[Study of the resistome of human microbial communities using a targeted panel of antibiotic resistance genes in COVID-19 patients].

AIM: To study overall drug resistance genes (resistome) in the human gut microbiome and the changes in these genes during COVID-19 in-hospital therapy. MATERIALS AND METHODS: A single-center retrospective cohort study was conducted. Only cases with laboratory-confirmed SARS-CoV-2 RNA using polymerase chain reaction in oro-/nasopharyngeal swab samples were subject to analysis. The patients with a documented history of or current comorbidities of the hepatobiliary system, malignant neoplasms of any localization, systemic and autoimmune diseases, as well as pregnant women were excluded. Feces were collected from all study subjects for subsequent metagenomic sequencing. The final cohort was divided into two groups depending on the disease severity: mild (group 1) and severe (group 2). Within group 2, five subgroups were formed, depending on the use of antibacterial drugs (ABD): group 2A (receiving ABD), group 2AC (receiving ABD before hospitalization), group 2AD (receiving ABD during hospitalization), group 2AE (receiving ABD during and before hospitalization), group 2B (not receiving ABD). RESULTS: The median number of antibiotic resistance (ABR) genes (cumulative at all time points) was significantly higher in the group of patients treated with ABD: 81.0 (95% CI 73.8-84.5) vs. 51.0 (95% CI 31.1-68.4). In the group of patients treated with ABD (2A), the average number of multidrug resistance genes (efflux systems) was significantly higher than in controls (group 2B): 47.0 (95% CI 46.0-51.2) vs. 21.5 (95% CI 7.0-43.9). Patients with severe coronavirus infection tended to have a higher median number of ABR genes but without statistical significance. Patients in the severe COVID-19 group who did not receive ABD before and during hospitalization also had more resistance genes than the patients in the comparison group. CONCLUSION: This study demonstrated that fewer ABR genes were identified in the group with a milder disease than in the group with a more severe disease associated with more ABR genes, with the following five being the most common: SULI, MSRC, ACRE, EFMA, SAT.

[Efficacy of Saccharomyces boulardii CNCM I-745 probiotic drug in the prevention and treatment of diarrhea in hospitalized patients with new coronavirus infection COVID-19].

AIM: To evaluate the efficacy of Saccharomyces boulardii (S. boulardii) CNCM I-745 probiotic drug in preventing and treating diarrhea in hospitalized patients with COVID-19. MATERIALS AND METHODS: A prospective comparative study was conducted in two parallel groups. The study included males and females aged 18 to 60 with the following diagnosis confirmed by polymerase chain reaction: U07.2 Coronavirus infection COVID-19, caused by SARS-CoV-2 virus (grade 1-3 pneumonia according to CT scan). All patients received antibiotic therapy. The patients were subdivided into two equal groups (n=60) depending on the administration of S. boulardii CNCM I-745 probiotic drug in addition to standard treatment. The probiotic was prescribed by the attending physician; the dose was 2 capsules per day (500 mg/day) 30 min before the meal for 10 days. All patients were monitored for main clinical, laboratory, and instrumental parameters during the study. In addition, the symptom of diarrhea (stool with a frequency of more than 3 times a day of type 6 and 7 according to the Bristol stool scale), including its frequency, duration, and the number of bowel movements of loose stool per day were precisely evaluated in both groups. RESULTS: In the overall patient pool, diarrhea was reported in 21.7% of in-patients during the observation period (95% confidence interval [CI] 14.2-29.1) with a mean duration of 4.6154 days (95% CI 3.7910-5.4398). The incidence of diarrhea in group 1 was 13.3% (95% CI 4.5-22.2), and in group 2, it was 30.0% (95% CI 18.1-41.9). Relative risk showed that the use of the S. boulardii CNCM I-745 probiotic drug leads to a significant reduction in the risk of diarrhea in hospitalized patients with COVID-19 infection receiving antibiotic therapy (odds ratio [OR] 0.3590, 95% CI 0.1421-0.9069; p=0.0303). In group 1, the duration of diarrhea was 3.1250 days (95% CI 2.5892-3.6608) versus 5.2778 days (95% CI 4.2290-6.3265) in group 2, p=0.0112. The mean daily frequency of loose stools in patients with diarrhea in group 1 was 3.2500 (95% CI 2.6588-3.8412) versus 4.3889 (95% CI 3.7252-5.0525) in group 2, p=0.0272. The secondary endpoint, duration of hospital stay, was also significantly shorter in group 1 patients - 11.6833 days (95% CI 11.2042-12.1625) versus 12.7333 days (95% CI 12.1357-13.3309) in group 2, p=0.0120. CONCLUSION: The present prospective comparative study demonstrated that adding S. boulardii CNCM I-745 probiotic drug into the standard treatment regimen of patients with new coronavirus infection COVID-19 receiving antibiotic therapy helps reduce the incidence of diarrhea and its severity during hospitalization, as well as the duration of hospital stay.

[Visual and acoustic interventions for improving mental health in advanced age.]

Data accumulated in the last years indicate that certain visual and acoustic interventions are of geroprotective potential. Among them are bright light, white noise, and also rhythmic sensory stimulation (flickering light, binaural rhythms), etc. It should be noted that visual and acoustic interventions are simple in use, safe and practically do not have adverse side effects and do not need special medical control. Here, we review the studies on using the visual and acoustic interventions for improving mental health with regard to the advanced age and age-related pathology. We also discuss possible mechanisms of their therapeutic action and points for the future investigations.

[Composition of oropharyngeal microbiota in patients with COVID-19 of different pneumonia severity].

AIM: To identify features of the taxonomic composition of the oropharyngeal microbiota of COVID-19 patients with different disease severity. MATERIALS AND METHODS: The study group included 156 patients hospitalized with confirmed diagnosis of COVID-19 in the clinical medical center of Yevdokimov Moscow State University of Medicine and Dentistry between April and June 2021. There were 77 patients with mild pneumonia according to CT (CT1) and 79 patients with moderate to severe pneumonia (CT2 and CT3). Oropharyngeal swabs were taken when the patient was admitted to the hospital. Total DNA was isolated from the samples, then V3V4 regions of the 16s rRNA gene were amplified, followed by sequencing using Illumina HiSeq 2500 platform. DADA2 algorithm was used to obtain amplicon sequence variants (ASV). RESULTS: When comparing the microbial composition of the oropharynx of the patients with different forms of pneumonia, we have identified ASVs associated with the development of both mild and severe pneumonia outside hospital treatment. Based on the results obtained, ASVs associated with a lower degree of lung damage belong predominantly to the class of Gram-negative Firmicutes (Negativicutes), to various classes of Proteobacteria, as well as to the order Fusobacteria. In turn, ASVs associated with a greater degree of lung damage belong predominantly to Gram-positive classes of Firmicutes Bacilli and Clostridia. While being hospitalized, patients with severe pneumonia demonstrated negative disease dynamics during treatment significantly more often. CONCLUSION: We have observed differences in the taxonomic composition of the oropharyngeal microbiota in patients with different forms of pneumonia developed outside hospital treatment against COVID-19. Such differences might be due to the presumed barrier function of the oropharyngeal microbiota, which reduces the risk of virus titer increase.

Measurement of Lepton-Jet Correlation in Deep-Inelastic Scattering with the H1 Detector Using Machine Learning for Unfolding.

The first measurement of lepton-jet momentum imbalance and azimuthal correlation in lepton-proton scattering at high momentum transfer is presented. These data, taken with the H1 detector at HERA, are corrected for detector effects using an unbinned machine learning algorithm (multifold), which considers eight observables simultaneously in this first application. The unfolded cross sections are compared with calculations performed within the context of collinear or transverse-momentum-dependent factorization in quantum chromodynamics as well as Monte Carlo event generators.

Non-invasive transcranial ultrasound stimulation for neuromodulation.

Transcranial ultrasound stimulation (TUS) holds great potential as a tool to alter neural circuits non-invasively in both animals and humans. In contrast to established non-invasive brain stimulation methods, ultrasonic waves can be focused on both cortical and deep brain targets with the unprecedented spatial resolution as small as a few cubic millimeters. This focusing allows exclusive targeting of small subcortical structures, previously accessible only by invasive deep brain stimulation devices. The neuromodulatory effects of TUS are likely derived from the kinetic interaction of the ultrasound waves with neuronal membranes and their constitutive mechanosensitive ion channels, to produce short term and long-lasting changes in neuronal excitability and spontaneous firing rate. After decades of mechanistic and safety investigation, the technique has finally come of age, and an increasing number of human TUS studies are expected. Given its excellent compatibility with non-invasive brain mapping techniques, such as electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), as well as neuromodulatory techniques, such as transcranial magnetic stimulation (TMS), systemic TUS effects can readily be assessed in both basic and clinical research. In this review, we present the fundamentals of TUS for a broader audience. We provide up-to-date information on the physical and neurophysiological mechanisms of TUS, available readouts for its neural and behavioral effects, insights gained from animal models and human studies, potential clinical applications, and safety considerations. Moreover, we discuss the indirect effects of TUS on the nervous system through peripheral co-stimulation and how these confounding factors can be mitigated by proper control conditions.

[Prevalence and prognostic value of gastroenterological manifestations of COVID-19: data from the Russian University Clinic].

AIM: Assessment of the prevalence and prognostic value of gastroenterological manifestations in patients with COVID-19. MATERIALS AND METHODS: A single-center retrospective cohort study was carried out. Only cases with laboratory confirmed detection of SARS-CoV-2 virus RNA using polymerase chain reaction in oro-/nasopharyngeal smear samples were subject to analysis. Patients with documented (according to anamnestic data and/or according to examination data during hospitalization) organic pathology of the gastrointestinal tract (GIT) and/or hepatobiliary system, malignant neoplasms of any localization, as well as pregnant patients were excluded from the general register of retrospective data. The final cohort was divided into two groups depending on the presence of gastrointestinal symptoms: COVID-19 with gastrointestinal symptoms (cases) and COVID-19 without gastrointestinal symptoms (control). RESULTS: The final sample consisted of 3764 patients, including 2108 (56%) women and 1656 (44%) men. The average age of the subjects included in the analysis was 58.0 years (95% confidence interval CI 48.663.0). In the study cohort, gastroenterological manifestations (alone or in combination) were recorded in 885 (23.51%) patients. Calculation of the odds ratio (OR) of unfavorable and lethal outcomes between the analyzed groups showed that the presence of gastroenterological symptoms significantly increases the chances of lethal outcome in a cohort of elderly and senile patients (OR 1.6817, 95% CI 1.03352.7364; p=0.0364), determines a higher risk of hospitalization or transfer to the intensive care unit (OR 1.2959, 95% CI 1.05471.5922; p=0.0136), development of acute respiratory distress syndrome (OR 1.5952, 95% CI 1.31641.9329; p0.0001), as well as the need for mechanical ventilation (OR 1.2849, 95% CI 1.0771.5329; p=0.0054). CONCLUSION: The present study has demonstrated that gastroenterological symptoms are detected in about one in four patients infected with the SARS-CoV-2 virus and multiply the risk of adverse and life-threatening complications of COVID-19.

[Antibiotic resistance of Helicobacter pylori in the European part of the Russian Federation: first results].

AIM: Determine the primary antibiotic resistance of Helicobacter pylori (H. pylori) strains isolated from patients living in the European part of the Russian Federation. MATERIALS AND METHODS: As part of a clinical laboratory study, from 2015 to 2018, 27 gastrobiopsy samples obtained from H. pylori-infected patients were analyzed. H. pylori infection was verified using a rapid urease test or a 13C-urea breath test. The values of the minimum inhibitory concentration (MIC) of antibiotics were determined by the diffusion method using E-test strips (BioMerieux, France) according to the recommendations of the manufacturer. The sensitivity of the isolates was determined for 6 antibacterial drugs (amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, rifampicin). RESULTS: According to the data obtained, resistance to amoxicillin was 0%, clarithromycin 11.1%, metronidazole 59.3%, levofloxacin 3.7%, tetracycline 0%, and rifampicin 14.8%. Dual resistance to clarithromycin and metronidazole was recorded in two isolates (7.4%). CONCLUSION: Thus, the first results of the evaluation of H. pylori antibiotic resistance in the European part of the Russian Federation indicate a low resistance of the microorganism to clarithromycin and quite high to metronidazole.

Determination of the strong coupling constant α s ( m Z ) in next-to-next-to-leading order QCD using H1 jet cross section measurements: H1 Collaboration.

The strong coupling constant α s is determined from inclusive jet and dijet cross sections in neutral-current deep-inelastic ep scattering (DIS) measured at HERA by the H1 collaboration using next-to-next-to-leading order (NNLO) QCD predictions. The dependence of the NNLO predictions and of the resulting value of α s ( m Z ) at the Z-boson mass m Z are studied as a function of the choice of the renormalisation and factorisation scales. Using inclusive jet and dijet data together, the strong coupling constant is determined to be α s ( m Z ) = 0.1157 ( 20 ) exp ( 29 ) th . Complementary, α s ( m Z ) is determined together with parton distribution functions of the proton (PDFs) from jet and inclusive DIS data measured by the H1 experiment. The value α s ( m Z ) = 0.1142 ( 28 ) tot obtained is consistent with the determination from jet data alone. The impact of the jet data on the PDFs is studied. The running of the strong coupling is tested at different values of the renormalisation scale and the results are found to be in agreement with expectations.

[Use of structural MNA descriptors for designing profiles of protein families]. / Primenenie strukturnykh MNA-deskriptorov dlia postroeniia profilei belkovykh semeistv.

A new approach to constructing the profiles of protein families is proposed, which uses only structural similarity of amino acid residues. We derived multiple alignments of protein sequences from 3D superpositions of the protein structures and constructed protein family profiles using structural molecular MNA descriptors. MNA (Multilevel Neighborhoods of Atoms) descriptors were developed earlier and are successfully applied for predicting the biological activity in drug-like compounds. In our approach, each aligned position was described by a set of MNA descriptors calculated for each amino acid residue in the alignment column. In this study, we constructed MNA profiles for trypsin, subtilase, and cytochrome P450 protein families and scanned SWISSPROT with some fragments of these profiles. We also calculated the Independence Accuracy of Prediction for each profile fragment. It was shown that the approach developed could be applied to predict protein function.

[Factors influencing the remote patency of distal shunts in patients with atherosclerosis of lower extremity arteries]. / Faktory, vliiaiushchie na otdalënnuiu prokhodimost' distal'nykh shuntov u bol'nykh aterosklerozom arterii nizhnikh konechnostei.

Under study was the prognostic value of local risk factors of the development of late reocclusion of distal shunts in 149 patients with critical ischemia of lower extremities. It was found that the greatest influence on the remote patency of transplants is exerted by the state of the arterial wall in the area of the distal and in less degree of the proximal anastomoses. In a less degree the duration of functioning of the shunt depended on its length, position in soft tissues, transplant material and the level of the proximal anastomosis. The distal anastomosis level, the history of the simultaneous or previously made aorto-femoral shunt, geometry of the proximal and distal anastomoses did not have any reliable influence on the distal shunt patency.

[Interaction of GABA-ergic component of NAD with benzodiazepine receptors during epileptogenesis]. / Uchastie GAMK-eergicheskogo komponenta vo vzaimodelstvii NAD s benzodiazepinovymi retseptorami pri 'epileptogeneze

Nitrozepam has been shown to decrease specific binding of [14C]NAD by the synaptic mem-branes approximately by 40%. Alongside with the latter GABA in the concentration of 10(-5) M potentiates the effect observed. Blocking in vitro of GABA receptors by bicuculin removes both the tranquilizer and GABA effect. While simulating epileptogenesis in animals the nitrazepam effect on [14C]NAD specific binding sites was somewhat more expressed in comparison with the norm. The interaction of NAD reception systems with benzodiazepine under the pathology is capable to be mediated not only by increasing GABA-ergic transfer, but it can occur place without GABA-ergic component of GABA-benzodiazepine receptor complex.

[Effect of withdrawal of phenazepam and nicotinamide on the status of the system of reception of benzodiazepines and NAD]. / Vliianie otmeny fenazepama i nikotinamida na sostoianie sistem retseptsii benzodiazepinov i NAD.

Comparative investigations in reception of NAD, benzodiazepines and GABA by synaptic membranes under a single and multiple administration of phenazepam and nicotinamide to animals as well as after withdrawal of long-term administration of these drugs have been carried out. The both drugs activate GABA-inhibiting system of synaptic membranes. Both the sections of specific binding of benzodiazepines and of NAD take part in realization of "cancellation" syndrome. Chronic administration of phenazepam and nicotinamide results in the change of coupling in GABA-benzodiazepine receptor complex. After the withdrawal of chronic administration of nicotinamide the function of GABA-benzodiazepine receptor complex is normalized more quickly.

[Participation of a diazepam-binding inhibitor in the interaction between NAD and GABA-benzodiazepine receptor complex in synaptic membranes]. / Uchastie diazepamsviazyvaiushchego ingibitora vo vzaimodeistvii NAD s GAMK-benzodiazepineovym retseptornym kompleksom sinapticheskikh membran.

Diazepam-binding inhibitor isolated from synaptic membranes exerts a pronounced inhibitory effect on the specific benzodiazepine-receptor binding of 3H-flunitrazepam and simultaneously leads to an increase of synaptosomal uptake of 14C-GAMA. At the same time the inhibitor also depresses the specific binding of 14C-NAD by synaptic membranes, but displaying a greater effect. In both cases the inhibition was competent. Whether the isolated neuropeptide may act as an intermediary in the interaction with the reception system of NAD with GABA-benzodiazepine-receptor complex.

[Participation of benzodiazepine receptors in the mechanism of action of nicotinamide in nerve cells]. / Uchastie benzodiazepinovykh retseptorov v mekhanizme deistviia nikotinamida v nervnoi kletke.

Bicucculine being introduced to rats has induced an increase of [14C]GABA capture with synaptosomes and simultaneous decrease of GABA and NAD level in the brain. The decrease of the inhibiting effect of GABA is accompanied by the increase of specific binding of [3H]flunitrazepam with benzodiazepine receptors at the expense of the increase of binding capacity from 0.33 to 0.45 g/mol per 100 mg of protein. Under these conditions the dissociation constant remains unchanged. Such an activation of benzodiazepine receptors was observed under the lack of NAD in the organism (model of PP-hypovitaminosis). Introduction of the surplus doses of nicotinamide neutralizes the convulsant effect on benzodiazepine receptors.

[The effect of NAD on binding and liberation of (14)C-GABA during convulsant administration]. / Vliianie NAD na zakhvat i vysvobozhdenie (14)C-GAMK pri vvedenii konvul'santa.

Administration of corazol into animals led to a decrease in content of NAD and gamma-aminobutyric acid (GABA) in brain. Under these conditions, binding of 14C-GABA was increased and its liberation was inhibited in the synaptosomes of the brain cortex. Additional administration of nicotinamide, accompanied by considerable increase in content of NAD and GABA, caused a decrease in accumulation of exogenous GABA in the synaptosomes and removed the effects produced by the convulsant agent. Kinetics of 14C-GABA binding in the presence of NAD demonstrated that the more effective inhibition of the binding occurred in the animals treated with the convulsant drug. NAD appears to affect the GABA-ergic transmission at the postsynaptic level.