Репозиторий Университета

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. The relative age effect (RAE) has been well studied in adolescent and adult soccer players; however, less information has been available about children engaged in regular soccer training and the role of performance. Thus, the aim of the present study was to examine the prevalence of RAE in children and adolescent soccer players, as well as the role of age and performance. Russian soccer players (n = 10,446) of various ages, playing positions and performance levels were examined for their date of birth. It was observed that RAE was widespread in Russian soccer teams of all age groups. RAE was most pronounced in children teams of the top tier Russian soccer academies and junior Russia national teams, where the proportions of soccer players born in the first quarter were 43.9% and 39.8%, respectively, whereas those born in the fourth quarter of the year were 7.7% and 6.3%, respectively. In top tier soccer academies, RAE did not vary by age group. In the middle tier soccer academies, RAE was less pronounced. It was still prevalent in the junior teams of the top tier clubs of the Russian Premier League, where 14.3% of the soccer players were born in the fourth quarter of the year compared to 42.9% born in the first quarter of the year. RAE can be observed in the top tier Russian adult teams as well, although it is less pronounced there. In summary, RAE is highly prevalent in Russian children and junior soccer and is associated with the level of competitiveness. At the same time, the proportion of players born in the fourth quarter of the year is higher in adult teams than in junior and youth teams, which is most likely due to the wider selection of players, not limited by their age and place of residence. In junior teams, RAE results in a bias towards selection of players who are more physically mature, whereas children who may be more talented but are less developed due to their younger chronological age tend to be overlooked.

Chronic hepatitis B virus infection (CHB) caused by the hepatitis B virus (HBV) is one of the most common viral infections in the world. Reactivation of HBV infection is a life-threatening condition observed in patients with CHB receiving chemotherapy or other medications. Although HBV reactivation is commonly attributed to immune suppression, other factors have long been suspected to play a role, including intracellular signaling activated in response to DNA damage. We investigated the effects of DNA-damaging factors (doxorubicin and hydrogen peroxide) on HBV reactivation/replication and the consequent DNA-damage response. Dose-dependent activation of HBV replication was observed in response to doxorubicin and hydrogen peroxide which was associated with a marked elevation in the mRNA levels of ataxia-telangiectasia mutated (ATM) and ATM- and RAD3-related (ATR) kinases. Downregulation of ATM or ATR expression by shRNAs substantially reduced the levels of HBV RNAs and DNA. In contrast, transcriptional activation of ATM or ATR using CRISPRa significantly increased HBV replication. We conclude that ATM and ATR are essential for HBV replication. Furthermore, DNA damage leading to the activation of ATM and ATR transcription, results in the reactivation of HBV replication.

© 2019 Wolters Kluwer Health, Inc. All rights reserved. Purpose of reviewThe frequency of hospitalization for anaphylaxis has increased over the last 20 years across Europe, Australia, and North America, particularly, for food and medication triggers. Adolescents show the highest risk for morbidity and fatality from food-induced anaphylaxis, yet there is little high-quality evidence addressing the reasons for this disproportionate vulnerability.Recent findingsRecent data seem to suggest a possible increasing burden of food-induced anaphylaxis among adolescents. Trends in anaphylaxis mortality are stable in North America and the United Kingdom, but not in Australia where the incidence of fatal anaphylaxis has recently doubled. The age distribution of fatal anaphylaxis varies according to the nature of the culprit trigger, with data suggesting an age-related predisposition to fatal food anaphylaxis in adolescents and young adults. Adolescence represents a critical phase of transition when rapid and substantial physical, emotional, and social changes occur. Therefore, adolescents show challenges in self-management that are different from other age groups, contributing to a higher risk of poor anaphylaxis outcomes.SummaryThe purpose of this review is to summarize recent data on epidemiology and elicitors of anaphylaxis in adolescents and to address currently known barriers and potential facilitators to self-management of anaphylaxis in this vulnerable age group.

© 2019, Pediatria Ltd. All rights reserved. Acute kidney damage (AKD) is characterized by rapidly progressing organ dysfunction, which often results in development of chronic kidney disease. There are difficulties in diagnosing initial stages of kidney damage, which are usually reversible. Molecular diagnostics is a sensitive method that can detect early nephron changes that are not detectable by conventional methods (by assessing serum creatinine and urinary albumin in urine, diuresis) before renal filtration function decrease. The review examines markers of AKD development key stages: Ischemia (Kidney Injury Molecule-1 (KIM-1), Clusterin), hypoxia (Vascular Endothelial Growth Factor), Hypoxia Inducible Factor (HIF)), inflammation (Monocyte Chemoattractact Protein-1 (MCP-1), Interleukin 18 (IL18)), kidney tubule damage proximal (Beta-2-Microglobulin (B2M), Cystatin C, Neutrophil gelatinase associated lipocalin (NGAL)), distal (NGAL, Calbindin, Osteopontin). The study of these biomarkers in children's urine can be recommended for non-invasive screening, diagnosis and monitoring of AKD.

© 2019, Pediatria Ltd. All rights reserved. In the article the authors present relevant information on the criteria for assessing the activity of juvenile dermatomyositis (JDM) and modern approaches to its treatment. In clinical practice, various scales are currently used to assess the overall JDM activity and severity of damage to various organs, primarily muscles and skin. The article provides modern recommendations for JDM treatment: The use of glucocorticosteroids, disease-modifying antirheumatic drugs (methotrexate, calcineurin inhibitors, cyclophosphamide, mycophenolate mofetil, azathioprine, hydroxychloroquine, intravenous immunoglobulin), genetically engineered drugs (rituximab, infliximab, adalimumab, golimumab, certolizumab, etanercept), as well as promising new drugs and methods of maintenance therapy. The modern JDM treatment algorithm is described.

© 2019, Pediatria Ltd. All rights reserved. Urinary tract infection (UTI) is one of the most common diseases of the urinary system faced by pediatricians. Objective of the research: To study and analyze outpatient records of patients in their first year of life, sent to a nephrologist for a consultation due to microbial inflammatory changes in urine general analysis. Materials and methods: Outpatient records of 160 children aged from 1 month to 1 year, who were sent in 2017 for a consultation with a nephrologist in consultative diagnostic clinic of G.N. Speransky City Children's Hospital № 9 with directing diagnosis UTI. Results: Authors performed an assessment of guiding diagnoses, age and gender composition of patients, an assessment of life anamnesis and disease clinical symptoms dynamics before referring patients for consultation with a nephrologist. The article discusses mistakes and issues of diagnosing UTI in young children. Conclusion: Authors substantiates pediatrician’s tactics for timely UTI diagnosis in young children and correct tactics of managing these patients.

© 2019, Pediatria Ltd. All rights reserved. Objective of the research: To study the effect of different temperature conditions and shelf life of expressed mother and donor breast milk (BM) on its microbiological safety. Materials and methods: N open prospective study was performed, which included 120 lactating women. BM samples were microbiologically evaluated under various storage conditions. Seeding of biological material was performed by a semi-quantitative method. Species identification of the obtained microorganisms was performed using a MALDI-TOF-MS Biotyper MicroFlex mass spectrometer and a VITEK bacteriological analyzer. Results: In 66% of women, samples of expressed BM showed an increase (103–105 CFU/ml) of conditionally pathogenic bacteria (CPB) with a predominance of S. epidermidis (55%). None of the samples of the expressed BM stored for 3 hours at room temperature (t° + 23°C) during the day in the refrigerator (t° + 4–6°C) and for 1 month in the freezer (t ° –18°C), the growth of CPB was not recorded. However, a decrease in the growth of bacteria total number was revealed, including S. epidermidis, when storing expressed milk for 24 hours at t° + 4–6°С and for 1 month at t° –18°С. It was found that BM pasteurization leads to a significant decrease in the number of CPB. The study revealed no increase in the total number of bacteria during storage of donor milk at t° –18°C for both 1 and 3 months.

The article analyzes the indicators of population reproduction on the example of the Kostroma region, presents the dynamics of the main medical and demographic indicators of the region: age structure of the population, mortality, fertility, migration, marriage and divorce rates, as well as the starting positions for overcoming reproductive and demographic disadvantages.

© 2019 The Authors Eighty years after the last published record of human leishmaniasis from Dagestan, Russian Federation, we report two recent cases which were most probably acquired locally: one case of visceral leishmaniasis in a 2-year old child, and one cutaneous leishmaniasis case in a 39-year-old man co-infected with HIV, both resident in Dagestan.

© 2019 European Association of Urology In this review, we investigated the treatment options for primary urethral cancer. While organ-confined disease can be managed with local resection, growth beyond the organ calls for a combination of different treatment modalities, such as surgery, chemotherapy, and radiotherapy, to improve the survival of patients.

© 2019, The Author(s). Purpose: To assess the accuracy of [68Ga]-PSMA-11 PET/CT or [68Ga]-PSMA-11 PET/MRI (PSMA-11 PET/CT(MRI)) for lymph node (LN) staging using salvage LN dissection (SLND) in patients with biochemical recurrence (BCR) after radical prostatectomy (RP). Patients and methods: In a prospective study, 65 consecutive patients who developed BCR after RP underwent SLND after PSMA-11 PET/CT(MRI) between 2014 and 2018. Extended SLND up to the inferior mesenteric artery was performed in all patients. Regional and template-based correlations between the presence of LN metastases on histopathology and whole-body PSMA-11 PET/CT(MRI) results were evaluated. The diagnostic accuracy of PSMA-11 PET/CT(MRI) was also evaluated in relation to PSA level at the time of SLND. Results: The median age of the patients at the time of SLND was 65 years (IQR 63–69 years) and the median PSA level was 1.4 ng/ml (IQR 0.8–2.9 ng/ml). Before SLND, 50 patients (77%) had additional therapy after RP (26.2% androgen-deprivation therapy and 50.8% radiotherapy). The median number of LNs removed on SLND was 40 (IQR 33–48) and the median number of positive nodes was 4 (IQR 2–6). LN metastases were seen in 13.8% of resected LNs (317 of 2,292). LNs positive on PSMA-11 PET/CT(MRI) had a median diameter of 7.2 mm (IQR 5.3–9 mm). Metastatic LNs in regions negative on PSMA-11 PET had a median diameter of 3.4 mm (IQR 2.1–5.4 mm). In a regional analysis, the sensitivity of PSMA-11 PET/CT(MRI) ranged from 72% to 100%, and the specificity from 96% to 100%. Region-specific positive and negative predictive values ranged from 95% to 100% and 93% to 100%, respectively. Conclusion: PSMA-11 PET/CT(MRI) has a very good performance for the identification of LN metastases in patients with BCR after RP. The high diagnostic accuracy in the regional and subregional analyses demonstrates the potential of this approach to enable a region-directed instead of a complete bilateral therapeutic intervention. The performance of PSMA-11 PET/CT(MRI) is dependent on the PSA level and the size of the metastatic deposit.

© 2019 John Wiley  &  Sons Ltd Aims and objectives: To examine how nurses' knowledge of behaviours indicating pain in mechanically ventilated patients and self-perceived collaboration between nurses and physicians affects the adequacy of departmental pain management. Background: Pain management is a vital factor of medical treatment in a hospital setting. Inadequate pain management requires attention both from a patient-focused perspective and from a departmental one. It would be particularly troubling in the case of inadequate pain management of mechanically ventilated patients. Design: The study utilised a cross-sectional design. The instruments developed were validated by a focus group of 25 pain management nurses, who reviewed the questionnaire for face validity, feasibility and comprehensibility, and who did not participate in the study. The questionnaire was revised, readjusted and formulated based on their responses and comments. Methods: A self-administered questionnaire administered in Israel with a convenience sample of 187 registered nurses (RN) from internal medicine and surgical departments and ICUs. Data were collected during February–May 2015. The “STROBE” EQUATOR checklist was used. Results: Nurses working in the ICU scored significantly higher on knowledge of behaviours indicating pain in mechanically ventilated patients and on self-perceived collaboration between nurses and physicians. Self-perceived collaboration between physicians and nurses was positively correlated with perceived departmental pain treatment adequacy. Self-perceived collaboration between nurses and physicians, knowledge of behaviours indicating pain in mechanically ventilated patients and seniority (with a borderline significance) explained 27% of the variance of perceived departmental pain management. Conclusion: Nurses' knowledge of behaviours indicating pain in mechanically ventilated patients, as well as self-perceived collaboration between nurses and physicians, promotes reported adequate pain management. Relevance to clinical practice: Pain management would benefit from being conducted as a well-performed interprofessional self-perceived collaborative practice. Knowledgeable nurses tend to critically assess the level of departmental pain management.

© 2018, Pleiades Publishing, Ltd. The gene for Kunitz peptidase inhibitor-like protein (KPILP) contains nested alternative open reading frame (aORF) that controls expression of the maternal mRNA. The content of NbKPILP mRNA in intact leaves of Nicotiana benthamiana plant is low but increases significantly upon extended dark exposure or when foreign nucleic acid is overexpressed in the cells. The NbKPILP gene promoter along with the expressed nested aORF are likely to play an important role in maintaining the levels of NbKPILP mRNA. To elucidate the role of NbKPILP promoter, we isolated a fragment of N. benthamiana chromosomal DNA upstream of the NbKPILP transcription start, sequenced it, and created constructs in which reporter E. coli uidA gene coding for β-D-glucuronidase (GUS) was placed under control of the NbKPILP promoter. By assessing the efficacy of uidA mRNA synthesis directed by the NbKPILP promoter and 35S promoter of the cauliflower mosaic virus in a transient expression system, we showed that the levels of GUS accumulation were comparable for both promoters. Prolonged incubation of the agroinjected plants in the darkness stimulated accumulation of the uidA mRNA directed by the NbKPILP promoter. Our experiments indicate that along with regulation at the transcriptional level, expression of NbKPILP mRNA can be affected by expression of the nested aORF controlled by the polypurine block (PPB) located upstream of its start codon, since introduction of mutations in the PPB resulted in significant accumulation of the NbKPILP mRNA. Nucleotide replacement in the aORF start codon led to the drastic increase in the amounts of NbKPILP mRNA and its protein product.

© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Abstract: Osteoarthritis (OA), the most common form of arthritis, is characterized by inflammation of joints and cartilage degradation leading to disability, discomfort, severe pain, inflammation, and stiffness of the joint. It has been shown that adenosine, a purine nucleoside composed of adenine attached to ribofuranose, is enzymatically produced by the human synovium. However, the functional significance of adenosine signaling in homeostasis and pathology of synovial joints remains unclear. Adenosine acts through four cell surface receptors, i.e., A1, A2A, A2B, and A3, and here, we have systematically analyzed mice with a deficiency for A3 receptor as well as pharmacological modulations of this receptor with specific analogs. The data show that adenosine receptor signaling plays an essential role in downregulating catabolic mechanisms resulting in prevention of cartilage degeneration. Ablation of A3 resulted in development of OA in aged mice. Mechanistically, A3 signaling inhibited cellular catabolic processes in chondrocytes including downregulation of Ca2+/calmodulin-dependent protein kinase (CaMKII), an enzyme that promotes matrix degradation and inflammation, as well as Runt-related transcription factor 2 (RUNX2). Additionally, selective A3 agonists protected chondrocytes from cell apoptosis caused by pro-inflammatory cytokines or hypo-osmotic stress. These novel data illuminate the protective role of A3, which is mediated via inhibition of intracellular CaMKII kinase and RUNX2 transcription factor, the two major pro-catabolic regulators in articular cartilage. Key messages: Adenosine receptor A3 (A3) knockout results in progressive loss of articular cartilage in vivo.Ablation of A3 results in activation of matrix degradation and cartilage hypertrophy.A3 agonists downregulate RUNX2 and CaMKII expression in osteoarthritic human articular chondrocytes.A3 prevents articular cartilage matrix degradation induced by inflammation and osmotic fluctuations.A3 agonist inhibits proteolytic activity of cartilage-degrading enzymes.

© 2018; Pediatria Ltd. All rights reserved. Among the leading forms of socially significant pathology is chronic kidney disease (CKD), which has a variety of causes and often originates in early childhood. Risk factors and causes of CKD in children are associated with congenital anomalies in urinary tract (UT) development, accompanied by a persistent chronic infection, urodynamic disorder, remodeling of renal blood flow. Kidneys homeostatic functions disorder causes morphofunctional changes in various organs and tissues, incl. dentoalveolar system (DAS). The negative effect of CKD on the formation of maxillofacial region in children is studied. The data on disorders of jaw bones structures, temporomandibular joint (TMJ) and its function, oral cavity mucous membrane pathology, periodontal diseases, quantitative and qualitative changes in saliva, the defects of teeth hard tissues, pulp calcification caused by this pathology are systematized. The lack of a holistic view of DAS abnormalities development mechanisms in children with kidney damage makes it difficult for the dentist to conduct a timely diagnosis and combine work with doctors of other specialties, such as a pediatrician and a pediatric nephrologist. An integrated approach to managing children with CKD would allow to personify patient management tactics and improve treatment and rehabilitation results.

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Articular hyaline cartilage is extensively hydrated, but it is neither innervated nor vascularized, and its low cell density allows only extremely limited self-renewal. Most clinical and research efforts currently focus on the restoration of cartilage damaged in connection with osteoarthritis or trauma. Here, we discuss current clinical approaches for repairing cartilage, as well as research approaches which are currently developing, and those under translation into clinical practice. We also describe potential future directions in this area, including tissue engineering based on scaffolding and/or stem cells as well as a combination of gene and cell therapy. Particular focus is placed on cell-based approaches and the potential of recently characterized chondro-progenitors; progress with induced pluripotent stem cells is also discussed. In this context, we also consider the ability of different types of stem cell to restore hyaline cartilage and the importance of mimicking the environment in vivo during cell expansion and differentiation into mature chondrocytes.

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Neonatal sepsis is one of the major causes of mortality and morbidity in newborns, greatly associated with severe acute kidney injury (AKI) and failure. Handling of newborns with kidney damage can be significantly different compared to adults, and it is necessary to consider the individuality of an organism’s response to systemic inflammation. In this study, we used lipopolysaccharide (LPS)-mediated acute kidney injury model to study mechanisms of kidney cells damage in neonatal and adult rats. We found LPS-associated oxidative stress was more severe in adults compared to neonates, as judged by levels of carbonylated proteins and products of lipids peroxidation. In both models, LPS-mediated septic simulation caused apoptosis of kidney cells, albeit to a different degree. Elevated levels of proliferating cell nuclear antigen (PCNA) in the kidney dropped after LPS administration in neonates but increased in adults. Renal fibrosis, as estimated by smooth muscle actin levels, was significantly higher in adult kidneys, whereas these changes were less profound in LPS-treated neonatal kidneys. We concluded that in LPS-mediated AKI model, renal cells of neonatal rats were more tolerant to oxidative stress and suffered less from long-term pathological consequences, such as fibrosis. In addition, we assume that by some features LPS administration simulates the conditions of accelerated aging.

© 2018, Wuhan Institute of Virology, CAS and Springer Nature Singapore Pte Ltd. Enteric viruses are the most common cause of acute gastroenteritis (AGE) in young children and a significant public health problem globally. Hospital admissions of children under 5 years of age with diarrhea are primarily associated with group A rotavirus (RVA) infection. In this retrospective study, the population structure of viruses linked to AGE etiology in young children hospitalized with AGE in Moscow was evaluated, and molecular characterization of RVA strains was performed. Fecal specimens were collected from children under 5 years old hospitalized with AGE between 2009 and 2014 in Moscow, Russia. Multiplex real-time reverse transcription PCR was used to detect enteric viruses and for G/[P]-genotyping of isolated RVAs. Sequencing of RVA VP7 and VP4 cDNA fragments was used to validate the data obtained by PCR-genotyping. The main causes for hospitalization of children with AGE were RVA (40.1%), followed by noroviruses (11.4%), while adenoviruses, astroviruses, sapoviruses, enteroviruses, and orthoreoviruses were detected in 4.7%, 1.9%, 1.4%, 1.2%, and 0.2% of samples tested, respectively. Nosocomial infections, predominantly associated with RVAs and noroviruses, were detected in 24.8% of cases and occurred significantly more frequently in younger infants. The predominant RVA genotype was G4P[8], detected in 38.7% of RVA-positive cases, whereas genotypes G1P[8], G9P[8], G3P[8], and G2P[4] were found in 11.8%, 6.6%, 4.2%, and 3.3% of cases, respectively. Together, the presence of circulating RVA strains with rare VP7 and VP4 gene variants (G6 and P[9]) highlights the need to conduct continuous epidemiological monitoring of RVA infection.

© Kolosova et al. P62/SQSTM1, a multi-domain protein that regulates inflammation, apoptosis, and autophagy, has been linked to age-related pathologies. For example, previously we demonstrated that administration of p62/SQSTM1- encoding plasmid reduced chronic inflammation and alleviated osteoporosis and metabolic syndrome in animal models. Herein, we built upon these findings to investigate effect of the p62-encoding plasmid on an agerelated macular degeneration (AMD), a progressive neurodegenerative ocular disease, using spontaneous retinopathy in senescence-accelerated OXYS rats, as a model. Overall, the p62DNA decreased the incidence and severity of retinopathy. In retinal pigment epithelium (RPE), p62DNA administration slowed down development of the destructive alterations of RPE cells, including loss of regular hexagonal shape, hypertrophy, and multinucleation. In neuroretina, p62DNA prevented gliosis, retinal thinning, and significantly inhibited microglia/macrophages migration to the outer retina, prohibiting their subretinal accumulation. Taken together, our results suggest that the p62DNA has a strong retinoprotective effect in AMD.

© 2018 The American Society of Gene and Cell Therapy Treatment of myocardial infarction (MI) with bone marrow cells (BMCs) improves post-MI cardiac function in rodents. However, clinical trials of BMC therapy have been less effective. While most rodent experiments use young healthy donors, patients undergoing autologous cell therapy are older and post-MI. We previously demonstrated that BMCs from aged and post-MI donor mice are therapeutically impaired, and that donor MI induces inflammatory changes in BMC composition including reduced levels of B lymphocytes. Here, we hypothesized that B cell alterations in bone marrow account for the reduced therapeutic potential of post-MI and aged donor BMCs. Injection of BMCs from increasingly aged donor mice resulted in progressively poorer cardiac function and larger infarct size. Flow cytometry revealed fewer B cells in aged donor bone marrow. Therapeutic efficacy of young healthy donor BMCs was reduced by depletion of B cells. Implantation of intact or lysed B cells improved cardiac function, whereas intact or lysed T cells provided only minor benefit. We conclude that B cells play an important paracrine role in effective BMC therapy for MI. Reduction of bone marrow B cells because of age or MI may partially explain why clinical autologous cell therapy has not matched the success of rodent experiments. Implantation of bone marrow cells into mouse hearts after myocardial infarction is therapeutic, but if the cells are from donors that are older or post-MI (mimicking autologous cell therapy), they are less effective. This report presents evidence that a decrease in B lymphocytes is responsible for the reduced therapeutic response.