[Features of inflammatory endotypes and phenotypes in chronic rhinosinusitis]. / Osobennosti endotipov i fenotipov vospaleniya pri khronicheskom rinosinusite.

Recently, significant progress has been made in identifying the cellular and molecular mechanisms responsible for the pathogenesis of chronic rhinosinusitis (CRS). Cohort studies of CRS have led to advances in the clinical understanding of this disease. New therapeutic agents have been approved or are undergoing clinical trials to expand treatment options for this disease. One of the promising areas in medicine is the provision of personalized clinical care. From this perspective, CRS can be divided into three different endotypes depending on the type of underlying inflammatory response. In the United States, CRS with and without nasal polyps is predominantly characterized as the second inflammatory endotype. CRS with nasal polyps (about 17%) and without nasal polyps (up to 20%) belongs to the 1st and 3rd inflammatory endotypes, respectively. And if for the second inflammatory endotype the effectiveness of targeted biological therapy is beyond doubt, then for the first and third inflammatory endotypes the principles of such conservative therapy are under active development. Moreover, large validated studies to confirm associations between CRS phenotypes and endotypes, as well as to find effective biological markers of inflammatory endotypes, remain to be performed.

[Hydrogen effect on the mechanisms of mucosal immunity in patients with COVID-19].

AIM: To study the inhalation of an active form of hydrogen effect to mucosal and system immunity in a rehabilitation program for health workers. MATERIALS AND METHODS: The study involved patients that survived COVID-19 after therapy with inhaled hydrogen for 90 minutes (n=30), and a control group of patients treated according to standard protocol for managing patients that survived COVID-19 during the rehabilitation period (n=30). Biomaterial was carried out in 2 stages: on the first day of the study, before the accepted therapy and on the 10th day of the study. The indicators of humoral and cellular immunity were studied. The levels of secretory immunoglobulin A (sIgA) and IgG were investigated using the method of enzyme-linked immunosorbent assay. Phagocytosis was assessed on a Beckman Coulter FC-500 flow cytometer. Statistical data processing was carried out in the GraphPad Prism 7.00 software using nonparametric methods. RESULTS: It was shown that the phagocytic index (PI) of monocytes in nasal scrapings after inhaled hydrogen treatment did not significantly change relative to the first day of treatment and control, while the PI of granulocytes in nasal scrapings significantly increased relative to the first day by 2.5 times (p=0.000189), as well as relative to the control by 1.1 times (p=0.047410). PI of monocytes in pharyngeal scrapings showed a significant increase relative to the first day of treatment by 2.8 times (p=0.041103), however, did not differ relative to the control. PI of granulocytes of pharyngeal scraping did not differ significantly relative to the first day and control. PI of granulocytes and blood monocytes of the studied group did not change significantly. PI of granulocytes and monocytes of peripheral blood relative to control during therapy did not change. The sIgA level in nasal scrapings significantly increased by 2.9 times, while in pharyngeal scrapings the level of sIgA significantly decreased by 2 times. Сonclusion. We have shown an increase in granulocytes PI in the nasal cavity and oral monocytes, as well as in the level of sIgA in the nasal cavity during therapy with active hydrogen. The data obtained indicate the effectiveness of therapy, which can be used both in the treatment of COVID-19, and in post-COVID syndrome as an additional therapy. The absence of changes in blood parameters, as well as individual links in nasal and pharyngeal scrapings, requires further study to develop ways to overcome treatment tolerance.

[Rational strategy for studying microbiome of the ocular surface of people using hard contact lenses by method of 16S rRNA gene metabarcoding]. / Ratsional'naya strategiya izucheniya mikrobioma glaznoi poverkhnosti pol'zovatelei zhestkikh kontaktnykh linz metodom metabarkodinga po genu 16S rRNK.

The study is based on the hypothesis that high taxonomic diversity of bacteria detectable on the eye surface by molecular genetic methods is attributed to the high level of its contamination by skin microflora. Such contamination would make it problematic to identify the fractions of real ocular surface microbiome, which remains behind the one-percent cut-off threshold adopted in the metagenomic analysis. Hard contact lenses for long-wearing act as a physical filter preventing DNA contamination from random microorganisms, and at the same time providing adhesion to the living cells of bacteria and fungi. To confirm this assumption, a detailed analysis of references was carried out, supplemented by original laboratory research. MATERIAL AND METHODS: The analysis included 16 hard contact lenses obtained from 11 patients with impaired refraction (myopia). Additionally, conjunctival mucosa scrapings were collected from 42 patients. Samples were cross-analyzed by 16S rRNA gene sequencing using 454 GS Junior (Ion Torrent) and Illumina MiSeq platforms. RESULTS: Results obtained by the Illumina platform (analysis of the V3-V4 variable region of the 16S rRNA gene) showed better convergence with the data of culture tests reported in the literature. The major microorganism groups found were: Acinetobacter (39%), Gluconacetobacter (10.8%), Propionibacterium (9.3%), Corynebacterium (9.3%), Staphylococcus (7.2%), Streptococcus (7%), Pseudomonas (4.1%), Micrococcus (3.3%), Yersinia (3%), Chondromyces (2.4%), Serratia (2.3%), and Bacillus (2.1%). Analysis of the samples obtained directly from the mucosa revealed dominance of typical skin-associated microorganisms. CONCLUSION: The present study proposes a contamination-reduction algorithm for microbiological testing of the ocular surface using hard contact lenses for prolonged wearing as a carrier for microbial DNA.

Comparison of Different Commercial Conducting Materials as Ion-to-Electron Transducer Layers in Low-Cost Selective Solid-Contact Electrodes.

Simple, robust, sensitive and low-cost all-solid-state ion-selective electrodes (SCISEs) are of interest in different fields, such as medicine, veterinary, water treatment, food control, environmental and pollution monitoring, security, etc. as a replacement for traditional ion-selective electrodes with liquid inner contact. In spite of their potential advantages, SCISEs remain mainly in the research laboratories. With the motivation of developing simple and low-cost SCISEs with possible commercial applications, we report a comparison study of six different commercial conducting materials, namely, polypyrrole-block-polycaprolactone (PPy-b-PCaprol), graphene/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) ink, poly(3,4-ethylenedioxythiophene):polyethylenglycol (PEDOT:PEG), high conductivity PEDOT:PSS, polyethylenimine (PEI) with PEDOT:PSS for their possible use as ion-to-electron transducer in polyurethane based pH-SCISEs. Among all studied pH-SCISES, PEDOT:PEG based electrodes exhibited the best results in terms of sensitivity, reproducibility and lifetime. Finally, these sensors were tested in different real samples showing good accuracy.

3D impedimetric sensors as a tool for monitoring bacterial response to antibiotics.

The presence of antimicrobial contaminants like antibiotics in the environment is a major concern because they promote the emergence and the spread of multidrug resistant bacteria. Since the conventional systems for the determination of bacterial susceptibility to antibiotics rely on culturing methods that require long processing times, the implementation of novel strategies is highly required for fast and point-of-care applications. Here the development and characterization of a novel label-free biosensing platform based on a microbial biosensor approach to perform antibiotic detection bioassays in diluted solution is presented. The microbial biosensor is based on a three-dimensional interdigitated electrode array (3D-IDEA) impedimetric transducer with immobilized E. coli bacteria. In 3D-IDEA to increase the sensitivity to superficial impedance changes the electrode digits are separated by insulating barriers. A novel strategy is employed to selectively immobilize bacteria in the spaces over the electrode digits between the barriers, referred to here as trenches, in order to concentrate bacteria, improve the reproducibility of the E. coli immobilization and increase the sensitivity for monitoring bacterial response. For effective attachment of bacteria within the trenches an initial anchoring layer of a highly charged polycation, polyethyleneimine (PEI), was used. To facilitate immobilization of bacteria within the trenches and prevent their deposition on top of the barriers an important novelty is the use of poly(N-isopropylmethacrylamide) p(NIPMAM) microgels working as antifouling agents, deposited on top of the barriers by microcontact printing. The reported microbial biosensor approach allows the bacterial response to ampicillin, a bacteriolytic antibiotic, to be registered by means of impedance variations in a rapid and label-free operation that enables new possibilities in bioassays for toxicity testing.

[Clinical and laboratory diagnosis of tick-borne rickettsioses in areas of low risk of infection Rickettsia sibirica.]

For the first time, a comparative description of clinical and laboratory parameters in patients with clinical signs of tick-borne rickettsiosis in a natural focus with a low risk of infection with R. sibirica and circulation of R. raoultii is given, depending on the results of serological verification of the diagnosis. Established almost complete coincidence of clinical and laboratory parameters in patients with tick-borne rickettsiosis, regardless of the presence of antibodies to R. sibirica and / or R. raoultii. It was shown that even the complex use of complement fixation test, indirect immunofluorescent test and ELISA for the detection of antibodies to R. sibirica does not allow verification of the diagnosis in a third part of patients with pathognomonic signs of tickborne rickettsiosis. In seropostive patients, antibodies to R. sibirica prevailed, which makes it impossible to differentiate cases of tick-borne rickettsiosis of different species etiology. The possible reasons of the phenomenon of «seronegativeness¼ of patients with tick-borne rickettsiosis and approaches to its study are discussed. It is concluded that with the existing diversity and insufficient knowledge of rickettsiae circulating in natural foci, and the current state of laboratory diagnostics, the basis for the diagnosis of «Tick-borne rickettsiosis¼ should be the clinical and epidemiological signs of this infectious disease, which must be recorded in the established order even no serological verification. For such cases, ICD-10 has two encoding options: A 79.9 - Rickettsiosis, unspecified (infection caused by rickettsia, no other indication) and A 77.9 - Spotted fever, unspecified (tick-borne fever, no other indication) [mkb-10.com].

[Evaluation of the effectiveness of the serological methods for the identification of antibodies in patients with tissue ricketsiosis on the territories of a different risk of Rickettsia sibirica infection.]

Cases of tick-borne rickettsiosis in Siberia and the Far East are associated with R. sibirica, the causative agent of Siberian tick typhus (STT). In connection with a sharp reduction in the nomenclature of diagnostic products and an increase in the spectrum of species of founding rickettsiae on the territory of Russia, new approaches to the laboratory verification of diagnoses are needed. We present an evaluation of the effectiveness of serological research methods (complement fixation test, indirect immunofluorescence, and ELISA) in patients with tick-borne rickettsioses in areas of different risk of infection with R. sibirica. Patients were diagnosed with STT from the highly endemic territory of the Altai Republic and from the Naziayevsky district of the Omsk region, where natural foci of rickettsioses of the spotted fever group was detected with the circulation of two species of pathogenic rickettsia, R. sibirica and R. raoultii. As a control group, samples of sera from epidemic seasons from clinically healthy people in Omsk were used. To verify the diagnosis of Siberian tick typhus, the use of serological methods is most appropriate, of which the most sensitive is ELISA, which allows detecting antibodies at an earlier time. In the ELISA for confirmation of the diagnosis, the first serum can be examined only on IgM. Investigation of the 2nd serum should be performed in ELISA for the presence of IgM and IgG antibodies with R. sibirica antigen. Reaction of indirect immunofluorescence (RNIF) for the study of paired sera should be conducted with specific antigens of rickettsia circulating in this focus. In laboratories not equipped for setting ELISA, it was recommended to use CFT. When the titer increases in two or more times and IgM and IgG are detected in the second serum, taking into account clinical manifestations, the diagnosis of "Siberian tick typhus" can be considered confirmed.

[The micro-ecology of burn hospitals.]

The article analyzes agents of wound burn infection on departments of the Privolzhskii` Federal medical research center during last 2.5 years. The leading role in infection etiology in the burnt ones belongs to staphylococci. At that, in adult patients more frequently S.aureus is separated and in children - coagulase-negative strains. During current year, the second place in the structure of wound burn infection factually is divided in equal proportions A. baumannii, P. aeruginosa and K. pneumoniae. About 80% of isolates of K. pneumoniae are produced by ß-lactamase. No producers of metallo-ß-lactamases were detected among Klebsiella. Annually, number of wound enterococci increases, making up to 15.3% in children and 11.1% in adults.

Comparative Analysis of Antioxidant Properties of Comenic Acid and Potassium Comenate in Modeled Immobilization Stress.

We studied antioxidant protective effect of comenic acid and potassium comenate in doses of 2, 4, and 8 mg/kg under conditions of oxidative stress in the brain of mice exposed to immobilization stress. Administration of potassium comenate and comenic acid in the above doses for 3 days before stress prevented the development of oxidative processes in the brain of stressed animals. The antioxidant effect of potassium comenate more pronounced.

[The role of assessing UGT1A1 gene polymorphism in the prediction of irinotecan-induced toxicity in the course of chemotherapy for colorectal cancer].

There was performed a molecular genetic study of UGTlAl gene allelic variants polymorphism in patients with colorectal cancer who had had chemotherapy irinotecan-containing regimens FOLFIRI. Comparison of toxicity and the results of polymorphism of UGTlAl showed that dose-limiting hematologic and non-hematologic toxicities in patients with moderate and high risk of toxicity were higher (p = 0.050- 0.061) and the frequency of thrombocytopenia (p = 0.0257) and hyperbilirubinemia (p = 0.0439) were significantly higher compared to the low-risk group. Molecular genetic study of a complex examination of patients, which was planned to irinotecan should be performed to select the optimal dose and reduce the risk of toxicity of chemotherapy.

[ON THE ROLE OF RICKETTSIA RAOULTII IN THE EPIDEMIOLOGY OF RICKETTSIOSES IN RUSSIA].

The paper analyzes data on the prevalence and possible epidemiological importance of Rickettsia raoultii. The possible risk of infection in the population was assessed from the results of a serological study of patients after tick suction and from those of molecular biological determination of contamination of removed carriers. The place of Rickettsia raoultii among other rickettsia causing rickettsioses of a tick-borne spotted fever group is assessed in Russia.

[Influence of lithium salt of comenic acid on the state of oxidative processes in brain of stressed animals].

The influence of a new substance, lithium salt of comenic acid, on the oxidative processes in the brain of animals under the conditions of acute and long combined stress has been investigated. It is established that lithium comenate (1 and 2 mg/kg) exhibits pronounced dose-dependent antioxidative stress-protective effect, which is manifested in suppression of the hyperproduction of free radicals and depression of the content of malonic dialdehyde (a secondary product of lipid peroxidation) in the brain of stressed animals. The maximum antioxidative stress protection effect under the conditions of acute and long combined stress has been observed for lithium salt ofcomenic acid in a dose of 2 mg/kg.

[Efficacy of dermoplasty and the dermal equivalent in treatment of vast leg ulcers of mixed genesis].

The most frequent causes of leg ulcers (90-95%) are chronic venous insufficiency (45-60%), obliterating atherosclerosis of the lower extremity arteries (10-20%), diabetes mellitus (15-25%) and their combinations (10-15%). The leg ulcers, specified as pyoderma gangrenosum, are the rare and severe pathology, which is very often misdiagnosed. The case history of a 58-year old female patient with vast leg ulcers of the both shanks is analyzed. The leg ulcers were caused by pyoderma gangrenosum and chronic venous insufficiency due to the varicose disease. Complete epithelization of both ulcers was achieved by means of dermoplasty combined using the dermal equivalent against the background of system immunosuppressive therapy.

New flow-through analytical system based on ion-selective field effect transistors with optimised calcium selective photocurable membrane for bovine serum analysis.

An analytical system based on ion-selective field effect transistors (ISFETs) with Ca(2+) ion selective photocurable membranes is developed to offer a semiautomatic analysis of serum calcium concentration of ruminants. Optimisation of ion-sensitive membrane composition containing different copolymerised plasticizers was performed to minimise the effect of a highly lipophilic samples on sensors characteristics. To improve the system reliability the set of calibration solutions and measurement sequence were also optimised. The system was used to determine total calcium concentration in bovine sera. The precision of the ion determination was higher than reported for double charge ions with a standard deviation of about 3-7%. It is shown that the presence of coagulant in blood serum samples does not affect the determined total calcium concentration.

Recent trends in potentiometric sensor arrays--a review.

Nowadays there exists a large variety of ion sensors based on polymeric or solid-state membranes that can be used in a sensor array format in many analytical applications. This review aims at providing a critical overview of the distinct approaches that were developed to build and use potentiometric sensor arrays based on different transduction principles, such as classical ion-selective electrodes (ISEs) with polymer or solid-state membranes, solid-contact electrodes (SCE) including coated wire electrodes (CWE), ion-sensitive field-effect transistors (ISFETs) and light addressable potentiometric sensors (LAPS). Analysing latest publications on potentiometric sensor arrays development and applications certain problems are outlined and trends are discussed.

[Medical treatment for Graves' disease: principles, markers of a relapse and remission].

Graves' disease (diffuse toxic goiter) is a systemic autoimmune disease that develops as a result of the production of antibodies to the thyroid stimulating hormone receptor (AT-rTSH), which is clinically manifested by thyroid damage with the development of thyrotoxicosis syndrome in combination with extrathyroid pathology (pretibial endocrine) myxedema, acropathy). The disease was first described by S. Ives in 1722, then Peri in 1786 and Flayani in 1802. In 1835, R. Graves associated the occurrence of the described symptom complex, now known as thyrotoxicosis syndrome, with thyroid pathology. In 1840, K. Bazedov singled out a triad in the clinical picture: goiter, buccalis, tachycardia.

[Thyroid-stimulating hormone receptor antibodies in the differential diagnosis of toxic goiter].

The production of stimulating thyroid-stimulating hormone (TSH) receptor antibodies (TSHR-Ab) whose level measurement has come into clinical use underlies the pathogenesis of Graves'disease (GD). This paper deals with the diagnostic and differentially diagnostic value of measurement of TSHR-Ab levels using two first-generation techniques (with heterological TSH): radioreceptor assay ("CIS bio international", France) and enzyme immunoassay ("Medizym" T.R.A."). The levels of TSHT-Ab, as well as thyroid peroxidase antibodies (TH-Ab) and thyroglobulin antibodies (TG-Ab) were studied in 206 patients among whom 176 patients were diagnosed as having GD and 30 had clinical thyroid functional autonomy (FA) generally appeared as multinodal toxic goiter. A comparative analysis of these two assays did not reveal some advantages of them and their results showed a significantly positive correlation (r = 0.91; p < 0.001). The diagnostic sensitivity of the assays was about 80-88% and their specificity was 60-70%. The findings led to the conclusion that in the absence of significant endocrine ophthalmopathy (EOF), clinical and routine instrumental and laboratory studies fail to differentiate GD and throid FA to sufficient accuracy whereas the measurement of the levels of TSHR-Ab substantially makes diagnosis easier. Moreover, it has been shown that the determination of the level of TBII using the test systems containing heterological TSH may not be used for the evaluation of the course of EOF.

[Higher cortical functions in children with spastic forms of cerebral palsy]. / Vysshie psikhicheskie funktsii u detei so spasticheskimi formami tserebral'nykh paralichei.

Kinestatic praxis was studied in 75 children, aged 7-11 years, with spastic forms of cerebral palsy (CP) and in 30 of them other higher cortical functions were examined. The disturbances of kinestatic praxis were more expressed in hemiparetic forms of CP, being observed in all the cases, and frequently occurred in spastic diplegias (75-94.3%) as well. Dynamic praxis was disturbed in 90% cases, spatial praxis--in 53.3%, visual-acoustic gnosis--in 36.6%, visual-object gnosis--in 50%, visual-spatial--in 80%, visual memory--in 40%, visual imaging reasoning--in 30%, verbal logic reasoning--in 43.3%.

Stimulatory effect of green tea extract on the growth of neurites in the rat spinal ganglion culture.

Addition of green tea extract in concentrations of 0.004-0.006% to the nutrient medium markedly stimulated the growth of spinal ganglion neurites of 1-2-day-old rats.