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TNF-α inhibitors are used in the treatment of non-systemic variants of juvenile idiopathic arthritis (JIA) in case of ineffectiveness or intolerance to methotrexate. Despite 20 years of experience of using of etanercept in pediatric rheumatology, a long-term study of the efficacy and safety of the drug in real clinical practice remains necessary. Objective of the study: to study the efficacy and safety of etanercept for treatment of various non-systemic JIA subtypes in real clinical practice. Materials and methods of research: data from the case histories of 375 patients (242 girls and 133 boys) with articular forms of JIA for 2010–2020 were included in a retrospective, open, uncontrolled, nonrandomized, continuous multicenter cohort study. The age of debut was 6.3 (2.9; 10.7) years. Demographic characteristics, subtypes of arthritis, indicators of laboratory activity of inflammation, and outcomes were estimated: achievement of remission, exacerbation, and switching from etanercept to another genetically engineered biological drug (GEBD) were assessed. Results: remission was recorded in 78.9% on average after 6 months. The factors that determine the likelihood of achieving remission were the absence of previous therapy with GEBD (p=0.001) and compliance with therapy – OR=2.5 (95% CI: 1.3; 4.7), p=0.006. Exacerbations were recorded in 29.5% and were associated with the presence of the HLA B27 antigen – OR=2.6 (95% CI: 1.1; 6.0), p=0.028, antinuclear factor seropositivity (p=0.060). Change of etanercept to another GEBD was made in 17.4% of children and was associated with a failure to achieve remission – OR=7.7 (95% CI: 4.0–14.3), p=0.000001, with previous exacerbations – OR=14,8 (5.3; 41.2), p=0.0000001 and the development of de novo uveitis – OR=2.4 (95% CI: 1.1–5.3), p=0.038. The arthritis subtype and the presence of concomitant methotrexate therapy did not significantly affect treatment outcomes. Conclusion: achievement of remission, compliance with therapy, history of previous therapy with GEBD, exacerbation of JIA and development of de novo uveitis determined the main outcomes of etanercept therapy. The JIA subtype, as well as concomitant therapy with methotrexate, did not significantly affect the outcomes of the disease, which makes it possible to consider etanercept therapy a very effective and safe method of treating JIA as a genetically engineered first-line therapy of any variants of articular forms of JIA, even in monotherapy with ineffectiveness or intolerance to methotrexate.

In recent years, in the pedagogical literature, it has become a common place to talk about the need to modernize, reform not only the entire education system, but also its specific components, that is, restructuring the educational process itself, in particular, the classroom system. The author considers options for methodological approaches and methodological techniques for the implementation of a modern lesson-research in the museum space. For example, a lesson in literature for grade 11 is used on the topic: “Symbolism, Acmeism, Futurism as Styles of Life and Creativity”, which was developed at the State Literary Museum within the framework of the “Lesson in the Museum” project. The analysis of the results obtained is carried out, and practical recommendations are given

The data and the main demographic characteristics of the Russian population dynamics are analyzed on the basis of Rosstat’s official published data for 1995 – 2018. G matrix of the vector transition of the age groups from year to year was designed, its characteristics were determined. Model estimates of the probability of contracting tuberculosis and recovering from it were made.

The “Museum StarTrack” project was launched in Moscow, which aims to unite the efforts of museum workers and employees of social service centers in working with the older generation. One of the first stages of the project was the holding of a practical conference “Museums and the Older Generation: The Practice of Participation in the Age of Social Challenges”, the main theses of which are set out in this article.

Pressure sores remain an important clinical problem with significant socioeconomic implications. The pressure sores treatment via reparative processes activation in tissues by low-temperature plasma discharges was studied in the present work. Low-temperature plasma discharges were initiated by high-frequency 0.11, 2.64, 6.78, and 13.56 MHz current. It is shown that the optimal current frequency for the generation of the cold plasma is 6.78 MHz. This current frequency was used in clinical studies of pressure sores treatment with cold plasma discharges of the glow type. The efficiency of treatment was evaluated by analysis of histological samples, histochemical and bacteriological methods. Low-temperature plasma discharge treatment improved the dynamic of pressure sore healing, activated reparative processes in injured tissues, and decreased bacteria numbers in a wound. The most pronounced effect was observed after 14-21 days. The low-temperature plasma discharges accelerated pressure sores healing from 14 to 16% compared with non-treated by cold plasma wound. The effect depended on the pressure sores etiology. Low-temperature plasma discharges of glow type may be considered as an effective approach to pressure sores therapy.

To assess the efficacy of treatment of cricopharyngeal insufficiency in chronic critical illness caused by severe brain injury using non-invasive magnetic stimulation with endoscopic navigation.Thirty patients (19 men and 11 women, mean age 50±12 years) were studied. The exposure was carried out by a bipolar alternating magnetic field using an inductor located in the projection of the hyoid bone. The study compared the standard therapy and the complex of therapeutic measures, in which the proposed non-invasive magnetic stimulation method with endoscopic navigation was included. The procedure was carried out daily without regime changes, with objective control 1 time in 10 days. The duration of the first course was 10 days, followed by a decision to extend the course for another 10 days, depending on the objective dynamics. Evaluation was performed with the Rosenbek Penetration and Aspiration Scale (PAS), the Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS), The Mann assessment of swallowing ability (MASA) and the Functional oral intake scale (FOIS).Improvements of swallowing function were observed in both groups, but qualitative changes were more pronounced in the main group. The use of the proposed method made it possible to obtain a more stable and predictable result.Оценить эффективность лечения крикофарингеальной недостаточности у пациентов в хроническом критическом состоянии, обусловленном тяжелым поражением головного мозга, методом неинвазивной стимуляции биполярным переменным магнитным полем с эндоскопической навигацией.В исследовании участвовали 30 пациентов, из них 19 мужчин и 11 женщин, средний возраст составил 50±12 лет. Воздействие осуществляется биполярным переменным магнитным полем при помощи индуктора, который располагается в проекции подъязычной кости. В исследовании сравнивалась группа пациентов, получающих стандартную терапию данной патологии, и группа, в комплекс лечебных мероприятий которой был включен предложенный способ воздействия. Процедура проводилась ежедневно без изменений режима, с объективным контролем (инструментально и в баллах по шкалам) 1 раз в 10 дней. Длительность первого курса процедур 10 дней, с последующим решением о продлении курса еще на 10 дней в зависимости от объективной динамики. Оценка производилась по шкалам видеофлюороскопия Rosenbek (PAS), фиброоптическая эндоскопическая оценка глотания (FEES) FEDSS, логопедические The Mann assessment of swallowing ability (MASA) и Functional oral intake scale (FOIS).Улучшение функции глотания наблюдалось в обеих группах, однако в основной группе изменения были более выраженными. Кроме того, использование предложенного метода позволило получить более стабильный и прогнозируемый результат.

Background: The development of cholinergic deficit is considered an early sign of a number of pathological conditions, including Alzheimer’s disease. Cholinergic dysfunction underlies cognitive decline associated with both normal aging and Alzheimer’s disease. Objective: Here, we studied a possible mechanism of functional impairment of cholinergic neurons using an olfactory bulbectomy model. Methods: Male mice were subjected to olfactory bulbectomy or sham surgery. Three weeks after that they were trained in Morris water maze and then euthanized one month after surgery. The cholinergic indices as well as the indices of oxidative stress were studied using immunohistochemistry, western blot and ELISA. Gene expression was studied using RT-qPCR. Results: The experimental treatment was followed by impaired learning of a standard spatial task in a water maze. This was associated with a decrease in the number of cells containing choline acetyltransferase (ChAT), in relation to total number of neurons in the medial septum and lower ChAT enzymatic activity in the hippocampus. However, the levels of mRNAs of ChAT, vesicular ACh transporter and acetylcholine esterase remained unchanged in bulbectomized mice compared to sham-operated animals. These alterations were preceded by the accumulation of protein-bound carbonyls, indicating oxidative damage of proteins, whereas oxidative damage of nucleic acids was not detected. Conclusion: We assume that in olfactory bulbectomy model, oxidative damage of proteins may cause cholinergic dysfunction rather than irreversible neuronal damage. These data indicate that cholinergic neurons of the basal forebrain are very sensitive to oxidative stress, which may be responsible for the appearance of early cognitive decline in Alzheimer’s disease.

The article discusses the main methods of manufacturing products by layer-by-layer polymer fusion using non-planar layers. Conclusions are drawn about the disadvantages of these approaches. A proprietary method of manufacturing products on a multi-axis FFF 3D printer is proposed.

We report on the formation and comprehensive study of atomic and electronic structures of a new Tl-Mg two-dimensional compound reconstruction with $\sqrt{3}\ifmmode\times\else\texttimes\fi{}\sqrt{3}$ periodicity on a Si(111) substrate. Owing to properties of its constituent elements and crystal structure with a breathing kagome lattice of Mg and a dense Tl layer (4/3 monolayer), this double-layer system displays promising features, including spin-split metallic bands, nearly flat bands, and a saddle point with corresponding divergences in the local density of states. These features indicate the possibility that strongly correlated electronic states exist in this structure after tuning the Fermi level position. In accordance with the ${C}_{3}$ symmetry, we observe spin-orbit-coupling-driven Rashba-type spin splitting with spin degeneracy at the $\overline{M}$ point and Zeeman-like splitting at the $\overline{K}$ point. In contrast to the previously reported cases, splitting at the $\overline{K}$ point is significant to produce fully out-of-plane spin-polarized cones. Due to opposite Berry curvatures at the $\overline{K}$ and ${\overline{K}}^{\ensuremath{'}}$ points of the hexagonal surface Brillouin zone, spins at these valleys have opposite signs, which ensure effective spin-pseudospin coupling.

2D compounds made of Group-III and Group-V elements on the surface of silicon and germanium attract considerable attention due to prospects of creating III-V binary monolayers, which are predicted to hold advanced physical properties. In the present work, we have investigated two such systems, (Tl, Sb)/Ge(111) and (Tl, Bi)/Ge(111) using scanning tunneling microscopy, low energy electron diffraction observations and density-functional-theory calculations. In addition to the previously reported surface structures of 2D (Tl, Sb) and (Tl, Bi) compounds on Si(111), we found new ones, namely, 7 × 7 and 3 × 3. Formation processes and plausible models of their atomic arrangements are discussed.

Long-term laboratory studies resulted in the improvement of the regime of keeping and testing of voles: Microtus arvalis Pall., M. rossiaemeridionalis Ognev and M. socialis Pall.. Methods of primary testing of new rodenticides and bait products, determination of LD50 and estimation of resistance to anticoagulant rodenticides were adapted for gray voles of the genus Microtus. Rodenticides testing on laboratory bred individuals in group testing scheme included experimental reconstruction of field treatments conditions, such as cool temperature regime and alternative juicy feed. The test methods with temporally kept wild-caught Microtus voles were used in the study of level of resistance and bait preference in certain habitats, and also as an additional method for testing the water vole Arvicola terrestris L., for which the method of maintenance of laboratory colonies, evaluated for Microtus voles, were not applicable. New scheme of estimation of resistance level in lab conditions is based on discrimination doses, given to experimental samples of voles, i.e. 30 mg/kg of Etilfenacin in 3 days for anticoagulants of first generation, or single dose 1 mg/kg of Brodifacoum for second generation.

A novel low-dimensional structure of Pb is found to form on the B-segregated heavily doped p-type Si(111) substrate. The hole doping changes the growth mode of the Pb/Si(111) layer resulting in the formation of a double-layer film, which structure drastically differs from the typical single-layer hexagonal incommensurate (HIC) or striped incommensurate (SIC) phases in the Pb/Si(111) system. Using scanning tunneling microscopy, angle-resolved photoelectron spectroscopy, and density functional theory calculations, the atomic arrangement and electronic band structure of this surface reconstruction were examined. Two possible models were proposed both being constructed from the similar Pb bilayer ( Θ P b = 2 ML) with 3 × 3 periodicity, but having different orientations relative to the B-segregated Si(111) substrate. Both models produce a similar electronic band structure consistent with an experimentally obtained ARPES spectrum.

Exosomes and microvesicles, collectively referred to as small extracellular vesicles (sEV) are vesicles with an average size of about 100-150 nm. Currently, the role of sEV in various aspects of signaling in the body is being actively investigated; in addition, sEV can often serve as markers of various pathologies. The active study of the sEV composition is continuing. In this study we have demonstrated that in sEV it is possible to determine cholesterol and triglycerides concentration by using commercial kits designed for serum. The technique was tested on sEV from the blood of patients diagnosed with depression and on healthy volunteers. No differences were found in the concentration of cholesterol and triglycerides in mEV from the blood serum of depressed patients and the control group. The concentration of cholesterol and triglycerides in the samples is several times higher than the sensitivity threshold of the methods set by the manufacturer of the kits.

Studying the In and Bi coadsorption onto the Si(100) surface at elevated temperatures using Scanning Tunneling Microscopy, Angle-Resolved Photoelectron Spectroscopy, and Density Functional Theory, we have found the formation of a 2 × 4 array of In-Bi heterogeneous dimers. The surface is closely related to a Bi-induced Si(100)2 × n-Bi ( n = 5 − 12 ) reconstruction and can be visualized as that with one Bi atom in a Bi-Bi dimer replaced by In atom, and the length of dimer rows stabilized on 4 periods. The In-Bi dimers are buckled, with Bi atoms being 0.62 A higher than In. STM simulations revealed that the contribution of a Bi atom into experimental STM contrast is dominant. The asymmetric In-Bi heterodimers orient in a unit cell independent of each other producing chaotically looking STM images despite the 2 × 4 lattice itself is well-ordered. The surface is semiconductor featuring noticeable Rashba-type spin-splitting of surface states. This structure is believed to be an interesting object for theoretical and experimental studies on the influence of lack of symmetry and chemical disorder to spin polarization in the low-dimensional materials.

The concentration of ciliary neurotrophic factor (CNTF) was measured in lacrimal fluid (LF) using Human CNTF Quantikine ELISA kit (“R&D Systems”, USA) on a ChemWell 2910 automatic analyzer (“Awareness Technology Inc.”, USA). We initially attempted to use commercial kits, designed for serum and plasma CNTF detection, to quantify lacrimal CNTF. The results, however, were rarely above the minimum detection level of the kits, most likely due to matrix complexity and low concentrations of CNTF in diluted LF (LF had to be diluted because of the small volume of collected samples). The optimal sensitivity and the lowest background for the best minimum quantifiable value were determined empirically. Phosphate buffer solution containing 1% bovine serum albumin was selected as an optimal diluent for CNTF measurements in small fluid samples. A standard curve was produced using the calibrating solutions 0-250 pg/ml. Acid treatment of LF samples before the analysis allowed to increase the detectable concentration of the CNTF two-fold. The 1:3 dilution was selected based on the available volume of collected LF and a reasonable variation coefficient. The described protocol allowed to develop a sandwich ELISA optimized for lacrimal CNTF., Определение цилиарного нейротрофического фактора – ciliary neurotrophic factor (CNTF) в слёзной жидкости (СЖ) человека рутинными лабораторными методами затруднено из-за его низкой концентрации в структурах глаза и недостаточного количества материала для анализа. Были подобраны условия для определения CNTF в СЖ твердофазным методом иммуноферментного анализа (ИФА) на основе набора Human CNTF Quantikine ELISA Kit (“R&D Systems”, США) с использованием автоматического иммуноферментного анализатора ChemWell 2910 Combi (“Awareness Technology Inc.”, США). Предварительная кислотная обработка проб СЖ позволила вдвое повысить концентрацию CNTF. Полностью автоматизированная система проведения анализа и выбор разбавителя с низкой оптической плотностью бланка (0.011) обеспечили линейную зависимость калибровочного графика от 0 до 250 пг/мл с возможностью его использования для расчета концентрации CNTF в области низких значений. Рабочие характеристики оптимизированной тест-системы ИФА (линейность метода, предел обнаружения, воспроизводимость, интерференция матрицы) в указанном диапазоне концентраций соответствовали критериям приемлемости для используемого метода определения. Разведение образцов СЖ в четыре раза, совмещённое с кислотной обработкой проб, оказалось оптимальным для получения стабильных результатов при проведении анализа. В этом случае концентрация CNTF в пробе составляла в среднем 10.4±0.4 пг/мл с коэффициентом вариации 4.2% и близостью определяемых значений к ожидаемым величинам на уровне 104%.

Research engineering methods allow to essentially reduce terms and costs of design researches when developing new products and technologies. The implementation of new cooling methods in the cutting area demands developing the relevant design of the device and this is an uncommon task. The work describes the creation process of such a device by means of the research designing method.

Two-dimensional (2D) topological insulator is a promising quantum phase for achieving dissipationless transport due to the robustness of the gapless edge states resided in the insulating gap providing realization of the quantum spin Hall effect. Searching for two-dimensional realistic materials that are able to provide the quantum spin Hall effect and possessing the feasibility of their experimental preparation is a growing field. Here we report on the two-dimensional (In, Sb)2[Formula: see text]2[Formula: see text] compound synthesized on Si(111) substrate and its comprehensive experimental and theoretical investigations based on an atomic-scale characterization by using scanning tunneling microscopy and angle-resolved photoelectron spectroscopy as well as ab initio density functional theory calculations identifying the synthesized 2D compound as a suitable system for realization of the quantum spin Hall effect without additional functionalization like chemical adsorption, applying strain, or gating.

Blood exosomes and microvesicles, collectively known as small extracellular vesicles (sEV), are vesicles about 100-150 nm in size. Small EV are involved in various aspects of signaling in the body; in addition, they can serve as markers of various pathologies. For biochemical studies, vesicle solubilization is often required. We tested the ability of various detergents to dissolve membranes of the sEV. Small EV were isolated from the blood serum of healthy volunteers by gel filtration on Sepharose CL-2B and tried to solubilize them using the anionic detergent DOC (sodium deoxycholate), non-ionic detergent Brij 35 (polyoxyethyleneglycol dodecyl ether), zwitterionic detergent CHAPS (3 - [(3-chloramidopropyl) dimethylammonio] -1-propanesulfonate), and cationic detergent CTAB (cetyl trimethylammonium bromide). The concentration of sEV in the solution was determined by dynamic light scattering. We find DOC is the most effective for sEV solubilization., Экзосомы и микровезикулы, совместно называемые малые экстраклеточные везикулы (мЭВ), представляют собой везикулы размером около 100-150 нм. Малые ЭВ принимают участие в самых разных аспектах сигналинга в организме; кроме того, они могут служить маркерами разных патологий. Для биохимических исследований зачастую требуется солюбилизация везикул. Мы проверили способность различных детергентов растворять мембраны мЭВ. Малые ЭВ выделяли из сыворотки крови здоровых добровольцев с помощью гель-фильтрации на Sepharose CL-2B и пытались их солюбилизировать с помощью анионного детергента DOC (дезоксихолат натрия), неионного детергента Brij 35 (додециловый эфир полиэтиленгликоля), цвиттерионного детергента CHAPS (3-[(3-хлорамидопропил) диметиламмонио]-1-пропансульфонат), катионного детергента CTAB (цетил триметиламмония бромид). Концентрацию мЭВ в растворе определяли с помощью динамического светорассеяния. Самым эффективным детергентом для солюбилизации мЭВ из сыворотки крови оказался DOC.

Using scanning tunneling microscopy (STM) observations, it has been found that deposition of 0.8–1.3 monolayer of Ag onto the mixed Si(111)α − √ 3 × √ 3 / β − √ 3 × √ 3-Bi surfaces followed by annealing at 150–250°C induces formation of new ordered and quasi-ordered (Bi,Ag)/Si(111) metastable structures, √ 19 × √ 19, 4 × 4, 2 √ 3 × 2 √ 3, and ‘3 √ 3 × 3√3’. Scanning tunneling spectroscopy has demonstrated that the 2√3 × 2√3 structure is semiconducting, while the √19 × √19 and 4 × 4 structures are metallic. Structural models of the √19 × √19 and 4 × 4 have been proposed based on placing a single Ag(111)1 × 1 layer with selected Ag atoms being substituted for Bi atoms onto the bulk-like Si(111)1 × 1 surface. The models have been proved with DFT calculations and comparison of simulated and experimental STM images. Calculated band structure of the Si(111)4 × 4 structure displays a spin–split metallic surface-state band with splitting of ∆k ≈ 0.002 A − 1 and ∆E ≈ 10 meV in the vicinity of the Fermi level.

Aim. To analyse the causes of death of individuals infected with the human immunodeficiency virus (HIV)/patients with acquired immunodeficiency syndrome (AIDS) in the Clinical Infectious Diseases Hospital named after S.P. Botkin in 2008-2010 taking into account the timing of disease, comorbidities, and clinical and laboratory data. Methods. The study included 439 HIV-infected individuals, who died in the Clinical Infectious Diseases Hospital named after S.P. Botkin in 2008-2010. Two groups of patients were identified: deaths from HIV/AIDS (n=306) and from other diseases (n=133, HIV infection was considered to be a concomitant disease). In both groups, analyzed were the short-term mortality rates, the presence of drugs and/or alcohol dependency, and the main causes of death (according to autopsy results). Results. In the group of patients who died of HIV-infection/AIDS and who did not receive antiretroviral therapy, generalized tuberculosis was diagnosed most often (65.7% of cases). Other rare diseases were pneumocystis pneumonia, cryptococcosis, cerebral toxoplasmosis, generalized fungal infection, cerebral lymphoma, and cytomegalovirus infection. The most frequent causes of death in the group of patients whose HIV-infection was considered to be a concomitant diseases were chronic viral hepatitis in the cirrhotic stage (42.9%) and septic thromboendocarditis, which were mainly diagnosed in social maladjusted patients: patients with alcoholism or intravenous drugs users. During evaluation of the short-term mortality rates it was established that 21 to 29% of patients in different years died on the 1st-3rd day after admission, which was related to extremely severe conditions of the patients. In Russia, including St. Petersburg, an annual increase in the number of new cases of HIV infection and increased mortality are registered, which indicates the severity of the epidemic and makes it possible to predict the increase in the number of patients requiring hospital treatment. Conclusion. The main causes of death among HIV-infected individuals in 2008-2010 were generalized tuberculosis and chronic viral hepatitis in the stage of cirrhosis; the high index of short-term mortality among HIV-infected patients suggests the need for measures for early detection of HIV-positive individuals and their medical examination, as well as an increase in the number of beds in order to provide specialized care to HIV-infected individuals in St. Petersburg.