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The COVID-19 pandemic has significantly changed the understanding of the safety profile of therapies for immunoinflammatory rheumatic diseases (IRDs). This is primarily due to the negative impact of a number of basic disease-modifying antirheumatic drugs (DMARDs) and genetically engineered biological drugs (biological DMARDs, or biologics) on the course and outcomes of a new coronavirus infection. A number of studies have shown that anti-B-cell therapy (rituximab) gave a statistically significant increase in the risk of severe COVID-19 and an increase in mortality. At the same time, the analysis of real clinical practice data dictated the need to establish a number of restrictions on the use of certain classes of biologics and to search for alternative therapy programs to maintain control over disease activity. Purpose of the study. The purpose of the study was to evaluate the efficacy and safety of the drug Artlegia® (olokizumab), solution for subcutaneous injection, 160 mg/ml-0.4 ml, manufactured by R-Pharm JSC, Russia) for the treatment of patients with rheumatoid arthritis in real clinical practice after switching with rituximab during the COVID-19 pandemic. Materials and methods. The study included 14 patients with a confirmed diagnosis of rheumatoid arthritis (RA), who were previously on rituximab therapy at a dose of 1000–500 mg twice with an interval of 2 weeks, who received at least one course of therapy with this drug. As RA worsened, patients were switched to olokizumab against the background of standard DMARDs. On weeks 0, 4, 8, and 12 after the switch, the severity of pain was assessed on the VAS scale, the number of tender and swollen joints (TJC28 and SJC28), the level of acute-phase inflammation markers, the DAS28 (disease activity score), ESR, CRP, CDAI (clinical activity index), and the functional state index HAQ (Health Assessment Questionnaire) were determined, as well as the safety profile of therapy was assessed. Results. Data analysis was performed using median values (Me) were used for data analysis. A significant decrease in TJC28 was detected after 8 and 12 weeks of treatment with olokizumab (Artlegia®) (Me baseline = 10, Me 8 weeks = 4, Me 12 weeks = 4, p < 0.05) and a decrease in TSC28 was detected after 4, 8, and 12 weeks of treatment (Me baseline = 9, Me 4 weeks = 3.5, Me 8 weeks = 2.5, Me 12 weeks = 2.0, p < 0.05). Laboratory markers of inflammation showed a decrease in CRP and ESR levels after 4 weeks of treatment (CRP: Me4 weeks = 21, Me4 weeks = 1, p < 0.05, ESR: Mesno = 31, Me4 weeks = 7, p < 0.05). Positive dynamics persisted on 8 and 12 weeks (CRP: Me 8 weeks = 1, Me 12 weeks = 0; ESR: Me 8 weeks = 4, Me 12 weeks = 5). The level of CRP by week 4 became within the normal range, regardless of the initial values. All activity indices improved from week 4 in each evaluation period compared to baseline: DAS28-ESR: Me baseline = 5.52, Me 4 weeks = 3.59, Me 8 weeks = 3.33, Me 12 weeks = 3.22, p < 0.05; DAS28CRP: Me baseline = 5.39, Me 4 weeks = 3.71, Me 8 weeks = 3.35, Me 12 weeks = 3.45, p < 0.05; CDAI: Me baseline = 28.5, Me 4 weeks = 18.0, Me 8 weeks = 16.5, Me 12 weeks = 16.0, p < 0.05. All patients showed a reduction in pain (VAS scale) by week 8. The functional status of patients, according to the HAQ index, showed a significant decrease only by week 12 of the study: Me baseline = 1.62, Me 12 weeks = 1.31, p < 0.05. Conclusions. The study found that switching from rituximab to olokizumab was effective and safe during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

We studied the influence of breathing exercises (BEs) with a paced rhythm on the dynamics of heart rate variability (HRV) parameters in order to study the nature of adaptive processes in the body of girls with different initial levels of total HRV. Heart rate (HR), the temporal indicators SDNN, mNN, RMSSD, pNN50, the spectral parameters TP, HF and HFnu, LF and LFnu, LF/HF, as well as the sympathovagal balance index (SBI) and the stress index (SI), were evaluated. According to the SDNN level, individuals with conditionally low and conditionally high total HRV levels were identified—the LV (40 (31; 47) ms) and HV (64 (58; 70) ms) groups. At rest, HRV parameters in HV girls were significantly higher than in the LV subgroup. After BEs, a significant increase in SDNN and TP was observed in the LV subgroup against the background of a decrease in HF and HFnu and an increase in LF and LFnu, and the LF/HF ratio after BEs increased by 80%. In HV girls after BEs, a 6% increase in heart rate, but not in the total HRV parameters was recorded; a decrease in HF and HFnu was compensated for by an increase in LFnu; as a result, the LF/HF ratio increased significantly almost 1.5-fold compared to the rest level. In LV girls, the SBI and SI values were 2.6–2.7 times higher than in the HV subgroup. After BEs, a 24 and 19% decrease in SBI and SI was observed in the LV, but not in the HV subgroup. Thus, the adaptation of the work of the heart to BEs occurred in a similar way in LV and HV individuals; however, it differed in different adaptation costs of such an effort for LV and HV subjects. [ABSTRACT FROM AUTHOR]

A constructive method is proposed for solving the problem of time-optimal two-channel boundary control of two physically inhomogeneous objects with distributed parameters described by linear heat conduction equations under conditions of a perfect thermal contact of interacting media with estimates of the target sets of controlled temperature fields in a uniform metric that are typical for engineering applications. The developed technique uses a special method for describing the studied temperature fields in a form containing uniformly converging series. The approach under development is based on the parameterization procedure for the desired control actions and the subsequent reduction to the problem of semi-infinite optimization, which is solved by the scheme of the alternance method under the additional restriction on the same duration of the control process for both control actions. [ABSTRACT FROM AUTHOR]

Flavonoids, the most common plant polyphenols are widely distributed in every species and possess a broad range of pharmacological activities. The genus Astragalus is the largest in the Fabaceae family with more than 2,500 species spread. They are known to contain different metabolites such as flavonoids, saponins, and polysaccharides. Plants from the genus have been used in the traditional medicine of many countries for centuries. This paper is focused on the large group of flavonoid compounds. Details on structure as well as information about the pharmacological properties of flavonoids, isolated from Astragalus species have been discussed. This review is based on publications until the first half of 2014 and includes also the results from our phytochemical investigations of the genus. [ABSTRACT FROM AUTHOR]