[Predictors of severe course of new coronavirus infection (COVID-19): study design].

AIM: To identify predictors of the severe course of a new coronavirus infection. MATERIALS AND METHODS: A retrospective analysis of 120 clinical case histories of patients hospitalized in hospitals in Tyumen with a confirmed diagnosis of COVID-19 within one year (01.08.2020-01.08.2021) was carried out. The patients were divided into two groups: 1st - with a favorable outcome (n=96), 2nd - with an unfavorable (fatal) outcome (n=24). For a more complete analysis, scales for assessing the clinical condition of patients (SHOCK-COVID), severity assessment (NEWS2) were used. Information processing was carried out in the IBM.SPSS.Statistics-19 program (USA). RESULTS: As a result of the study, the median age for the 1st group was significantly lower (58 years) than for patients of the 2nd group (69 years; p=0.029). A certain set of laboratory parameters for group 2 patients deviate significantly from the reference values (C-reactive protein - CRP - 7.6 [4.7; 15.2] mg/dl, D-dimer - 1.89 [1.36; 5.3] mcg/ml, ferritin - 605 [446.7; 792] ng/ml). When analyzed in groups, taking into account the main markers of the severity of the disease, using the V.Yu. Mareev CCAS-COVID (Clinical Condition Assessment Scale) scale, for the 1st group, the sum of the set of parameters was 6 [2; 7] points, which corresponds to the average severity of coronavirus infection, for the 2nd group 13 [9; 16] points - severe course. For patients of the 2nd group, a significant increase in the indicators of an unfavorable prognosis was revealed in comparison with the 1st group. CONCLUSION: Thus, in this study, the level of CRP, ferritin, D-dimer, the percentage of lung tissue damage according to computed tomography results, SaO2 were significantly associated with an unfavorable prognosis.

Primary Immunodeficiencies in Russia: Data From the National Registry.

Introduction: Primary immunodeficiencies (PID) are a group of rare genetic disorders with a multitude of clinical symptoms. Characterization of epidemiological and clinical data via national registries has proven to be a valuable tool of studying these diseases. Materials and Methods: The Russian PID registry was set up in 2017, by the National Association of Experts in PID (NAEPID). It is a secure, internet-based database that includes detailed clinical, laboratory, and therapeutic data on PID patients of all ages. Results: The registry contained information on 2,728 patients (60% males, 40% females), from all Federal Districts of the Russian Federation. 1,851/2,728 (68%) were alive, 1,426/1,851 (77%) were children and 425/1,851 (23%) were adults. PID was diagnosed before the age of 18 in 2,192 patients (88%). Antibody defects (699; 26%) and syndromic PID (591; 22%) were the most common groups of PID. The minimum overall PID prevalence in the Russian population was 1.3:100,000 people; the estimated PID birth rate is 5.7 per 100,000 live births. The number of newly diagnosed patients per year increased dramatically, reaching the maximum of 331 patients in 2018. The overall mortality rate was 9.8%. Genetic testing has been performed in 1,740 patients and genetic defects were identified in 1,344 of them (77.2%). The median diagnostic delay was 2 years; this varied from 4 months to 11 years, depending on the PID category. The shortest time to diagnosis was noted in the combined PIDs-in WAS, DGS, and CGD. The longest delay was observed in AT, NBS, and in the most prevalent adult PID: HAE and CVID. Of the patients, 1,622 had symptomatic treatment information: 843 (52%) received IG treatment, mainly IVIG (96%), and 414 (25%) patients were treated with biological drugs. HSCT has been performed in 342/2,728 (16%) patients, of whom 67% are currently alive, 17% deceased, and 16% lost to follow-up. Three patients underwent gene therapy for WAS; all are currently alive. Conclusions: Here, we describe our first analysis of the epidemiological features of PID in Russia, allowing us to highlight the main challenges around PID diagnosis and treatment.

Altered subcortical emotional salience processing differentiates Parkinson's patients with and without psychotic symptoms.

OBJECTIVE: Current research does not provide a clear explanation for why some patients with Parkinson's Disease (PD) develop psychotic symptoms. The 'aberrant salience hypothesis' of psychosis has been influential and proposes that dopaminergic dysregulation leads to inappropriate attribution of salience to irrelevant/non-informative stimuli, facilitating the formation of hallucinations and delusions. The aim of this study is to investigate whether non-motivational salience is altered in PD patients and possibly linked to the development of psychotic symptoms. METHODS: We investigated salience processing in 14 PD patients with psychotic symptoms, 23 PD patients without psychotic symptoms and 19 healthy controls. All patients were on dopaminergic medication for their PD. We examined emotional salience using a visual oddball fMRI paradigm that has been used to investigate early stages of schizophrenia spectrum psychosis, controlling for resting cerebral blood flow as assessed with arterial spin labelling fMRI. RESULTS: We found significant differences between patient groups in brain responses to emotional salience. PD patients with psychotic symptoms had enhanced brain responses in the striatum, dopaminergic midbrain, hippocampus and amygdala compared to patients without psychotic symptoms. PD patients with psychotic symptoms showed significant correlations between the levels of dopaminergic drugs they were taking and BOLD signalling, as well as psychotic symptom scores. CONCLUSION: Our study suggests that enhanced signalling in the striatum, dopaminergic midbrain, the hippocampus and amygdala is associated with the development of psychotic symptoms in PD, in line with that proposed in the 'aberrant salience hypothesis' of psychosis in schizophrenia.

The supramolecular polymer complexes with oppositely charged calixresorcinarene: hydrophobic domain formation and synergistic binding modes.

The association of branched polyethyleneimine (PEI) with a series of octacarboxy-calixresorcinarenes bearing different low-rim substituents leads to the formation of nanosized supramolecular complexes. The PEI-macrocycle complexes have fine-tunable sizes regulated by variations in the self-association capacity of the calixresorcinarenes. In the supramolecular complexes, hydrophobic fragments of the polymer and calixresorcinarenes form cooperative hydrophobic domains which provide synergistic enhancement of guest molecule binding. The formation of the supramolecular complexes was investigated by NMR FT-PGSE, NMR 2D NOESY, DLS and TEM methods. In addition, fluorimetry and UV-vis methods were used with the help of optical probes, namely water-soluble Crystal Violet and water-insoluble Orange OT. The investigation demonstrates the first example of the formation of cooperative hydrophobic domains in supramolecular polyelectrolyte-macrocycle complexes which enhance the binding of both water-soluble and water-insoluble organic compounds. The presented supramolecular systems have potential as sensory and drug delivery systems.

Unusual nanosized associates of carboxy-calix[4]resorcinarene and cetylpyridinium chloride: the macrocycle as a glue for surfactant micelles.

The association of cetylpyridinium chloride (CPC) micelles in the presence of octaacetated tetraphenyleneoxymethylcalix[4]resorcinarene (CR) leads to the formation of unusual spherical supramolecular nanoparticles (SNPs). Within the range of CR/CPC molar ratios from 10/1 to 1/10 (except for 1/8), CR, acting as a counterion, decreases the critical micelle concentration of CPC by one order of magnitude and leads to the formation of SNPs with an average hydrodynamic radius of 164 nm and an average zeta potential of -60 mV. The formation of SNPs was studied by NMR FT-PGSE and 2D NOESY, DLS, TEM, fluorimetry, and UV-Vis methods. The stability of SNPs at different temperatures and pH values and in the presence of electrolytes was investigated. The specificity of the interactions of the SNPs with substrates that were preferentially bound by a macrocycle or CPC micelle was studied. The enhancement of cation dye binding in the presence of SNPs is shown. The presented supramolecular system may serve as a nanocapsule for water-soluble and water-insoluble compounds.

[The study of the antiviral activity of polyelectrolytes with respect to the influenza virus].

It is well known that polyelectrolytes (PE) have a damaging effect on the secondary structure of the proteins and enzymes. It is also known that some PEs exert an immunostimulating action on T- and B-lymphocytes. However, currently, almost nothing is known about the impact of the PE of the viral proteins and viral envelope. Therefore, a detailed study of the mechanisms of the antiviral action of various polyelectrolytes would create the scientific-practical base for the construction of the antiviral drugs on the polyelectrolyte basis. In these works, for the first time the influence of PE polystyrene sulfonate (PSS) with varying degrees of polymerization and polyallylamin (PAA) and with molecular mass 6 and 8 kDa on the infectivity of different strains of the influenza virus was studied. It was shown that the expressed antiviral action PSS with degree of polymerization-8 (ETS-8) and PAA (6 kDa) against the influenza viruses was characterized by a significant reduction in the infectious titer of the virus. It was determined that the span of the nontoxic concentrations for the ETS-8 was 1-40 mM; for PAA (6 kDa), 1-40 µM, with IC50 = 3.8 ± 0.19 mm and 1.8 ± 0.09 µM, respectively. For the first time the impact of the PE on the structural-functional state of the viral membrane was assessed on the basis of monomolecular monolayers used as models of cell membranes.

Detection of a few metallo-protein molecules using color centers in nanodiamonds.

Nanometer-sized diamonds containing nitrogen-vacancy defect centers (NV) are promising nanosensors in biological environments due to their biocompatibility, bright fluorescence, and high magnetic sensitivity at ambient conditions. Here we report on the detection of ferritin molecules using magnetic noise induced by the inner paramagnetic iron as a contrast mechanism. We observe a significant reduction of both coherence and relaxation time due to the presence of ferritin on the surface of nanodiamonds. Our theoretical model is in excellent agreement with the experimental data and establishes this method as a novel sensing technology for proteins.

[Wound treatment using the flow of an ozonized solution under high pressure]. / Lechenie ran s ispol'zovaniem potoka ozonirovannogo rastvora pod vysokim davleniem.

New method for treatment of infected and festered, among them wounds with lingering healing was developed. The method was based on local application of fine-dispersion ozonized solution stream high pressure. This stream of ozonized fluid is generated under pressure of 350 ATM with the help of "Device for hydro-pressive treatment of wounds", ozonization of the solution is performed by the "OZh-2" apparatus developed by the authors. Application of the method of hydropressive ozonization provides fast cleansing of wound surface from pyonecrotic masses, promotes elimination of infection and thus substantially reduces the period of treatment of the patients.

[The relationship of the clinical status of the periodontium and the cytochemical indices of the enzyme activity of the peripheral blood leukocytes]. / Izuchenie vzaimosviazi klinicheskogo sostoianiia parodonta i tsitokhimicheskikh pokazatelei fermentativnoi aktivnosti leikotsitov perifericheskoi krovi.

Measurements of the mean activities of succinate dehydrogenase and a-glycerophosphate dehydrogenase in peripheral blood lymphocytes, entropy, asymmetry, variation, and excess coefficients in patients with periodontitis of different severity revealed a significant correlation of these parameters with the clinical status of the periodontium. The authors draw a conclusion about the high sensitivity of the cytochemical method for assessment of the severity of the pathological process in periodontal tissues.

[Phosphorylation of glyceraldehyde-3-phosphate dehydrogenase]. / Fosforilirovanie glitseral'degid-3-fosfat degidrogenazy.

Phosphorylation of D-glyceraldehyde-3-phosphate dehydrogenase (GPDH) by Ca2+/phospholipid- and Ca2+/calmodulin-dependent protein kinases was shown to take place in rabbit skeletal muscle and brain extracts. The kinases could be "picked up" from the extract, using GPDH immobilized on CNBr-activated Sepharose 4B as an affinity adsorbent. Washing of the column with GPDH solutions resulted in elution of the protein kinases; the same effect was observed when anti-GPDH antibodies were used. The most effective elution took place under the conditions favouring the dissociation of the immobilized GPDH into dimers. Based on these findings, a method for purification of Ca2+/calmodulin-dependent protein kinase has been elaborated, which includes chromatography on phenyl-Sepharose to separate the kinase from GPDH. The susceptibility of GPDH to phosphorylation by tissue protein kinases was confirmed by analyses of GPDH preparations purified from rabbit muscle for endogenous phosphate content: 0.7-1.5 moles of covalently bound phosphate were found per mole of the enzyme.