[Restoration of hand function in patients with hemiparesis using mirror therapy in combination with myofascial stretching and postisometric relaxation]. / Vosstanovlenie funktsii kisti u patsientov s gemiparezom s primeneniem metoda zerkal'noi terapii v sochetanii s miofastsial'nym rastyazheniem i postizometricheskoi relaksatsiei.

The increase in the number of cerebral strokes is accompanied by the accumulation of patients with hemiparesis. It is especially difficult to restore the function of the upper limb, in particular the hand, which significantly limits the social, domestic and labor adaptation of patients. This makes it relevant to search for new methods for restoring the functions of the hand. Today, mirror therapy is becoming increasingly popular, which, however, does not eliminate myogenic contractures in the joints of a paralyzed limb. PURPOSE OF THE STUDY: Rationale for the use of mirror therapy in combination with myofascial stretching and postisometric relaxation in patients with hemiparesis. MATERIAL AND METHODS: 277 patients with hemiparesis were examined, of which 68 patients were included in the main group; 209 - to the comparison group. All patients underwent a course of rehabilitation treatment for 10 days. Patients of the main group additionally received mirror therapy in combination with myofascial stretching and post-isometric relaxation: course - 10 individual sessions, session duration - 30 minutes. Upon admission and before discharge, patients were evaluated for neurological status, severity of spastic and pain syndromes; the strength of the muscles of the paralyzed upper limb according to the Lovett scale; tested self-service skills in accordance with the International Classification of Functioning, Disabilities and Health. RESULTS: In patients of both groups, the severity of spastic and pain syndromes decreased, muscle strength increased. In the main group, these changes were more pronounced; 35 patients of the main group mastered new types of grip, which statistically significantly improved their social adaptability. CONCLUSION: Mirror therapy in combination with soft manual therapy techniques is able to restore precise targeted movements in the joints of the hand and fingers, form different grip options, which expands the possibilities of self-care for patients.

Assessment of rat polyclonal antisera's suitability in hemagglutination inhibition assay for influenza surveillance and antigenic mapping.

This paper presents comparative hemagglutination inhibition (HI) assay data obtained using ferret or rat antisera to analyze influenza viruses. The results indicate that rat antisera can be successfully applied both for identification and for antigenic analysis of human influenza A and B viruses. Data gained with rat antisera were comparable to those obtained with ferret antisera. In-depth statistical analysis, based on Confusion Matrix analysis and Receiver Operating Characteristic (ROC) analysis, confirmed good coincidence between ferret antisera-based and rat antisera-based results. Two-dimensional antigenic mapping, based on HI assays using rat and ferret antisera, supported these findings. Both antisera types yielded identical antigenic attributions for the viruses analyzed, and both permitted visualization of contemporary human influenza virus evolutionary trends.

Chickens productivity selection affects immune system genes.

The quantitative trait loci associated with the immune properties of chickens are of interest from the point of view of obtaining animals resistant to infectious agents using marker-assisted selection. In the process of selecting markers for genomic selection in broiler-type chickens, a non-standard genotype frequency of the RACK1 gene allele (SNP Gga_rs15788101) in the B5 line of broiler-type chicken cross Smena 8 was identified and it was suggested that this gene was involved in selection. Therefore, it was decided to investigate the available polymorphisms in the three genes responsible for the IgY titer (DMA, RACK1 and CD1B). Molecular typing of single nucleotide polymorphisms of three loci revealed an approach to fixation of the unfavorable allele of the DMA gene (SNP Gga_rs15788237), an approach to fixation of the unfavorable allele of the RACK1 gene and the prevalence of the favorable CD1B gene allele (SNP Gga_rs16057130). Analysis of the haplotypes revealed a strong linkage disequilibrium of these genes. This suggests that these genes experience selection pressure. Analysis of the protein-coding sequences of the CD1B and DMA genes of various breeds of chickens revealed a negative selection of these genes. In order to understand whether the fixation of the studied alleles is the result of artificial selection of the B5 line of the cross Smena 8, an analysis of similar loci in layer chickens Hisex White was carried out. The frequencies of the alleles at the loci of the CD1B gene (Gga_rs16057130) and the RACK1 gene (Gga_rs15788101) in the Hisex White chicken genome differ from the frequencies of the alleles obtained for chickens of the B5 line of the cross Smena 8. It can be assumed that the fixation of the allele in the DMA gene (SNP Gga_rs15723) is associated with artificial or natural selection, consistent in broilers and layers. Changes in the loci Gga_rs16057130 and Gga_rs15788101 in the B5 line of the Smena 8 chickens are most likely associated with artificial selection of broiler productivity traits, which can subsequently lead to fixation of alleles at these loci. Artificial breeding of chickens leads to degradation of the variability of genes encoding elements of the immune system, which can cause a decrease in resistance to various diseases. The study of the negative impact of selection of economic traits on immunity should provide means to mitigate negative consequences and help find ways to obtain disease-resistant animals.

PROBLEMS OF ISOLATION, IDENTIFICATION AND ANTIGENIC CHARACTERIZATION OF RECENT HUMAN A(H3N2) INFLUENZA VIRUSES.

Human A (H3N2) influenza viruses are distinguished by a high rate of evolution and regularly cause epidemics around the world. Their ability to adapt and to escape from the host's immune response and to change their receptor specificity is very high. Over the past 20 years, these viruses have lost the ability to agglutinate red blood cells of chickens and turkeys and have practically ceased to propagate in chicken embryos - the main source of influenza vaccines. Isolation of viruses in the MDCK cell culture led to the selection of strains that lose one of the potential glycosylation sites. Many of the A (H3N2) strains have acquired mutations in neuraminidase, which distort the results of antigenic analysis in the hemagglutination inhibition test - the cornerstone method for the analysis of the match between viral isolates circulating in human population to strains selected for the influenza vaccines. In this regard, the characteristics of the antigenic properties of influenza A (H3N2) viruses by traditional methods become poorly informative, and the selection of vaccine strains of this subtype is erroneous, which is reflected in the discrepancy between vaccine and circulating A (H3N2) viruses in recent years (2013-2014, 2014 -2015, 2015-2016). The search, development and implementation of new algorithms for the isolation and antigen analysis of influenza A (H3N2) viruses are extremely urgent.

The Effectiveness of Cyclic Hydroxamic Acid CHA-5 against Drug-Resistant P388 Leukemia Strains.

We studied the effectiveness of cyclic hydroxamic acid CHA-5 against drug-resistant and multidrug-resistant murine P388 leukemia strains. More than 60% mice receiving transplantation of rubomycin-resistant leukemia P388 strain survived after CHA-5 monotherapy; combined therapy with CHA-5 and cisplatin was also highly effective. Vincristine-resistant tumor was highly sensitive to combined treatment with CHA-5 and cyclophosphamide. It should be emphasized that standard antitumor agents were used in very low doses in combination therapy and CHA-5 significantly potentiated their effect.

[The influence of STAT4 rs7574865 (G/T) polymorphism on the risk of clinical and immunological phenotypes of systemic sclerosis in a Russian patient population: Results of a pilot study]. / Vliianie polimorfizma rs7574865 (G/T) gena STAT4 na risk razvitiia klinicheskikh i immunologicheskikh fenotipov sistemnoi sklerodermii v russkoi populiatsii bol'nykh: rezul'taty pilotnogo issledovaniia.

AIM: To examine the association of signal transducer and activator transcription 4 (STAT4) rs7574865 G/T polymorphism with a predisposition to systemic sclerosis (SSC) and associated clinical and autoimmune phenotypes in a Russian population. SUBJECTS AND METHODS: A total of 102 patients with SSC and 103 healthy individuals as controls were examined. STAT4 rs7574865 polymorphism was investigated by real-time polymerase chain reaction. RESULTS: The carriers of the T allele showed a statistically significant association with SSC, a diffuse form (DF), the presence of interstitial lung disease (ILD), cardiac injury (CI), and seropositivity for anti-topoisomerase I antibodies (ATA). CONCLUSION: The findings results confirm the important role of STAT4 gene in the predisposition to SSC and its phenotypes, such as DF, ILD, CI, and ATA in the Russian population.

Synthesis and antiviral activity of novel glycyrrhizic acid conjugates with D-amino acid esters.

Glycyrrhizic acid (GA) conjugates with methyl and ethyl esters of D-amino acids (D-Trp, D-Phe, D-Tyr, D-Val, D-Leu) have been synthesized by the activated esters method using mixtures of N-hydroxybenzotriazole or N-hydroxysuccinimide with N,N'-dicyclohexylcarbodiimide. GA conjugate with D-Trp ethyl ester exhibited antiviral activity against influenza viruses A/H3N2, A/H1N1/pdm09, A/H5N1, B (SI > 10-29), and HRSV (SI > 25). GA conjugate with D-Trp methyl ester inhibited influenza virus A/H1N1/pdm09 (SI > 30).

Cowpox in a human, Russia, 2015.

We investigated the first laboratory-confirmed human case of cowpox virus infection in Russia since 1991. Phylogenetic studies of haemagglutinin, TNF-α receptor-like protein and thymidine kinase regions showed significant differences with known orthopoxviruses, including unique amino-acid substitutions and deletions. The described cowpox virus strain, taking into account differences, is genetically closely related to strains isolated years ago in the same geographical region (European part of Russia and Finland), which suggests circulation of viral strains with common origin in wild rodents without spread over long distances and appearance in other parts of the world.

[The identification of the AB0 blood type system by means of the single nucleotide polymorphisms analysis]. / Opredelenie gruppovoi prinadlezhnosti po sisteme AV0 metodom SNP-analiza.

The authors describe a domestically produced test-system for the determination of the AB0 blood type by means of the single nucleotide polymorphisms (SNP) analysis. The results of the trials indicate that the proposed test-system can be employed for the investigation of DNA specimens of individual origin obtained from any objects of expertise including micro-objects containing human nuclear DNA.

[Gene Polymorphism of the c-fms, ITGB3,CCR2, and DBH genes in the populations of old believers of the Tyumen oblast and Russian residents of Novosibirsk].

Old Believers of the Tyumen oblast have been studied compared with a control sample of Russian residents of the city of Novosibirsk. The former are a unique subpopulation, which has been relatively isolated from the rest of Russians in central and northern regions of Russia due to religious reasons since the middle of the 17th century. Polymorphisms in the genes for glycoprotein ITGB3, dopamine-ß-hydroxylase (DBH), and chemokine receptor CCR2 and two mutations in the c-fms gene have been analyzed. The populations are only similar in the c-fms indel. The frequencies of the rare alleles of CCR2, ITGB3, and 3'UTR of c-fms in the Old Believers are lower than in the sample of Novosibirsk Russians, and the rare allele of DBH is more frequent. A significant negative correlation is observed between DBH and CCR2 (r =-0.88; df = 4; P < 0.023). Apparently, these differences are related to the long-term isolation of Old Believers. This assumption is consistent with the fact that the levels of heterozygosity for most loci in Old Believers are lower than in Novosibirsk Russians.

[Clinical and laboratory presentation of the influenza A (H1N1pdm 2009) in children and adults during the period of 2009-2013 in St. Petersburg].

Comparative analysis of the clinical laboratory data from 419 children and 468 adults hospitalized during the pandemic of A (H1N1pdm 2009) and pre- and post-pandemic periods (2010-2013) showed that the clinical presentation of the pandemic influenza in patients of all ages is generally typical for influenza, and its character is determined by the degree of involvement of lungs in the process. Besides, the incidence of pneumonia in adults is statistically significantly higher than in children. During all compared periods hyperthermia (≥ 39 degrees C), hemorrhagic and dyspeptic syndrome were observed. Some differences in the main clinical manifestations of pneumonia in recovered patients and patients who died of the severe pandemic influenza were observed. The regularities of the cytokine reactions depending on the intensity of intoxication and occurrence of complications were determined in patients of all ages. Medical efficacy of inclusion of antiviral chemotherapeutic agents into complex influenza treatment was proved.

[Polymorphism of mitochondrial DNA in old believers from Siberia].

The polymorphism of mtDNA was examined in populations of Old Believers (n = 104) and Russians from Novosibirsk oblast (n = 270). Most of the haplogroups identified belonged to West Eurasian lineages. The frequencies of these haplogroups constituted 96.6% in Russians from Novosibirsk and 93.2% in Old Believers from Tyumen oblast. The populations examined were characterized by a high mtDNA diversity level (h = 0.98) compared to other population samples of Russians from Russia. Among the West Eurasian haplogroups, the most common (a frequency of more than 10%) were haplogroups H, U, J, and T, the proportion of which constituted 77.9% in Old Believers and 83.1% in Russians from Novosibirsk. The Mongoloid admixture in Russians (3.3%) and Old Believers (6.7%) was represented by haplogroups A, D, Z, and C, D, M*, respectively. Statistically significant differences (P < 0.05) were revealed between the Old Believers examined and Bosnians, Czechs, Slovenes, and Russians from the cities of Nizhny Novgorod and Tula. The data obtained confirm the earlier hypothesized influence of the Finno-Ugric component on the East Slavic populations.

[Direct human DNA damage by unfavorable environmental and climatic factors].

AIM: To study the impact of simulated climatic conditions of the 2010 summer in Moscow on the telomere repeats of chromosomes in human blood cells. MATERIALS AND METHODS: The climatic conditions of July-August 2010 in Moscow were simulated at the Medical Technical Complex, Institute of Biomedical Problems, Russian Academy of Sciences. The relative length of the telomeric repeats of blood cell chromosomes from 6 apparently healthy volunteers was measured by quantitative real-time polymerase chain reaction. RESULTS: These conditions were ascertained to lead to a statistically significant decline in the length of telomere repeats in the terminal portions of chromosomes by 15%. CONCLUSION: Environmental changes and abnormal temperature rises may result in oxidative stress accompanied by telomere shortening, which can be, in turn, a factor of premature aging.

[Cyclic hydroxamic acids as chemosensitizers in cytostatic therapy].

In experimental animals with tumors it was studied antitumor activity of spirocyclic hydroxamic acids which could be classified as targeted agents as their target was enzyme histonedeacetylase, which was involved in the neoplastic process. The results showed that the hydroxamic acids were chemosensitizers for anticancer agents increasing their efficacy and enabling the researchers to reduce significantly the therapeutic dose. Also it was showed that hydroxamic acid, containing nitrogen mustard, was effective in the action on tumors with phenotype and genotype of multidrug resistance.

[The use of hydroxamic acids and sodium nitrate to enhance the antitumor effect of cyclophosphamide].

It has been showed that the introduction of nitrocompounds (as nitic oxide donors) in to the compositions of cyclophosphamide and hydroxamic acids for curing animals having leukemia P-388 increased duration of life by 290%. Thereby 40% of animals have recovered. The therapeutic dose cyclophosphamide have been reduced by 6 times.

[Development of influenza surveillance in Russia in the system of the WHO national influenza center].

Analysis of development influenza activity season 2010-2011 is presented. Significant participation of influenza A(H1N1)pdm09 virus and influenza B of Victoria lineage virus in the epidemic morbidity structure with minor participation ofA(H3N2) virus was revealed. The influenza viruses isolated in Russia according to antigenic properties were similar to the strains included in the vaccine composition. Drift variants of influenza A(H1N1)pdm09 viruses isolated in Astrakhan and St.-Petersburg were recognized using WHO CC in London as representatives of three new genetic groups.

[Antileukemic activity and development of resistance to cisplatin (CPT) and platinum (IV)-nitroxyl complex VS118].

Treatment with low doses (1/10 of LD50) of cisplatin and platinum (IV)-nitroxyl complex VS118 [e-ammin-d-(4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl)-a,f-bi s(acetate)-b,c-dichlorplatinum (IV)] was followed by a synergistic therapeutic effect (a 100% cure of animals) as compared with monotherapy with either drug. There was no synergistic increase in toxicity. The rates of resistance development decreased in the following order: P388/cPt+VS118, P388/cPt, P388/VS118. Resistant strains P388/cPt+VS18 and P388/VS118 were highly sensitive to doxorubicin, etoposide and cyclophoshamide. Further research in cPt+VS 118 combinations should be continued.

[Analysis of pandemic influenza in Russia as a part of the global process based on data of an influenza monitoring reference center].

AIM: Characterization of features of influenza pandemic development in Russia in relation to global process. MATERIALS AND METHODS: Pandemic monitoring was performed by using results of integrative analysis of laboratory diagnostic and population morbidity data from 49 supporting bases of Federal center of influenza from various cities in Russian Federation. Isolation of influenza virus was carried out in MDCK cells and chicken embryos under BSL-3 conditions. Reference virus A/California/07/09 obtained from CDC (Atlanta, USA) and antisera against this strain contained in WHO kit were used for antigenic analysis; rat antisera, new monoclonal antibodies against pandemic influenza virus developed by Research institute of influenza were also used. RESULTS: Based on PCR monitoring during epidemic peak, rate of pandemic influenza identification reached 45-49% of examined patients. About 53% of lethal cases of respiratory infections were caused by pandemic influenza virus, while predominately young people died from pneumonia and acute respiratory distress syndrome. Russian isolates generally were antigenically and genetically similar to the parent pandemic strain--influenza virusA/California/07/09, but contained S203T substitution in hemagglutinin. A number of strains contained D222G mutation that is responsible for the expansion of substrate specificity, as well as strain specific substitutions in hemagglutinin and neuraminidase molecules. The investigated isolates were resistant to remantadin, but sensitive to oseltamivir. CONCLUSION: Due to the formation of population immunity after the end of the first pandemic wave new drift variants of the virus capable of overcoming this formed immunity should be expected that apparently will require the correction of vaccine composition for the 2011 - 2012 season.

[Polymorphisms of genes CYP2C9 and VKORC1 in patients with venous thromboembolic complications in Moscow population: effects on stability of anticoagulant therapy and frequency of hemorrhage].

AIM: To investigate frequency of carriage of genetic polymorphisms CYP2C9 and VKORC1 in patients with venous thromboembolic complications (VTEC) in Moscow population given warfarin treatment and effects of this carriage on stability of anticoagulation and frequency of hemorrhagic complications (HC) in warfarin treatment. MATERIAL AND METHODS: The study included 111 patients with the history of deep vein thrombosis and/ or pulmonary artery thromboembolism. All the patients received non-fractionated or low-molecular heparin for at least 5 days, then warfarin (target INR 2.0-3.0). Warfarin dose was selected empirically. Gene CYP2C9 and VKORC1 polymorphisms were studied. HC were endpoints. RESULTS: Genotype CYP2C9*1/*1 (a "wild" type) was detected in 94 (84.7%) patients. Of other genotypes - heterozygotes CYP2C9*1/*2 (4.5%) and CYP2C9*1/*3 (10.8%). Genotyping by VKORC1 detected genotype GG (a wild type) in 42.3%, genotype GA--in 48.6%, genotype AA--in 9.1% patients. A mean warfarin dose, supporting an adequaite INR, was asspciated with both genotype CYP2C9 and VKORC1. Warfarin doses were highest in carriers of wile genotypes CYP2C9 and VKORC1 (6,9 and 8,8 mg/day), the lowest--in patients with genotypes CYP2C9*1/*3 and VKORC1 (4,5 and 4,0 mg/day). The carriers of polymorphisms CYP2C9*1/*3 and VKORC1 showed less stable anticoagulation vs carriers of allele variants CYP2C9*1/*1, CYP2C9*1/*2 and genotypes GG, GA VKORC1. An HC rate depended, as a rule, on carriage of genotypes CYP2C9*1/*3 and AA VKORC1. The highest risk of HC was associated with genotype CYP2C9*1/*3. The results of multifactorial regression analysis also indicated that carriage of genotype CYP2C9*1/*3, a female gender and the range of INR in warfarin treatment > or = 2,66 are independent predictors of HC in VTEC patients on warfarin treatment. CONCLUSION: Carriage of gene CYP2C9 and VKORC1 polymorphisms affects suppoting dose of warfarin and rate of hemorrhage in patients with VTEC in Moscow population. Frequency of HC is the highest in carriers of genotypes CYP2C9*1/*3 and AA VKORC1, they need minimal supporting dose of warfarin. Carriage of genotype CYP2C9*1/*3 in line with a female gender and instability of INR is an independent predictor of HC in VTEC patients in Moscow population on warfarin treatment.

[Pandemic influenza 2009 in Russia. Characteristics of the isolation and biological properties of viruses].

Research Institute of Influenza, Ministry of Health and Social Development of Russia, Saint Petersburg The characteristics of the isolation of pandemic influenza A(H1N1)v viruses were studied on chick embryos (CE) and MDCK cell culture. The materials (nasal swabs and autopsies) were collected in different regions Russia in the period from 20 July to 30 December 2009. The paper gives the data of the antigenic analysis of isolates, their capacity to multiply in different species-specific and tissue cell cultures. The viruses isolated on CE were shown to have higher hemagglutination titers and to be more stable. Isolation from the autopsies was effective only on CE. All the test cell lines other than MDCK were insensitive to the isolated pandemic influenza strains. The antigenic analysis showed no significant antigenic drift of the viruses isolated during the first wave of the pandemic in the Russian Federation.