Рандомизированное контролируемое исследование эффективности электрофизиологического мониторинга дексмедетомидина у пациентов с повреждением головного мозга различного генеза

Background.At the same time, the main effect of the use of this drug is the elimination of the autonomic nervous system dysfunction and sympatholysis. It seems important to search for a method of indications and selection of a dose of dexmedetomidine in intensive care.Aims to improve the clinical effectiveness of the electrophysiological navigation of the prolonged use of dexmedetomidine in patients with brain pathology of various origins.Methods.The study included 83 patients 2050 days after the traumatic brain injury, anoxic damage; consequences of acute disorders of cerebral. 37 patients comprised the 1st intervention group with a clinical course of dexmedetomidine (male 28; female 9; average age 49.62.3 years) and 46 patients comprised the 2nd control group without pharmacological correction with dexmedetomidine (male 23; female 23, average age 512.5 years). Criteria for the inclusion of prolonged infusion of the drug dexmedetomidine (Orion Pharma, Finland) are based on heart rate variability (HRV) indicators characteristic of sympathetic hyperactivity, the target task of titration of doses of dexmedetomidine served as the parameters for achieving normal HRV indicators, the appearance of parasympathetic hyperactivity served as the basis for reducing the dosage of the drug or stopping it of application. HRV parameters were recorded before dexmetomedine infusion-initially, on 13; 45; 910; 1520 days of drug administration.Results.The starting dose of dexmedetomidine with sympathetic hyperactivity in patients was 0.12 to 0.24 g.kg1.hr1(average dose 0.160.01; total 200 mg/day). According to digital data from HRV, the effective dose of dexmedetomidine ED50 was 0.260.03 g.kg1.hr1(total daily 353.835.1 g) and was achieved on day 910 using dexmedetomidine.Conclusions.The protective role of dexmedetomidine with correction of sympathetic hyperactivity based on electrophysiological navigation according to the HRV is reliable in the following indicators: The improvement of consciousness; a significant decrease in the incidence of distress lung syndrome; septic shock; mortality.Обоснование. Дексмедетомидин используетсяприпроцедурной седациииликвидации симптомов симпатической гиперактивности (ажиотация, тахикардия, гипертензияит.п.). Основной эффект применения данного препарата устранение дисфункции автономной нервной системыисимпатолизис. Представляются важными поиск метода объективизации показанийиподбор дозы дексмедетомидинавинтенсивной терапии.Цель исследования улучшить возможности мониторингаиклиническую эффективность примененияидозирования дексмедетомидинаспомощью электрофизиологической навигацииупациентовспатологией головного мозга различного генеза.Методы.Висследование включено 83 пациента (51 мужчина, 32 женщины; средний возраст 50,381,7 года)впериод более 20днейспоследствиями: черепно-мозговой травмы (ЧМТ) (n=24; 28,9%); острого нарушения мозгового кровообращения (ОНМК) (n=17; 20,5%); аноксического повреждения головного мозга (n=16; 19,3%); субарахноидального кровоизлияния (n=23; 27,7%); нейрохирургических операцийнаголовном мозге (n=3; 3,6%). 37 пациентов (28 мужчин, 9 женщин; средний возраст 49,62,3 года) составили первую группу вмешательстваcкурсом клинического применения дексмедетомидинаи46 пациентов (23 мужчины, 23 женщины; средний возраст 512,5 года) вторую (контрольную) группубезфармакологической коррекции дексмедетомидином. Критерии начала пролонгированной инфузии препарата дексмедетомидина (фирмаOrionPharma, Финляндия) основанынапоказателях вариабельности ритма сердца (ВРС), характерныхдлясимпатической гиперреактивности; таргетированной задачей титрования дозы дексмедетомидина служили параметры достижения нормы показателей ВРС; появление парасимпатической гиперактивности служило основанием уменьшения дозировки препаратаилипрекращения его применения (использовались 5-минутные записи кардиоинтервалов (прибор Полиспектр-8 ЕХ фирмы Нейрософт, Россия)). Регистрировали следующие показатели ВРС: SI стресс-индекс Баевского (индекс напряжения регуляторных систем индекс напряжения)внормализованных единицах (н.е.); SDNN среднеквадратичное отклонение RR-кардиоинтерваловвмс; rMSSD среднеквадратичное отклонение разности двух смежных отсчетов RR-кардиоинтерваловвмс; pNN50% доля RR-кардиоинтерваловвпроцентах, отличающихсяотпредыдущего более чемна50 мс;TP общая мощность спектра частотвмсек2. Параметры ВРС регистрировалидоинфузии дексметомидина исходно,на13-и, 45-е, 910-е, 1520-е сут применения лекарственного препарата.Результаты.Стартовая доза дексмедетомидинапри симпатической гиперактивности составилаупациентовот0,12до0,24 мкг/кг/ч (средняя доза 0,160,01; суммарно 200 мкг/сут).Поцифровым данным ВРС эффективная доза дексмедетомидина ЭД50составила 0,260,03 мкг/кг/ч (суммарнозасутки 353,835,1 мкг)ибыла достигнутана910- й день применения дексмедетомидина.Заключение.Коррекция симпатической гиперактивностиприприменении дексмедетомидина вызывает повышение уровня сознания, снижает частоту возникновения септического шока, дистресс синдрома легких, летальность

Setting thresholds for potentially toxic chemicals migrating from medical devices

Summary Introduction. As part of ensuring the safety of medical devices, the formation of a list of priority substances that are part of medical devices and pose an increased danger, is a necessary step that precedes the procedure for establishing permissible levels of toxic components from medical devices entering the human body during their use. The aim of the study is to analyze the components of medical devices and data on the toxicity of potentially hazardous substances, followed by the formation of a list of substances hazardous to health. Materials and methods. Analytical studies were carried out on the formation of a list of priority substances that are part of medical devices, as well as on the properties of these components hazardous to health. Results. For the first time, a toxicological dossier of chemicals was formed taking into account the available information on the quantitative characteristics of carcinogenic and non-carcinogenic risks, a list of substances was developed to establish acceptable levels of entry into the human body when using medical devices. Conclusion. The toxicological dossiers formed within the framework of these studies on the list of substances dangerous to health, in the future, will allow to scientifically substantiate the choice of relevant toxicity indicators and uncertainty factors to establish acceptable levels of intake into the human body when using medical devices

ИЗМЕНЕНИЯ СТРУКТУРНО-ФУНКЦИОНАЛЬНОЙ ПЛАСТИЧНОСТИ ГОЛОВНОГО МОЗГА, ИНДУЦИРОВАННЫЕ ОБОГАЩЕННОЙ СРЕДОЙ

The review contains current data on structural and functional brain plasticity mechanisms under the enriched environment. Enriched environment contains social and non-social stimuli acting on different aspects of the development and functioning of the brain.  Special attention is devoted to the modeling of enriched environment in the experiment. Enriched environment implies the action of social stimuli, new objects, therefore the enriched environment in animals can be considered as an adequate model to study changes in brain structure and function in people during learning or acquiring complex skills. The review describes the theory of  enriched environment’s influence on neurogenesis, the neuron-glia relationships, and the impact of enriched environment on damaged brain as well as  the possibilities of using the paradigm of enriched environment for neurorehabilitation. Molecular mechanisms of synaptic transmission, which has a correlation with the performance of cognitive functions, are the possible target for the action of environmental factors at the brain under (patho)physiological conditions. The considerable progress has been done in understanding the mechanisms that mediate the effects of  enriched environment on the brain, but still there are many non-resolved questions in the neurochemistry and neurobiology of this phenomenon. Overall, the experience-induced neuroplasticity is a unique mechanism for the development and recovery of brain functions. It opens new perspectives in neuropharmacology and neurorehabilitation.В обзоре литературы представлены данные о структурных и функциональных механизмах пластичности головного мозга при воздействии обогащенной среды. Обогащенная среда содержит социальные и несоциальные стимулы, воздействующие на различные аспекты развития и функционирования головного мозга. Особое внимание посвящено моделированию обогащенной среды в эксперименте. Поскольку формирование обогащенной среды подразумевает действие социальных стимулов, новых объектов, поэтому воспроизведение обогащенной среды у животных может считаться адекватной моделью для изучения изменений в структуре мозга и функций, которые происходят при обучении или приобретении сложных профессиональных навыков у человека. Описаны теории влияния обогащенной среды на нейрогенез, нейрон-глиальные взаимоотношения, на поврежденный мозг и возможности использования обогащенной среды при нейрореабилитации. Молекулярные механизмы синаптической передачи, имеющей корреляцию с эффективностью когнитивных функций, являются одной из возможных мишеней действия факторов окружающей среды на мозг в физиологических и патофизиологических условиях. Несмотря на значительный прогресс, достигнутый в понимании механизмов, которые опосредуют эффекты обогащенной среды, в нейрохимии и нейробиологии этого феномена остается много нерешенных проблем. В целом, опыт-индуцированная нейропластичность представляет собой уникальный механизм развития и восстановления головного мозга, применение которого открывает новые перспективы в нейрофармакологии и нейрореабилитации.

НАД+-КОНВЕРТИРУЮЩИЕ ФЕРМЕНТЫ В КЛЕТКАХ НЕЙРОНАЛЬНОЙ И ГЛИАЛЬНОЙ ПРИРОДЫ: CD38 КАК НОВАЯ МОЛЕКУЛА-МИШЕНЬ ДЛЯ НЕЙРОПРОТЕКЦИИ

The review contains current data on molecular mechanisms which control NAD+ homeostasis in brain cells. It also deals with the role of NAD+-converting enzymes in regulation of functional activity, viability and intercellular communication of neuronal and glial cells. Special attention is paid to involvement of CD38 into regulation of NAD+ levels in brain cells in normal and pathological conditions. В обзоре представлены данные о молекулярных механизмах поддержания гомеостаза НАД+ в клетках головного мозга и о роли НАД+-конвертирующих ферментов в регуляции функциональной активности и жизнеспособности клеток нейрональной и глиальной природы, реализации нейрон–глиальных взаимодействий. Особое внимание уделено механизмам участия CD38 в контроле содержания НАД+ в клетках головного мозга в норме и при развитии патологии.

Body appreciation around the world: Measurement invariance of the Body Appreciation Scale-2 (BAS-2) across 65 nations, 40 languages, gender identities, and age.

The Body Appreciation Scale-2 (BAS-2) is a widely used measure of a core facet of the positive body image construct. However, extant research concerning measurement invariance of the BAS-2 across a large number of nations remains limited. Here, we utilised the Body Image in Nature (BINS) dataset - with data collected between 2020 and 2022 - to assess measurement invariance of the BAS-2 across 65 nations, 40 languages, gender identities, and age groups. Multi-group confirmatory factor analysis indicated that full scalar invariance was upheld across all nations, languages, gender identities, and age groups, suggesting that the unidimensional BAS-2 model has widespread applicability. There were large differences across nations and languages in latent body appreciation, while differences across gender identities and age groups were negligible-to-small. Additionally, greater body appreciation was significantly associated with higher life satisfaction, being single (versus being married or in a committed relationship), and greater rurality (versus urbanicity). Across a subset of nations where nation-level data were available, greater body appreciation was also significantly associated with greater cultural distance from the United States and greater relative income inequality. These findings suggest that the BAS-2 likely captures a near-universal conceptualisation of the body appreciation construct, which should facilitate further cross-cultural research. [Abstract copyright: Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition

ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in three infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALKrearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (seven and twelve from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated-ERK, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, while CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, ten with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis, and provides guidance for the clinical management of this emerging histiocytic entity.Molecular tumour pathology - and tumour genetic

LANGUAGE POLICY AND MULTICULTURAL TEACHING IN ZAMBIA

Language education is an essential tool for successful human life in a multicultural and multilingual community of people. Knowledge of a foreign language of international significance gives an individual a chance to take a more prestigious position in society, both socially and financially. Moreover, it is becoming increasingly clear that the wealth of culture in the modern market economy and the development of information technologies are human resources, which act as the primary strategic factor of economic and social progress. In solving this problem, an important role is given to language education as a factor that turns a person into a developed personality. It expands his/her social and economic freedom and mobility. The article considers problems of the language policy and multicultural teaching, peculiarities of multilingual and multicultural education in Zambia. Integrative learning of two or more languages involves the formation of bilingualism or multilingualism. The concept of 'multilingualism' is determined as the development of interlanguage and intercultural relationship. It is a necessary condition for communication between people representing different societies and ethnicities. The interpenetration of languages is a tool for uniting peoples, understanding and strengthening friendly and good-neighborly relations between representatives of different countries. It contributes to the preservation of the multi-ethnic and multicultural heritage on a global scale. The modern process of teaching a foreign language (FLT), built on a communicative basis, with a focus on the student's personality and taking into account the language situation in the multinational country, forms a broad humanistic view of the world around the people, based on universal values, and makes a significant contribution to improving the humanitarian content of national education. As a result of comparative analyses, the author discovered that the curriculum and its teaching and learning in educational institutions of Zambia are thoroughly multicultural. Zambian students can critically evaluate various language policies, teaching practices, and planning programs implemented in multilingual education settings

Problems of implementation of personalized medicine in medical cosmetology in Russia

At the present time, the 4P concept (predictive, preventive, personalised and participatory) is a prospective trend in development of clinical medi-cine. The concept is being actively introduced into different medical specialities. However, the development of personalised approach in medical cosmetology as a speciality at the intersection of medical sciences (dermatology, maxillofacial surgery, plastic surgery, restorative medicine, general practice, psychiatry, clinical pharmacology, etc.) is at the stage of discussion. The concept of 4P medicine suggests, among other things, analysis of genetic risks and development of preventive procedures based thereon that would decrease the risk of cosmetological complications development. The review includes analysis of literature dated 2010-2020. The following databases in Russian and foreign languages were searched using the keywords and advanced search builders: E-Library, PubMed, Springer, Clinicalkeys, Google Scholar. In this paper, we introduce a novel compilation of the known gene polymorphisms that may be used for determination of the genetic risks in cosmetological patients

Start of reproduction and allozyme heterozygosity in Pinus sibirica under different techniques of artificial forest stand establishment

<p>Siberian stone pine (Pinus sibirica Du Tour) is one of the main forest-forming tree species in boreal forests of Eurasia. Large edible<br />seeds of this species have an important resource value because of their high nutritious properties. Development of approaches to<br />establishment of early cone producing Siberian stone pine stands including utilization of corresponding genetic background is one of the priorities of forest resource management. The goal of our study was to evaluate the effect of stand density on the differentiation of trees by<br />the age of first reproduction and the relationship of allozyme heterozygosity and morphological traits variability in Siberian stone pine.<br />Morphological and allozyme variability in artificial Pinus sibirica stands with high and low density was investigated. In the high-density<br />stand the distance between trees was 0.7 and 3 meters (4080 trees per ha) while in the lowdensity stand it was 8 and 8 meters (144 trees<br />per ha). Age of formation of first male and female cones was evaluated by retrospective method based on analysis of tracks of cones on<br />a shoot bark. Tree height, diameter and number of male, female and vegetative shoots in a crown of model trees were measured.<br />Genotypes of the trees were determined by 29 isozyme loci coding for 16 enzymes (ADH, FDH, FEST, GDH, GOT, IDH, LAP, MDH, MNR, PEPCA, 6-PGD, PGI, PGM, SDH, SKDH, SOD). In the low-density stand, the portion of generative trees was higher and differentiation of trees by age of reproduction starting was lower in spite of the smaller age of trees as compared to the high-density stand. In<br />both samples, the age of formation of first generative organs was related negatively with stem height, stem diameter and number of<br />female shoots. In the high-density stand, positive relation of age of first reproduction with total number of shoots and number of<br />male shoots was found. In both samples nonreproductive trees were less heterozygous at isozyme loci as compared to trees starting cone<br />production. Allozyme heterozygosity correlated positively with the age of first cone production in the high-density stand only. We<br />conclude that the degree of competition between trees due to different stand density determined age and timing of first reproduction<br />and development of tree crowns. The relationship of allozyme heterozygosity and the age of first reproduction was expressed more in the high-density stand of Siberian stone pine.</p