[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.

[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.

[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.

High-sensitive absorption measurement in transparent isotropic dielectrics with time-resolved photothermal common-path interferometry.

We propose a time-resolved photothermal common-path interferometry scheme at fast heating in the absence of heat diffusion and employ it to measure absorption in Suprasil 311 silica glass (2.8·10-6 cm-1) at a wavelength of 1071 nm and continual absorption in laboratory air (2.9·10-8 cm-1) for a signal-to-noise ratio of 100/1. The absorption was measured at a thermally induced phase incursion of less than 0.1 rad in a heating beam, which guaranteed correct calibration. To calibrate this scheme, we developed a theory of diffraction on deformations taking into account the stresses arising in an inhomogeneous temperature field. This allowed us to use a standard glass K8 for calibration. The low level of noise and time resolution of pulsed signals allowed the distinguishing of the contributions of Kerr and striction nonlinearities to absorption measurements in Suprasil 311 silica glass and enabled the observance of the time evolution of strictional deformations. Additionally, an anomalous temporal development of the absorption of broadband laser radiation in atmospheric air at 2.9·10-8 cm-1 has been revealed.

Lactic acid fermentation of human urine to improve its fertilizing value and reduce odour emissions.

During storage of urine, urea is biologically decomposed to ammonia, which can be lost through volatilization and in turn causes significant unpleasant smell. In response, lactic acid fermentation of urine is a cost-effective technique to decrease nitrogen volatilization and reduce odour emissions. Fresh urine (pH = 5.2-5.3 and NH4+-N = 1.2-1.3 g L-1) was lacto-fermented for 36 days in closed glass jars with a lactic acid bacterial inoculum from sauerkraut juice and compared to untreated, stored urine. In the lacto-fermented urine, the pH was reduced to 3.8-4.7 and the ammonium content by 22-30%, while the pH of the untreated urine rose to 6.1 and its ammonium content increased by 32% due to urea hydrolysis. The concentration of lactic acid bacteria in lacto-fermented urine was 7.3 CFU ml-1, suggesting that urine is a suitable growth medium for lactic acid bacteria. The odour of the stored urine was subjectively perceived by four people to be twice as strong as that of lacto-fermented samples. Lacto-fermented urine induced increased radish germination compared to stored urine (74-86% versus 2-31%). Adding a lactic acid bacterial inoculum to one week old urine in the storage tanks in a urine-diverting dry toilet reduced the pH from 8.9 to 7.7 after one month, while the ammonium content increased by 35%, probably due to the high initial pH of the urine. Given that the hydrolyzed stale urine has a high buffering capacity, the lactic acid bacterial inoculum should be added to the urine storage tank of a UDDT before urine starts to accumulate there to increase the efficiency of the lactic acid fermentation.

[THERAPEUTIC FEEDING FEATURES OF PATIENTS WITH CHRONIC PANCREATITIS].

The article presents the principles of diet therapy in chronic pancreatitis taking into account the pathophysiological aspects of the development of malnutrition.

Strain-induced charge ordering above room temperature in rare-earth manganites.

Most known mixed manganites containing rare-earth elements demonstrate a pronounced charge ordering (CO) state below room temperature. The behavior of the magnetic susceptibility and electronic magnetic resonance of polycrystalline Pr1-xSrxMnO3/YSZ (x = 0.2 and x = 0.4) films without a pronounced texture indicates the formation of the CO phase in the samples at temperatures close to and above room temperature. Moreover, this phase manifests itself with a typical sign of martensitic transformation. The same phenomenon has been traced for textured polycrystalline La0.7Sr0.3MnO3/YSZ films. Electron microscope data indicate the presence of internal strain within the films, which is probably responsible for the formation of the CO phase. It is assumed that the reasons for the appearance of such strain include the crystallite size and the boundary between them. The results obtained provide the basis for the development of new research and technological tasks for the generation of the high-temperature CO state in various polycrystalline rare-earth manganites, since this state contributes to the manifestation of interesting magnetocaloric, magnetoelectric and multiferroic properties. In addition, recent data has opened up new opportunities for studying the strain-induced phenomena in such materials.

Forward-looking insights in laser-generated ultra-intense γ-ray and neutron sources for nuclear application and science.

Ultra-intense MeV photon and neutron beams are indispensable tools in many research fields such as nuclear, atomic and material science as well as in medical and biophysical applications. For applications in laboratory nuclear astrophysics, neutron fluxes in excess of 1021 n/(cm2 s) are required. Such ultra-high fluxes are unattainable with existing conventional reactor- and accelerator-based facilities. Currently discussed concepts for generating high-flux neutron beams are based on ultra-high power multi-petawatt lasers operating around 1023 W/cm2 intensities. Here, we present an efficient concept for generating γ and neutron beams based on enhanced production of direct laser-accelerated electrons in relativistic laser interactions with a long-scale near critical density plasma at 1019 W/cm2 intensity. Experimental insights in the laser-driven generation of ultra-intense, well-directed multi-MeV beams of photons more than 1012 ph/sr and an ultra-high intense neutron source with greater than 6 × 1010 neutrons per shot are presented. More than 1.4% laser-to-gamma conversion efficiency above 10 MeV and 0.05% laser-to-neutron conversion efficiency were recorded, already at moderate relativistic laser intensities and ps pulse duration. This approach promises a strong boost of the diagnostic potential of existing kJ PW laser systems used for Inertial Confinement Fusion (ICF) research.

[Diagnosis and correction of thrombohemorrhagic complications in cardiosurgical patients in the early postoperative period].

The methods of the prevention, diagnosis, and correction of hemostatic disorders are discussed in cardiosurgical patients. Prevention of hemorrhages requires hemostatic history data collection that allows identification of patients with concomitant hemophilia and those, taking antithrombotic drugs. The benefits of an extended study of blood coagulation disorders are shown in neonates and babies of the first year of life due to the physiological features of the hemostatic system and the pattern of heart disease. Algorithms are proposed for the diagnosis and treatment of hemorrhagic diathesis in the early postoperative period; a complex of minor signs of surgical hemorrhage is formulated, which makes it possible to timely perform rethoracotomy and to reduce blood transfusion. Efficiency evaluation and exclusion criteria for the use of recombinant factor VIIa are given. The efficiency of using the Russian drug tranexam versus epsilon-aminocapronic acid and aprotinin in the perioperative period was evaluated. The blood coagulative system was monitored in the treatment of disseminated intravascular coagulation in multiple organ dysfunction and sepsis, which promoted the timely use of recombinant human activated protein C and human antithrombin III. A diagnostic and treatment algorithm for replacement therapy of congenital heart disease concurrent with hemophilia A is given.

[Combined therapy of acid-dependent gastrointestinal disorders with the use of antacidic drug Relcer].

The aim of the study was to evaluate clinical efficiency of antacidic drug Relcer included in combined therapy of gastroesophagal reflux disease (GERD) and ulcer disease (UD). Group 1 comprised 47 patients with GERD and group 2 49 patients with gastric and duodenal UD. Each group was divided into study (A) and control (B) subgroups. All GERD patients were given rabeprazole and metoclopramide, patients with UD received rebaprazole, clarithromycin and amoxicillin. Relcer was additionally prescribed to 24 patients in group 1A and 26 in 2A. Duration of therapy in all groups was 14 days. By the end of the study, all symptoms of GERD were eliminated in 100% of the patients in group 1A and in 78.3% in 1B. Pain and heartburn in group 1A were reduced or eliminated within 5 and 7.8 min respectively after the first dose of Relcer. The same complaints in 69.9% of 1B patients were resolved by the end of the first day. The remaining ones benefited from combined treatment on day 2 Rapid and complete elimination of UD symptoms was finally achieved in 21.7-26.1% of 2A patients whereas moderate dyspeptic syndrome persisted in those of subgroup 2B. Ulcer scarring completed by day 14 in 88.5 and 87% of the patients in subgroups 2A and 2B respectively. Eradication of H. pylori was achieved in 92.3 and 87% of the patients in these groups. It is concluded that introduction of Relcer into combined therapy of GERD and UD improves its results and accelerates elimination of clinical symptoms.

[Helicobacter pylori infection as additional risk factor of the development of NSAID-gastropatia effects at the patients with osteoarthritis].

Prevalence of osteoartrosis disease is high among the population. The main places in treatment of this pathology occupy NSAID. Intake of NSAID is lead to the development of NSAID-gastropatia. During last years H. pylori infection was numbered with risk factors of the NSAID-gastropatia development. In this review considered researches which are devoted to studying ties between H. pylori and NSAID. Data of the using eradication therapy with purpose of prevention and treatment of NSAID-gastropatia associated with H. pylori are shown in this review.

[Early symptoms of hepatic encephalopathy in patients with chronic diffuse hepatic diseases].

Four hundred and twenty-three patients with chronic diffuse hepatic diseases (hepatitis and viral hepatic cirrhosis) underwent complex clinico-instrumental examination; the control group consisted of 30 healthy individuals. Hepatic encephalopathy syndrome was a much more frequent finding in patients with hepatic cirrhosis. Association of chronic viral hepatic lesion with alcohol abuse increased the frequency of latent central nervous system lesions.

[Etiology of chronic diffuse liver damages].

Patients with chronic diffuse liver damages have cases of chronic hepatitis associated with alcoholic liver disease being transformed to cirrhosis 2.1 times more often when having mostly equal frequency of chronic damage of viral and alcoholic origin on the stage of chronic hepatitis or in the case of pure viral damage against a background of significant prevalence (3 times) of viral etiology. Infection associated with HCV in patients with alcoholic liver cirrhosis doesn't significantly influence the course of disease, aftereffects and prognosis of patients.

Sub-terahertz microsecond optically controlled switch with GaAs active element beyond the photoelectric threshold.

We study an unusual working regime of a recently developed sub-terahertz microwave cavity-based switch. The resonator cavity includes a semiconductor plate which is illuminated by laser emission beyond the photoelectric threshold. Despite a significant change to the conventional process of photoelectric effect we have found that the switch works. Typical switching performance rate is about 1 µs for the regime. A process of carrier density relaxation beyond the photoelectric threshold is discussed. An idea of diagnostic method for the semiconductor's quality is proposed.

Opioids suppress spontaneous activity of polymodal nociceptors in rat paw skin induced by ultraviolet irradiation.

Changes in chemical sensitivity of peripheral nociceptors following injury or inflammation have been studied in in vitro preparation of the saphenous nerve-hind paw skin from adult rats. Heat hyperalgesia in the hind paw was induced by a prior ultraviolet irradiation and the skin from these animals was investigated five days later. Polymodal nociceptors were quiescent in normal skin but were spontaneously active in the majority of fibres after ultraviolet exposure. Capsaicin-induced activation of fine fibres was enhanced after ultraviolet pretreatment. Direct administration of morphine, DAGOL (mu-receptor agonist) and U-69593 (kappa-receptor agonist), but not DPDPE (delta-receptor agonist) to the receptive field produced a concentration-related and naloxone-reversible suppression of spontaneous firing in polymodal nociceptors of ultraviolet-treated skin. Morphine did not reduce the activity of fibres in normal skin when these were driven by KCl depolarization. These data show that polymodal nociceptors change their activity and sensitivity to exogenous chemicals following the induction of peripheral hyperalgesia by ultraviolet irradiation. Specifically, evidence is provided for the expression of opioid sensitivity and inhibition of polymodal nociceptor activity through mu- and kappa-opioid receptors. These observations may account for peripheral antinociceptive actions of opioids during specific states of peripheral hyperalgesia.

New pulse sequences for T1- and T1/T2-contrast enhancing in NMR imaging.

Improved pulse sequences DIFN (abbreviation of the words: DIFferentiation by N pulses), 90 degrees - tau1 - 180 degrees tau1 - . . . 180 degrees - tau1 with optimised time intervals tau1- for T1 measurement and contrast enhancing in NMR imaging are presented. The pulse sequences DIFN have a better sensitivity to T1 than the well-known pulse sequence SR. In contrast to the IR pulse sequence, the information given by the DIFN pulse sequence is more reliable, because the NMR signal does not change its sign. For a given time interval tau0 < or = (0.1 - 0.3) T(1) the DIFN pulse sequences serve as T1-filters. They pass the signal components with relatively short T1 < T(1) and suppress the components with relatively long T1 < T(1). The effects of the radiofrequency field inhomogeneity and inaccurate adjusting of pulse lengths are also considered. It is also proposed in this work to use the joint T1T2-contrast in NMR imaging obtained as a result of applying the DIFN pulse sequences in combination with the well-known Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence. The region of interest, where the contrast should be especially enhanced, is specified by the two times at which measurements are performed, which allow the amplitudes of pixels to reach some defined levels by spin-lattice and spin-spin relaxation.

Propagation of short intense laser pulses in gas-filled capillaries.

The guided laser pulse propagation and wake-field generation are studied in a wide (in comparison with the laser spot size) gas-filled capillary with an on-axis gas density depletion, which can be produced by a rapid spin of the capillary around its axis or by radially propagating shock waves generated in a piezoceramic tube. A single equation for the wake-field potential, which describes the fully relativistic plasma response in the presence of optical field ionization (OFI) of a gas, is derived and used to demonstrate a guided propagation of a short intense laser pulse over many Rayleigh lengths in a leaky plasma channel produced by the pulse due to OFI in the capillary filled with a radially inhomogeneous gas. The efficient generation of a regular wake field over long distances suitable for the laser wake-field accelerators is shown.

Nonlinear propagation of short intense laser pulses in a hollow metallic waveguide.

The propagation of a short intense laser pulse in the femtosecond range in a hollow metallic waveguide gives rise to heating of the metallic wall. The temperature of the degenerate electron gas in the wall is increased during the pulse duration and this heating affects the propagation and dissipation of the laser pulse. Analytical and numerical analysis shows that, as the dissipation is increased, the leading edge of the pulse decreases more slowly than the rear, resulting in a pulse shortening.

Eigenmodes for capillary tubes with dielectric walls and ultraintense laser pulse guiding.

The properties of the eigenmodes of a capillary tube are examined in the context of ultrashort intense laser pulse guiding. The dispersion relation for the eigenmodes of a cylindrical hollow waveguide is derived and the family of eigenmodes EH(nus) is shown to be a solution of the wave equation up to the first order under the condition k(0)a >>1, where k(0) is the light wave number and a the capillary tube radius. The expressions of the fields for the eigenmodes are given at zero and first order of a small parameter equal to the ratio of the perpendicular to longitudinal wave number and the absorbed intensity at the wall is estimated.