[Effective Viral Delivery of Genetic Constructs to Neuronal Culture for Modeling and Gene Therapy of GNAO1 Encephalopathy].

GNAO1 encephalopathy is an orphan genetic disease associated with early infantile epilepsy, impaired motor control, and severe developmental delay. The disorder is caused by mutations in the GNAO1 gene, leading to dysfunction of the encoded protein Gao1. There is no cure for this disease, and symptomatic therapy is ineffective. Phenotypic heterogeneity highlights the need for a personalized approach for treating patients with a specific clinical variant of GNAO1 and requires the study of the disease mechanism in animal and cell models. Towards this aim, we developed an approach for modeling GNAO1 encephalopathy and testing gene therapy drugs in primary neurons derived from healthy mice. We optimized the delivery of transgenes to Gαo1-expressing neurons using recombinant adeno-associated viruses (rAAV). We assessed the tropism of five neurotropic AAV serotypes (1, 2, 6, 9, DJ) for Gαo1-positive neurons from the whole mouse brain. The DJ serotype showed the highest potential as a reporter delivery vehicle, infecting up to 66% of Gαo1-expressing cells without overt cytotoxicity. We demonstrated that AAV-DJ also provides efficient delivery and expression of genetic constructs encoding normal and mutant Gαo1, as well as short hairpin RNA (shRNA) to suppress endogenous Gnao1 in murine neurons. Our results will further simplify the study of the pathological mechanism for clinical variants of GNAO1, as well as optimize the testing of gene therapy approaches for GNAO1 encephalopathy in cell models.

High-Throughput Platform for B-Cell Screening Based on Fluorescent Phage-Display Technology.

A system for detection of malignantly transformed cells, including follicular lymphoma Bcells, was developed and experimentally validated. The system is based on the use of bacteriophages carrying exposed ligands for pathogenic B-cell receptors. The efficiency of binding to target cells is several times higher than in systems with chemically synthesized biotinylated peptides. The new method is proposed as a noninvasive diagnostic test for mapping B-cell lymphoma and for determining the specificity of B-cell receptors and high-throughput combinatorial selection of various repertories of B cells.

B Cell Regulation in Autoimmune Diseases.

Antibody-independent B cell effector functions play an important role in the development and suppression of the immune response. An extensive body of data on cytokine regulation of the immune response by B lymphocytes has been accumulated over the past fifteen years. In this review, we focused on the mechanisms of inflammatory response suppression by subpopulations of regulatory B cells in health and autoimmune pathologies.

Analysis of Immunogenicity of Intracellular CTAR Fragments of Epstein-Barr Virus Latent Phase Protein LMP1.

Intracellular fragments of latent phase protein LMP1 of Epstein-Barr virus, denoted as CTAR1/2/3, can trigger a variety of cell cascades and contribute to the transforming potential of the virus. Generation of recombinant proteins CTAR1/2/3 is expected to yield more ample data on functional and immunogenic characteristics of LMP1. We created genetic constructs for prokaryotic expression of LMP1 CTAR fragments and selected optimal conditions for their production and purification. Using a new library of LMP1 CTAR fragments, we carried out epitope mapping of a diagnostic anti-LMP1 antibody S12. Analysis of polyclonal serum antibodies from mice immunized with full-length LMP1 confirmed immunogenicity of CTAR elements comparable with that of full-length protein.

[Preparation for assisted reproductive technology in the course of infertility treatment in the female soldiers].

The level of obstetric morbidity in servicewomen remains high. Infertility occurs more often among the families of servicemen, than among the other families. The leading causative factor among the families suffering from infertility is tuboperitoneal or tubal (up to 85%). Assisted reproductive technologies are often the only possible mean to solve the problem of infertility in case of these forms of infertility.. The families of servicemen suffering from infertility were suggested the echelon principle of health care in military-medical institutions of the Ministry of Defence of the Russian Federation. Defined selection rules and directions, requiring the separation of the assisted reproductive technologies Clinic of Obstetrics and Gynaecology of the Kirov Military Medical Academy to carry out in vitro fertilization procedures.

[The role of the vaccine prophylaxis of cervical cancer among female military personnel].

The authors presented results of the study concerning human papillomavirus infecting of military students of higher military educational institutions of the Ministry of Defence of the Russian Federation. In the Center for Obstetrics and Gynaecology of the Kirov Military-Medical Academy was performed a dynamic examination of 478 female cadets aged 17-25. The high level of high-risk HPV viruses was revealed during the examination what proves the necessity of prophylaxis enhancing with the aim to prevent gynecological diseases and reproductive health promotion. The main ways of cervical cancer prophylaxis are health education, in-depth medical examination of women with the aim to reveal and treat gynecological diseases (this medical examination should be carried out twice a year), primary prevention of cervical cancer by vaccination.

[Obstetric-gynecologic care for female soldiers: status and prospects].

The article presents the analysis of primary gynecologic pathology in female soldiers for the last years. The basic disease groups are marked out. The information about the very medical help standard in different hospitals is given. This paper presents the perspective directions of development of the delivery of obstetrical and gynecological care for women due to level of military medical establishments of the Russian Federation Ministry of Defense.

[Evaluation of gynecologic morbidity in female cadets of military universities of St. Petersburg].

In-depth medical examination carried out a comprehensive survey of the dynamic female cadets of higher military educational institutions of the city of St. Petersburg in order to analyze the health of the troops of the Russian Federation Ministry of Defense personnel in the learning process, their level of gynecological diseases, as a possible consequence of influence of combat training. Following the study, shape, volume and frequency of activities to assess the health of women students, as well as a set of measures for the prevention of gynecological morbidity and dispensary of the contingent were developed.

[Therapeutic morbidity rate among female military personnel, with exposure to occupational hazards in the period of service in the Armed Forces its influence on the course of pregnancy and fetal development].

The study was made into therapeutic incidence among female military personnel who had contact with various kinds of occupational hazards in the period of military service, its impact on pregnancy and fetal development. Special attention was also paid to long-term consequences of obstetric and therapeutic pathological comorbidity on the development of the child. It has been established, that in the spectrum of therapeutic morbidity among female military personnel chronic gastritis, pyelonephritis and autoimmune thyroiditis prevail and often have a chronic stress as a background for their development. Children born to mothers, who in the period of pregnancy showed the combination of chronic pyelonephritis, autoimmune thyroiditis and late gestosis are a group of high risk for the development of the intracranial hypertension in children and/or infectious diseases.

[Formation and development of the military gynecology].

Data about formation and development of the system of delivery health and obstetric-gynecologic care in the Russian army since 19th century is represented in this article. Special attention is paid to delivery of care during the conduct of operations. A lot of archival documents are published for the first time. Department of Obstetrics and Gynecology of the Military Medical Academy made an outstanding contribution to development of military gynecology.

[The results of using an immunoenzyme method in an epizootiologic survey of natural Siberian foci of plague]. / Itogi primeneniia immunofermentnogo metoda pri épizootologicheskom obsledovanii sibirskikh prirodnykh ochagov chumy.

The approbation of the enzyme immunoassay in the study of diverse field material (corpses of animals, ectoparasites, soil, feces of birds of prey, etc.) for the presence of Yersinia pestis contamination has shown the advantages of this assay over the existing serological tests: the passive hemagglutination test and the antigen (or antibody) neutralization test. The use of the immunoperoxidase preparation obtained on the basis of staphylococcal protein A makes it possible to detect antibodies to Y. pestis in animals of various species known to be the main carriers, as well as less important ones, in the natural foci of plague in Siberia. The enzyme immunoassay is recommended for use in the study of not only active natural foci, but also territories, dangerous with respect to plague, as well as for controlling the state of such territories after the realization of relevant sanitation measures.