Репозиторий Университета

© 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.

© 2018, Dynasty Publishing House. All rights reserved. The objective. To evaluate the incidence and prevalence of hepatitis C in Russia and estimate the impact of hepatitis C virus on liver cirrhosis, hepatocellular carcinoma and liver-related mortality before the implementation of the national program for the elimination of viral hepatitis. Materials and methods. We analyzed statistical data on the incidence of hepatitis C in Russia in 2001–2017, the incidence, prevalence and mortality rates from liver cirrhosis and malignant liver tumors in 2011–2015. An analysis of the incidence and prevalence of HCV was carried out in various age-sex groups. The structure of genotypes of the hepatitis C virus was determined in patients at different stages of liver fibrosis and with different levels of viral load. Results. In 2017, 50 798 cases of HCV were registered in Russia (34.6 per 100 thousand of the population). As of January 1, 2017, the total number of patients with chronic hepatitis C under medical observation was 591 830 (405 per 100 thousand population). The incidence rate of fibrosis and cirrhosis in Russia in 2015 was 12.7 per 100000 population (18640 cases), the total number of registered patients – 75.9 per 100 thousand population (110951 people). The incidence rate of malignant liver tumors in 2015 was 5.5 per 100 thousand population (8083 cases), the total number of patients on dispensary observation was 5.0 per 100 thousand population (7360 people). In 2015, the estimated number of deaths from liver cirrhosis and hepatocellular carcinoma in the outcome of chronic hepatitis C was 14 792 and 1635, respectively. Conclusion. Hepatitis C is the main cause of liver cirrhosis (excluding alcoholic etiology), hepatocellular carcinoma and liver-related mortality in Russia. To reduce the prevalence of HCV and mortality from liver cirrhosis and primary liver cancer, it is necessary to provide all patients with HCV with antiviral drugs.

© 2018 by the authors; licensee Modestum Ltd., UK. Objective: The first interferon-free regimen became available in Russia in 2015. It brought hope to HCV Gt1 patients with cirrhosis for whom interferon-based schemes found to be non-effective or contraindicated. 3D therapy was the only available etiotropic option for them. New safety data published after the start of our study significantly limited usage of this regimen among patients with non-compensated cirrhosis. The aim of this study was to evaluate efficacy and safety of the 3D interferon-free regimen among HCV Gt1b patients with non-compensated cirrhosis. Method: 66 patients (26 males and 40 females) with HCV Gt1b and non-compensated cirrhosis were enrolled. All of them were treated with ombitasvir/paritaprevir/ritonavir, dasabuvir and ribavirin for 12 weeks. Ribavirin was discontinued after 4 weeks of therapy due to onset of new data on the efficacy of 3D regimen without ribavirin in Turquoise III study published in September 2015 before the change of package insert. Child-Pugh score was assessed before the start of antiviral therapy as follows: 21 patients (31,8%) – 9 points, 11 patients (16,7%) – 8 points, 34 patients (51,5%) – 7 points. The key method used to evaluate study results was modified intent-to-treat (mITT) analysis because number of analyzed patients within treatment period changed after withdrawal caused by safety reasons but followed by assessment of efficacy among patients who discontinued treatment. Per protocol (PP) method was also used in addition to mITT. Results: Aviremia after 14 days of treatment was reached among 35 out of 65 patients (53,8%), rapid virologic response – among 79,7% patients (51/64). Each patient who received full 12-week course of treatment (n=60) including those who discontinued due to safety reasons (n=3) between 14th and 30th days of therapy reached SVR12 and SVR24. Assessment of Child-Pugh score in 6 months after EOT demonstrated decrease by 3-4 points among 21 patients (33,9%) and by 1-2 points among 35 patients. 66,1% patients reached clinical improvement in MELD score. Treatment discontinuation was caused by progression of hepatic encephalopathy and/or jaundice (4 cases). Those adverse events regressed among majority of patients after discontinuation of therapy. 3 deaths were reported (bacterial endocarditis, progression of hepatic encephalopathy and bleeding from gastric ulcers) during treatment period and 1 death in follow-up period due to progression of hepatocellular carcinoma. Conclusion: 3D therapy was effective in 100% patients (mITT) with HCV GT1b and non-compensated cirrhosis both among those who completed full therapy course and those who discontinued the therapy due to safety reasons. Safety analysis demonstrated that the rate of severe adverse events was comparable with natural course of HCV-infection in patients on non-compensated cirrhotic stage without antiviral treatment.

© ABC-press Publishing House. All rights reserved. Today it is noted that the most cases of the hypospadias, cryptorchidism, testicular microlithiasis, as well as problems of semen quality and testicular germ cell tumours can be a clinical manifestation of testicular dysgenesis syndrome caused by abnormal development of reproductive organs. In the last decade, technological progress in the molecular genetics has made possible to carry out a directed search for genetic factors associated with reproductive disorders in men. In the review we attempted to analyze available literature data on the testicular dysgenesis syndrome and its constituent condition and also to consider the risk factors associated with its development. We give particular attention to the consideration of genetic factors that determine the manifestation of testicular microlithiasis, cryptorchidism and testicular germ cell tumors, both individual clinical conditions and in the syndrome of testicular dysgenesis. Knowledge of the genetic aspects of reproductive damage will allow us to characterize the complex interconnection of the human genome with the clinical phenotype, clarify the role of unfavorable factors of the environment and the lifestyle of the individual, and suggest new approaches to treatment.

© 2017 Izdatel'stvo Meditsina. All rights reserved. Chronic hepatitis B is caused by a persistent form of hepatitis B virus, covalentiy closed circular DNA (cccDNA). Stability of cccDNA is associated with intracellular localization of cccDNA and formation of minichromosome, regu-lated by epigenetic mechanisms. One of the key mechanisms in epigenetics is methylation of DNA on CpG islands. Expression levels of DNA-methyltransferases (DNMTs) in chronic hepatitis B patients were shown to be upregu-lated. Nevertheless, the role of DNMTs in the life cycle of HBV and their effects on the cell remain elusive. In this review, we discuss latest achievements on the role of DNMTs in chronic hepatitis B and HBV in vitro models.

© 2018 Publishing House of the Union of Pediatricians. All rights reserved. Background. Cystic fibrosis is a hereditary disease that occurs as a result of mutations in the regulator gene of chloride ion transmembrane transport (CFTR). Finding mutations in the CFTR gene is necessary for identification of the clinical features of cystic fibrosis. Objective. Our aim was to identify genotype-phenotype correlations between mutations of the first class of pathogenicity and clinical manifestations of cystic fibrosis based on studying the prevalence and structure of CFTR gene mutations. Methods. The study included children under 18 years with cystic fibrosis admitted to hospital between 2013 and 2017. Biallelic mutations in the CFTR gene were the non-inclusion criterion. The CFTR gene variants were analyzed by next-generation sequencing method. Results. In 125 patients with cystic fibrosis, 59 different variants of the CFTR gene were detected, 11 of them not previously described. The most common was the deletion c.1521-1523del found in 98 (39.2%) of the 250 analyzed CFTR gene alleles and the deletion c.1545-1546del found in 22/250 (8.8%) alleles. It has been shown that the mutation c.1545-1546del, p.Y515∗ was more often found in children of the Chechen nation-odds ratio (OR) 139 (95% confidence interval 15-1,257). It has been established that meconium ileus, pancreatic deficiency and cirrhosis are more common in patients with mutations of the first category of pathogenicity: OR 3.9 (95% CI 1.0-15.0), 4.4 (95% CI 1.8-11.1), and 351 (95% CI 17.5-7,046), respectively. The association of CFTR gene mutations with the development of bronchiectases and polypous pancinusitis has not been found. Conclusion. Correlations between the genotype and clinical manifestations of cystic fibrosis in Russian children with CFTR gene mutations of the first class of pathogenicity have been established.