Finite-size scaling from self-consistent theory of localization

Accepting validity of self-consistent theory of localization by Vollhardt and Woelfle, we derive the finite-size scaling procedure used for studies of the critical behavior in d-dimensional case and based on the use of auxiliary quasi-1D systems. The obtained scaling functions for d=2 and d=3 are in good agreement with numerical results: it signifies the absence of essential contradictions with the Vollhardt and Woelfle theory on the level of raw data. The results \nu=1.3-1.6, usually obtained at d=3 for the critical exponent of the correlation length, are explained by the fact that dependence L+L_0 with L_0>0 (L is the transversal size of the system) is interpreted as L^{1/\nu} with \nu>1. For dimensions d\ge 4, the modified scaling relations are derived; it demonstrates incorrectness of the conventional treatment of data for d=4 and d=5, but establishes the constructive procedure for such a treatment. Consequences for other variants of finite-size scaling are discussed.Comment: Latex, 23 pages, figures included; additional Fig.8 is added with high precision data by Kramer et a

Viral Load in COVID-19: Underestimated Clinical and Epidemiological Marker

Background. The viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the new coronavirus infection, is becoming increasingly important in clinical and epidemiological contexts. Despite this, there are significant complexities in the implementation of viral load quantitative measurement into clinical practice due to the limited approaches to its assessment.The aim of this work was to develop an approach for SARS-CoV-2 viral load analysis by the value of sample threshold cycles (Ct) relative to the Ct of the internal control sample obtained in routine PCR diagnostics of the COVID-19, and to use this approach for quantitative monitoring of viral load in patients with first positive SARS-CoV-2 test from the Irkutsk region.Materials and methods. Using regression models based on the least squares method, an approach to determine the number of copies of SARS-CoV-2 RNA in 1 ml of nasopharyngeal secretion was developed. The viral load of SARS-CoV-2 was assessed in nasopharyngeal and pharyngeal samples obtained from 1370 patients from Irkutsk and Angarsk with primary diagnosed positive PCR result in the period from July 1 to November 10, 2020.Results. A tenfold increase in the average monthly viral load among patients in September-October 2020 was revealed. We assume that the change in the epidemiological pattern of the spread of the new coronavirus infection during this period is associated with an increase in the number of contacts in the population due to the school year beginning. Higher viral loads are observed in populations at risk for COVID-19 – among healthcare workers and adults/elderly patients. Conclusion. The development of a standardized quantification of SARS-CoV-2 viral load in the nasopharyngeal samples can be a predictive clinical marker and a reliable tool for improving COVID-19 surveillance using the proposed approach to assess average viral load in a local population

Online service for interpretation of the resistance prediction results to bedaquiline by the molecular data

Background. Bedaquiline is a new and promising anti-tuberculosis drug, but longterm use requires resistance. This is due to mutations in the atpE and mmpR genes in M. tuberculosis (MBT).The aim of the research was to test a system for automated interpretation of results for predicting resistance to bedaquiline by the molecular data.Materials and methods. DNA was isolated from strains of M. tuberculosis in the Irkutsk region and Yakutia. The total quantity of DNA samples was 27 strains from Yakutia and 21 strains from the Irkutsk region. The study of MBT genomes was carried out on the DNA previously obtained by the authors in the territories of the Irkutsk region (n = 5), Yakutia (n = 4), Buryatia (n = 3), Zabaykalskiy kray (n = 4) and the Far East (n = 8). We used the BSATool program to detect bedaquiline resistance based on  Sanger and genomic data. Sanger sequencing analyzed the atpE and  mmpR genes, and whole genome sequencing examined mutations in the same sequences, as well as additionally in mmpL5, mmpS5, Rv0678, Rv1979c, and pepQ.Results. Complete agreement between the phenotypic and genotypic analysis of resistance to bedaquiline was found for three strains from Yakutia. One genome with significant mutations to bedaquiline was identified. A conclusion was made about the importance of molecular analysis of target genes with subsequent detection of resistance to bedaquiline in silico

COMPARATIVE STUDY OF M. TUBERCULOSIS GENOTYPES FROM BORDER DISTRICTS OF MONGOLIA AND BURYATIA

MIRU-VNTR genetic polymorphism of 156 strains of M. tuberculosis was studied. On the background of significant presence of Beijing genotype strains (44/57 (77,2 %)) we discovered prevalence of epidemically significant Beijing subtype MIT17 (29/44 (65,9 %)) in patients from Mongolia

DUET: A phase 2 study evaluating the efficacy and safety of sparsentan in patients with FSGS

Background: We evaluated and compared the effects of sparsentan, a dual endothelin type A (ETA) and angiotensin II type 1 receptor antagonist, with those of the angiotensin II type 1 receptor antagonist irbesartan in patients with primary FSGS. Methods: In this phase 2, randomized, double-blind, active-control Efficacy and Safety of Sparsentan (RE-021), a Dual Endothelin Receptor and Angiotensin Receptor Blocker, in Patients with Focal Segmental Glomerulosclerosis (FSGS): A Randomized, Double-blind, Active-Control, Dose-Escalation Study (DUET), patients aged 8-75 yearswith biopsy-proven FSGS, eGFR>30ml/min per 1.73m2, and urinary protein-to-creatinine ratio (UP/C)≥1.0 g/g received sparsentan (200, 400, or 800 mg/d) or irbesartan (300mg/d) for 8 weeks, followed by open-label sparsentan only. End points atweek 8 were reduction from baseline inUP/C(primary) and proportion of patients achieving FSGS partial remission end point (FPRE) (UP/C:≤1.5 g/g and>40%reduction [secondary]). Results: Of 109 patients randomized, 96 received study drugs and had baseline and week 8 UP/C measurements. Sparsentan-treated patients had greater reductions in UP/C than irbesartan-treated patients didwhen all doses (45%versus 19%; P=0.006) or the 400 and 800mg doses (47%versus 19%; P=0.01) were pooled for analysis. The FSGS partial remission end point was achieved in 28% of sparsentan-treated and 9% of irbesartan-treated patients (P=0.04). After 8 weeks of treatment, BP was reduced with sparsentan but not irbesartan, and eGFR was stable with both treatments. Overall, the incidence of adverse events was similar between groups. Hypotension and edema were more common among sparsentan-treated patients but did not result in study withdrawals. Conclusions: Patients with FSGS achieved significantly greater reductions in proteinuria after 8 weeks of sparsentan versus irbesartan. Sparsentan was safe and well tolerated

PHENOTYPIC AND FUNCTIONAL CHARACTERISTICS OF MICROVESICLES PRODUCED BY NATURAL KILLER CELLS

Natural killer (NK) cells are of special interest among a multitude of microvesicle (MV) source cells. NK cells are a lymphocyte subpopulation performing contact cytolysis of virus-infected cells and tumor cells. Each of the NK cell populations has a unique receptor repertoire on its surface and, thus, unique functions. During their contact with a target cell, the most common mechanism of cytolysis is an exocytosis of lytic granules. However, some indirect evidence suggests that MV with CD56 phenotype and leukocyte-derived MV with various phenotypes are present in the peripheral blood plasma.This research is aimed to study the phenotype, composition and cytotoxic activity of microvesicles produced by NK cells. The analysis of receptor expression showed that MV, as well as source cells of the NK-92 cell line, had a similar CD56 molecule expression profile. The expression profile in MV differs from the same in source cells by higher CD119 and CD11b expression and by lower CD18 expression. Culturing of NK-92 cells in the presence of PMA, IL-1β, TNFα, IFNγ resulted in alterations of cell phenotypes and MV. Immunoblots revealed a change of perforin and granzyme B (GrB) in MV. The analysis of the cytotoxic activity of NK-92 cells in a natural killer in vitro assay employing K562 target cells demonstrated that MV obtained from TNFα-activated cells of the NK-92 cell line increased the cytotoxicity of the same TNFα-activated NK-92 cells regarding cytotoxicity levels. This coincides with the previously revealed increased content of GrB in MV obtained from TNFα-activated cells of the NK-92 cell line. To sum up depending on the cytokine NK-92 cells produce MV that differ in their phenotype, composition and activity. Any changes in MV composition can result in changes in their functional activity: in particular, changes can increase the cytotoxic activity of NK cells of the NK-92 cell line. Thus, besides a well-known and proved way for GrB delivery to a target cell, we can suggest an additional way – the transportation of GrB within MV

Genotypic and phenotypic characteristics of <i>Mycobacterium tuberculosis</i> drug resistance in TB children

Background. Russian Federation is included in the list of 30 countries with the highest burden of tuberculosis, including MDR tuberculosis. The most important part of this problem is the primary MDR/XDR TB in children.The aim: a comparative analysis of the phenotypic and genotypic profile of drug resistance to anti-tuberculosis drugs (ATP) according to whole genome sequencing of M. tuberculosis strains from children.Materials and methods. Whole genome sequencing (WGS) results of 61 M. tuberculosis isolates from children with tuberculosis in 2006–2020 in the Russian Federation were analyzed for anti-TB drug resistance mutations, according to the WHO catalog and were compared with the results of phenotypic drug sensitivity.Results. The M. tuberculosis belonged to two genetic groups: Beijing genotype – 82 % (50/61) dominant Central Asian Russian (31/50) and B0/W148 (16/50) subtypes, and non-Beijing (Ural, S, LAM) – 18 % (11/61). Three isolates belonged to Asian Ancestral subtype (3/50). Of the 61 isolates, only 14.7 % (9/61) were sensitive to antiTB drugs, 49.2 % (30/61) were MDR and 14.7 % (9/61) were pre-XDR. Comparison of the resistance profile (MDR/pre-XDR) with genotype revealed an upward shift for Beijing isolates, in particular Beijing B0/W148 (15/16) subline compared to other Beijing (19/34) (Chi-square with Yates correction = 5.535; p &lt; 0.05) and nonBeijing (5/12) (Chi-square with Yates correction = 6.741; p &lt; 0.05) subtypes. Discrepancies between genotypic and phenotypic drug resistance profiles were found in 11.5 % (7/61) of cases.Conclusions. Based on the analysis of WGS data, the genotypic characteristics of M. tuberculosis and the most complete set of drug resistance mutations were obtained, indicating a significant prevalence in MDR and pre-XDR TB of cases caused by epidemic subtypes of Beijing (B0/W148 and Central Asian Russian). The molecular mechanisms of adaptation of M. tuberculosis to the treatment of anti-TB drugs are not unique for the child population but reflect the general processes of the spread of MDR/XDR in Russia

НЕКОТОРЫЕ КРИСТАЛЛОСКОПИЧЕСКИЕ СВОЙСТВА ДЕЗИНФЕКТАНТОВ И ПЕРСПЕКТИВЫ ПРИМЕНЕНИЯ КРИСТАЛЛОСКОПИЧЕСКОЙ ОЦЕНКИ В ДЕЗИНФЕКЦИИ И ДЕЗИНВАЗИИ

Simultaneous usage of microbiological, ecological and crystalloscopic methods can be used for estimation of disinfectants antibacterial and toxic activity. Disinfection action of the substance was made on the model of helminths eggs and pathogenic microorganisms (Staphylococcus aureus, Enterobacter aerogenes, Bacillus anthracis). Toxicity in vivo was estimated on mice urine.Одновременное применение микробиологических, экологических и кристаллоскопических методов можно использовать для оценки токсичности и антибактериальной активности дезинфектантов. Дезинфицирующее действие растворов азида натрия изучено на модели патогенных микроорганизмов (Staphylococcus aureus, Enterobacter aerogenes, Bacillus anthracis) и аборигенной микрофлоры. Токсичность азида натрия оценивали на основании анализа мочи мышей после его дачи

Construction and Approval of the Test-System for the Detection of Antibodies to Anthrax Agent Using Indirect Fluorescent Immunoassay

Constructed and validated has been the test-system for the detection of antibodies to anthrax agent using indirect fluorescent immunoassay. The panel consists of antigen preparation, positive control sample, negative control, and FITS-labeled rabbit antibodies. Studied have been 10 acapsular B. anthracis strains with different plasmid content and colony morphology. B. anthracis vaccine strain STI-1 is demonstrated to be the optimal one as antigen preparation. Sensitivity of this test-system is not less than 1:40, the working dilution of FITC-conjugate being 1:16. Specificity of the panel has been studied using 100 sera of healthy donors. Approved is 100 % reproducibility of the technique at different time intervals, as well as when carried by different specialists. The test-system allows for confirmation of anthrax diagnosis in humans

cGMP-Dependent Protein Kinase Type I Is Implicated in the Regulation of the Timing and Quality of Sleep and Wakefulness

Many effects of nitric oxide (NO) are mediated by the activation of guanylyl cyclases and subsequent production of the second messenger cyclic guanosine-3′,5′-monophosphate (cGMP). cGMP activates cGMP-dependent protein kinases (PRKGs), which can therefore be considered downstream effectors of NO signaling. Since NO is thought to be involved in the regulation of both sleep and circadian rhythms, we analyzed these two processes in mice deficient for cGMP-dependent protein kinase type I (PRKG1) in the brain. Prkg1 mutant mice showed a strikingly altered distribution of sleep and wakefulness over the 24 hours of a day as well as reductions in rapid-eye-movement sleep (REMS) duration and in non-REM sleep (NREMS) consolidation, and their ability to sustain waking episodes was compromised. Furthermore, they displayed a drastic decrease in electroencephalogram (EEG) power in the delta frequency range (1–4 Hz) under baseline conditions, which could be normalized after sleep deprivation. In line with the re-distribution of sleep and wakefulness, the analysis of wheel-running and drinking activity revealed more rest bouts during the activity phase and a higher percentage of daytime activity in mutant animals. No changes were observed in internal period length and phase-shifting properties of the circadian clock while chi-squared periodogram amplitude was significantly reduced, hinting at a less robust oscillator. These results indicate that PRKG1 might be involved in the stabilization and output strength of the circadian oscillator in mice. Moreover, PRKG1 deficiency results in an aberrant pattern, and consequently a reduced quality, of sleep and wakefulness, possibly due to a decreased wake-promoting output of the circadian system impinging upon sleep