18 research outputs found

    R-helix Movement during Common Gating Affects Cl Binding in the CLC-0 Channel Pore

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    The world of visual images of the Tuva Old Believers: from icons and popular prints to photos

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    The article analyzes visual images that fill the life environment of Chasovennye (‘chapel-going’) Old Believers of Tuva. The coding of information through visual streams is augmented by the religious activities of the Old Believer community and finds expression in various forms of folk art. Our systemic analysis of visual culture is based on expedition research materials which had been in use at Old Believers' settlements in the upper reaches of the Yenisei (Erzhey, Uzhep, Sizim and Saryg-Sep, Kaa-Khem kozhuun (raion) of the Republic of Tuva) in 2016-2017. How sacred space is filled with religious objects is regulated by doctrinal guidelines established by Council (Sobor) ordinances. The world of sacred images is built into that of everyday culture; it opens into the profane space without losing its sacred meaning. Having refused the use of television and computers, Old Believers are active subscribers to print magazines, both for children and adults, and frequently use postcards for congratulations. Copied fragments of magazine graphics or book illustrations can often be found in works of folk art of Old Believers. Despite the prohibition to take photos of people, Old Believer houses often feature photo albums focusing on the daily life of a family from the 1960s up to this day. We can conclude that among the Old Believers of Tuva, traditional and mass culture interact and support each other, although lip service is paid to the declarative denial of the latter on confessional grounds

    Predictors of thromboembolic complications in patients with severe SARS-CoV-2 coronavirus infection

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    Aim. To identify predictors of the development of thromboembolic complications (TECs) in patients with severe SARS-CoV-2 coronavirus infection. Materials and methods. A single-center observational retrospective study included 1634 patients with a confirmed diagnosis of SARS-CoV-2 coronavirus infection. The patients were divided into 2 groups depending on the availability of the feasibility study. The criterion for inclusion of patients in the main group was the presence of venous feasibility studies in 127 patients (group I), the comparison group consisted of 1507 patients in whom the course of COVID-19 was not complicated by the development of feasibility studies (group II). Results. When performing computed tomography of the chest organs, it was revealed that patients with a feasibility study had a higher percentage of lung tissue damage than patients in the comparison group: 55% [37.5; 67.5] and 37.5% [25.0; 47.5], respectively (p0.001). The average values of C-reactive protein in I patients group were 129 [60.1; 211] ng/l, which was significantly higher than in II patients group – 41.0 [12.2; 97.6] ng/l (p0.001), interleukin-6 – 176 [52.9; 471] pg/ml and 39.4 [11.0; 107] pg/ml (p0.001), respectively. A one-factor regression analysis proved a significant contribution of comorbid pathology to the development of feasibility studies in patients with COVID-19. The presence of three nosologies at the same time: arterial hypertension, coronary heart disease (CHD) and chronic kidney disease increased the probability of a feasibility study by 4.81 times (odds ratio 4.8117, 95% confidence interval 3.2064–7.2207), in patients with arterial hypertension, CHD, chronic kidney disease and type 2 diabetes – by 5.63 times (odds ratio 5.6321, 95% confidence interval 3.1870–9.9531). Conclusion. The presence of severe comorbid pathology significantly increased the risk of developing a feasibility study in patients with COVID-19. The most significant predictors of the development of feasibility studies in patients with severe SARS-CoV-2 coronavirus infection. They are: CHD, arterial hypertension and type 2 diabetes

    Interaction between Floral Merism and Symmetry: Evidence from Fasciated Mutant of Lupinus angustifolius L. (Leguminosae)

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    A significant diversity of flower structure in angiosperms is defined by few parameters, among which one may list floral merism and symmetry as the most important. However, observation of normal variation in different taxa indicates that high floral merism (more than six organs) is very rarely associated with a monosymmetry. Precise mechanisms underlying this tendency, as well as the mode of interaction between regulatory pathways of floral symmetry and merism, remain unidentified. In this work, we observed the floral ontogeny in normal plants of Lupinus angustifolius L. (Leguminosae), described the floral structure and its variations in fasciated mutant. Our results suggest that monosymmetry is regulated independently from the floral merism, so three types of petals differentiate properly even in flowers with an anomalously high number of organs. However, the adaxial floral domain is the most stable floral part, which is the least susceptible to the fluctuations of merism. This means that some genes responsible for the development of the adaxial flower domain may additionally stabilize it and hence prevent fluctuations of merism in the adaxial domain. The monosymmetry in Leguminosae is a character connected with pollination by insects and requires a precise interaction between all floral parts. That is why fluctuations, which impair this interaction and symmetry, may decrease the pollination efficiency

    Transduction of Brain Neurons in Juvenile Chum Salmon (<i>Oncorhynchus keta</i>) with Recombinant Adeno-Associated Hippocampal Virus Injected into the Cerebellum during Long-Term Monitoring

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    Corpus cerebelli in juvenile chum salmon is a multiprojective region of the brain connected via afferent and efferent projections with the higher regions of the brainstem and synencephalon, as well as with multiprojection regions of the medulla oblongata and spinal cord. During the postembryonic development of the cerebellum in chum salmon, Oncorhynchus keta, the lateral part of the juvenile cerebellum gives rise to the caudomedial part of the definitive cerebellum, which is consistent with the data reported for zebrafish and mouse cerebellum. Thus, the topographic organization of the cerebellum and its efferents are similar between fish (chum salmon and zebrafish) and mammals, including mice and humans. The distributions of recombinant adeno-associated viral vectors (rAAVs) after an injection of the base vector into the cerebellum have shown highly specific patterns of transgene expression in bipolar neurons in the latero-caudal lobe of the juvenile chum tectum opticum. The distribution of rAAVs in the dorsal thalamus, epithalamus, nucleus rotundus, and pretectal complex indicates the targeted distribution of the transgene via the thalamo-cerebellar projections. The detection of GFP expression in the cells of the epiphysis and posterior tubercle of juvenile chum salmon is associated with the transgene’s distribution and with the cerebrospinal fluid flow, the brain ventricles and its outer surface. The direct delivery of the rAAV into the central nervous system by intracerebroventricular administration allows it to spread widely in the brain. Thus, the presence of special projection areas in the juvenile chum salmon cerebellum, as well as outside it, and the identification of the transgene’s expression in them confirm the potential ability of rAAVs to distribute in both intracerebellar and afferent and efferent extracerebellar projections of the cerebellum

    Experience of cytokine therapy in the treatment of recurrent cervical cancer

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    Cervical cancer is the most common malignant tumor of the female genital organs. In general, the prognosis in patients with advanced cervical cancer is unfavorable. The option of choice for stage IV of the disease and relapses is systemic platinum-containing chemotherapy. Its effectiveness is about 20–26%, life expectancy is 12–13 months. Undoubtedly, the search and development of new methods of treating this disease is an extremely urgent task. Immuno-oncology has emerged as a potential new strategy to improve the treatment outcomes of patients with malignant neoplasms. Much research attention is focused on the possibility of using interleukin-2, tumor necrosis factor (TNF) and interferon-gamma (IFN-γ) for tumor immunotherapy, since these cytokines play a particularly important role in the antitumor protection of the body. Thanks to the active search for new hybrid molecules based on TNF-a, the modern practice of oncologists includes specially developed domestic recombinant genetically engineered antitumor drugs, in particular the drugs "Refnot" (TNF-a-thymosin-a1) and "Ingaron" (IFN-γ). We analyzed the result of combined treatment (standard polychemotherapy of the 1st line with the addition of cytokinotherapy in the Refnot + Ingaron mode) 1 patient with recurrent cervical cancer. According to the control examination, upon completion of the polychemotherapy course, a complete tumor response was registered according to the Recist 1.1 criteria. The patient continued to receive cytokine therapy in monorode as support. Currently, according to control examinations, a complete regression of a recurrent tumor persists every 3 months, the follow-up time from the end of polychemotherapy is 28 months. It should be noted that when monitoring the state of the immune system during therapy with Refnot and Ingaron, an increase in the absolute and relative number of T-lymphocytes to a normal level was noted, an increase in the cytotoxic and antitumor potential of NK cells without increasing their number. The patient has a good tolerability of therapy, there is an improvement in the quality of life, there are no clinically significant side effects. Thus, in this clinical example, therapy with the drugs "Refnot" (tumor necrosis factor a-thymosin-a1) and "Ingaron" (interferon gamma) is a safe method of maintenance therapy with a positive therapeutic effect that allows effective control of recurrent cervical cancer for more than 2 years, as well as significantly improve the quality of life of the patient. This type of therapy can be recommended for use in clinical oncology

    Vitamin D Status and Immune Response in Hospitalized Patients with Moderate and Severe COVID-19

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    A low 25-hydroxyvitamin D (25(OH)D) level is considered as an independent risk factor for COVID-19 severity. However, the association between vitamin D status and outcomes in COVID-19 is controversial. In the present study we investigate the association between the serum 25(OH)D level, immune response, and clinical disease course in patients with COVID-19. A total of 311 patients hospitalized with COVID-19 were enrolled. For patients with a vitamin D deficiency/insufficiency, the prevalence of severe COVID-19 was higher than in those with a normal 25(OH)D level (p &lt; 0.001). The threshold of 25(OH)D level associated with mortality was 11.4 ng/mL (p = 0.003, ROC analysis). The frequency of CD3+CD4+ T helper (Th) cells was decreased in patients with 25(OH)D level &le; 11.4 ng/mL, compared to healthy controls (HCs). There were no differences in the frequency of naive, central memory (CM), effector memory (EM), and terminally differentiated effector memory Th cells in patients with COVID-19 compared to HCs. The frequency of T-follicular helpers was decreased both in patients with 25(OH)D level &gt; 11.4 ng/mL (p &lt; 0.001) and 25(OH)D level &le; 11.4 ng/mL (p = 0.003) compared to HCs. Patients with 25(OH)D level &gt; 11.4 ng/mL had an increased frequency of Th2 CM (p = 0.010) and decreased Th17 CM (p &lt; 0.001). While the frequency of Th2 EM was significantly increased, the frequency of Th17 EM was significantly decreased in both groups compared to HCs. Thus, 25(OH)D level is an independent risk factor for the disease severity and mortality in patients with COVID-19. We demonstrate that the serum 25(OH)D level &le; 11.4 ng/mL is associated with the stimulation of Th2 and the downregulation of Th17 cell polarization of the adaptive immunity in patients with COVID-19

    Vitamin D Intake May Reduce SARS-CoV-2 Infection Morbidity in Health Care Workers

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    In the last 2 years, observational studies have shown that a low 25-hydroxyvitamin D (25(OH)D) level affected the severity of infection with the novel coronavirus (COVID-19). This study aimed to analyze the potential effect of vitamin D supplementation in reducing SARS-CoV-2 infection morbidity and severity in health care workers. Of 128 health care workers, 91 (consisting of 38 medical doctors (42%), 38 nurses (42%), and 15 medical attendants (16%)) were randomized into two groups receiving vitamin D supplementation. Participants of group I (n = 45) received water-soluble cholecalciferol at a dose of 50,000 IU/week for 2 consecutive weeks, followed by 5000 IU/day for the rest of the study. Participants of group II (n = 46) received water-soluble cholecalciferol at a dose of 2000 IU/day. For both groups, treatment lasted 3 months. Baseline serum 25(OH)D level in health care workers varied from 3.0 to 65.1 ng/mL (median, 17.7 (interquartile range, 12.2; 24.7) ng/mL). Vitamin D deficiency, insufficiency, and normal vitamin D status were diagnosed in 60%, 30%, and 10%, respectively. Only 78 subjects completed the study. Vitamin D supplementation was associated with an increase in serum 25(OH)D level, but only intake of 5000 IU/day was accompanied by normalization of serum 25(OH)D level, which occurred in 53% of cases. Neither vitamin D intake nor vitamin D deficiency/insufficiency were associated with a decrease in SARS-CoV-2 morbidity (odds ratio = 2.27; 95% confidence interval, 0.72 to 7.12). However, subjects receiving high-dose vitamin D had only asymptomatic SARS-CoV-2 in 10 (26%) cases; at the same time, participants who received 2000 IU/day showed twice as many SARS-CoV-2 cases, with mild clinical features in half of them
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