COMPUTER METHODS OF GENETIC ANALYSIS.

Рассматриваются основные статистические методы, которые используются при проведении генетического анализа признаков человека. Исследованы методы сегрегационного анализа, анализа сцепления и аллельных ассоциаций. Разработано программное обеспечение для реализации этих методов.The basic statistical methods used in conducting the genetic analysis of human traits. We studied by segregation analysis, linkage analysis and allelic associations. Developed software for the implementation of these methods support

MODELLING OF CONCENTRATION LIMITS BASED ON NEURAL NETWORKS.

Изучаются модели прогнозирования концентрационных пределов с использованием нейросетевых технологий. Разработано программное обеспечение для реализации этих моделей. Показана эффективность работы системы на экспериментальном материале.We study the forecasting model with the concentration limits is-the use of neural network technology. The software for the implementation of these models. It is shown that the efficiency of the system in the experimental material

Synthesis and tribological properties of new fluoro-containing oligomers

Oligomers based on (polyfluoroalkyl)methyl oxiranes and thiiranes was first synthesized by the cationic polymerization in the presence of boron trifluoride etherate. Molecular weights of the products were defined by cryoscopic method. It was found that synthesized oligomers can be used as additives to industrial lubricants and sulfur oligomers are of the greatest positive tribological effect. © Pleiades Publishing, Ltd., 2013

EXPERIENCE OF SUCCESSFUL ACNEFORM ERUPTIONS TREATMENT IN PATIENT WITH MULTIPLE MELANOMA

Objective: to describe the results of the joint monitoring and diversified treatment of oncologists and dermatologists those patient with multiple recurrent melanoma who received over a long period a targeted anti-cancer therapy, which was complicated by side-effect as widespread acneform rush, resistant to traditional treatment. Patient A., born in 1988, was followed up and got a treatment more than 2 years in oncology out-patient clinic diagnosed with “Melanoma of the front surface of the left leg T2bN0M0 IIA”. Subsequently, the patient was verified metastasis in the inginal lymph nodes, in the soft tissues of the hips, to liver. Acute adverse reaction has developed in a short time after getting the anti-tumor target therapy as generalized acneform rush and itching of the skin. Skin symptoms accompanied by pronounced psychological and emotional stress, therefore, dermatologists have been invited to provide additional medical assistance to this patient. Due to the fact that subsequent traditional anti-acne algorithms of topical and oral treatment was not such effective, there was made a decision to use an alternative supporting external therapy, which did not have similar examples of usage previously. Results. External application of tacrolimus ointment in combination with other drugs and then as a mono-therapy, allows us in a rather short period achieve a stable and pronounced regression of skin pathological lesions, to return to the previously cancelled initial drug dose of the anti-tumor target therapy, to change significantly components of the patient’s quality of life. Conclusion. The search for additional and alternative treatment approaches for similar patients, as in our case, remains relevant for specialists and patients themselves. This case is an example of alternative approach to the tacrolimus topical application in patient with drug-mediated acneform rush

Results of Immunological Screening for Natural-Focal and «Exotic» Infectious Diseases among Certain Population Groups of the Khabarovsk Territory, the Amur Region and the Jewish Autonomous Region

Displayed are the results of examination of immuno-competent local population of the Khabarovsk Territory, the Jewish Autonomous Region, the Amur Region, as well as foreign residents living and temporarily working in the areas, on a wide range of natural-focal bacterial and viral infectious diseases including the causative agents of some “exotic” infections too. Investigations have been carried out with the participation of experts from the specialized anti-epidemic team No. 1 (Irkutsk Research Anti-Plague Institute), who worked in the Amur Region, and a group of laboratory-epidemiological specialists from the team No. 2 - deployed in the Khabarovsk Territory and the Jewish Autonomous Region during the flooding in August-September 2013. The total of 1335 blood sera samples has been tested using serological methods. The findings have revealed the presence of immuno-competent population in the three regions of the Far Eastern Federal district in reference to the agents of natural-focal infectious diseases: tularemia, leptospirosis, yersinioses, hemorrhagic fever with renal syndrome, human granulocytic anaplasmosis, tick-borne borrelioses, tick-borne viral encephalitis, Californian encephalitis serogroup, Sindbis, West Nile and Dengue fevers. Circulation of Batai and Crimean-Congo hemorrhagic fever viruses has not been revealed based on serological assays

Epidemiological Situation on Natural Focal Infectious Diseases of Bacterial and Viral Etiology in 2012 in the Territory of Siberia and Far East, and Prognosis for 2013

Analyzed is the incidence rate as regards natural focal infections of bacterial and viral etiology. Displayed is the data on the performed laboratory diagnostics of these infections in the territory of Siberia and Far East in 2012 and forecast of the epidemiological situation development in 2013. Analysis is carried out based on the data received by the Reference Center for surveillance over natural focal infections at the Irkutsk Research Anti-Plague Institute, from Rospotrebnadzor Institutions of Siberian, Far-Eastern and Ural Federal districts, as well as reviews and prognoses on the current state of natural foci of infections available from Altay, Tuva, Chita, Khabarovsk and Primorsk plague control stations

Defects in Mitochondrial Dynamics and Metabolomic Signatures of Evolving Energetic Stress in Mouse Models of Familial Alzheimer's Disease

The identification of early mechanisms underlying Alzheimer's Disease (AD) and associated biomarkers could advance development of new therapies and improve monitoring and predicting of AD progression. Mitochondrial dysfunction has been suggested to underlie AD pathophysiology, however, no comprehensive study exists that evaluates the effect of different familial AD (FAD) mutations on mitochondrial function, dynamics, and brain energetics.We characterized early mitochondrial dysfunction and metabolomic signatures of energetic stress in three commonly used transgenic mouse models of FAD. Assessment of mitochondrial motility, distribution, dynamics, morphology, and metabolomic profiling revealed the specific effect of each FAD mutation on the development of mitochondrial stress and dysfunction. Inhibition of mitochondrial trafficking was characteristic for embryonic neurons from mice expressing mutant human presenilin 1, PS1(M146L) and the double mutation of human amyloid precursor protein APP(Tg2576) and PS1(M146L) contributing to the increased susceptibility of neurons to excitotoxic cell death. Significant changes in mitochondrial morphology were detected in APP and APP/PS1 mice. All three FAD models demonstrated a loss of the integrity of synaptic mitochondria and energy production. Metabolomic profiling revealed mutation-specific changes in the levels of metabolites reflecting altered energy metabolism and mitochondrial dysfunction in brains of FAD mice. Metabolic biomarkers adequately reflected gender differences similar to that reported for AD patients and correlated well with the biomarkers currently used for diagnosis in humans.Mutation-specific alterations in mitochondrial dynamics, morphology and function in FAD mice occurred prior to the onset of memory and neurological phenotype and before the formation of amyloid deposits. Metabolomic signatures of mitochondrial stress and altered energy metabolism indicated alterations in nucleotide, Krebs cycle, energy transfer, carbohydrate, neurotransmitter, and amino acid metabolic pathways. Mitochondrial dysfunction, therefore, is an underlying event in AD progression, and FAD mouse models provide valuable tools to study early molecular mechanisms implicated in AD

Evaluating the SERCA2 and VEGF mRNAs as Potential Molecular Biomarkers of the Onset and Progression in Huntington's Disease

Abnormalities of intracellular Ca2+ homeostasis and signalling as well as the down-regulation of neurotrophic factors in several areas of the central nervous system and in peripheral tissues are hallmarks of Huntington\u2019s disease (HD). As there is no therapy for this hereditary, neurodegenerative fatal disease, further effort should be made to slow the progression of neurodegeneration in patients through the definition of early therapeutic interventions. For this purpose, molecular biomarker(s) for monitoring disease onset and/or progression and response to treatment need to be identified. In the attempt to contribute to the research of peripheral candidate biomarkers in HD, we adopted a multiplex real-time PCR approach to analyse the mRNA level of targeted genes involved in the control of cellular calcium homeostasis and in neuroprotection. For this purpose we recruited a total of 110 subjects possessing the HD mutation at different clinical stages of the disease and 54 sex- and agematched controls. This study provides evidence of reduced transcript levels of sarco-endoplasmic reticulum-associated ATP2A2 calcium pump (SERCA2) and vascular endothelial growth factor (VEGF) in peripheral blood mononuclear cells (PBMCs) of manifest and premanifest HD subjects. Our results provide a potentially new candidate molecular biomarker for monitoring the progression of this disease and contribute to understanding some early events that might have a role in triggering cellular dysfunctions in HD

Многоцентровое наблюдательное неинтервенционное исследование применения комбинированных противотуберкулезных препаратов при лечении больных туберкулезом легких

The objective of the study: to run a multicenter non-interventional observational study to assess treatment outcomes in tuberculosis patients receiving combination drugs with fixed doses, and to evaluate tolerability and safety of these drugs.Subjects and methods. 13 TB units participated in this study which lasted from 2016 to 2018. The primary population (PP) included of 489 patients, after applying the exclusion criteria – the subpopulation (subPP) included 267 patients with newly detected pulmonary tuberculosis and relapses who received treatment as per chemotherapy regimen I or III. Descriptive statistics methods were used for statistical data processing.Results. Of all PP, 267 (54.6%) completed the main course of chemotherapy. (subPP). Out of 489 patients, treatment was discontinued in 118 (24.1%) of them. Primary drug resistance was detected in 30 (6.1%) patients out of 489 patients, secondary drug resistance – in 74 (15.1%) of 489. In subPP, by the end of the intensive phase the sputum conversion was achieved in 78 (96.3%) of 81 patients. Clinical and X-ray changes had been observed in this subgroup for 106.2 to 63.3 days (median 90). The duration of the intensive phase in the subPP made 107.9 ± 50.5 days. In safety assessment, 191 adverse events (AE) were registered in 149 (30.5%) of 489 patients. By severity, most AEs were minor (164 out of 191), moderate AEs were less frequent (20 out of 191), and there were 7 cases of serious AEs. 61 AEs in 57 (38.2%) out of 149 patients were confidently associated with in-take of the studied drugs. The structure of those AEs, transient transaminase level elevation prevailed (45 (73.8%) of 61 AEs, but there was a single case (1.6%) drug-induced hepatitis). Among the serious AEs, two cases were safely resolved by the end of the protocol, two of them were fatal in TB/HIV co-infection, and three cases were diagnosed with cancer.Цель исследования: оценка в многоцентровом неинтервенционном наблюдательном исследовании результатов лечения больных туберкулезом с использованием комбинированных препаратов с фиксированными дозами, переносимости и безопасности этих препаратов.Материалы и методы. В исследовании, проходившем с 2016 по 2018 г., участвовали 13 противотуберкулезных учреждений. Сформированы первичная популяция (РР) из 489 пациентов, после применения критериев исключения – субпопуляция (subPP) из 267 пациентов с впервые выявленным туберкулезом легких и рецидивом, которые получали лечение по I или III режиму химиотерапии. Для статистической обработки данных использовали методы описательной статистики.Результаты. Из РР основной курс химиотерапии завершили 267 (54,6%) (subPP). Досрочно прекратили лечение 118 (24,1%) пациентов из 489. Первичная лекарственная устойчивость выявлена у 30 (6,1%) из 489, вторичная – у 74 (15,1%) из 489. В subPP прекращение бактериовыделения обнаруживалось к концу интенсивной фазы в 78 (96,3%) случаях из 81. Клинико-рентгенологическая динамика отмечалась в этой подгруппе в течение 106,2 ± 63,3 дня (медиана 90). Длительность интенсивной фазы в subPP составила 107,9 ± 50,5 дня. При оценке безопасности зарегистрировано 191 нежелательное явление (НЯ) у 149 (30,5%) из 489 пациентов. По степени тяжести большинство НЯ были легкой степени (164 из 191), реже (20 из 191) – средней степени и 7 – серьезные НЯ. С приемом исследуемых препаратов установлена связь при 61 НЯ у 57 (38,2%) из 149 пациентов. В структуре этих НЯ преобладало транзиторное повышение уровня трансаминаз (45 (73,8%) из 61 НЯ, но в единичном случае (1,6%) зарегистрирован лекарственный гепатит). Среди серьезных НЯ два случая благополучно разрешились к завершению протокола, два ‒ закончились летальным исходом при сочетании ВИЧ-инфекции и туберкулеза, а в трех случаях диагностированы онкологические заболевания