Detection and full-genotype determination of rare and reassortant rotavirus A strains in Nizhny Novgorod in the European part of Russia.

Reassortant DS-1-like rotavirus A strains have been shown to circulate widely in many countries around the world. In Russia, the prevalence of such strains remains unclear due to the preferred use of the traditional binary classification system. In this work, we obtained partial sequence data from all 11 genome segments and determined the full-genotype constellations of rare and reassortant rotaviruses circulating in Nizhny Novgorod in 2016-2019. DS-1-like G3P[8] and G8P[8] strains were found, reflecting the global trend. Most likely, these strains were introduced into the territory of Russia from other countries but subsequently underwent further evolutionary changes locally. G3P[8], G9P[8], and G12P[8] Wa-like strains of subgenotypic lineages that are unusual for the territory of Russia were also identified. Reassortant G2P[8], G4P[4], and G9P[4] strains with one Wa-like gene (VP4 or VP7) on a DS-1-like backbone were found, and these apparently had a local origin. Feline-like G3P[9] and G6P[9] strains were found to be phylogenetically close to BA222 isolated from a cat in Italy but carried some traces of reassortment with human strains from Russia and other countries. Thus, full-genotype determination of rotavirus A strains in Nizhny Novgorod has clarified some questions related to their origin and evolution.

The use of Dapagliflozin in Acute Decompensated Heart Failure: Results of the Randomized Study.

Aim      To determine the effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on kidney function in acute decompensated heart failure (ADHF).Material and methods  A controlled randomized study on the dapagliflozin treatment in ADHF was performed. Patients were randomized to a main group (standard therapy supplemented with dapagliflozin) or a control group (standard therapy for ADHF). The primary endpoint was the development of acute kidney injury (AKI). 200 patients were included (mean age, 74±12 years; 51% men). 31% of patients had type 2 diabetes mellitus (DM2). Mean left ventricular ejection fraction (LV EF) was 47±14 %; in 44.5% of patients, LV EF was less than 45%. Median concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) was 5225 [3120; 9743] pg / ml, glomerular filtration rate (GFR) was 51 [38; 64] ml / min / 1.73 m2.Results In-hospital mortality was 6.5%. Analysis of the dynamics of body weight loss showed significant differences (4200 [2925; 6300] g vs. 3000 [1113; 4850] g; p=0.011) in favor of the dapagliflozin group. The requirement for increasing the daily dose of furosemide and adding an another class diuretic (thiazide or acetazolamide) did not differ between the groups. However, median furosemide dose during the stay in the hospital was lower in the dapagliflozin group (80 [67; 120] mg vs. 102 [43; 120] mg; p=0.016). At 48 hours after randomization, GFR significantly decreased in the dapagliflozin group (-5.5 [-11; 3] ml/min/ 1.73 m2) compared to the control group (-0.3 [-4; 5] ml / min/1.73 m2, р=0.012). Despite this, GFR did not differ between the groups at discharge (51 [41; 66] ml/min/1.73 m2 and 49 [38; 67] ml/min/1.73 m2, respectively; p = 0.84). In the dapagliflozin group, frequency of AKI episodes was not increased compared to the control group (13 and 9.4%, respectively; p = 0.45).Conclusion      The dapagliflozin treatment in ADHF is associated with more pronounced body weight loss and lower average doses of loop diuretics during the period of stay in the hospital, with no associated clinically significant impairment of renal function.

The use of Dapagliflozin in Acute Decompensated Heart Failure: Results of the Randomized Study.

Aim      To determine the effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on kidney function in acute decompensated heart failure (ADHF).Material and methods  A controlled randomized study on the dapagliflozin treatment in ADHF was performed. Patients were randomized to a main group (standard therapy supplemented with dapagliflozin) or a control group (standard therapy for ADHF). The primary endpoint was the development of acute kidney injury (AKI). 200 patients were included (mean age, 74±12 years; 51% men). 31% of patients had type 2 diabetes mellitus (DM2). Mean left ventricular ejection fraction (LV EF) was 47±14 %; in 44.5% of patients, LV EF was less than 45%. Median concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) was 5225 [3120; 9743] pg / ml, glomerular filtration rate (GFR) was 51 [38; 64] ml / min / 1.73 m2.Results In-hospital mortality was 6.5%. Analysis of the dynamics of body weight loss showed significant differences (4200 [2925; 6300] g vs. 3000 [1113; 4850] g; p=0.011) in favor of the dapagliflozin group. The requirement for increasing the daily dose of furosemide and adding an another class diuretic (thiazide or acetazolamide) did not differ between the groups. However, median furosemide dose during the stay in the hospital was lower in the dapagliflozin group (80 [67; 120] mg vs. 102 [43; 120] mg; p=0.016). At 48 hours after randomization, GFR significantly decreased in the dapagliflozin group (-5.5 [-11; 3] ml/min/ 1.73 m2) compared to the control group (-0.3 [-4; 5] ml / min/1.73 m2, р=0.012). Despite this, GFR did not differ between the groups at discharge (51 [41; 66] ml/min/1.73 m2 and 49 [38; 67] ml/min/1.73 m2, respectively; p = 0.84). In the dapagliflozin group, frequency of AKI episodes was not increased compared to the control group (13 and 9.4%, respectively; p = 0.45).Conclusion      The dapagliflozin treatment in ADHF is associated with more pronounced body weight loss and lower average doses of loop diuretics during the period of stay in the hospital, with no associated clinically significant impairment of renal function.

[Social networks as a space of communication on health issues].

Social media is bringing a new dimension to healthcare as it offers an environment through which the public, patients, and healthcare professionals can report health issues with the possibility of potentially improving health outcomes. Social networks are a powerful tool that ensures cooperation between users and is a mechanism of social interaction for a wide range of people. Although the use of social networks for communication in the field of health has a number of advantages, the exchange of information must be monitored for quality and reliability, as well as to preserve the confidentiality of users.

Permeation of Nanoparticles into Pulmonary Surfactant Monolayer: In Situ X-ray Standing Wave Studies.

High-resolution X-ray techniques were applied to examine the effects of gold nanoparticles (size <5 nm) on natural pulmonary surfactant and pure DPPC monolayers preliminarily formed on water subphase in a Langmuir trough. Hydrophobic and hydrophilic nanoparticles were delivered from nanoaerosol using electrodeposition method. Grazing incidence diffraction, X-ray reflectivity, and X-ray standing wave measurements allow to monitor the changes in molecular organization of lipid monolayer and to locate the position of gold nanoparticles. X-ray experiments were performed over a period of 9-14 h. The obtained results evidenced that, on a long time scale, the deposition of nanoparticles, even at low doses, can induce pronounced alterations in lipid monolayer. The presented data can help to elucidate the mechanism of pulmonary translocation of inhaled nanoparticles that is of special interest for biomedical investigations of potential risk of nanoaerosols for human health.

An increase in prevalence of recombinant GII.3[P12] norovirus in sporadic acute diarrhea in children in Nizhny Novgorod, Russia, 2018-2021.

Noroviruses are important etiological agents causing acute intestinal infection in humans. In the last decades, the most common norovirus genotype was GII.4 despite a significant genetic diversity among strains, while the active circulation of noroviruses with other genotypes was observed periodically. This study shows an increase in the detection rate of recombinant GII.3[P12] norovirus in Nizhny Novgorod, Russia, from 6.8% in 2018-2019 to 34.9% in 2020-2021. We performed a phylogenetic analysis based on the nucleotide sequences of noroviruses possessing this genotype obtained in this work, as well as presented in the GenBank database. It has been shown that the circulation of GII.3[P12] noroviruses in the study area was the result of several independent introductions, either directly from the Western Pacific region, or through the Asian part of Russia. The polyphyletic origin, the geographical expansion, and the growth of the epidemic significance of the recombinant GII.3[P12] noroviruses were noted.

[POPULARIZATION OF TOURISM, HEALTHY LIFESTYLE, PHYSICAL AND SOCIAL ACTIVITY IN THE PROGRAMS OF ACTIVE LONGEVITY OF SENIOR CITIZENS].

The article presents data on sports, active forms of leisure, travel among elderly Russians. An important conclusion is made that health promotion by means of active recreation and sports among senior citizens in Russia is one of the directions of active longevity policy. An overview of charitable foundations for senior citizens of the Russian Federation and their activities in promoting an active lifestyle among elderly citizens is presented.

Long-term monitoring of G1P[8] rotaviruses circulating without vaccine pressure in Nizhny Novgorod, Russia, 1984-2019.

The G1P[8] genotype is one of the most common among rotaviruses circulating in the last 40 years. Therefore, this genotype is a component of rotavirus vaccines licensed throughout the world. This paper presents the results of a 35-year (1984-2019) observation of the circulation of G1P[8] rotaviruses among children under 14 in one region (Nizhny Novgorod, Russia) without vaccine pressure. Several complementary approaches were used: RNA electropherotyping by polyacrylamide gel electrophoresis, PCR genotyping, and cDNA sequencing of rotavirus VP4 and VP7 genes. A total of 8375 rotavirus-positive samples were examined, and the proportion of genotype G1P[8] rotaviruses was 39.9% (4.3-98.9%). Two cycles of high circulation activity (1984-1993 and 1993-2007) and one cycle of low activity (2007-2019) were noted. Phylogenetic analysis revealed the presence of rotaviruses of two VP4 gene lineages (P[8]-1 and P[8]-3) and two VP7 gene lineages (sublineages IA, IB, ID, II-B, II-C, and II- E). The prolonged circulation of rotaviruses of only one sublineage (G1-II-E) and then a change of the prevailing sublineage within the G1-II lineage (from E to C) during the active circulation were shown. Since 2011, when the circulation intensity of G1P[8] rotaviruses was low, the appearance of strains of the G1-I lineage and their co-circulation with strains of the G1-II lineage were observed in the population.

[Hyper-Resistance of the Bacillus licheniformis 24 Strain to Oxidative Stress Is Associated with Overexpression of Enzymatic Antioxidant System Genes].

At the International Space Station (ISS), artificial living conditions are created and maintained to satisfy human needs, these conditions are also favorable for the growth of numerous microorganisms, molds and bacteria. Among the microorganisms detected on the ISS are those from the automicroflora of crew members, and a significant number of spore-forming bacteria. In most cases, this group of microorganisms gives rise to strains that are able to colonize, grow and reproduce on interior materials and equipment of stations, and may be involved in biodestructive processes. These bacteria show increased resistance to various stress factors, for example, DNA-damaging and oxidizing agents. The molecular mechanisms of this resistance to stress are poorly understood. As part of the sanitary-microbiological monitoring of the ISS habitat, the Bacillus licheniformis 24 strain was isolated. Here, we demonstrated that this strain has increased resistance to hydrogen peroxide and Paraquat when compared to the "terrestrial" B. licheniformis B-10956 strain. B. licheniformis 24 overexpressed genes encoding enzymes that neutralize reactive oxygen species, such as KatX catalase and the superoxide dismutases SodA and SodF. Apart from this, in comparison with B. licheniformis B-10956, of B. licheniformis 24 cells had lower hydrogen sulfide production that was associated with sharply reduced expression of the cysIJ operon that encodes sulfite reductase. The results indicate that enzymatic antioxidant protective systems make a more significant contribution to the hyper-resistance of Bacillus strains to oxidizing agents than components of non-enzymatic systems, such as hydrogen sulfide.

The Biological Threat: The Threat of Planetary Quarantine Failure as a Result of Outer Space Exploration by Humans.

The paper presents the results of experiments with spore-forming bacteria and microscopic fungi performed in the framework of the Russian Research Program outside the International Space Station. It has been found that microorganisms not only survive in this extreme environment, but also retain reproductive ability. Moreover, most microorganisms exhibit an increase in biochemical activity and resistance to antimicrobial agents, specifically antibiotics. These findings are of obvious interest to the developers of both planetary quarantine methods and biomedical safety systems for manned space exploration missions. In addition, they demonstrate the necessity of experiments on the exposure of bio-objects to simulated environmental factors beyond Earth's magnetosphere.

[Patient's way from acute pulmonary embolism to chronic thromboembolic pulmonary hypertension: diagnostic and treatment options].

Сhronic thromboembolic pulmonary hypertension (CTEPH) is a serious, under - diagnosed but potentially curable complication of pulmonary embolism (PE) due to medicine advancements. Lack of specific symptoms and signs makes its diagnosis challenging, requiring clinicians to be ready to suspect its presence in patients with dyspnea of unknown origin or persistent symptoms after the pulmonary embolism event. The success of the treatment of this disease depends entirely on early diagnosis. The complexity of the differential diagnosis is due to the problematic aspects including the lack of doctors' awareness of both the pathology itself and the possibilities of its modern treatment. Recently, in our country, the problem of the availability of expert centers with sufficient experience in providing highly specialized medical care to this rather difficult category of patients who need specific therapy has become very actual. The aim of this review is to provide contemporary information about epidemiology, pathophysiology, and clinical features of treating patients with CTEPH, and also, to increase awareness of potential PE→CTEPH transformation. In the article a 4-year - period of experience of the Meshalkin National Medical Research Center on management of CTEPH patients has been presented.

[Use of extracorporeal membrane oxygenation for pulmonary haemorrhage after pulmonary endarterectomy]. / Primenenie ékstrakorporal'noi membrannoi oksigenatsii pri legochnom krovotechenii posle legochnoi éndarteréktomii.

Pulmonary haemorrhage is one of the most severe complications of pulmonary endarterectomy. To the most effective methods of combating this potentially fatal complication belongs extracorporeal membrane oxygenation (ECMO). In this article we describe a clinical case report regarding intraoperative use of central veno-arterial ECMO for pulmonary haemorrhage following thromboendarterectomy from the pulmonary arteries. According to the data of some authors, long-term ECMO support (for more than 4 days) may lead to such severe consequences as rethrombosis of pulmonary arteries and impairment of cerebral circulation. In our case we managed to avoid such complications, taking into consideration that the duration of ECMO amounted to 21 days. Resulting from the carried out comprehensive therapeutic measures by the time of discharge from hospital, a significant decrease in pulmonary artery pressure was achieved, with events of residual pulmonary hypertension.

Phylogenetic comparison of the VP7, VP4, VP6, and NSP4 genes of rotaviruses isolated from children in Nizhny Novgorod, Russia, 2015-2016, with cogent genes of the Rotarix and RotaTeq vaccine strains.

Group A rotaviruses (RVA) are one of the leading causes of gastroenteritis in young children worldwide. The introduction of universal mass vaccination around the world has contributed to a reduction in hospitalizations and outpatient visits associated with rotavirus infection. Continued surveillance of RVA strains is needed to determine long-term effects of vaccine introduction. In the present work, we carried out the analysis of the genotypic diversity of RVA strains isolated in Nizhny Novgorod (Russia) during the 2015-2016 epidemic season. Also we conducted a comparative analysis of the amino acid sequences of T-cell epitopes of wild-type and vaccine (RotaTeq and Rotarix) strains. In total, 1461 samples were examined. RVAs were detected in 30.4% of cases. Rotaviruses with genotype G9P[8] (40.5%) dominated in the 2015-16 epidemic season. Additionally, RVAs with the following genotypes were detected: G4P[8] (25.4%), G1P[8] (13%), G2P[4] (3.2%). Rotaviruses with genotypes G3P[9], G6P[9], and G1P[9] totaled 3%. The number of partially typed and untyped RVA samples was 66 (14.9%). The findings of a RVA of G6P[9] genotype in Russia were an original observation. Our analysis of VP6 and NSP4 T-cell epitopes showed highly conserved amino acid sequences. The found differences seem not to be caused by the immune pressure but were rather related to the genotypic affiliations of the proteins. Vaccination against rotavirus infection is not included in the national vaccination schedule in Russia. Monitoring of the genotypic and antigenic diversity of contemporary RVA will allow providing a comparative analysis of wild-type strains in areas with and without vaccine campaign.

[Radiofrequency Pulmonary Artery Ablation for Treatment of Residual Pulmonary Hypertension After Pulmonary Endarterectomy].

OBJECTIVE: to assess the safety and efficiency of radiofrequency pulmonary artery ablation for treatment of residual pulmonary hypertension after pulmonary endarterectomy. MATERIAL AND METHODS: Radiofrequency pulmonary artery denervation (PADN) was performed in 16 patients (10 men, mean age 39 years [26; 51]). Indication for PADN was mean pulmonary artery pressure (PAP) >25 mm Hg with absence of proximal pulmonary artery lesion according to computer tomography. PADN procedure was performed with nonfluoroscopic 3D navigation system. RESULTS: After PADN mean PAP decreased from 37.3 mm Hg [29; 38] to 24.6 mm Hg [17; 30] (p=0.01); pulmonary vascular resistance decreased from 672 dyn·s·c -5 [387; 566] to 386 dyn·s·c -5 [155; 449] (р=0.02); cardiac output increased from 3.4 l / min [3.2; 3.4] to 3.5 l / min [3.2; 4.0] (p=0.4); 6­minute walk test distance increased from 427 meters [352; 510] to 447 meters [370; 525] (p=0.16), respectively. CONCLUSION: Initial results allow to assume that radiofrequency pulmonary artery denervation combined with optimal medical therapy may take its rightful place in the treatment of this category of patients.

Case of thrombosis of the portal vein and its branches in a patient seropositive for Borrelia antigens.

Borreliosis after sucking ticks is an acute problem in the world. People do not go to doctors after that often, which leads to the development of various complications. Thrombosis of veins of various localization can be one of them. Thrombosis of the portal vein represents a significant problem too with high morbidity and mortality. The risk factors for splanchnic vein thrombosis include infections, but its relationship with borreliosis has not been studied. А 34-year-old man with chronic helicobacter-associated gastritis and gallstones was hospitalized due to development during the last 11 days of epigastric pain and fever to 38.7 °C after a picnic at the forest without a registered tick bite. The blood leukocytes were increased to 11.2*109/l, lymphocytes 70%, C-reactive protein 34.6 mg/l, procalcitonin 0.195 ng/ml. The multispiral computed tomography of the abdominal cavity revealed thrombosis of portal, lienalis and superior mesenteric veins. D-dimer was 1.98 mcg/ml, antithrombin III 75%. JACK2V617F, oncological, rheumatic, thrombophilia markers, blood and urine cultures were negative. A high concentration of anti-Borrelia burgdorferi IgM 62.2 U/ml and its increasing to 190 U/ml in dynamics was revealed at the immunofluorescence assay. Anti-Borrelia IgM to OspA, p31 and OspC, p25 were detected at the immunoblotting assay. Anticoagulation, doxycycline, detoxification therapy reduced pain and normalized temperature and inflammation markers. Vein thrombosis was not detected at the control tomography after 2 weeks. Despite that the combination of thrombosis and borreliosis is rare, it is necessary to screen for Borrelia antigens in patients with splanchnic vein thrombosis and fever.

Predominance of new G9P[8] rotaviruses closely related to Turkish strains in Nizhny Novgorod (Russia).

Genotype G9P[8] rotaviruses are rare in the territory of Russia. They were found in Nizhny Novgorod only in 2011-2012 for the first time, when their proportion was 25.9%. During the next two seasons, G9P[8] strains were detected in only 1.8% of cases. Their proportion substantially increased again in 2014, and they became predominant in the city by 2016. Phylogenetic analysis on the basis of gene VP7 nucleotide sequences showed that this increase was accompanied by the emergence of new strains in the population. These isolates were related to Turkish strains, but not to Russian ones detected earlier.

Effect of Skin Application of Dorogov's Antiseptic-Stimulant on Behavioral Reactions in Rats.

Local application of the Dorogov's antiseptic-stimulant onto the skin of 2-month-old male Sprague-Dawley rats in a low dose (0.5 g/kg/day) for 1 week increased motor and ultrasonic activity of experimental animals and the content of activated c-Fos+ neurons on the cingular, motor, insular, and pyriform cortex and in the striatum.

[The Complex Program of Rehabilitation of Patients With Ischemic Heart Disease After Coronary Artery Bypass Surgery in Ambulatory Cardiorehabilitational Department: Clinical Effects of Third Stage of Rehabilitation].

PURPOSE: to assess clinical efficacy of early post discharge rehabilitation of patients with ischemic heart disease (IHD) after coronary artery bypass grafting (CABG) in conditions of a polyclinical department of cardiological rehabilitation (stage III of cardiorehabilitation). MATERIAL AND METHODS: We included in this study 36 men with IHD in 3-8 weeks (mean 7.8+/-1.6 weeks) after CABG. Patients were randomized in 2groups: patients of the main group attended special "School for patients recovering after CABG" [School] (60-80 min sessions once a week for 5 weeks) and participated in a program of monitored (up to 60 min 3 times a week for 4 months) and unmonitored (home based) exercise training. Patients of the control group attended School and were given advice to do physical exercises at home. Follow up duration was 1 year. RESULTS: Main group. Compared with baseline values after 4 months exercise duration increased 32.6% (p<0.05), this effect persisted at 12 month; threshold exercise load increased 35.2% (p<0.05) after 4, 53.9% after 6, and 49.5% after 12 month. After 4 and 12 months of training some increases of left ventricular (LV) ejection fraction and stroke volume, and decrease of LV end systolic volume occurred. Physical training in this group was associated with improvement of parameters of quality of life. During 12 months of follow up there were no significant changes of concentrations of total and low density lipoprotein cholesterol (TC, LDLC). In the control group slight increase of exercise duration was observed only at 12 months (9.8%, p<0.05), and it was not accompanied by dynamics of exercise tolerance. Increases of concentrations of TC (10.2%, p<0.05) and LDLC (15.6%, p<0.05) were registered at 12 months. Serious cardiovascular complications in the main group (physical training + educational School) were three times less frequent than in the control group (attendance of School only) (11.1 vs. 39.2%, respectively.

[Antibiotic-free poultry production based on innovative nutritional programs with the involvement of probiotics].

EU banned antibiotic growth promoters (AGP) for farm animals and poultry since 2006 in relation to the problem of drug resistance. This requires alternative products for equally efficient prevention and treatment of certain alimentary poultry diseases. One of the most actual trends is the development of innovative nutritional strategies for poultry providing an effective symbiosis between the host and its intestinal microbiota. The study presented was aimed at the comparative evaluation of productivity, nutritive value of meat, and composition of intestinal microbial populations in broiler chicks fed different diets (corn - soybean meal, wheat - sunflower cake, barley - sunflower cake) supplemented with AGP or a probiotic (cellulolytic and lactic microorganisms). In three trials straight-run Cobb 500 broilers reared from 1 to 36 days of age were fed these diets supplemented with bacitracin from 1 to 29 days of age (control) or probiotic preparation from 1 to 36 days of age (70 birds per dietary treatment in each trial). There were no differences in live bodyweight and carcass yield between the treatments in all three trials. In the two trials with sunflower cake, protein content in breast meat was significantly higher by in birds fed probiotic in compare to birds fed AGP (by 10.0 and 6.8%, p<0.05), while fat content in thigh meat was lower by 12.0% (p<0.05) and 14.1% (p<0.01), respectively. Content of amino acids in meat did not differ. Vitamin content in the poultry meat of the experimental groups was significantly higher compared to control (p<0.001). The resulting concentrations of bacitracin in meat in control treatments (no more than 0.02 U/g) did not exceed local legislative limitations. The substitution of the probiotic for AGP beneficially affected the composition of bacterial populations in the duodenum and cecae determined using T-RFLP analysis. It was concluded that the supplementation of diets with probiotic allows to produce antibiotic-free broiler meat without detrimental effects on the productive performance.

Metagenomic bacterial community profiles of chicken embryo gastrointestinal tract by using T-RFLP analysis.

Thirty microbial phylotypes of microorganisms were found in the gastrointestinal tract of chicken belonging to the Hajseks White breed, and 38 phylotypes were found in the gastrointestinal tract of chicken belonging to the Hajseks Brown breed. The microbiome of the gastrointestinal tract of the chicken embryos of the Hajseks White breed was dominated by the typical representatives of avian intestinal microflora--bacteria of the family Enterobacteriaceae (47.3%), orders Actinomycetales (13.6%) and Bifidobacteriales (20.6%), and the family Lachnospiraceae (1.1%). The microbiome of the gastrointestinal tract of the chicken embryos of the Hajseks Brown breed was dominated by the pathogenic bacteria of the order Rickettsiales (94.8%). The metagenome of gastrointestinal tract of both breeds also contained a small number of genes of unidentified bacteria.