A Biomorphic Approach to Designing Special-Purpose Vehicles for Arctic Conditions.

The paper explores the potential of the biomorphic approach to context-based design with a focus on special-purpose mobility in the Arctic. The study seeks to contribute to the analytical and conceptual basis for developing the transport component of the Arctic life-support system, i.e., a set of objects and technologies, and knowledge and skills for handling them, allowing a person to survive and comfortably exist in severe environmental conditions. The central argument is that the system should incorporate structural components that possess not only technical but also artistic and emotional characteristics that align with the geographic (environmental and climatic), socio-cultural, and psychological peculiarities of use. This can be achieved by drawing inspiration from local nature. We probe the visual image of "soft military presence" using two case studies in different parts of the Russian Arctic: the Yamal and Chukchi peninsulas.

Epidemiology of small intestinal bacterial overgrowth.

Small intestinal bacterial overgrowth (SIBO) is defined as an increase in the bacterial content of the small intestine above normal values. The presence of SIBO is detected in 33.8% of patients with gastroenterological complaints who underwent a breath test, and is significantly associated with smoking, bloating, abdominal pain, and anemia. Proton pump inhibitor therapy is a significant risk factor for SIBO. The risk of SIBO increases with age and does not depend on gender or race. SIBO complicates the course of a number of diseases and may be of pathogenetic significance in the development of their symptoms. SIBO is significantly associated with functional dyspepsia, irritable bowel syndrome, functional abdominal bloating, functional constipation, functional diarrhea, short bowel syndrome, chronic intestinal pseudo-obstruction, lactase deficiency, diverticular and celiac diseases, ulcerative colitis, Crohn's disease, cirrhosis, metabolic-associated fatty liver disease (MAFLD), primary biliary cholangitis, gastroparesis, pancreatitis, cystic fibrosis, gallstone disease, diabetes, hypothyroidism, hyperlipidemia, acromegaly, multiple sclerosis, autism, Parkinson's disease, systemic sclerosis, spondylarthropathy, fibromyalgia, asthma, heart failure, and other diseases. The development of SIBO is often associated with a slowdown in orocecal transit time that decreases the normal clearance of bacteria from the small intestine. The slowdown of this transit may be due to motor dysfunction of the intestine in diseases of the gut, autonomic diabetic polyneuropathy, and portal hypertension, or a decrease in the motor-stimulating influence of thyroid hormones. In a number of diseases, including cirrhosis, MAFLD, diabetes, and pancreatitis, an association was found between disease severity and the presence of SIBO. Further work on the effect of SIBO eradication on the condition and prognosis of patients with various diseases is required.

Impact of vaccination against the novel coronavirus infection (COVID-19) with Sputnik V on mortality during the delta variant surge.

OBJECTIVES: The aim is to study impact of vaccination against the novel coronavirus disease (COVID-19) with Sputnik V on mortality during the period of predominance of the delta variant of SARS-CoV-2. METHODS: This was a retrospective cohort study of individuals with state health insurance at the Moscow Ambulatory Center. The cohorts included 41,444 persons vaccinated with Sputnik V, 15,566 survivors of COVID-19, and 71,377 non-immune persons. The deaths of patients that occurred from June 1, 2021, to August 31, 2021, were analyzed. RESULTS: Overall (0.39 % vs. 1.92 %; p < 0.001), COVID-19-related (0.06 % vs. 0.83 %; p < 0.001), and non-COVID mortality (0.33 % vs. 1.09 %; p < 0.001) was lower among vaccinated individuals than among non-immune individuals. The efficacy of vaccination against death from COVID-19 was 96 % [95 % CI 91-98 %] in the general population, 100 % among those aged 18-50 years, 97 % [95 % CI 76-100 %] among those aged 51-70 years, 98 % [95 % CI 90-100 %] among those aged 71-85 years, and 88 % [95 % CI 49-97 %] among those aged > 85 years. CONCLUSION: COVID-19 vaccination with Sputnik V is associated with a decrease in overall and COVID-19-related mortality and is not with increased non-COVID mortality.

Intrinsically disordered regions couple the ligand binding and kinase activation of Trk neurotrophin receptors.

Receptor tyrosine kinases (RTKs) are key players in development and several diseases. Understanding the molecular mechanism of RTK activation by its ligand could lead to the design of new RTK inhibitors. How the extracellular domain is coupled to the intracellular kinase domain is a matter of debate. Ligand-induced dimerization and ligand-induced conformational change of pre-formed dimers are two of the most proposed models. Recently we proposed that TrkA, the RTK for nerve growth factor (NGF), is activated by rotation of the transmembrane domain (TMD) pre-formed dimers upon NGF binding. However, one of the unsolved issues is how the ligand binding is conformationally coupled to the TMD rotation if unstructured extracellular juxtamembrane (eJTM) regions separate them. Here we use nuclear magnetic resonance in bicelles and functional studies to demonstrate that eJTM regions from the Trk family are intrinsically disordered and couple the ligand-binding domains and TMDs possibly via the interaction with NGF.

Interleukin 17 antagonist netakimab is effective and safe in the new coronavirus infection (COVID-19).

Cytokine release syndrome is a serious complication of the new coronavirus infection (COVID-19). The aim of the study was to assess effectiveness and safety of the IL-17 antagonist nekatimab for its treatment. The retrospective study included COVID-19 patients with C-reactive protein levels >60 mg/L. Patients received either netakimab (group NET), IL-6 antagonist tocilizumab (group TOC) or no anti-cytokine treatment (group CON). Forty-four patients were enrolled in the NET group, 27 patients in the TOC group, and 47 patients in the CON group. Mortality was lower in the NET group than in TOC and CON groups (2.3% vs. 14.8% and 31.9%; p = 0.018 and p < 0.001). NET group patients required intensive care unit admission (6.8% vs. 25.9% and 46.3%; p = 0.025 and p < 0.001) and mechanical ventilation (4.6% vs. 22.2% and 31.9%; p = 0.022 and p = 0.002) less frequently than patients of the TOC and CON groups. After 7-10 days of anti-cytokine drug administration, a reduction in lung lesion volume (p = 0.016) and an increase in the proportion of patients who did not need oxygen support (p = 0.005) or stayed in prone position (p = 0.044) was observed in the NET group only group; C-reactive protein levels were the same in the TOC and NET groups (p = 0.136) and lower in the CON group (p < 0.001 and p = 0.005). IL-6 levels decreased in the NET group (p = 0.005) and did not change in the TOC group (p = 0.953). There was no difference in the incidence of side effects between groups. The IL-17 antagonist netakimab is effective and safe in the treatment of cytokine release syndrome in COVID-19.

Tofacitinib reduces mortality in coronavirus disease 2019 Tofacitinib in COVID-19.

BACKGROUND AND AIM: Cytokine release syndrome is a dangerous complication of the coronavirus disease 2019 (COVID-19). This study aimed to evaluate the efficacy and safety of tofacitinib in the management of this complication. METHODS: The retrospective study included COVID-19 patients with C-reactive protein (CRP) levels of 60-150 mg/L. RESULTS: Thirty-two patients who received tofacitinib (TOF group) and 30 patients who did not receive any anti-cytokine drugs (control [CON] group) were enrolled. Mortality and the incidence of admission to the intensive care unit were lower in the TOF group than in the CON group (16.6% vs. 40.0%, p = 0.009; and 15.6% vs. 50.0%, p = 0.004). There was a significant decrease in the volume of the affected part of the lungs (p = 0.022) and a significant increase in oxygen saturation (p = 0.012) in the TOF group than in the CON group 7-10 days after the beginning tofacitinib administration. CRP level was lower in the TOF group than in the CON group (7 [3-22] vs. 20 [5-52] mg/L; p = 0.048) 7-10 days after the start of the administration of tofacitinib. During this period, the number of patients requiring mechanical ventilation or those in the prone position increased in the CON group compared to those in the TOF group (26.7% vs. 0.0%, p = 0.002; 33.3% vs. 6.7%, p = 0.020). There was no significant difference in the development of secondary infections, liver or kidney injury, and cytopenia between the two groups. CONCLUSION: Tofacitinib was effective and safe for managing the cytokine release syndrome in COVID-19. Randomized controlled double-blind trials with tofacitinib with and without the simultaneous use of glucocorticoids are required to confirm our findings.