ЭКСПЕРИМЕНТАЛЬНАЯ МОДЕЛЬ АУТОИММУННОГО ПРОЦЕССА: РОЛЬ ЭПИГЕНЕТИЧЕСКОЙ ИЗМЕНЧИВОСТИ В ПОПУЛЯЦИИ МЫШЕЙ-ГИБРИДОВ

Background: At the development of graft versus host disease in genetically homogeneous population of (C57Bl/6 x DBA/2) F1 mice two clinical phenotypes of SLE-like disease were revealed: lupus+ (immune complex glomerulonephritis and hemolytic anemia) and lupus – (hemolytic anemia). The GvHD phenotypic heterogeneity is determined by the Th1 /Th2-polarization: Th2 lymphocyte predominant activity, leads to the lupus+ development, or prevalence activity of Th1 cells, leads to the lupus– development. Objective: Our aim was to evaluate the possibility of using an experimental model of autoimmune disease for studying and testing of epigenetic modifications, shifting Th1 /Th2-balance in vivo. Methods: Сhronic GVHD was induced in B6D2F1 mice by the transplantation of 130×10 6 parental DBA/2 splenocytes. Аnti-ds-DNA, total IgG and IgG1, IgG2а Abs were measured by ELISA. Results: Six- to 8-week-old female DBA/2 and B6D2F1 mice were obtained from Biological Research Laboratory (Novosibirsk). It was established that regular moderate physical activity (unladed swimming) shifted Th1 /Th2 balance towards Th1. This leads to a decrease in a population of recipients the lupus+ mice from 57 to 26% (p 0,001) with significantly reduced hypergammaglobulinemia (IgG from 2,8 to 2,0 mg/ml; p 0,047) and DNA antibodies titer from 0,18 to 0,12 OD (p =0,05). Administration of epigenetic modificator bisphenol A at low doses, which mimicking estrogen effects, enhances the proportion of lupus+ mice in experimental groups from 33 to 64% (p 0,001) and impairs their clinical status by the increasing the urine protein level from 2.8 to 4,2 mg/ml (p 0,001) in animals. Conclusion: Th1 /Th2 – balance presumably is determined by the immune system epigenetic modification in experimental mice, formed on the previous stages of ontogeny and defines the direction of immune processes development in individual animal.В генетически однородной популяции мышей (гибриды F1) при индукции СКВ-подобного заболевания на основе реакции трансплантат против хозяина (РТПХ) выявляются клинические фенотипы lupus+ (гемолитическая анемия + иммунокомплексный гломерулонефрит) и lupus- (гемолитическая анемия). Механизм развития фенотипической гетерогенности обусловлен поляризацией Т-хелперного (Tх1 /Tх2) иммунного ответа: преимущественной активацией Tх1 (lupus-) или Tх2 популяции лимфоцитов (lupus+). Цель исследования: оценить возможность использования экспериментальной модели аутоиммунного заболевания для изучения и тестирования эпигенетических модификаций, сдвигающих Tх1 /Tх2 баланс in vivo. Методы: хроническую РТПХ индуцировали введением B6D2F1 мышам-гибридам 130×10 6 клеток селезенки от родителя DBA/2. Антитела к ДНК, IgG1, IgG2а-подклассам IgG и общий IgG оценивали с помощью иммуноферментного анализа. Результаты: 6–8-недельные самки мышей DBA/2 и B6D2F1 получены из экспериментально-биологической клиники лабораторных животных (Новосибирск). Установлено, что продолжительные регулярные физические нагрузки умеренной интенсивности (плавание без груза) сдвигают баланс Tх1 /Tх2 у реципиентов в сторону Tх1, т.е. в популяции достоверно уменьшается доля мышей lupus+ (с 57 до 26%; p 0,001), у которых достоверно снижается степень выраженности гипергаммаглобулинемии (с 2,8 до 2,0 мг/мл; p 0,047) и титр антител к ДНК (от 0,18 до 0,12 OD; p =0,05). Введение в низких дозах эпигенетического модификатора бисфенола А, имитирующего действие эстрогенов, не только увеличивает долю мышей lupus+ (c 33 до 64%; p 0,001), но и утяжеляет их состояние: концентрация белка у них достоверно повысилась (с 2,8 до 4,2 мг/мл; p 0,001). Заключение: эпигенетические изменения в иммунной системе, сформировавшиеся на предыдущих этапах онтогенеза у мышей-гибридов и связанные с условиями лабораторного содержания животных (двигательная активность, эндокринный статус), по-видимому, определяют соотношение активностей Tх1 и Tх2 субпопуляций, контролирующее выбор варианта, по которому пойдет развитие иммунного процесса в каждом конкретном случае.

The assessment of physicians' and senior medical students’ knowledge in the field of communityacquired pneumonia: preliminary results of the KNOCAP-II project (2017-2019)

Внебольничная пневмония (ВП) относится к одной из самых актуальных проблем современной медицины. На сегодняшний день ВП занимает 4 место в структуре смертности (после сердечно-сосудистых, цереброваскулярных заболеваний и злокачественных новообразований) и 1 место среди всех смертей от инфекционных заболеваний. Цель – оценка уровня знаний врачей терапевтического профиля и студентов старших курсов медицинских вузов в вопросах ведения пациентов с ВП. В рамках многоцентрового исследования KNOCAP (полное название проекта – «The assessment of physician and students’ knowledge of community-acquired pneumonia basics») представлены результаты анонимного проспективного опроса по оценке знаний и предпочтений врачей терапевтического профиля и студентов старших медицинских курсов в вопросах ведения пациентов с ВП. По итогам первого периода проекта (2017-2019 гг.) получены и проанализированы результаты анкетирования 588 врачей терапевтического профиля и 394 студентов-медиков из 17 центров России, Украины и Кыргызстана. За основу взят метод анонимного анкетирования, для чего была разработана оригинальная анкета на основании актуальных клинических рекомендаций. Наибольшие сложности вызвали следующие вопросы: сроки проведения повторного рентгенологического исследования при положительной динамике лечения, выбор основного диагностического признака при ведении пациента с ВП, указать типовые ошибки фармакотерапии ВП и выбор стартовой антимикробной терапии у пациентов с факторами риска и без них. В целом исследование показало значимое несоответствие знаний в вопросах ведения пациентов с ВП актуальным клиническим рекомендациям 2010 г. и проектом новых клинических рекомендаций 2018-2019 гг. В настоящее время существует необходимость в повышении уровня знаний и совершенствовании профессиональной деятельности врачей терапевтического профиля и студентов старших медицинских курсов, так как проведенный многоцентровой срез знаний и предпочтений специалистов во многих вопросах выявил их недостаточный уровень для корректного ведения пациентов с ВП. Community-acquired pneumonia (CAP) is one of the most relevant problems of modern medicine. Today, CAP takes 4th place in the structure of mortality (after cardiovascular, cerebrovascular diseases and malignant neoplasms) and 1st place among all deaths from infectious diseases. The aim of the study is to assess the level of general physician’ and senior medical students’ basic knowledge in CAP treatment. The article represents the results of anonymous prospective surveys within the framework of the second stage of KNOCAP multi-centered research project (full name of the project «The assessment of physician’ and students’ knowledge of community-acquired pneumonia basics») aimed at accessing the knowledge and preferences of doctors and students on the fundamental issues in diagnosis and treatment of community-acquired pneumonia. The survey conducted in 2017-2019 involved 588 physicians and 394 students from seventeen Russian, Kyrgyzstan and Ukrainian centers. The method of anonymous questioning was used in this study, for which an original questionnaire was developed on the basis of current clinical recommendations. The following fundamental questions caused the greatest difficulties in the respondents: terms for a repeated X-ray examination in positive dynamics of CAP treatment, the choice of main diagnostic criteria of CAP, the choice of the typical mistakes of CAP treatment, the choice of the initial antimicrobial therapy. In general, the respondents’ knowledge in CAP patients’ management deviates significantly from the current clinical guidelines, as of 2010, and from the new clinical guidelines draft, 2018-2019. Currently, there is a need to increase the level of knowledge and improve the professional activities of therapists and senior medical students, as a multicenter section of the knowledge and preferences of specialists in many issues revealed their insufficient level for the correct management of patients with CAP

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe

Linguistic abilities and its cognitive determinants: contemporary research perspectives

The article presents contemporary studies of linguistic abilities in psychology. The different approaches to the linguistic abilities structure are discussed in relation to empirical results on peculiarities of the second language mastering. The special attention is paid to the cognitive determinants of linguistic abilities. So the empirical data concerning the interaction between language-aptitude test scores and different abilities, e.g. verbal intelligence and working memory, are analyzed in more details. In the conclusion the research perspectives in different cognitive processes which determine the efficiency of the second language mastery are discusse

Intermolecular Interactions in Gas Chromatography on Carbon Black Coated with Monolayers of Hydrocarbons with Different Electronic Structures

The adsorption and chromatographic properties of surfaces obtained by the adsorptive modification of thermally graphitized carbon black (TGCB) with hydrocarbons differing in composition and electronic structure (n-dotriacontane and coronene) were studied by gas chromatography (GC). The contributions towards the retention of methylene groups in homologous series of n-alkanes, alkylbenzenes, ethers, esters and n-alcohols were estimated for TGCB coated with monolayers of the above-mentioned hydrocarbons. The thermodynamic characteristics of the adsorption process were also measured for molecules of the various classes of organic compounds described. In addition, differences in the mechanism of chromatographic retention on n-alkane monolayers, when the latter may exist as solid-like, transitional or liquid-like states, and on coronene monolayers were studied. The influence of the electronic configuration of the carbon atoms in the modifier molecules on the adsorption energy of the various organic compounds studied has been demonstrated. The possibility of employing GC methods for demonstrating phase transitions in long-chain alkane monolayers adsorbed on carbon black is discussed. Furthermore, the possibility of controlling the retention selectivity during GC by TGCB modification with adsorbed monolayers of hydrocarbons is presented

The Interaction of Digital Technologies with the Development of Cognitive and Communication Processes of Adolescents and Young Adults: a Review of Empirical Research

The article presents an overview of empirical research on the interaction of digital technologies with the development of cognitive and communication processes of adolescents and young adults. The studies are divided into blocks in accordance with the three types of childrens&rsquo; activity, such as leisure (including video games), communicative and educational activity &ndash; taking the impact of digital technologies into account. Contradictory empirical data are explained by the many limitations that exist for the organization of this type of research. They also do not allow to identify clear causal relationships between the use of digital technologies by adolescents and young adults and the development of their cognitive and communication skills. The analysis of scientific results, studies led to the conclusion that digitalization qualitatively changes development of cognitive and communication processes of adolescents and young adults.</p

Blue sclerae and their association with glaucoma (a review and case report)

T.A. Beletskaya1,2, E.V. Kozina1, D.V. Dmitrenko1, Yu.I. Gavrilova2 1Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, Russian Federation 2Prof. P.G. Makarov Krasnoyarsk Regional Ophthalmological Clinical Hospital, Krasnoyarsk, Russian Federation This paper reviews the key risk factors and clinical manifestations of blue sclerae, which include a large group of diseases of various origins. Generally, this syndrome is genetically determined and is a constant phenotypic sign of osteogenesis imperfecta. In addition to the classic triad of blue sclera, brittle bones, and hearing loss, many authors refer glaucoma to as an ocular manifestation of brittle bone disease in addition to thin cornea and low corneoscleral rigidity. The combination of osteogenesis imperfecta type 1 and primary open-angle glaucoma is a novel phenotypic association. The most effective way of controlling intraocular pressure (IOP) in this condition is surgical intervention. Case report of a combination of glaucoma and syndromic connective tissue disease that appeared 15 years after the first visit to an ophthalmologist for recurrent ocular hypertension is presented. Selective laser trabeculoplasty and a fixed-dose combination of 0.3% bimatoprost and 0.5% timolol provided normal IOP levels. Ultrathin corneas and systemic hypotension do not rule out the need for further surgery. Keywords: blue sclera, glaucoma, osteogenesis imperfecta, corneal thickness. For citation: Beletskaya T.A., Kozina E.V., Dmitrenko D.V., Gavrilova Yu.I. Blue sclerae and their association with glaucoma (a review and case report). Russian Journal of Clinical Ophthalmology. 2023;23(4):225–230 (in Russ.). DOI: 10.32364/2311-7729-2023-23-4-9. </p

Response of wild Avena species to fungal infection of grain

Sixty-six accessions belonging to Avena species (A. atlantica, A. canariensis, A. clauda, A. damascena, A. hirtula, A. longiglumis, A. wiestii, A. agadiriana, A. barbata, A. vaviloviana, A. insularis, A. magna, A. murphyi, A. fatua, A. ludoviciana, A. occidentalis, A. sterilis, A. sativa, and A. byzantina) obtained from the N. I. Vavilov Institute of Plant Genetic Resources (VIR) were tested for the infection of grain by Alternaria and Cladosporium at the genus level and by a group of trichothecene-producing Fusarium fungi. Real-time PCR was performed to quantify fungal abundance and ELISA was performed for mycotoxin analysis in grain. The average amounts of all tested fungi in tetraploid Avena species were higher than those in diploid and hexaploid species. Low amounts of deoxynivalenol (DON) were detected in seven hexaploid genotypes (A. sterilis, A. byzantina, A. sativa, and A. fatua) and one diploid genotype (A. wiestii). The relationship between some morphological traits (1000-grain weight, percent of husk, trichome density, and plant height) of Avena species and grain infection by fungi and mycotoxins was investigated. Alternaria and Cladosporium fungi could not penetrate the husk. A highly negative correlation of the amounts of their DNA with the proportions of husk in grain as well as with trichome density was found. In contrast, a significant positive correlation between the amount of Fusarium DNA and these traits was found. A strong negative correlation between plant height and DNA of the analyzed fungi was found. The oats least infected by Alternaria, Cladosporium, and Fusarium fungi and containing low amounts of DON were accessions of the hexaploids A. byzantina, A. fatua, A. sativa, A. sterilis, and the diploid A. wiestii. Keywords: Avena species, Grain, Fungal DNA, Mycotoxi

Conjugation of L-lysine A-oxidase with antibodies

The conjugation of the drugs with vector molecules enables to obtain therapeutic preparation, which may be transported to the selected target organ. In the present work the methods of conjugation of antineoplastic enzyme L-lysine α-oxidase with antibodies were elaborated. Conjugates were worked out through the attachment of amino groups on the antibody surface either with the aldehyde groups which were created in L-lysine α-oxidase molecule (0.2% of initial enzymatic activity) or with the aldehyde groups of cross-linking molecules. Maximal (78%) L-lysine α-oxidase activity in conjugates was observed when oxidized peroxidase which contained the aldehyde, groups was used as crosslinking agent. The glutaraldehyde method yielded 70% of initial enzyme activity