The Soviet and Russian historians about the reasons of losses of archival documents in days of the Great Patriotic War (1941-1945)

This article emphasizes the main reasons for disappear of documents in days of th

About Development and Verification of Software for Finite Element Analysis of Beam Systems

AbstractThe distinctive paper is devoted to author's software (Windows application) for finite element analysis (FEA) of beam systems. Program application package provides convenient graphical interface to the user for quick creation of layout design in accordance with given coordinates of nodes. User can specify various boundary conditions in the corresponding nodes or apply external loads. The results of FEA are displayed in text and graphical forms (including visualization of deformed scheme). Moreover, these results can be exported into a Microsoft Word document. Open source and freeware program has been created by Microsoft Visual C++. Information about verification samples is presentedClic

PCSK9 Inhibitors in Clinical Practice: Experience of a Specialized Lipid Center

Aim. To characterize patients receiving PCSK9 inhibitors, and assess the efficiency of their treatment in a specialized lipid center.Material and methods. A retrospective analysis of the medical records of patients who visited the Lipid clinic of the National Medical Research Center for Therapy and Preventive Medicine (Moscow, Russia), receiving PCSK9 inhibitor and having lipid profile in dynamics, was carried out (n=77). Cardiovascular risk (CVR) and low-density lipoprotein cholesterol (LDL-C) target levels were evaluated in accordance with the Russian guidelines for the diagnostics and correction of dyslipidemias 2020.Results. Of 77 patients taking PCSK9 inhibitors (44.2% males, the median of age 56 [47; 66] years), the majority (64.0%) had a probable or definite familial hypercholesterolemia (FH). The proportion of other lipid metabolism disorders, pure hypercholesterolemia and combined hyperlipidemia was 21% and 15%. More than half of the patients (68.8%) had a very high CVR, mainly due to the presence of coronary heart disease (84.9%). The proportion of patients receiving PCSK9 inhibitors as monotherapy was 7.8%, in combination with high-intensity statin therapy – 33.8%, as part of triple lipid-lowering therapy (high-intensity statin, ezetimibe, PCSK9 inhibitors) – 50.6%. Addition of PCSK9 inhibitors to combined lipid-lowering therapy enabled to reduce the LDL-C level to 1.02 [0.62; 1.39] mmol/l with its total decrease from the baseline by 87.3%. While taking PCSK9 inhibitors, LDL-C <1.8 mmol/l and <1.4 mmol/l achieved at 78.3% and 57.7% FH patients with high and very high CVR, respectively. Among patients with other hyperlipidemias, 74.1% of patients with very high CVR was achieved the target LDL-C level <1.4 mmol/l.Conclusion: In a specialized lipid center, PCSK9 inhibitors are prescribed to patients with high or very high CVR, most of whom are FH patients. The effectiveness of the use of PCSK9 inhibitors in real-world practice is comparable to the results of clinical trials

Discovery of small molecules that activate RNA-methylation through cooperative binding to the METTL3/14/WTAP complex active site

Chemical modifications of RNA provide an additional, epitranscriptomic, level of control over cellular functions. N-6-methylated adenosines (m6As) are found in several types of RNA, and their amounts are regulated by methyltransferases and demethylases. One of the most important enzymes catalyzing generation of m6A on mRNA is the trimer N-6-methyltransferase METTL3-14-WTAP complex. Its activity has been linked to such critical biological processes as cell differentiation, proliferation, and death. We used in silico-based discovery to identify small-molecule ligands that bind to METTL3-14-WTAP and determined experimentally their binding affinity and kinetics, as well as their effect on enzymatic function. We show that these ligands serve as activators of the METTL3-14-WTAP complex

A combination of three muramyl peptides derived from gramnegative bacteria in immunotherapy of chronic pyodermia

The aim of the present study was to evaluate the clinical efficacy of a standardized combination of three muramyl peptides containing a residue of meso-diaminopimelic acid (Polymuramyl), as well as effects of this immunomodulator on the lymphocyte subpopulation profile, function of circulating neutrophils, and concentrations of serum immunoglobulins in the patients with chronic recurrent pyoderma. Thirty-five men (34.5±10 years) with exacerbation of chronic pyoderma (osteofolliculitis, folliculitis, sycosis, furunculosis) were randomized into two groups matched by age and clinical manifestations of the disease. In the comparison group (n = 17), the patients received standard treatment. In the main group (n = 18), in addition to the same standard treatment, the patients received intramuscular injections of Polymuramyl at a dose of 200 mg daily from day 1 to 5 of the study. The overall assessment of the treatment efficacy was performed on the day 14, and at 1 and 6 months of observations. Induction and maintenance of complete clinical remission were assessed as “significant improvement”; induction and maintenance of partial remission were considered to be “improvement”; persistent signs of skin inflammation and lack of remission were assessed as “lack of effect”. Immunological parameters were studied on days 0 and 14, and then at 1 and 6 months of the study. Addition of Polymuramyl to the standard treatment caused a marked tendency towards increased proportion of the patients with «significant improvement» or «improvement» on the day 14: total ratio of the patients with any clinical improvement was 24% higher, and the relative number of the patients with "lack of effect" was five-fold lower than in the comparison group (p=0.076). A trend towards improved clinical efficacy, according to the above criteria, was maintained after 1 and 6 months of the study. At 6 months of the follow-up, the proportion of patients without pustules/furuncles in the main group (9 out of 18) exceeded that in the comparison group (3/17, p = 0.047). Significant inter-group differences and dynamics of indicators of neutrophil functions, subpopulation composition of lymphocytes and concentrations of immunoglobulins in serum were not detected. However, in the main group after the 6-month observation, there was an upward trend in the absolute number of T-cells due to CD3+CD4+ subpopulation, as well as serum IgA concentration. The results of this study are in accordance with previously published data, thus indicating the ability of Polymuramyl to accelerate regression of clinical manifestations of chronic pyoderma and induce sustained remission of this disease. At the same time, the design of present investigation and the timing of taking biological samples for laboratory tests did not allow to register significant changes in most of the studied systemic immunological parameters under the influence of immunomodulator, except for the previously described modulation at the level of pro- and anti-inflammatory cytokines

Comparative assessment of organizational aspects of medical care in Russia and France in the first quarter of the xviii century

The article identifies the features of the organization of medical care for citizens of Russia and France in the first quarter of the XVIII centuryВ статье определены особенности организации медицинской помощи в России и Франции в первой четверти XVIII века

Bedaquiline, linezolid, pretomanid: their adverse events

The article discusses the clinical cases and tactics of treatment with bedaquiline, linezolid, and pretomanid in patients with multiple and extensive drug resistance. The main undesirable effects of bedaquiline, linezolid, pretomanid are considered and their qualitative assessment is given.В статье рассмотрены клинические случаи и тактики лечения бедаквилином, линезолидом, претоманидом пациентов с множественной и широкой лекарственной устойчивостью. Рассмотрены основные нежелательные явления бедаквилина, линезолида, претоманида и дана их качественная оценка

A Rapid Synthesis of Oriented Palladium Nanoparticles by UV Irradiation

Palladium nanoparticles of average size around 8 nm have been synthesized rapidly by UV irradiation of mixture of palladium chloride and potassium oxalate solutions. A rod-shaped palladium oxalate complex has been observed as an intermediate. In the absence of potassium oxalate, no Pd nanoparticles have been observed. The synthesized Pd nanoparticles have been characterized by powder X-ray diffraction (XRD), transmission electron microscopy (TEM), selective area electron diffraction and energy dispersive analysis by X-rays (EDAX) analyses. XRD analysis indicates the preferential orientation of catalytically active {111} planes in Pd nanoparticles. A plausible mechanism has been proposed for the formation of anisotropic Pd nanoparticles

ОЦЕНКА КОНЦЕНТРАЦИИ РАСТВОРИМОГО РЕЦЕПТОРА CD14 В ПЛАЗМЕ У ВИЧ-ИНФИЦИРОВАННЫХ ПОТРЕБИТЕЛЕЙ ОПИАТОВ

Chronic immune activation is one of the main causes of HIV disease progression. Bacterial components passed to the bloodstream from the gut as a result of microbial translocation, are known to induce immune activation. Component of Gram-negative bacteria’s cell walls, the lipopolysaccharide (LPS), is considered to be the major marker of microbial translocation. Through the activation of myeloid cells (predominantly monocytes) LPS causes the secretion of soluble CD14, thus making it a marker of LPS bioactivity. Besides sCD14 was shown to correlate with immune status in HIVinfected patients and to be an independent predictor of disease progression.Hypothesis: opiates increase microbial translocation from the gut in HIV-infected patients that is manifested by a higher concentration of sCD14 in plasma.Aim: to estimate the influence of opiate use on the level of sCD14 in plasma of HIV-infected patients.Materials and methods. Longitudinal study of 351 HIV positive individuals. Concentration of sCD14, was evaluated at 3 time points: baseline, after 12 and 24 months. Following groups were studied: 1) current opiate users – opiate use within past 30 days; 2) opiate users, who denied consumption of opiates within past 30 days; 3) people claiming to never have used opiates.Results. In dynamic assessment sCD14 mean was significantly higher in current opiate users (2222,46±39,02 ng/ml) against patients who denied opiates within past 30 days (1930±597 ng/ml) and those, claiming to never have used opiates (1915±577 ng/ml) (p<0,001).Conclusion. Opiate use in the course of HIV disease leads to increase in LPS induced monocyte activation which therefore signifies more intensive microbial translocation.Хроническая активация иммунной системы является одним из основных факторов патогенеза ВИЧ-инфекции. Значительная роль в хронической иммунной активации принадлежит транслокации бактериальных компонентов из кишечника в кровоток, в первую очередь липополисахарида (ЛПС) клеточной стенки грамотрицательных микроорганизмов. Растворимая форма рецептора CD14 (sCD14) является маркером моноцитарной активации, индуцированной ЛПС. Гипотеза исследования: у больных ВИЧ-инфекцией потребление опиатов способствует усилению микробной транслокации из кишечника, проявляющейся более высокой концентрацией sCD14 в плазме крови.Цель исследования: оценить влияние употребления опиатов на концентрацию sCD14 в плазме крови у больных ВИЧ-инфекцией.Материалы и методы: у 351 больного ВИЧ-инфекцией определена концентрация растворимого рецептора CD14 в плазме в трёх временных точках: при включении в исследование, через 12 и 24 мес. Сопоставлены значения концентрации sCD14 в группах: 1) активных потребителей опиатов; 2) наркопотребителей, отрицающих употребление опиатов за последние 30 дней; 3) пациентов, отрицающих факт употребления опиатов в анамнезе.Результаты: у активных опиатных наркопотребителей выявлено значимо более высокое среднее значение концентрации sCD14 в плазме крови (2213±596 нг/мл) в сравнении с пациентами, не употреблявшими опиаты за последние 30 дней (1930±597 нг/мл), и лицами, отрицающими употребление опиатов (1915±577 нг/мл) (р<0,001).Заключение: полученные результаты указывают, что у больных ВИЧ-инфекцией употребление опиатов приводит к усилению ЛПС-индуцированной моноцитарной активации, что, в свою очередь, свидетельствует о более интенсивной транслокации бактериальных компонентов