Search

Neuropathic pain (NP) affects approximately 7% of the general population and is often accompanied by depressive symptoms with up to 85% of NP patients are suffering from comorbid depression (CD). The noninvasive neuromodulation technique of transcranial magnetic stimulation (TMS) is an established proven clinically effective nonpharmacological treatment for depression, and considered a highly promising option also for reducing the burden of NP by relieving pain perception and increasing patients' quality of life. In this article, we systematically review the various clinical protocols used in TMS treatments in patients suffering from NP and comorbid depression.Using Scopus, Elsevier, and PubMed databases, our keyword search identified 639 articles, of which 22 were selected for detailed analysis based on the inclusion criteria and in consideration of the heterogeneous study design of the majority of small trials. We evaluated the clinical efficacy in NP and comorbid depression, in relation to various TMS protocol parameters including coil type, target brain area, locus of increased evoked motor potential, amplitude of stimulation, duration of session, number of sessions per day/month, as well as inter-session-intervals, number and frequency of trains, and number and frequency of pulses.The most effective TMS protocols for treating comorbid NP and depression, as marked by decreased pain and depression scores proved to entail figure-of-8 coils targeting the primary motor area (M1), and applying at least ten daily rTMS sessions using high frequency stimulation (10-20 Hz) with a sub threshold intensity of 80-90% RMT and a total number of pulses of at least 1500 per session. Performing an additional maintenance phase after the acute treatment phase may strengthen and prolong the therapeutic effects of rTMS.Our database analysis suggests that a specific combination of TMS parameters is most effective for treating NP and comorbid depression. Although results are promising, the heterogeneity within the literature is such that many underpowered studies contribute rather little to the outcome, as evident by our inclusion / exclusion analysis. Moreover, we see a need for consensus on clinical protocols and inclusion of much larger clinical samples. Furthermore, we conclude that future research should entail advanced TMS procedures with multiple brain region stimulation (sequential or concurrent), and address issues of TMS maintenance and improved coil engineering for targeting deeper structures.

Modular nanotransporters (MNTs) are multifunctional chimeric polypeptides for the multistep transport of locally acting cytotoxic agents into the nuclei of cancer target cells. MNTs consist of several polypeptide domains (functional modules) for the recognition of a cell-surface internalizable receptor, pH-dependent endosomal escape and subsequent transport into the nucleus through the nuclear pores. MNTs are a promising means for cancer treatment. As has been shown previously, all of the modules of MNTs retain their functionalities. Despite their importance, there is no structural information available about these chimeric polypeptides, which hampers the creation of new MNT variants. Here, a low-resolution 3D structure of an MNT is presented which was obtained by atomic force microscopy, transmission electron microscopy and small-angle X-ray scattering coupled to size-exclusion chromatography. The data suggest that the MNT can adopt two main conformations, but in both conformations the protein N- and C-termini are distanced and do not influence each other. The change in the MNT conformation during acidification of the medium was also studied. It was shown that the fraction of the elongated conformation increases upon acidification. The results of this work will be useful for the development of MNTs that are suitable for clinical trials and possible therapeutic applications.

We developed a new test system to detect the omicron variant of SARS-CoV-2 using allele-specific reverse transcription PCR and estimated the frequency of its detection in patients living in the Novosibirsk Region. Clinical samples were divided into 3 groups: samples collected from December 1 to December 30, 2021 (group 1; n=66), from December 30, 2021 to January 10, 2022 (group 2; n=20), and from January 11 to January 22, 2022 (group 3; n=101). Based on the identification of 5 mutations specific to SARS-CoV-2 (B.1.1.529), two systems of oligonucleotide primers and probes were developed for detecting this coronavirus genotype in clinical samples. Limit of detection (LOD

The paper addresses the problem of spinal muscular atrophy in Russia, in particular in Samara region. There are 58 alive patients, including 19 children, registered to June 2019 in the Samara Regional Clinical Hospital n.a. V.D. Seredavin. The authors discuss the classification and etiopathogenesis of spinal muscular atrophy, prospects for its pathogenetic therapy and prevention in Russia.В статье подробно освещается проблема спинальных амиотрофий в России, в частности в Самарской области. В Самарской областной клинической больнице им. В.Д. Середавина по состоянию на июнь 2019 г. зарегистрированы 58 живых пациентов со спинальными мышечными атрофиями, из них 19 детей. Обсуждаются вопросы классификации и этиопатогенеза, перспективы патогенетической терапии и профилактики спинальных мышечных атрофий.

The article discusses the problematic issues of the organization of medical nutrition of sick people both in medical organizations and outside of their stay, reflecting the current understanding of the organization of therapeutic nutrition as the main structural element of the patient-oriented health care system. The authors declare the need for an evidence-based assessment of the effectiveness of personalized diet therapy and the use of specialized enrichment of patients 'diet. The article presents the rationale for the correctness of using for this purpose a proven methodology for assessing the effectiveness of alternative technologies in healthcare. The integral efficiency indicator used in this methodology includes the calculation of the social satisfaction coefficient, which is proposed to be used by one of the levers of control from public organizations of patients, and above all their flagship All-Russian Union of Patients.

The article is the third in the series of four that present the results of a study on environmental contaminants in coastal Chukotka, which was conducted in the context of a multi-disciplinary investigation of indigenous foodways in the region. The article presents the results of the analysis of metals found in the samples of locally harvested terrestrial, freshwater, and marine biota collected in 2016 in coastal Chukotka. For some species of local fauna and flora, the metals content was demonstrated for the first time. Lead and Hg were low in all foods, while As concentrations were up to four mg/kg ww in fish and marine mammals blubber. Wild plants showed accumulations of Mn (up to 190 mg/kg ww), Al (up to 75 mg/kg ww), Ni, Ba, and Sr. Seaweed contained high levels of As (14 mg/kg) and Sr (310 mg/kg), ascidians (sea squirts) contained Al (up to 560 mg/kg), Cr, and Sr, and blue mussels contained Cd (2.9 mg/kg) and Al (140 mg/kg). Exceedances over the Russian allowable levels were revealed for As, Cd, and Al in different food items. Absence of the established limits for Al and Sr in seafood, and Mn in wild plants and berries, impedes the determination of excess levels. Temporal trends and geographic comparisons of metals in foods have been carried out. The estimated daily intakes (EDIs) of metals by local food consumption were calculated based on the food intake frequencies. Follow-up (15 years after the first study) analyses of Hg, Pb, and Cd concentrations in local foods has not revealed any increase, while a slight decrease tendency was noted for some of the metals in several foods.

Polyepitope DNA vaccine inducing T-cell-mediated immune response against cancer-specific antigens is a promising tool for selective elimination of tumor cells. Breast cancer-specific polyepitope DNA vaccine was designed using TEpredict and PolyCTLDesigner software on the basis of immunogenic peptides of HER2 and Mammaglobin-1 (Mam) tumor antigens. LPS-free preparations of plasmid DNA encoding polyepitope T-cell antigen and full-length copies of HER2 and Mam antigens were obtained. TaqMan-PCR systems for evaluation of the expression of immunogens in cells were created. The protocol of vaccine DNA delivery into dendritic cells was optimized. Expression of the target immunogens in dendritic cells derived from human peripheral blood mononuclear fraction after transfection with plasmid DNA preparations is demonstrated.

Microbiome spectra serve as critical clues to elucidate the evolutionary biology pathways, potential pathologies, and even behavioral patterns of the host organisms. Furthermore, exotic sources of microbiota represent an unexplored niche to discover microbial secondary metabolites. However, establishing the bacterial functionality is complicated by an intricate web of interactions inside the microbiome. Here we apply an ultrahigh-throughput (uHT) microfluidic droplet platform for activity profiling of the entire oral microbial community of the Siberian bear to isolate Bacillus strains demonstrating antimicrobial activity against Staphylococcus aureus . Genome mining allowed us to identify antibiotic amicoumacin A (Ami) as responsible for inhibiting the growth of S. aureus . Proteomics and metabolomics revealed a unique mechanism of Bacillus self-resistance to Ami, based on a subtle equilibrium of its deactivation and activation by kinase AmiN and phosphatase AmiO, respectively. We developed uHT quantitative single-cell analysis to estimate antibiotic efficacy toward different microbiomes and used it to determine the activity spectra of Ami toward human and Siberian bear microbiota. Thus, uHT microfluidic droplet platform activity profiling is a powerful tool for discovering antibiotics and quantifying external influences on a microbiome.

Modern multiple sclerosis therapy with disease-modifying drugs is characterized by the risks of dangerous infectious complications. In the last 5 years, there have been several reports of severe, sometimes lethal, listeriosis infection in patients treated with alemtuzumab. This article presents a clinical case of lethal listeriosis meningoencephalitis, which developed within 7 days after the completion of the first cycle of alemtuzumab therapy. In January 2018, a meeting of the expert Council was held, at which the clinical recommendations published in 2017 were revised and updated.Современная терапия препаратами, изменяющими течение рассеянного склероза, характеризуется рисками опасных инфекционных осложнений. В последние 5 лет появились сообщения о развитии тяжелой, иногда летальной, листериозной инфекции у пациентов, получавших терапию алемтузумабом. Представлен клинический случай летального листериозного менингоэнцефалита, возникшего через 7 сут после завершения первого цикла терапии алемтузумабом. В январе 2018 г. прошло заседание Экспертного совета, на котором были пересмотрены и обновлены клинические рекомендации, опубликованные в 2017 г.

The main results of a medical-sociological study aimed at the evaluation of the level of satisfaction with treatment in patients with primary progressive multiple sclerosis (PPMS) are presented. The survey was conducted in 19 regions of the Russian Federation and involved 437 patients with confirmed diagnosis of PPMS and 80 neurologists specialized in multiple sclerosis. The research was carried out by the All-Russian Public Organization of Disabled People with Multiple Sclerosis with the participation of the Russian Committee for Treatment and Research in Multiple Sclerosis. This is the first medical-sociological study in the Russian Federation involving patients with PPMS and neurologists. The study revealed typical medical and social problems patients with PPMS faced. A significant decrease in quality-of-life of PPMS patients was shown.Представлены основные результаты медико-социологического исследования, проведенного с целью изучения уровня удовлетворенности терапией пациентов с первично-прогрессирующим рассеянным склерозом (ППРС). В опросе, проведенном в 19 регионах Российской Федерации, приняли участие 437 пациентов с установленным диагнозом ППРС и 80 неврологов, специализирующихся в области данного заболевания. Исследовательский проект был осуществлен Общероссийской общественной организацией инвалидов - больных рассеянным склерозом (ОООИБРС) при научном участии Российского комитета исследователей рассеянного склероза (РОКИРС). Это первый опыт проведения медико-социологического исследования на территории РФ, охватывающий и больных ППРС, и неврологов. Выявлены типичные медицинские и социальные проблемы, с которыми сталкиваются пациенты с ППРС, отмечено существенное снижение качества жизни данной группы больных.

Multiple sclerosis is a chronic demyelinating and neurodegenerative disease of the central nervous system, in which autoimmune inflammation and oxidative stress play essential pathogenetic roles. Activation and infiltration of immune cells in brain tissues, lipid peroxidation products, mitochondrial dysfunction, defective antioxidant protection, and many other pathological factors result in demyelination, axonal injury and death, and apoptosis of oligodendrocytes and neurons, all of which causes constant progression of the disease. The new oral agent for the treatment of relapsing-remitting multiple sclerosis (RRMS), dimethyl fumarate (DMF), helps change the pathogenetic mechanisms of the disease, thus decreasing the rate of exacerbations, slowing down disease progression, and reducing the risk of radiological progression of the disease.Рассеянный склероз (РС) - хроническое демиелинизирующее и нейродегенеративное заболевание ЦНС, важными патологическими факторами развития которого являются аутоиммунное воспаление и оксидантный стресс. Активация иммунных клеток и их инфильтрация в ткани мозга, продукты перекисного окисления липидов, дисфункция митохондрий, дефект антиоксидантной защиты и многие другие патологические процессы ведут к демиелинизации, повреждению и гибели аксонов, апоптозу олигодендроцитов и нейронов, что является причиной неуклонного прогрессирования заболевания. Новый препарат для лечения ремиттирующе-рецидивирующего РС (РРРС) - диметилфумарат, позволяет воздействовать на патогенетические механизмы болезни, уменьшая частоту обострений, замедляя темпы прогрессирования и снижая риск радиологической прогрессии заболевания.Рассеянный склероз (РС) — хроническое демиелинизирующее и нейродегенеративное заболевание ЦНС, важными патологическими факторами развития которого являются аутоиммунное воспаление и оксидантный стресс. Активация иммунных клеток и их инфильтрация в ткани мозга, продукты перекисного окисления липидов, дисфункция митохондрий, дефект антиоксидантной защиты и многие другие патологические процессы ведут к демиелинизации, повреждению и гибели аксонов, апоптозу олигодендроцитов и нейронов, что является причиной неуклонного прогрессирования заболевания. Новый препарат для лечения ремиттирующе-рецидивирующего РС (РРРС) — диметилфумарат, позволяет воздействовать на патогенетические механизмы болезни, уменьшая частоту обострений, замедляя темпы прогрессирования и снижая риск радиологической прогрессии заболевания.

Alemtuzumab (Lemtrada) is a recombinant humanized IgG1 kappa monoclonal antibody to the surface cell glycoprotein, a CD52 differentiation cluster. The drug is approved for use in more than 65 countries, including the Russian Federation. The drug is one of the most effective methods of treating patients with aggressive multiple sclerosis, but the risk management plan should be followed. The safety profile of the drug includes infusion-associated reactions, thyroid dysfunction, immune cytopenia, acute cardiovascular events, infections, and other autoimmune diseases. This publication provides updated practical recommendations for the use of the drug and ensuring the safety of patients treated with alemtuzumab.Алемтузумаб (Лемтрада) — рекомбинантное гуманизированное IgG1 каппа моноклональное антитело к поверхностному клеточному гликопротеину, кластеру дифференцировки CD52. Препарат разрешен к применению в более чем 65 странах мира, включая Российскую Федерацию. Препарат является одним из наиболее эффективных методов лечения пациентов с агрессивным течением рассеянного склероза, но при его применении необходимо тщательное соблюдение плана управления рисками. Профиль безопасности препарата включает инфузионные реакции, дисфункцию щитовидной железы, иммунные цитопении, острые сердечно-сосудистые состояния, инфекции и другие аутоиммунные заболевания. В данной публикации представлены обновленные практические рекомендации по применению препарата и обеспечению безопасности пациентов, получающих терапию алемтузумабом.

The article is the second in the series of four that present the results of a study on environmental contaminants in coastal Chukotka, conducted in the context of a multi-disciplinary investigation of indigenous foodways in the region. The article presents the results of the analysis of legacy Persistent Organic Pollutants (POPs) found in the samples of locally harvested food and indoor matters, collected in 2016 in coastal Chukotka. Temporal trends and circumpolar comparisons of POPs in food have been carried out. Estimated daily intakes (EDIs) of POPs by local food consumption were calculated based on the food intake frequencies (questionnaire data). Concentrations of the studied legacy POPs in marine mammal blubber were relatively high (up to 100&ndash, 200 &micro, g/kg ww) but not exceeding the allowable limits. Gray whale blubber and whale mantak were the most contaminated foods, followed by the ringed, spotted and bearded seal blubber, then by walrus blubber and fermented walrus (deboned walrus parts aged in subterranean pits, typically over a period of 6 months). At the backdrop of general decrease or invariability (compared to the previous coastal Chukotka study 15 years ago) of the majority of POPs, an increasing tendency of HCB, mainly in marine mammals, were noted. Legacy POPs in marine mammals sampled in Chukotka were generally much lower than in those sampled in Alaska and northern Canada. We suggest that the Alaska Coastal Current from the Bering Sea plays a major role in this phenomenon. Analyses of the additional sources of in-home food contamination (home-brewed alcohol, domestic insecticides) have revealed relatively high levels of HCHs, DDTs and PCBs, which still represent a share of dietary exposure of local people to POPs.

As part of AMAP's human circumpolar study of POPs, an international effort was initiated to extend coverage to communities across the Russian Arctic. Two additional laboratories were invited to join the analytical component of this effort, resulting in four participating analytical centres. Although quality assurance measures were put in place, and the level of performance of the laboratories was generally acceptable, deficiencies in the analytical protocols used were recognized subsequent to the collection and analyses of the plasma specimens. The current paper describes the criteria employed to critically appraise the four data bases and guide their integration into a single data set. Summary statistics are presented for plasma concentrations of major PCBs, p,p'-DDE, p,p'-DDT, beta-HCH, and HCB for communities/regions across the arctic/subarctic Russian continent, and for one community located in the Aral Sea area of Uzbekistan (a control group). Highly exposed people were identified in the coastal communities of Chukotka, which appears mainly related to marine mammal intake, but recent pesticide use is also suspected. Other communities with intermediate levels of PCBs had relatively elevated beta-HCH, p,p'-DDT and HCB concentrations and low DDE/DDT ratios (10), suggesting recent pesticide use.

The morbidity of tick-borne encephalitis (TBE) varies yearly by as much as 10-fold among the people of Western Siberia. This long-term variation is dependent on many factors such as the density of the tick populations, the prevalence of TBE virus (TBEV) among sub-adult ticks, the yearly virulence of the TBEV, and prophylactic measures. Here we highlight the role of small mammal hosts in the circulation of TBEV through the ecosystem. Refining classical models of non-viremic horizontal transmission, we emphasize the recently understood fact that the physiological and immunological status of the small mammal hosts affects the tick and virus-host interactions. In addition to its theoretical interest, our approach may lead to some practical improvements in the precision of epidemiological forecasts and perhaps in forestalling the severity of outbreaks of TBE, or, at least, in forewarning medical authorities and the general public of impending TBE outbreaks.

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disorder of the central nervous system. Nowadays some disease-modifying drugs (DMD) in the Russian Federation (RF) are biosimilars. Their full spectrum of tolerability and efficacy is to be determined. Here we present results of two retrospective-prospective studies on efficacy and safety of a biosimilar interferon beta-1a (genfaxon) in treatment of MS in the RF.determination of safety and efficacy profile of genfaxon in a routine neurological practice in the RF.Trials were performed in 18 MS centers in the RF. A total of 649 patients aged from 18 to 68 years with the EDSS score no more than 6.0 were treated with genfaxon for 12 months. The first group was comprised of 'naïve' patients without previous history of DMD administration. There were patients in the second group which have already received some of DMD. Statistical analysis was performed with the help of significance criteria (χ-square), t-criteria of Student for analysis of independent samplings.There were no serious adverse events during the period of the study. "Naïve" patients had significantly lower number of adverse events, than patients with previous history of DMD usage. Efficacy results were comparable with results published for the Rebif.Data, received from the studies show equal efficacy and tolerability of genfaxon compared with original DMD Rebif.

Background: Identification of MS registries and databases that are currently in use in Europe as well as a detailed knowledge of their content and structure is important in order to facilitate comprehensive analysis and comparison of data. Methods: National MS registries or databases were identified by literature search, from the results of the MS Barometer 2011 and by asking 33 national MS societies. A standardized questionnaire was developed and sent to the registries’ leaders, followed by telephone interviews with them. Results: Twenty registries were identified, with 13 completing the questionnaire and seven being interviewed by telephone. These registries differed widely for objectives, structure, collected data, and for patients and centres included. Despite this heterogeneity, common objectives of the registries were epidemiology ( n=10), long-term therapy outcome ( n=8), healthcare research ( n=9) and support/basis for clinical trials ( n=8). While physician-based outcome measures (EDSS) are used in all registries, data from patients’ perspectives were only collected in six registries. Conclusions: The detailed information on a large number of national MS registries in Europe is a prerequisite to facilitating harmonized integration of existing data from MS registries and databases, as well as comprehensive analyses and comparison across European populations.

Analysis of DNA epigenetic mutations in the blood circulating DNA is a prospective trend for creation of noninvasive methods for the diagnosis and treatment effi ciency monitoring in cancer. The methylation status of target genes in circulating DNA was evaluated by methods based on preliminary bisulfi te conversion of DNA. We used a different approach based on selection of hypermethylated sequences of circulating DNA by means of DNA-methyl-binding protein (methylated CpG island recovery assay, MIRA). Methylation was evaluated for RARβ2 tumor suppression gene in circulating DNA in lung cancer and a trend was detected to higher methylation of this gene in the patients in comparison with healthy donors.

Currently in Russia, there is a rather complicated situation with the distribution of expensive disease modifying drugs (DMD) purchased by the state for treatment of patients with multiple sclerosis. In this regard, it is necessary to carry out a serious organizational work in the direction of assessment of equivalence of biosimilars and original drugs concerning, first of all, efficacy and safety. Also, there is a problem of the replacement of one biosimilar by another in connection with organizational problems of shipping DMD to country regions. We present the results of the sociological research on the assessment of expensive drug provision by patients. The research has been carried out in 35 regions of the country. Based on these results, a strategy of the development of the program of provision with DMD should be developed all over the country.

We followed up 102 patients with a monofocal clinically isolated syndrome (CIS) during 8 years. Factors determining its transition to definite multiple sclerosis were singled out according to the data of anamnesis and MRI scans. Age of patients at the onset of CIS and the volume of demyelination measured by the first MRI were the most significant predictors of the transition of CIS to definite multiple sclerosis. A mathematical model based on logistic regression analysis for the estimation of the risk of this transition is suggested.

Results of a sociological research studying characteristics of reintegration of people with multiple sclerosis (MS) in a society are presented. During the research, people with MS living in the territory of the Samara region and experts, representatives of a region profile medical community, have been interrogated. The analysis of medical and social factors influencing the process of rehabilitation of the target group of patients is given. The role of Samara regional public organization of disabled people with MS (structural division of the All-Russian Multiple Sclerosis Society) in the improvement of quality of medical and socially-psychological help to people with MS is studied.

A series of RNA-hydrolyzing constructions was synthesized on the basis of peptide-like molecules containing residues of L-lysine, histamine and histidine methyl ester. These were shown to hydrolyze RNA effectively at neutral pH values. The in vitro transcript of tRNA(Lys) from human mitochondria and a tRNA-like fragment of RNA of Turnip Yellow Mosaic Virus were used in the experiments. Our chemical RNases quantitatively depolymerize some definite sequences (CAor = UACGUC, CC, or CU) in both RNA molecules under optimum conditions. Moreover, no other sites were affected and no statistical hydrolysis was observed even after prolonged RNA incubation with the compounds of this series. The depolymerization rate of the RNA substrates exhibits a complex dependence on the concentration of ions of monovalent metals and on the concentration of the artificial ribonucleases.

The ability of artificial ribonucleases to cause in the concentration-dependent manner death of cancer cells has been studied. The cytotoxic activity of artificial ribonucleases is observed at rather low concentration of these compounds (10(-5) M). Analysis of the mechanism of artificial ribonucleases cytotoxicity revealed that compounds under the study exhibit membranotropic activity in addition to ribonucleases activity found earlier. This activity is responsible for effective penetration of these compounds inside cells. The results obtained show that artificial ribonucleases induce cell death via damage of cells membrane, detachment of plasmalemma and derangement its macromolecular organization. In the case of short-term exposure of cells to the compounds, cells, even with damaged membrane, survive.

A new technique of two-layer dynamical abdominal wall alloplasty was applied in 2005-2008 in 10 patients, ageing (55.3 +/- 12.6) yrs old at average, for giant postoperative abdominal hernia, based on a G. Valenti principle of dynamical self-regulating prosthesis and the method of temporary closure of operation wound, according to Wittmann Patch procedure. It was proved, that introduction of original technique of a two-layer dynamical self-regulating abdominal wall alloplasty permits to escape postoperatively the abdominal compartment syndrome development.

Small interfering RNAs (siRNA) are considered to be potent agents for specific gene silencing, but troubles in delivery of siRNA into cells limit their biomedical application. An accumulation of siRNA coupled with cholesterol residue at the 5'-end of the "passenger" strand (chol-siPHK) was investigated in HEK293, HepG2, SC1, and KB-8-5 cells. In the absence of a transfectant levels of both unmodified and chol-siRNAs were very low, whereas transfectant substantially increased transfection rate in all cell lines; in HEK293, SC1, and KB-8-5 cells transfection efficiency for the chol-siRNA being higher than that for the corresponding siRNA. Multiple drug resistance phenotype reversing activity of anti-MDR1-siRNAs targeted to the 557-577 region of MDR1 gene mRNA was investigated in KB-8-5 cancer cells. The chol-siRNA induced cancer cells' death in the presence of vinblastine doses tolerated before more effectively than the conventional siRNA did.

The results of treatment of 221 patients for inguinal hernia, including preperitoneal hernioplasty in 117 and hernioplasty according to Lichtenstein method in 104 of them, were analyzed. After the operation the testis shells watering had occurred in 6 patients, the postoperative cicatrix infiltrate--in 6, operative wound hematoma--in 4. The hernia recurrence had occurred, while fol-lowing patients up from 6 months till 4 years, in one patient only after operation, performed according to Lichtenstein method. In patients, to whom preperitoneal plasty of inguinal canal was per-formed, a specific complications, associated with the operation performance, were absent. Preperitoneal plasty secures a safe strengthening of hernial gates. The net implant fixation in preperi-toneal space permits to escape the feeling of a "foreign body" pres-ence in inguinal area of the patients.

To solve the problem of medical and social assistance to people with multiple sclerosis (MS) is possible in employing a system/ comprehensive approach which involves appropriate material basis and appropriate structures, systems, sub-systems with a definite area of their activities and functional interrelations between them. The quality of medical services is a complicated category that is defined by many characteristics. One needs certain equipment to manage in order to obtain the quality while based on the system approach. Experts in the area of quality management inform that, currently, the Russian healthcare is mostly characterized by primary level of quality, which is represented by unsystematic management of the quality and unsystematic (unstable) quality. The methodology of improving the quality is a multistage one. In accordance with the management cycle of Deming-Schuchart or the cycle of PDCA ('P' is for 'plan', 'D' is for 'deed', 'C' is for 'control' and checking the conformity of the result planned to that in the end, and, 'A' is for 'adjustment' of actions depending on the results achieved), the methodology comprises certain problems, an analysis of the system, an action plan development, testing proposed changes in pilot institutions, and practical application in the healthcare system. The article attempts to analyze basic problems and difficulties in setting up medical assistance for a resource-consuming group of patients, by the example of 382 patients with MS, taking into account the experience acquired in a test of application of management systems for medical assistance quality, which is based on international standards (ISO 9000), in order to find possible ways to overcome the existing negative processes and facts.

The state social policy with regard to disable people in the Russian Federation is developed in accordance with international instruments which include the "Declaration on the Rights of People with Disabilities" adopted by the UN General Assembly, the ILO Convention (No159) "Vocational Rehabilitation and Employment of Disabled Persons", the "Standard Rules on the Equalization of Opportunities for Persons with Disabilities" adopted by the UN General Assembly, the World Program of Action Concerning Disabled Persons etc. All these instruments mainly focus on the issue of social rehabilitation of people with health disabilities in order to offer them "equal opportunities" in different areas of their life. The paper is devoted to research of some backbone arrangements of rehabilitation of people with multiple sclerosis (MS) and major lines of proficiency training and retraining of professionals on issues of social rehabilitation of people with health disabilities as well as methods of rehabilitation of MS patients.

To study and evaluate clinic, diagnostics and operative treatment of patients with primary pulmonary sarcomas (PPS).During 24 years period, a total of 49 patients underwent surgery for PPS. There were 29 male and 20 female with a mean age of 52.6 years. Main presenting complaints were shortness of breath, cough, chest pain, weight loss and haemoptysis. Correct preoperative diagnosis was obtained in 12 (24.48%) of the patients by bronchoscopy or percutaneous core biopsy. Carcinoma was diagnosed in 14 (28.6%) of them. Almost half of the cases were operated on without histological confirmation for suspected malignancy. The histological diagnoses were fibrosarcoma (16), fibroleiomyosarcoma (10), leiomyosarcoma (6), rhabdomyosarcoma (7), hemangiopericytoma (3), epitheloid hemangioendothelioma (3), undifferentiated sarcoma (2), malignant schwannoma (1) and liposarcoma (2). Only 2 of the tumors were scored in grade 1. The rest were classified in higher grades of malignancy. The following operations were carried out: lobectomy--30 (59.2%), including 2 sleeve lobectomies; pneumonectomy--10 (20.4%), polysegmental resections--3 (6.2%) and atypical resection--1 (2%). The resections were extended to the thoracic wall, diaphragm or pericardium in 4 patients. Endoscopic laser resection was applied in 1 (2%) case. Exploratory thoracotomy was performed on 3 (6.1%) patients. There were 2 (4.1%) stage I A; 26 (53.1%) stage I B; 11 (22.4) stage II B; 5 stage III A; 4 stage III B and 1 stage IV.No postoperative death occurred. Postoperative empyema was observed in 2 cases (4.1%) and 1 patient (2%) was reoperated on for local recurrence 18 months after surgery. Adjuvant therapy was administered to 20 of the patients. Follow-up (range, 6 to 160 months) was available for 41 patients. The actuarial 5-year postoperative survival was 51.8% with mean survival of 40.8 months.The correct preoperative diagnosis of PPS still presents a challenge. There are no specific clinical, imaging and other signs for this tumor evaluation. Surgery with systematic lymphnode dissection is a treatment of choice with an acceptable 5-year survival rate. Only the complete resection and the low stages of the tumor significantly influence survival.

Extracellular DNA and RNA were extracted from blood plasma and cell surface-bound fractions of patients with breast tumors and healthy controls. Frequency of RASSF1A, Cyclin D2 and RARbeta2 methylation was detected using methylation-specific PCR in the extracellular DNA, extracted from plasma and cell-surface bound fractions of patient blood. Methylation of at least one of these genes was found in plasma of 13% patients with benign breast fibroadenoma and in 60% of breast cancer patients. Using cell-surface bound DNA as a substrate for PCR have lead to increase of gene methylation detection frequency up to 87% in fibroadenoma and 95% in breast cancer patients without false positive controls. GAPDH, RASSF8, Ki-67 RNA and 18S RNA were quantified using RT-qPCR of the extracellular RNA circulating in blood of patients with breast tumors and healthy controls. The main part of the extracellular RNA was shown to be cell-surface bound. Results show a higher amount of RASSF8, Ki-67 RNA and 18S RNA in plasma and cell-bound fraction of patients with breast cancer compared with patients with benign tumors and healthy controls. The data indicate that the specific RNA quantification in blood plasma is valuable for discrimination between cancer and benign tumors, which can be detected with high sensitivity using analysis of methylated RASSF1A, Cyclin D2 and RARbeta2 genes in extracellular circulating DNA.

Circulating nucleic acids were discovered more then 30 years ago and were intensively investigated for the last ten years. The manuscript review the data regarding sources of circulating deoxyribonucleic acids in blood, factors influence on their circulation, like blood nucleases, and excretion of DNA from blood. Application of circulating DNA in practical medicine is also discussed.

The data about deoxyribonuclease activity in blood of healthy donors and patients with malignant and autoimmune diseases are described. Methodological aspects of the analysis of DNase activity and factors which interfere with DNase activity in blood are discussed.

Intracellular localization of natural and fluorescent-labeled oligonucleotides in primary human endothelial cells was studied by means of fluorescence microscopy and radioisotope analysis. Transport and distribution of oligonucleotides in endotheliocytes depended on their structure and resistance to hydrolysis under the effect of cell nucleases. Modification of 5′-terminal phosphate and 3′-terminal oligonucleotide increased the stability and ensures nuclear localization of oligonucleotides in cells.

The review highlights analytics capacities of immunochemical and molecular-genetic methods used in the non-invasive test for prostate cancer and monitoring of efficacy of anticancer therapy. The perspectives of their applications in clinical practice also have been evaluated.

Small interfering RNAs (siRNA) provide a powerful approach for sequence-specific silencing of gene expression. In the present study we investigated inhibition of c-myc gene expression by siRNAs targeted to the sequence 1452-1470 b. in third exon of c-myc mRNA and to homologous regions in second exons of c-myc (697-715 b.) and N-myc (302-320 b.) mRNAs. siRNAs were prepared enzymatically according to the scheme, including dsDNA-templates preparation using Klenow fragment, separate in vitro transcription of each RNA strand with subsequent hybridization and removal of leader sequences by T1 RNase. Investigation of c-myc gene silencing by siRNAs revealed that enzymatically prepared siRNAs induce stronger inhibition of c-myc expression, than siRNA with the same sequence prepared by chemical synthesis. It was found that down-regulation of c-myc gene expression by investigated siRNAs results in efficient inhibition and even complete arrest of carcinoma cell proliferation, moreover, the extend of growth inhibition correlates with the level of siRNA-mediated reduction of c-myc mRNA.

The study of mechanisms of nucleic acid transport across the cell membrane is valuable both for understanding the biological function of extracellular nucleic acids and the practical use of nucleic acids in gene therapy. It has been clearly demonstrated that cell surface proteins are necessary for transport of nucleic acids into cells. A large amount of data has now been accumulated about the proteins that participate in nucleic acid transport. The methods for revealing and identification of these proteins, possible mechanisms of protein-mediated transport of nucleic acids, and cellular functions of these proteins are described.

Concentrations of extracellular deoxy- and ribonucleic acids in blood plasma and cell-surface-bound of blood cells were investigated in healthy donors and patients with malignant gastrointestinal tumors. Our results indicate that high concentration of extracellular DNA in blood plasma along with decreased level of extracellular RNA on the surface of blood cells correlate with development of gastrointestinal cancer. Ratio of nucleic acids in plasma to total amount of nucleic acids circulated in blood is a characteristic parameter distinguishing cancer patients from healthy persons.

The concentrations of extracellular DNA and RNA were measured in the plasma of donors and patients with fibroadenoma and breast cancer. The content of extracellular DNA surpassed the normal in 80% plasma samples from patients with mammary tumors. Extracellular RNA was detected in 30% plasma samples from donors and patients with breast tumors. No correlations were found between plasma concentration of extracellular DNA and size and stage of tumor growth. Hence, measurement of extracellular DNA in the plasma of patients can be used only as an accessory test for tumor diagnosis.

During Jan. 1990 and Dec. 2002 a total of 14 patients with bronchiectasis were operated on. They were 5 female and 9 male with mean age of 35.7 years. In two of them (14.3%) the disease was with bilateral localization. Patients were typically presented with cough and purulent sputum production 12(85.7%), recurrent pulmonary infections 8(57.1%), halitosis 6(42.9%) and hemoptysis 4(28.6%). The mean duration of clinical manifestations was 8.4 years. The indications for surgery were failure of medical treatment in 10(71.4%) patients, hemoptysis in 2(14.3%) and lung abscesus, as a complication in 2(14.3%) patients. The operative methods included 9(64.3%) lobectomies, 1(7.1%) pleuropneumonectomy, 1(7.1%) pneumonectomy, 1(7.1%) bilobectomy with broncho-esophageal fistula resection, 1(7.1%) middle lobectomy with polysegmental resection S7-10 and 1(7.1%) polysegmental resection S7-10. No 30-day postoperative death was faced. Major complications, followed by rethoracotomy, were found in 2(14.3%) of the cases. The postoperative results were excellent in 8(57.1%) of the patient, very good in 5(35.75) of them and in only 1 patient there was no clinical improvement. In conclusion, surgery for bronchiectasis is followed by acceptable postoperative complications and better long-term result after radical operation.

Multiple sclerosis (MS) today is a wide-spread disease of young adults of 22-25 years of age, which influences their everyday life, affecting movement, behavior and family life. After 2-5 years of untreated MS the patients become complete invalids. The organization of the process of rehabilitation for these patients includes the activity to restore MS patients' ability to work, serve themselves, continue education. Taking into consideration the increasing support from the state of different organizations of disabled patients, a new infrastructure of the system of rehabilitation of these disabled patients, new approaches to their organizations, law and information support should be introduced. Rehabilitation process in MS has five main directions--psychosocial, sociomedical, family, professional and legal.

Normal values are intervals covering the majority of cases detected in healthy individuals. They are gradually replaced by diagnostic criteria based on probability of differentiation between the healthy and ill (prognostic intervals). In 1970-ies, "recommended for health promotion" intervals appeared. The physician must know the origin of the criteria recommended for assessment of the results of the laboratory test or another measurement, in diagnosis, only diagnostic criteria must be used but not criteria designed for prophylactic programs. In the context of each disease diagnostic criteria should account for possible sequelae. Such criteria are multiple: for one test (e.g. plasma glucose concentration) there are different criteria for diagnosis of different diseases (diabetes type 1 or 2, hypothyroidism). Only such criteria should be included in recommendations (standards) on diagnosis and treatment of certain diseases. Conventional "normal values" should be used only in assessment of the results of prophylactic surveys and in search for explanation for the obscure states.