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Introduction. Previously, it was shown that the “classic” phenotypes of polycystic ovarian syndrome (PCOS) are associated with significant decrease in gut microbiota alpha diversity as compared with healthy women.The aim of the study. To establish cut-off points for alpha diversity indices, significant in polycystic ovarian syndrome with hyperandrogenism.Material and methods. The manuscript presents a sub-study of Eastern Siberia PCOS Epidemiology and Phenotype Study, conducted in Eastern Siberia (Russia) from 2016 to 2019. All participants (175 women of reproductive age: 26 women with PCOS (according to Rotterdam criteria (2003)) and hyperandrogenemia (increased levels of total testosterone (TT) and/or free androgenindex(FAI), and/ordehydroepiandrosterone sulphate (DHEAS)), 149 – without hyperandrogenemia) were recruited during the annual employment medical assessment. Methods included a questionnaire survey, anthropometry and modified Ferriman – Gallwey score, gynecological examination, pelvic ultrasound, and blood serum tests for TT, DHEAS, sex hormone-binding globulin, FAI, prolactin, thyroid-stimulating hormone, and 17-hydroxyprogesterone. Five indices of alpha diversity (amplicon sequencing variant, Shannon index, Simpson index, Chao index, and abundance-based coverage Index) were estimated for the gut microbiota using amplicon metasequencing. Statistical analysis included ROC-analysis for development of cut-off points for the indices, associated with hyperandrogenism in women of reproductive age with PCOS. Results. According to results of ROC-analysis, the greatest sensitivity with moderate specificity, with a high area under the curve was established for the Shannon and Simpson indices with cut-off points classifying women with or without hyperandrogenemia – 5.84 and 0.97, respectively.Conclusions. The developed criteria for assessing alpha diversity using cut-off points for the most significant indices can be useful for monitoring the results of different therapeutic interventions (prebiotics, probiotics, etc.) in hyperandrogenic phenotypes of PCOS.

Background. In recent years, special attention has been paid to the studying the consortia of probiotic bacteria. In these associations, the properties of individual microorganisms can be enhanced, in particular, their antagonistic activity which is an effective indicator for screening of probiotic potential. The development of probiotics based on such consortia with antibacterial properties is critical in the light of the growing problem of drug resistance in microorganisms.The aim of the work. To study the antagonistic activity of monocultures and consortia of lactobacilli against multidrug-resistant isolates of opportunistic bacteria. Materials and methods. The antagonistic activity of lactobacilli monocultures and their consortia was assessed simultaneously by two methods: the cross streak method and the well diffusion method.Results. All strains of lactobacilli and their consortia, depending on the research method, had varying degrees of antagonistic activity. Five consortia had stronger antagonism to test cultures as compared to monocultures, while in one consortium, the effect of antagonistic activity was reduced compared to monocultures. The results of studying the antagonistic activity of two consortia (Limosilactobacillus fermentum 44/1 and Lacticaseibacillus rhamnosus 12L, Latilactobacillus curvatus LCR-111-1 and Lactiplantibacillus plantarum 8PAZ) contradict data on the biocompatibility of strains in these consortia. Differences in the degree of antagonistic effects of lactobacilli on gram-positive and gram-negative species of opportunistic bacteria were revealed.Conclusion. The study showed that both the biocompatibility of the probiotic strains and the antagonistic activity of the consortium are the important requirements for creating a probiotic consortium with effective probiotic potential. To study the antagonistic properties of lactobacilli, the number of isolates of target gram-positive and gram-negative bacteria and normobiota should be increased. This will allow us to determine effective strategies for using probiotics in conditions of the spread of drug resistance of microorganisms.

Abstract Despite the significance of H2O2-metal adducts in catalysis, materials science and biotechnology, the nature of the interactions between H2O2 and metal cations remains elusive and debatable. This is primarily due to the extremely weak coordinating ability of H2O2, which poses challenges in characterizing and understanding the specific nature of these interactions. Herein, we present an approach to obtain H2O2–metal complexes that employs neat H2O2 as both solvent and ligand. SnCl4 effectively binds H2O2, forming a SnCl4(H2O2)2 complex, as confirmed by 119Sn and 17O NMR spectroscopy. Crystalline adducts, SnCl4(H2O2)2·H2O2·18-crown-6 and 2[SnCl4(H2O2)(H2O)]·18-crown-6, are isolated and characterized by X-ray diffraction, providing the complete characterization of the hydrogen bonding of H2O2 ligands including geometric parameters and energy values. DFT analysis reveals the synergy between a coordinative bond of H2O2 with metal cation and its hydrogen bonding with a second coordination sphere. This synergism of primary and secondary interactions might be a key to understanding H2O2 reactivity in biological systems.

Background. Methylmalonic aciduria (MMA) is a rare disease from the group of hereditary metabolic diseases. The MMA clinical picture is polymorphic and meanwhile similar to other metabolic disorders. Determination of specific metabolites in biological fluids and molecular genetic testing are crucial to diagnose this disease. Timely diagnosis mainly determines the treatment efficacy and, therefore, the prognosis of MMA development. Clinical case description. Two siblings with MMA caused by methylmalonyl-CoA mutase deficiency (OMIM #251000) have shown duplication chr6-49459106-T-TA: NM_000255.4c.360dupT (p.Lys121fs) in homozygous state in exon 2 of the MMUT gene. The disease was diagnosed in the first child with underlying metabolic crisis that finally led to irreversible changes in organs and systems and lethal outcome. The diagnosis in the second child was established antenatally, thus, therapy was initiated from the first day of life. Favorable clinical course of the disease was observed during 5 months of follow-up. Conclusion. Timely MMA diagnosis (antenatal or during neonatal screening) is crucial for effective management and relatively favorable life prognosis for infants.

Klebsiella pneumoniae (Kp) species complex is a genetically and ecologically diverse group of bacteria that causes a wide range of infections in humans and animals.The aim. To carry out biological characterization and genotyping based on the study of different loci of Klebsiella pneumoniae clinical isolates.Materials and methods. The object of the study was three Klebsiella pneumoniae clinical isolates from different biotopes of patients from a regional children’s multidisciplinary hospital. We used a complex of bacteriological, molecular genetic and bioinformatic methods. Genotyping of the isolates was carried out using the Pasteur Institute service for strains of the K. pneumoniae species complex.Results. All strains were sensitive to antimicrobial drugs from carbapenem (imipenem, meropenem) and tetracycline groups (tigecycline), and demonstrated high sensitivity to the Klebsiella polyvalent bacteriophage. The antibiotic resistance of the Kp ODKB-16 and ODKB-81 isolates to seven and eight antimicrobial drugs, respectively, was registeredBased on the results of multi-locus sequence typing, all strains were assigned to Kp1 phylogroup, K2 type and differed in sequence type, scgMLST629 profile and KL type. Kp ODKB-16 strain was identified as ST-65, scgST-11107, KL2; ODKB-07 strain – as ST-219, scgST-6401, KL125KL114; ODKB-81 strain – as ST-86, scgST-2800, KL2KL30. The virulence gene clusters AbST, CbST, YbST, SmST, and RmST have been characterized only in the genome of the Kp ODKB-16 isolate, allowing it to be characterized as highly virulent with multidrug resistance (MDR). Additionally, genes responsible for the synthesis of types 1 and 3 fimbrial adhesins were registered in all strains, and ter operon loci were identified only in Kp ODKB-16. Resistome analysis showed that all strains had 2b genotype. Plasmids were found in the genomes of Kp ODKB-81 (IncI2) and ODKB-16 (IncFIA + IncFIB + IncHI1B).Conclusion. We used a comprehensive framework for genomic taxonomy of clinical isolates, which can contribute to the unification of global and regional peculiarities of the developing and microevolution of bacterial pathogens.

Metalworking is the main industrial production and its technological process requires dust cleaning. The choice of dust-collecting units from a trivial approach turns into a compact-multi-criteria one and requires the study of methods for its implementation. This article uses the method of selection of dust-cleaning equipment of cyclone type based on dust from metalworking industries based on the Hierarchy Analysis Method.

Background. The study of the lower respiratory tract microbiome has been actively developed inrecent years with the help of whole genome sequencing (WGS) methods. Due to this, it became clear that the nature of the lungs microbiota is very different from other microbial communities inhabiting the human body. One of the important directions in the study of pathological lungs biocenosis is the study of the role of the satellite microbiota of the tuberculosis focus. The aim of the work. To isolate and characterize oxygen-tolerant anaerobes from the necrotic contents of tuberculomas. Materials and methods. Biopsy material from 5 patients with pulmonary tuberculosis was obtained during a planned surgical treatment of tuberculoma. A pure culture was isolated from one sample during anaerobic cultivation. Lipase activity of strain was determined by plating on brain heart infusion agar (HIMEDIA, India) supplemented with 0.1 % Tween-80 and 10 mM of CaCl2. Antibiotic susceptibility was determined by RAPMYCO and SLOWMYCO of TREK Diagnostic Systems (Thermo Fisher Scientific, USA). DNA from the sediment of the broth culture was isolated by the CTAB chloroform method. Whole genome sequencing was performed on a DNBSeq-G400 NGS sequencer by Genomed (Russia). Results. Based on WGS results and phylogenetic analysis, the strain was identified as Corynebacterium kefirresidentii. The strain was characterized by high lipase activity and resistance only to Isoniazid, Ethionamide and Trimethoprim/Sulfamethoxazolin. Conclusion. The isolation of a lipophilic anaerobic representative of the Corynebacterium tuberculostearicum species complex from a tuberculous focus indicates a possible role of the non-tuberculous microbiota in the liquefaction of caseous necrosis. We assumed that in some cases, favorable conditions are created inside the tuberculous focus for the development of satellite anaerobic lipophilic microbiota.

Background. Using probiotic preparations based on consortia of microorganisms not only helps to restore the balance of the intestinal microbiota, but also increases the therapeutic effect of probiotics. Promising sources for obtaining probiotic consortia are milk products that have undergone natural fermentation with the help of spontaneously formed microbial consortia. The aim. To study the structure of five microbial consortia with probiotic properties from naturally fermented milk products and to assess in vitro their antagonistic activity against opportunistic bacteria and a representative of the human normobiota – Escherichia coli. Materials and methods. The structure of bacterial consortia was analyzed by sequencing methods. The antagonistic activity of the consortia was assessed by the disk diffusion method. Results. It has been established that the studied microbial consortiums are represented by Enterococcus spp. and Streptococcus spp. bacteria. In consortiums No. 1, No. 2, and No. 3, Enterococcus bacteria dominated, while in consortiums No. 4 and No. 5, Streptococcus dominated. Antagonistic activity was shown against four isolates of opportunistic bacteria: Klebsiella pneumoniae No. 493, Enterobacter hormaechei No. 372, Staphylococcus aureus No. 4 and Pseudomonas aeruginosa No. 25 IMB, as well as against one representative of the human normobiota – Escherichia coli No. 495. The highest growth delay zone is found in E. coli No. 495 isolate. Three test cultures (K. pneumoniae No. 509, E. coli ATCC25922 and P. aeruginosa No. 3 IMB) exhibited more dense growth around probiotic consortia. Conclusion. The results of the study showed that the effect of probiotic consortia differing in the composition of microorganisms can be neutral and bactericidal. The presence of antagonistic activity in the studied microbial consortia against multiresistant isolates of opportunistic bacteria is a prospect for creating probiotics with antibacterial properties.

Objective. To evaluate prescribing patterns of antimicrobials and quantify them in relation to quality indicators in Russian multi-field hospitals. Materials and Methods. Point Prevalence Survey of Antimicrobial Consumption as a part of an international Global-PPS project was conducted in 8 multi-field hospitals in different Russian cities (Krasnoyarsk, Moscow, Omsk, Saratov, Smolensk, Ulan-Ude, Yakutsk) during the period from May till December 2021. Case records of patients who received therapeutic or prophylactic systemic antimicrobial agents were analyzed. Local practices of antimicrobials’ utilization were evaluated in relation to quality indicators defined by the study protocol. Results. Common mistakes requiring a prompt intervention included low adherence to clinical guidelines, absence of stop/review dates in the medical records, extended duration of surgical prophylaxis, III generation cephalosporin’s overuse and low rate of targeted therapy. Conclusions. The results of the project can be valuable for the improvement to antimicrobial utilization approaches at the study centers as well as for monitoring of antimicrobial stewardship programs’ implementation.

AbstractWith their considerable nutritive value, acorns have long been a natural feed source for pigs and, in recent years, fattening pigs with acorns has become very popular even in countries where it has not traditionally been customary. The meat of pigs finished with acorns has a unique flavour and fat profile as reflected by fatty acids content. We decided to determine the nutritional value of the most common species of acorns in Central Europe (Quercus robur) and examine the effects of this feed upon fattening performance, carcass value, and the composition of meat and fat produced by indoor finishing of pigs, as forest grazing is prohibited here. We conclude that the Prestice Black-Pied breed can be fattened utilizing a mixed feed containing acorns at the level of 10% under intensive conditions without significantly changing the performance parameters (average daily gain was 750 g versus 761 g in the control group). We found improvements in fatty acid profiles of intramuscular fat away from saturated toward monounsaturated. The improvements in the fatty acid profiles, similar to those seen in pigs raised in sylvan settings, create pork that may benefit human health. Acorns can constitute an alternative feedstuff even for pigs finished indoors and bring new benefits to agriculture in modern times.

Despite the presence of more than 100 different antibacterials in the therapeutic arsenal, beta-lactam antibiotics, in general, and the third-generation cephalosporins, in particular, remain the main option for the treatment of the most of infections in inpatients. At the same time, the widespread and oftentimes inappropriate use of the third-generation cephalosporins in Russian hospitals lead to the emergence and spread of antimicroabial resistance. The review covers the problems of antibiotic resistance to cephalosporins due to the production of beta-lactamases, the role of beta-lactamase inhibitors in overcoming this type of resistance, options for combinations of cephalosporins with beta-lactamase inhibitors, in vitro activity of cefotaxime/sulbactam and cefepime/sulbactam, the results of clinical studies, and the role of the above combinations in the treatment of infections in the hospital.

Background. The problem of antibiotic resistance has remained significant for the medical community for more than half a century, since the first cases of resistance to penicillin were registered. The aim. Analysis of the long-term dynamics of changes in the antibacterial resistance of microorganisms and the creation of a collection of multi-resistant strains of opportunistic microorganisms. Materials and methods. The study included data from 3173 bacteriological samples of various loci of the human body for 2010 and 2020–2021. The sensitivity of isolated cultures was determined by the disk diffusion method to antimicrobial drugs of the following groups: penicillins, cephalosporins, fluoroquinolones, aminoglycosides, carbapenems, tetracyclines, macrolides, lincosamides, oxazolidinones, glycopeptides and others. Results. In the general structure of conditionally pathogenic microorganisms, a significant increase in the frequency of isolation of multidrug-resistant representatives of the genus Staphylococcus by two or more times was observed in 2021 compared to 2010 and 2020. We also observed a significant increase in the proportion of multidrug-resistant Streptococcus spp. and non-fermenting gram-negative bacteria. These changes marked the beginning of the creation of a collection of conditionally pathogenic microorganisms with multiple antibacterial resistance. In the structure of multiresistant microorganisms included in the “Collection of human microbiota of the Irkutsk region”, the leading positions belong to Klebsiella pneumoniae (23.81 %), Escherichia coli (19.05 %) and Staphylococcus aureus (22.22 %). Conclusion. Antibiotic resistance monitoring is an important measure to control the resistance of community-acquired and nosocomial (nosocomial) microorganisms both within a particular country and globally.

Bacterial ecosystem of the gut plays a fundamental role in the normal functioning of the metabolic and immune systems. Functional bowel disease and obesity are highly prevalent in the population and place a heavy burden on healthcare system. Both comorbidity and multimorbidity are considered to be common for obesity and intestinal functional disorders. Changes in the microbiota can be both the cause and consequence of each disease: intestinal functional disorder changes the composition of the microbiota, resulting in obesity, and vice versa. Intestinal functional disorders and obesity are characterized by a similar type of dysbiosis.The aim of the review is to analyze the research findings available to date in order to establish the relationship between the gut microbiome, functional bowel disease and obesity. The researches have shown that patients with intestinal functional disorders have a different gut microbiome than healthy individuals. For intestinal functional disorders, the general patterns of the intestinal microbiota composition were described, and the characteristic taxonomic groups of bacteria were identified. On the other side, it must be noted that there is no clear correlation between intestinal functional disorders and obesity in terms of the microbiota. This can be explained by the high heterogeneity of intestinal functional disorders, as well as by the lack of a unified approach to creating a study design, by different sizes of population samples and also by different diagnostic criteria. The necessity to determine the criteria in the development of the design of future studies is discussed.

The gut microbiota is the largest human microbial community, comprising more than 1000 species of various microorganisms. It has been established that these are the gut microorganisms that play a decisive role in maintaining health, participating in the metabolism of proteins, carbohydrates, lipids, bile acids and the synthesis of vitamins. It has been shown that changes in the balance in the gut microbiocenosis lead not only to pathologies of the gastrointestinal tract, but also increase the risk of developing diseases of the cardiovascular and endocrine systems, and cause disturbances in the psycho-emotional state. To restore, correct and maintain the gut microbiota, probiotic preparations are recommended. In connection with the obvious relevance of the use of probiotics, this review aimed to describe the history of the emergence of the first probiotic products, current trends in the development of the concept of functional foods enriched with probiotics, as well as the prospects for developing probiotic preparations in the Russian Federation and abroad. This article presents an analysis of the market for probiotic preparations and dietary supplements, as well as functional food products that are produced in the Siberian Federal District. For an objective assessment of the development of the market for probiotic products, a generalization of analytical data from marketing services that monitor the movement of medicines in pharmacy chains and analyze consumer reviews was carried out.

Background. The formation of biofilm structures by microorganisms living in the hospital environment is a serious medical problem. To conduct correct experimental studies, it is necessary to know the speed and efficiency of biofilm formation by clinically significant species of opportunistic bacteria. Aim: to study the kinetics of plankton culture growth and the rate of biofilm formation by clinically significant pathogens of infections associated with medical care to substantiate the methodology of further research. Materials and methods. The strains from the working collection of the Laboratory for Microbiome and Microecology of the Scientific Сentre for Family Health and Human Reproduction Problems were used. Experiments were carried out with conditionally pathogenic microorganisms of the Enterobacteriaceae family and non-fermenting gram-negative bacteria. The optical density was measured, the total microbial number of the cell suspension was determined, and the morphological structure of the biofilm was evaluated using a light microscope on sterile cover glasses for thespecies Pseudomonas aeruginosa, Klebsiella pneumoniae and Serratia marcescens. Results. The duration of the lag phase of the kinetic curve of cell growth varied in isolates of S. marcescens, P. aeruginosa and K. pneumoniae from 1 to 4 and 6 hours of cultivation, respectively. Despite this, the exponential growth phase was the same for all tested isolates and amounted to 4 hours. Thus, isolates of clinically significant species entered the stationary growth phase after 5–10 hours of cultivation and were characterized as fast-growing. On abiotic surfaces, after 8 hours of incubation of the tested cultures, the initial stages of the formation of biofilm structures were observed, after 20 hours the formed multilayer biofilm was visualized, after 24 hours succession occurred, new single cells were attached to the place of the detached structures. Conclusion. The data obtained on the duration of the main stages of growth kinetics compared with the visualization of the formation of biofilm structures on abiotic surfaces should be taken into account when studying the effects of disinfectants, antiseptics and antibacterial drugs on planktonic cells and biofilm associations of clinically significant opportunistic microorganisms.

Introduction. Sequencing of the 16S rRNA gene is the predominant method for assessing microbial communities and strain molecular identification. The short reads (2nd generation sequencing)-based technology does not allow analysis beyond the 16S rRNA gene. The taxonomic verification level of samples usually remains at the genus or even family level. Currently, there have been proposed the latest versions of long-read technologies (Oxford Nanopore MinION, PacBio) for amplicon sequencing of near-complete ribosomal operon, including genes 16S, 23S, 5S, and internal transcribed spacer (ITS). At the moment, this approach has not been sufficiently studied, in addition, it involves PCR amplification of a very extended DNA region (more than 4000 bp-long). Materials and methods. The collection of non-tuberculous mycobacteria strains and their primary identification was carried out in the years 20192021. The strains were obtained by inoculation of positive cultures from the Bactec MGIT 960 bacteriological analyzer lacking MPT64 antigen in the MGIT TB Identification Test (Becton Dickinson, USA) on Lowenstein-Jensen medium. Preliminary species strain identification was carried out with the Speed-oligo Mycobacteria kit (Vircell, Spain) according to the manufacturers protocol. In this work, both known and newly developed universal bacterial primers flanking the near-complete 16S rRNA gene, ITS, and the beginning of the 23S rRNA gene are used. In the present study, both known and newly developed universal bacterial primers are used to flank the near-complete 16S rRNA gene, ITS, and start of the 23S rRNA gene. Results and discussion. Sanger sequencing of the amplicons (about 2000 bp) obtained shows the taxonomic level sufficient to determine species up to 8 strains of non-tuberculous mycobacteria isolated from humans that caused clinically and bacteriologically confirmed diseases. The method proposed for PCR amplification of a bacterial operon a fragment containing most of the 16S rRNA gene, ITS, and the beginning of the 23S rRNA gene is considered by us as an approbation of a methodological approach to study microbial communities in material with a high degree of degradation (necrotic foci, etc.). The results obtained indicate a significantly higher resolution of the approach used than the classical 16S rRNA gene sequencing.

Objective. To assess level and the structure of systemic antibiotic consumption in Russia over the period 2017 to 2021. Materials and Methods. Data were collected and analysed in compliance with the standard protocol of the World Health Organization Regional Office for Europe by the means of ATC/DDD methodology for J01 group – antibacterials for systemic use. Consumption was calculated for outpatients and inpatients separately as a number of DDDs per 1000 inhabitants per day (DID) for the main classes of antibiotics and the agents with the highest or the most diverse consumption levels for the given period of time, and was based on the data of wholesale purchases and public tenders. Results. Antibiotic consumption in Russia in 2017, 2018, 2019, 2020, and 2021 was 16.6 DID, 14.3 DID, 14.8 DID, 19 DID, and 15.7 DID respectively. Penicillins, macrolides and lincosamides, and quinolones had the highest levels of consumption in outpatients. Prominent increase in outpatient consumption of antibacterials in 2020 was related to three agents: azithromycin, levofloxacin and ceftriaxone. Cephalosporins (mainly III–V generations), quinolones and penicillins had the highest levels of consumption in inpatients. Hospital consumption of meropenem, tigecycline, and vancomycin increased and amikacin and ciprofloxacin decreased over the duration of the study. Conclusions. Levels of systemic antibiotic consumption in Russia for the period 2017 to 2019 were relatively low and consistent with the average means for European Union and European Economic Area countries. The steep increase in consumption in 2020 was probably due to the wide use of antibiotics for the management of COVID-19 patients. The results of the study can be of value for the development of targeted national antibiotic stewardship programs and awareness campaigns as well as for the analysis of trends of emergence and spread of antibiotic resistance.

Pseudomonas aeruginosa is one of the most problematic pathogens in medical institutions, which may be due to the ability of this microorganism to exist in a biofilm, which increases its resistance to antimicrobials, as well as its prevalence and survival ability in the external environment. This work aimed to evaluate the antimicrobial susceptibility of P. aeruginosa strains in planktonic and biofilm forms. We studied 20 strains of P. aeruginosa collected during 2018–2021 by specialists from the Laboratory of Microbiome and Microecology of the Scientific Centre for Family Health and Human Reproduction Problems. The identification of strains was carried out using test systems for differentiating gram-negative non-fermenting bacteria (NEFERMtest 24 Erba Lachema s.r.o., Czech Republic), and confirmed by mass spectrometric analysis and 16S rRNA gene sequencing. Antimicrobial activity was assessed by the degree of inhibition of cell growth in planktonic and biofilm forms (on a flat-bottomed 96-well plastic immunological plate). All clinical isolates of P. aeruginosa were biofilm formers, 47.6 % of the isolates were weak biofilm formers, and 52.4 % of the isolates were moderate biofilm formers. Planktonic cells and the forming biofilm of the tested P. aeruginosa strains were carbapenems-resistant. Biofilm formation was suppressed in more than 90 % of cases by the agents of the cephalosporin and aminoglycoside groups. Antimicrobial susceptibility of P. aeruginosa strains in the formed biofilm was significantly lower (p < 0.05). Carbapenems and cephalosporins did not affect the mature biofilms of the tested P. aeruginosa strains in more than 60 % of cases. Only non-beta-lactam antibiotics (ciprofloxacin and amikacin) suppressed the growth of planktonic cells and destroyed the mature biofilm. The revealed differences in the effect of the tested antimicrobials on the P. aeruginosa strains biofilms correlate with resistance to a number of antibiotics. To prevent biofilm formation in the hospital strains of P. aeruginosa, the use of ceftazidime may be recommended, and antimicrobials such as ciprofloxacin and amikacin may be used to affect mature biofilms of P. aeruginosa.

Studying the pathogenetic mechanisms in the formation and development of obesity in adolescence is essential due to its high prevalence. Obesity was found to be associated with chronic inflammation in adipose tissue, dyslipidemia, the development of oxidative stress (OS), microbiota composition disorder, and other factors. A consequence of the OS progression is the accumulation in the body of cytotoxic compounds, including endogenous aldehydes, acting as mediators of damage and provoking characteristic shifts in metabolism. Gut microbiota contributes significantly to the development of metabolic disorders and obesity by modeling the cascade of enzymatic reactions of the macroorganism, interacting with receptors directly and/or with its metabolites and signaling molecules. In this context, it may be relevant to investigate the significance of the interaction of these systems to substantiate personalized approaches to the prevention and treatment of adolescent obesity.

The research objective was to study the spectrum of the vagina and endometrium microorganisms in women with chronic endometritis (CE) in order to take adequate therapeutic measures. Methods and Results: We did a cross-sectional study in 47 women (average age of 35.38±5.19 years) with histologically confirmed CE. The vaginal microbiota and endometrial biopsies were assessed using microbiological research methods in accordance with the medical technology "Integral assessment of the state of the vaginal microbiota." To identify the share of different types of microorganisms in the structure of the biocenosis, the coefficient of constancy of the species (C) was used. Only 19% of patients had a titer of Lactobacillus spp. within the age norm, while the deficit was observed in 80% of women. Among the representatives of Enterobacteriaecae, Escherichia coli and Klebsiella aerogenes were sown, which are considered to be random species (C=11% and C=2.1%, respectively). The average titer for E. coli was 3.6±1.3 lg CFU/swab and for K. aerogenes - 2.14 lg CFU/swab. An atypical variant of E. coli with hemolytic properties was found in only one sample. All isolates of the genus Staphylococcus were also random species (C did not exceed 25%). Coagulase-negative staphylococci (CoNS) were detected in 7 patients (C=15%), while the average titer was 2.1±0.4 lg CFU/swab. S. aureus was isolated from only one patient at a titer of 5 lg CFU/swab. Corynebacterium spp. were isolated in 11% of cases (C = 11% - random species), in a titer of 3.2±0.8 lg CFU/swab. Enterococcus spp. also belonged to random species (C=23.4%). At the same time, E. faecalis was inoculated in 19% of cases and E. faecium was sown in 4.3%, the average titer of which was 3.1±0.9 and 5 lg CFU/swab. Streptococcus spp. were recorded in only one case at a concentration of 5 lg CFU/swab. Fungi of the Candida were isolated as a random species in 8.5% of cases. The growth of microorganisms in endometrial samples was obtained only in 3 examined women with CE (6.4% of cases). The endometrial microbiota were represented only by random species, for which the C index ranged from 2.1% to 4.3%. Conclusion: The microbiological study of the microbiota of vaginal discharge showed the presence of dysbiotic disorders with a significant deficiency of lactobacilli (80%) without the dominance of representatives of the Lactobacillus spp. In the structure of opportunistic microflora, Escherichia coli, coagulase-negative staphylococcus, Enterococcus spp., and E. faecalis prevailed as random species. Representatives of the microbiota in endometrial biopsies were identified only in 6.4% of cases, and are represented by random species.

Background. Obesity is a multifactorial disease that is one of the important public health problems in the 21st century. Functional bowel disorders in obese children and adolescents are one of the most common pathologies of the digestive tract. The aim: to characterize the bacteriological composition of the colon microbiota in obese adolescents and identify its associations with the clinical manifestations of functional bowel disorders.Materials and methods. The study included 20 adolescents aged 11–17 years. Stool consistency was assessed using the Bristol Stool Scale. The study of biological material was carried out using standard bacteriological methods. To assess the strength of the relationship between the nominal variables, Cramer’s V test was used.Results. It has been shown that in adolescents with obesity and functional bowel disorders, there is a decrease in the number of representatives of bifidoflora, an increase in the microbial density of Escherichia coli with altered enzymatic properties and an excessive growth of potentially pathogenic enterobacteria. In obese adolescents with functional bowel disorders, abdominal pain associated with the act of defecation is associated with the presence of enterobacteria and E. coli with altered enzymatic properties. Rare bowel movements are associated with an increased abundance of Enterococcus spp. and the presence of opportunistic Enterobacteriaceae microorganisms. Frequent bowel movements are associated with the presence of E. coli with altered enzymatic properties and Clostridium spp. In the presence of loose stool, Clostridium spp. is present; unstable stool (alternation of hard and liquid stools in one patient) is associated with a decrease in the number of lactobacilli and E. coli with normal enzymatic properties, the appearance of E. coli with altered enzymatic properties, opportunistic microorganisms of Enterobacteriaceae family and Clostridium spp. Conclusion. The relationship between the clinical symptoms of functional bowel disorders and changes in the composition of the gut microbiota in obese adolescents may be a justification for conducting in-depth studies aimed at finding early predictors of functional bowel diseases associated with obesity in the adult cohort.

Galactooligosaccharides obtained via β-galactosidase transgalactosylation have health-promoting properties and are widely recognized as effective prebiotics. Trehalose-based galactooligosaccharides could be introduced into food and pharmaceutical industries similarly to trehalose. In light of this, new technological approaches are needed. Recently, in vivo enzyme immobilizations for recombinant proteins have been introduced, and physiological aggregation into active inclusion bodies (aIBs) has emerged as one such method of in vivo immobilization. To prepare LacZ β-galactosidase in the form of aIBs, we used a short 10 amino acid aggregation-prone tag. These native protein particles were simply washed from the cell lysate and applied in trehalose galactosylation in a recycled batch mode. In this study, aIBs entrapped in alginate beads, encapsulated in alginate/cellulose sulfate/poly(methylene-co-guanidine) capsules and magnetized were compared with free aIBs. Alginate/cellulose sulfate/PMCG capsules showed more suitable properties and applicability for biotransformation of trehalose at its high concentration (25%, w/v) and elevated temperature (50 °C).

Background: the objective of this study was to propose a methodology for the assessment of antimicrobial consumption (AMC) in pediatric inpatients and to estimate variances in consumption levels in multi-field hospitals with pediatric inpatients, calculated by means of the pediatric-adjusted methodology vs. the conventional methodology. Methods: the pediatric-adjusted methodology based on the conventional ATC/DDD method and children’s DDDs (cDDD) for antimicrobials were proposed and validated in a series of probabilistic sensitivity analyses of real clinical data extracted from the receipt notes of three multi-field hospitals. Differences in AMC in multi-field hospitals with pediatric inpatients, calculated by means of the proposed methodology vs. the conventional methodology, were assessed for a virtual cohort of inpatients, with the pediatric share increasing by 1%. Results: in children ≤12 years old, assessment by the standard methodology resulted in a 59% underestimation of AMC from the levels based on prescribed doses, vs. a 25% underestimation for the proposed methodology. In a mixed-age virtual population of inpatients, the underestimation of consumption levels rose to 321% for the ATC/DDD methodology compared to the proposed one. Conclusions: the proposed methodology demonstrated a higher accuracy of AMC estimates compared to the conventional one and can be considered for the quantification of antimicrobial utilization in pediatric institutions and multi-field hospitals with a substantial share of pediatric inpatients.

Bacterial vaginosis (BV) is the most common infectious non-inflammatory disease in women of reproductive age. The key feature of BV is that in the absence of a specific pathogen, the disease develops against the background of vaginal biotope dysbiosis. According to the opinion of some authors, initially, the main role of BV in the pathogenesis was assigned to the species G. vaginalis. However, using of molecular methods made it possible to significantly expand the range of microorganisms found in women with BV, and to identify Gardnerella vaginalis, Atopobium vaginae, Mobiluncus spp., Prevotella spp. as the primary causative agents of BV. A number of studies have confirmed the sexual transmission of BV pathogens, with a new sexual partner being significant risk factors for episodic BV, and sexual contact with the same partner without using barrier methods of contraception for recurrent BV. At the same time, BV-associated bacterias rarely exist as planktonic forms of one species, more often, they thrive in complex polymicrobial communities surrounded by an extracellular matrix, the so-called biofilms. In patients with BV, biofilms are detected in 90% of cases. G. vaginalis and Prevotella bivia are widespread in women with BV and, being the primary colonizers, create a bacterial biofilm, to which secondary colonizers can subsequently join, including A. vaginae, Sneathia spp. and potentially other BVABs. The resistance of bacterias in the biofilm to antimicrobial drugs is 1000 times higher than of planktonic forms, which can lead to chronicity of the infectious process and torpid course of the disease.The aim of this review was analyzing of modern studies on the prevalence, characteristics of opportunistic microorganisms associated with BV, to present their clinical and diagnostic significance and role in the pathogenesis of diseases.

The interaction between (PNP)PdH (1); PNP = bis(2-diisopropylphosphino-4-methylphenyl)amide and different acids (CF3SO3H, HBF4∙Et2O, fluorinated alcohols and formic acid) was studied in benzene or toluene as well as in neat alcohols by IR and NMR spectroscopies. The structures of hydrogen-bonded complexes were also optimized at the DFT/ωB97-XD/def2-TZVP level. The nitrogen atom of the amidophosphine pincer ligand readily accepts proton not only from strong Brønsted acids but from relatively weak fluorinated alcohols. That suggests that binding to palladium(II) increases the diarylamine basicity, making it a strong base. Nevertheless, H+ can be taken from [(PN(H)P)PdH]+ (2) by pyridine or hexamethylphosphoramide (HMPA). These observations confirm the need for a shuttle base to form [(PN(H)P)PdH]+ (2) as the result of the heterolytic splitting of H2 by [(PNP)Pd]+. At that, a stoichiometric amount of formic acid protonates a hydride ligand yielding an unstable η2-H2 complex that rapidly converts into formate (PNP)Pd(OCHO), which loses CO2 to restore (PNP)PdH, whereas the relatively high acid excess hampers this reaction through competitive protonation at nitrogen atom.

Acid-base characteristics (acidity, pKa, and hydricity, ΔG°H− or kH−) of metal hydride complexes could be a helpful value for forecasting their activity in various catalytic reactions. Polarity of the M–H bond may change radically at the stage of formation of a non-covalent adduct with an acidic/basic partner. This stage is responsible for subsequent hydrogen ion (hydride or proton) transfer. Here, the reaction of tricarbonyl manganese hydrides mer,trans–[L2Mn(CO)3H] (1; L = P(OPh)3, 2; L = PPh3) and fac–[(L–L′)Mn(CO)3H] (3, L–L′ = Ph2PCH2PPh2 (dppm); 4, L–L′ = Ph2PCH2–NHC) with organic bases and Lewis acid (B(C6F5)3) was explored by spectroscopic (IR, NMR) methods to find the conditions for the Mn–H bond repolarization. Complex 1, bearing phosphite ligands, features acidic properties (pKa 21.3) but can serve also as a hydride donor (ΔG≠298K = 19.8 kcal/mol). Complex 3 with pronounced hydride character can be deprotonated with KHMDS at the CH2–bridge position in THF and at the Mn–H position in MeCN. The kinetic hydricity of manganese complexes 1–4 increases in the order mer,trans–[(P(OPh)3)2Mn(CO)3H] (1) < mer,trans–[(PPh3)2Mn(CO)3H] (2) ≈ fac–[(dppm)Mn(CO)3H] (3) < fac–[(Ph2PCH2NHC)Mn(CO)3H] (4), corresponding to the gain of the phosphorus ligand electron-donor properties.

Relevance. Microbiological monitoring in medical organizations is an essential part of ensuring epidemiological safety in the provision of medical care. The study of the sensitivity of pathogens to antibacterial drugs allows us to reasonably approach the prescription of empirical therapy and form a form of antibacterial agents for medical organization. The purpose of the work was to study the species composition of pathogens of generalized purulent septic infections (GPSI) in a children's multidisciplinary hospital and determine their resistance to antibacterial drugs. Materials and methods. Analysis of microbiological analysis data of material taken from patients with GPSI treated in children's multidisciplinary hospital in the period 2013-2018 was carried out. A total of 572 cultures were studied. Results. It was found that the largest specific gravity in the structure of GPSI was occupied by gram-negative microorganisms, the proportion of which significantly decreased from 73.0% in 2013 to 48.1% in 2018. Gram-positive microorganisms were found in 27.0 ± 8.1% cases, while a significant increase in the proportion of fungi from 5.4 to 30.7% was observed. The antibiotic resistance of the main pathogens has been studied. Among non-fermenting gram-negative bacteria, the highest (p < 0.05) multi-resistivity indicator was found in Acinetobacter baumannii (50.0 ± 6.8%). Enterococcus, having high natural resistance to a number of antibiotic groups, leave the possibility of effective action of the preparation of the group of glycopeptides (vancomycin) against Enterococcus faecium. Conclusions. High pathogens to applied antibacterial preparations is shown. The obtained data make it possible to form an up-to-date form of antimicrobial drugs for use in children's hospitals, to develop measures that inhibit the development of resistance in pathogens of purulent-inflammatory diseases.

Background. The development of functional gastrointestinal disorders (FGID) in children, especially in the first year of life, is a key factor in the formation of an altered colon microbiota and its formation in older age. The article presents both clinical-detailed anamnesis, symptoms of FGID, and bacteriological characteristics – qualitative and quantitative composition of the colon microbiota in children of the first year of life.Aim: to determine the features of the colon microbiota in children of the first year of life with FGID.Materials and methods. The objects of the study were children of the first year of life (n = 28) with a diagnosis of FGID established by a gastroenterologist. The material was divided into two comparison groups, depending on the age of the subjects: the first group included stool sample cultures of children aged from birth to 6 months (n = 17), the second – from 6 to 12 months (n = 11). The bacteriological study of the quantitative and qualitative composition of the contents of the colon was performed using standard methods.Results. According to the anamnesis, colic and flatulence were the key symptoms of FGID (p < 0.05). The results show that the formation of FGID in children from birth to 6 months and from 6 to 12 months may be associated with altered colon microbiota. There was a decrease in the quantitative indicators of the indigenous microbiota: bifidobacteria, E. coli with normal sensitivity and Enterococcus spp., and an increase in the degree of contamination of Klebsiella spp., S. aureus, Clostridium spp.Conclusion. It is shown that the determining factor in reducing the risk of developing FGID in children of the first year of life is a high concentration and diversity of indigenous microbiota.