth sleepiness scale was statistically significantly lower only in the group of patients without OSAS when compared with the group with a severe degree of OSAS, and is comparable with the scores in the groups of mild and moderate degrees of OSAS. In a multivariate model of logistic regression, independent predictors of OSAS were identified as: age over 45 years, indications of loud intermittent snoring, frequent nightly urination, overweight or obesity. According to the results of assessing the incidence of various cardiovascular diseases in patients referred to the sleep laboratory, no significant differences were detected. At the same time, a significant difference was found in the frequency of obesity in patients with severe OSAS compared with other groups, as well as the frequency of type 2 diabetes mellitus or impaired glucose tolerance when compared with groups without OSAS, and with mild OSAS. In one-factor logistic regression models, it was found that the likelihood of having a severe degree of OSAS increases with increasing both comorbidity and age. Conclusions. High prevalence of OSAS in patients of a cardiological hospital, referred to a sleep laboratory for verification study, was confirmed. Considering the data that early diagnosis and treatment of OSAS can affect the course of both nosologies, the quality of life and prognosis of these patients, it is advisable to routinely screen and verify the diagnosis of OSAS in patients with cardiovascular diseases.

Spherical copper-pectic gel particles (CuPGPs) were obtained from aqueous solutions of commercial apple pectin (AP) AU701 (2%, 4%) in the presence of copper ions (CuCl2, 1%-10%), and their morphological (diameter) and structural-mechanical (density) characteristics were studied. It was found that with an increase in the concentration of AP from 2% to 4%, the diameter of dry gel particles at all tested concentrations of copper chloride (1-10%) increased from 0.64-0.76 mm (2% AP) to 0.87-0.94 mm (4% AP), and that the density of dry gel particles with an increase in the concentration of AP also increased from 1.27-1.48 mg/mm3 (2% AP) to 1.42-1.55 mg/mm3 (4% AP). The swelling and degradation of the obtained CuPGPs in an artificial gastroenteric environment was studied. It has been established that the CuPGPs based on 4% AP with 10% CuCl2 have the highest degree of swelling in the acidic environment of the intestinal gastric fluid (SGF). CuPGPs, depending on the concentration of AP and copper ions, are degraded in different parts of the intestine—in simulated intestinal fluid (SIF) or simulated colonic fluid (SCF).

Background: The objective of our research was to study the ethnic-related characteristics of lipid and carbohydrate metabolism in the indigenous population of Yakutia. Methods and Results: The study was conducted under expeditionary conditions in the North of Yakutia (Nizhnekolymsky, Anabarsky, Verkhnekolymsky, Tomponsky, and Srednekolymsky districts). In total, 529 people aged between 20 and 70 years were examined in the primary health care units. For a comparative analysis, we formed 6 ethnic groups (Yakuts, Evenks, Evens, Dolgans, Chukchi, Yukagirs). In all ethnic groups, there was a high prevalence of atherogenic dyslipidemia, with the highest frequency in Evenks and Yakuts. Women had a higher frequency of lipid metabolism disorders than men did. The frequency of hyperglycemia was significantly higher among the Dolgans, Evenks and Yakuts than in other ethnic groups. Conclusion: This study showed a high frequency of MetS in the examined ethnic groups, which is caused by a change in the traditional lifestyle and the nature of nutrition.

The growth of E. coli on pectins isolated from various plant sources was studied. We used commercial apple pectin AU701 and low-methyl esterified pectins (6-22%) from callus cultures of tansy Tanacetum vulgare L. (TV, tanacetan), duckweed Lemna minor L. (LM, lemnan), and campion Silene vulgaris (M.) G. (SV, silenan). Bacterial growth was also tested on the enzymatic degradation products of tanacetan pectin. For comparison, bacterial growth was studied on easily metabolizable carbon sources - glucose and lactose. E. coli was cultivated on solid media in Petri dishes and in liquid nutrient media in Erlenmeyer flasks at a temperature of +37°C and at room temperature. It was found that E. coli colonies do not form with growth on gels of tanacetan, lemnan and silenan. When growing on a gel of AP, a weak bacterial growth is detected. However, E. coli is capable of growth on soluble products of enzymatic hydrolysis of tanacetan pectin - oligogalacturonides.

The urgency of the problem of vaginal infection is determined by its highest prevalence in the structure of obstetric-gynecological morbidity. Currently, the share of diseases of the lower genital tract associated with quantitative unbalance conditionally pathogenic microorganisms of bacterial and fungal origin vagina, which occur in 40-65% of pregnant women. Carried out a sufficient number of studies showing the role of vaginal microbiocenosis dysbiotic violations in the development of pathology of pregnancy, childbirth and postpartum infectious complications. It is known, that for vaginal infections and dysbiosis significantly more often increases the risk of chronic placental insufficiency, premature birth, low birth weight and postpartum endometritis, wound infection. In connection with the above, it is important to timely diagnose microflora disorders using clinical and laboratory research methods, followed by adequate etiotropic therapy. Timely and effective treatment of vaginal dysbiosis in pregnant women before delivery reduces the risk of postpartum infectious complications.

The authors assessed microbiological risks of acute intestinal infections (AII) with viral etiology caused by drinking water taken from centralized water supply systems among overall urban population in Arkhangelsk region over 2006-2017. The re-search was performed with Quantitative Microbial Risk Assessment (QMRA) procedure. It was revealed that acute intestinal viral infections prevailed among intestinal infections; the most widely spread ones were rotavirus infection (86.9%), norovirus infection (7.7%), and enterovirus infection (3.7%). The authors also performed comparative analysis of spatial distribution and long-term dynamics of incidence with AII which were possibly caused by infectious agents entering a body with water. The analysis revealed that rotavirus and norovirus infections frequently occurred in Arkhangelsk, Novodvinsk, Koryazhma, and Kotlas. Incidence with rotavirus infection among population in Koryazhma and Arkhangelsk grew 1.5-1.6 times faster than epidemiological processes on the reference territory. Coliphages contents were equal to Р95in drinking water taken from centralized water supply systems in Arkhangelsk and Koryazhma, and it was 1.4 and 2.2 times higher respectively than the hygienic standard. Rotavirus, norovirus, and enterovirus infections were highly likely to occur in Arkhangelsk (R=0.97-0.99), and rotavirus infection, in Koryazhma (R=0.95). Average probability of norovirus infection (R=0.58) and enterovirus infection (R=0.43) was detected in Koryazhma. The research results indicate that Quantitative Microbial Risk Assessment (QMRA) procedure is feasible and significant within the system of sanitary-epidemiologic surveillance over water treatment; it substantiates the necessity to create and implement virology monitoring over centralized drinking water supply.

Aim. To study the influence of the state of endothelium on the daily profile of arterial pressure (AP) in patients with rheumatoid arthritis (RA). Materials and methods. In 70 RA pts carried out C-reactive protein (CRP), vascular endothelial adhesion molecule type 1 (sVCAM-1), antigen von Willebrand Factor (AG WF), interleukin-8 (Il-8), rheumatoid factor (RF), IgG, endotheline-1 (ET-1), number of desquamated endotheliocytes cells (DE), VS, activity of renin by immunoenzyme analysis. The dysfunction of endothelium was evaluated by calculation of DE. The functional methods included the daily monitoring of arterial pressure (AP). Results. Arterial hypertension (AH) occurred in 40 (57.1%) pts. RA pts are revealed the signs of endothelial dysfunction, about which significant differences among the indices of activation of endothelium in comparison with control group testify. ET-1, sVCAM-1, vWF AG, Il-8, CRP content was higher in RA pts. Reliably above there was a number of DE. Reliable differences according to these indices depending of RA activity were discovered. With conducting of correlation analysis it is revealed, that markers of the activation of endothelium: sVCAM-1, vWF AG positively correlated with increasing RF IgG and indices of the immune inflammation: CRP, and DE number. In patients suffering from RA, showed signs of endothelial dysfunction. The positive correlation between endothelial damage and daily profile of AP show the relationship of these processes. Conclusion. Positive correlations between the damage of endothelium and disturbance of AP daily profile testify about the interrelation of these processes.

Any multicellular organism during its life is involved in relatively stable interactions with microorganisms. The organism and its microbiome make up a holobiont, possessing a unique set of characteristics and evolving as a whole system. This study aimed to evaluate the degree of the conservativeness of microbiomes associated with intertidal gastropods. We studied the composition and the geographic and phylogenetic variability of the gut and body surface microbiomes of five closely related sympatric Littorina (Neritrema) spp. and a more distant species, L. littorea, from the sister subgenus Littorina (Littorina). Although snail-associated microbiomes included many lineages (207-603), they were dominated by a small number of OTUs of the genera Psychromonas, Vibrio, and Psychrilyobacter. The geographic variability was greater than the interspecific differences at the same collection site. While the microbiomes of the six Littorina spp. did not differ at the high taxonomic level, the OTU composition differed between groups of cryptic species and subgenera. A few species-specific OTUs were detected within the collection sites; notably, such OTUs never dominated microbiomes. We conclude that the composition of the high-rank taxa of the associated microbiome ("scaffolding enterotype") is more evolutionarily conserved than the composition of the low-rank individual OTUs, which may be site- and / or species-specific.

To eliminate soil-transmitted helminth (STH) infections as a public health problem, the administration of benzimidazole (BZ) drugs to children has recently intensified. But, as drug pressure increases, the development of anthelmintic drug resistance (AR) becomes a major concern. Currently, there is no global surveillance system to monitor drug efficacy and the emergence of AR. Consequently, it is unclear what the current efficacy of the used drugs is and whether AR is already present. The aim of this study is to pilot a global surveillance system to assess anthelmintic drug efficacy and the emergence of AR in STH control programs. For this, we will incorporate drug efficacy trials into national STH control programs of eight countries (Bangladesh, Cambodia, Lao PDR, Vietnam, Ghana, Rwanda, Senegal and a yet to be defined country in the Americas). In each country, one trial will be performed in one program implementation unit to assess the efficacy of BZ drugs against STHs in school-aged children by faecal egg count reduction test. Stool samples will be collected before and after treatment with BZs for Kato-Katz analysis and preserved to purify parasite DNA. The presence and frequency of known single nucleotide polymorphisms (SNPs) in the β-tubulin genes of the different STHs will subsequently be assessed. This study will provide a global pattern of drug efficacy and emergence of AR in STH control programs. The results will provide complementary insights on the validity of known SNPs in the ß-tubulin gene as a marker for AR in human STHs as well as information on the technical and financial resources required to set up a surveillance system. Finally, the collected stool samples will be an important resource to validate different molecular technologies for the detection of AR markers or to identify novel potential molecular markers associated with AR in STH.

Water in its native form or as a component of various food products is the greatest and most frequently consumed part of daily nutrition. Scientifically justified criteria of its quality include epidemiologic and radiation safety, chemical harmlessness, and favorable organoleptic (aesthetic) properties. Over recent years in Russia more than 91.5 % population, and more than 96% in cities, have access to drinking water that conforms to all safety requirements. However, about 4–5 % of water samples taken from centralized water supply systems are not safe as per epidemiologic criteria. A drastic growth in chemical contamination of surface drinking water sources is another great concern. The authors focus on a modified procedure for detecting dextrose-positive bacteria that is, apart from being greatly in-formative, makes performance of sanitary-epidemiologic analysis much faster (approximately 1 day faster). It is confirmed that microbiologic control over blue pus bacilli occurrence is vital. The authors also show that when an internationally accepted term "mineral water" is divided into "mineral drinking curative water" and "mineral drinking curative and table water" accepted in Russia, it requires adjustment of some legal and regulatory documents and strict definition of parameters that are subject to control. It is recommended to develop regulatory and legal base so that it could promote manufacturing of bottled high quality water, including that for children nutrition. Overall, the authors show that development of drinking water market as a part of food market in the country requires updating of regulatory and methodical base for control over water quality and safety; improved systems of monitoring over epidemiologic safety based on up-to-date examination procedures and tools; putting health risk assessment methodology into practice in relation to consumption of water with diverse qualitative and quantitative structure.

Aim. Investigation of the influence of canceroembryonic antigen (CEA) on the immune cells in patients with breast tumors.Materials and methods. Peripheral blood of 67 patients with invasive ductal carcinoma (n = 44), fibroadenoma (n = 12) and breast pre-cancer (n = 11). In the supernatants of the blood cells cytokine production induced by CEA was determined by ELISA.Results. It was found that CEA stimulated production of IL-6, IL-8, IL-10, IL-1β, IL-1Ra, TNFα, G-CSF, GM-CSF and the protein MCP-1 by blood immune cells in patients with fibroadenoma compared with groups of patients with invasive ductal carcinoma and precancerous lesions. Stimulation index of CEA on cytokine production by immunocompetent cells in patients in these groups was lower than in groups of patients with fibroadenoma due to initially high levels of spontaneous cytokine production.Results. In patients with fibroadenoma CEA was found to stimulate the production of IL-6, IL-8, IL-10, IL-1β, IL-1Ra, TNFa, G-CSF, GM-CSF and MCP-1 compared with groups of patients with invasive ductal carcinoma and precancerous conditions. Indexes of the influence of CEA on cytokine production by immunocompetent cells in these groups was lower than in the fibroadenoma due to initially high spontaneous production of cytokines.Conclusion. Evident spontaneous cytokine-producing function of immunocompetent blood cells was revealed in patients with invasive ductal carcinoma and precancerous conditions compared to patients with fibroadenoma. The differences between the indices of CEA influence on cytokine production in patients with malignant, benign and precancerous conditions can serve as a basis for the development of methods of differential diagnosis of breast tumors.

Abstract Background Advances in mass spectrometry have accelerated biomarker discovery in many areas of medicine. The purpose of this study was to compare two mass spectrometry (MS) methods, isobaric tags for relative and absolute quantitation (iTRAQ) and sequential window acquisition of all theoretical fragment ion spectra (SWATH), for analytical efficiency in biomarker discovery when there are multiple methodological constraints such as limited sample size and several time points for each patient to be analyzed. Methods A total of 140 tear samples were collected from 28 glaucoma patients at 5 time points in a glaucoma drug switch study. Samples were analyzed with iTRAQ and SWATH methods using NanoLC-MSTOF mass spectrometry. Results We discovered that even though iTRAQ is faster than SWATH with respect to analysis time per sample, it loses in sensitivity, reliability and robustness. While SWATH analysis yielded complete data of 456 proteins in all samples, with iTRAQ we were able to quantify 477 proteins in total but on average only 125 proteins were quantified in a sample. 283 proteins were common in the datasets produced by the two methods. Repeatability of the methods was assessed by calculating percent relative standard deviation (% RSD) between replicate MS analyses: SWATH was more repeatable (56% of proteins

Medicinal products based on pollen allergen extracts are widely used for diagnosis and therapy of pollinosis. According to the requirements of the State Pharmacopoeia of the Russian Federation, 13th ed., the allergenic potency of such products is assessed against certified reference materials whose biological activity was confirmed in vivo in subjects sensitized to particular tested allergens. The finished dosage form of a candidate In-House Reference Material (IHRM) of timothy pollen allergen extract and the corresponding allergen pollen extract (intermediate) were characterized in terms of protein profile and allergenic composition using SDS-PAGE, gel- filtration HPLC, and western blotting. The test samples were compared to finished pharmaceutical products (FPP) and pollen allergen extracts produced at different dates and made from pollen harvested at different dates, as well as to the WHO International Standard (IS) of Timothy Pollen Extract (NIBSC code: 82/520). SDS- PAGE and gelfiltration HPLC showed that the candidate IHRM protein profile was comparable in terms of major protein fractions to those of all the FPP batches and pollen allergen extracts produced at different dates. HPLC confirmed the comparability of the protein profiles of the candidate IHRM and the IS (NIBSC code: 82/520), but showed minor variations in the ratio of the main protein fractions. Western blotting confirmed the presence of the main allergenic components with relative molecular masses ranging from 50 to 60 kDa and from 27 to 35 kDa. The composition of specific allergenic components of timothy pollen allergen products manufactured by JSC «SIC «Microgen» was identical with that of the WHO IS of Timothy Pollen Extract in terms of the main protein and allergenic components.

Abstract Objective Earlier, GLIS3 gene polymorphisms have been shown to be associated with the development of maturity onset diabetes of the young (MODY). We screened GLIS3 gene sequences among patients with MODY to identify probably pathogenic variants by whole-exome sequencing. We estimated frequency of rare single-nucleotide variants in the coding region of GLIS3 in a Caucasian population and among individuals with carbohydrate metabolism disorders in Russia. Results We identified 15 single-nucleotide variants in GLIS3. Three rare variants (minor allele frequency

Spherical calcium-pectic gel particles (CaPGPs) were obtained from pectins of callus cultures (CC) of campion Silene vulgaris (silenan) and duckweed Lemna minor (lemnan), as well as from commercial apple and citrus pectins by the method of ionotropic gelation. We studied the morphological characteristics of the obtained gel particles and found that the largest gel particles were formed from citrus pectin (CP), and the densest gel particles were formed from lemnan pectin (LP). The swelling and degradation of CaPGPs were comparatively evaluated by incubation in a simulated gastrointestinal environment. The swelling and degradation of CaPGPs formed from pectins of the silenan and lemnan callus cultures were studied at different concentrations of pectinase (0.4, 0.8 and 1.7 mg/ml) in the simulated fluid of the colon. It has been established that the CaPGPs obtained from lemnan are more resistant to degradation in the simulated colon fluid than CaPGP obtained from silenan. It was shown that the concentration of pectinase in the simulated fluid of the colon and the type of pectin affect the degradability of CaPGPs formed on the basis of pectins of callus cultures.

Researches of the last years convincingly showed negative influence of climatic factors (cold, a heat, changes of atmospheric pressure, etc.) on a state of health of the population. The aim is to study the specific features of the hemodynamic, rheological and bioenergetic indicators in weather-sensitive patients with the arterial hypertension. Information and methods: 160 patients with the arterial hypertension grade 2 were examined (weather-sensitive patients - 100, nonweather-sensitive patients - 60). Complex clinical examination, tests on hemodynamic, rheological and bioenergetic indicators were conducted. Results. In many cases weather-sensitive patients with the arterial hyperten-sion grade 2 have a hyperkinetic kind of the bloodflow, contructive function’s overwork of the left ventricle, the arterial hypertension grade 3; the strengthening of aggregation and the reduction of the red cells deflectivity leading to extension of the blood viscosity in the microcirculatory bloodstream with tendency to thrombosis; the reduction of adenine nucleotides concentration in blood, the extention of skin electrial capacity. Conclusion. The onset of meteopathic reactions in patients with the arterial hypertension lead to the development of the negative hemodynamic status and systematic abnormalities of the microcirculation. Studing of the bioenergetic characteristic of the body tissues allows to predict meteopathic reactions and do their correction.

Spherical hyaluronan-pectic gel particles (HPGPs) from hyaluronic acid (HA) and low-methyl esterified pectins of callus cultures (CC) of tansy, duckweed, campion and commercial apple pectin were obtained by the method of ionotropic gelation in the presence of calcium ions. We investigated the morphology, swelling and degradation of the obtained HPGPs in the conditions of a simulated gastrointestinal environment and established that the greatest stability in the artificial environment of the digestive tract is achieved with HPGPs obtained from the pectin of tansy CC. HPGPs can be used as potential carriers for drug delivery systems in parts of the small and large intestine.

Aim. To evaluate the influence of cardiovascular risk factors on antihypertensive therapy (AHT) efficiency escape (EE). Subjects and methods. Data on 59 patients with grades 1—3 hypertension (Stages I—II) were analyzed. During chosen AHT, 24-hour blood pressure monitoring was done at baseline, 1 and 3 months after beginning the observation to identify/rule out the AHT EE phenomenon. Results. The AHT EE group (Group 1) as compared with the group that needed no therapy correction within 3 months (Group 2) was observed to have the following: elevated fasting blood glucose levels (FBGL) (5.8±0.8 vs 5.3±0.7 mmol/l; p=0.008) and higher impaired glucose tolerance (IGT) rates (8 (27.6%) vs 4 (13.3%) cases (p=0.03)); a more number of smoking patients (8 (27.6%) vs 3 (10%) cases; p=0.02); a larger number of patients with a compromised family history of cardiovascular diseases (17 (58.6%) vs 11 (36%); p=0.02). Furthermore, in Group 1 baseline average systolic blood pressure during 24 hours (SBP-24) proved to be higher than that in Group 2 (127.4±4.2 vs 122.4±6.8 mm Hg; p=0.002). Odds ratio (OR) for developing the EE phenomenon increased by 60% with a rise of 0.5 mmol in FBGL (OR, 1.60; 95% confidence interval (CI), 1.06 to 2.4; p=0.02) and by 18% with an increase of 1 mm Hg in baseline SBP-24 (OR, 1.18; 95% CI, 1.05 to 1.33; p=0.004). Multivariate analysis indicated that the independent predictors of AHT EE were a compromised family history (OR, 3.7; 95% CI, 1.1 to 12.1; p=0.03) and IGT (OR, 4.1; 95% CI, 1.02 to 16.4; p=0.04). Conclusion. AHT EE was influenced by FBGL, IGT, smoking, a compromised family history, and baseline SBP-24 level.

Abstract Bioprinting is an emerging technique for the fabrication of living tissues that allows cells to be arranged in predetermined three-dimensional (3D) architectures. However, to date, there are limited examples of bioprinted constructs containing multiple cell types patterned at high-resolution. Here we present a low-cost process that employs 3D printing of aqueous droplets containing mammalian cells to produce robust, patterned constructs in oil, which were reproducibly transferred to culture medium. Human embryonic kidney (HEK) cells and ovine mesenchymal stem cells (oMSCs) were printed at tissue-relevant densities (107 cells mL−1) and a high droplet resolution of 1 nL. High-resolution 3D geometries were printed with features of ≤200 μm; these included an arborised cell junction, a diagonal-plane junction and an osteochondral interface. The printed cells showed high viability (90% on average) and HEK cells within the printed structures were shown to proliferate under culture conditions. Significantly, a five-week tissue engineering study demonstrated that printed oMSCs could be differentiated down the chondrogenic lineage to generate cartilage-like structures containing type II collagen.