[Glutathione unit of the antioxidant system activity in pregnant women depending on the sleep quality]. / Aktivnost' glutationovogo zvena antioksidantnoi sistemy u beremennykh v zavisimosti ot kachestva sna.

OBJECTIVE: To assess the enzymatic and non-enzymatic links of the glutathione system in pregnant women depending on the sleep quality. MATERIAL AND METHODS: The study included 64 pregnant women aged 18 to 40 years. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). The results of the clinical and anamnestic examination made it possible to divide the subjects into the control group (PSQI≤5, n=31, mean age 32±5.2 years, body mass index (BMI) 30.86±8.41 kg/m2) and the main group (PSQI>5, n=33, mean age 33±5.23 years, BMI 30.88±7.47 kg/m2). The distribution of women by trimesters between the groups was statistically comparable: I (48.4%), II (32.3%), III (19.3%) in the control group and 1 (48.5%), 2 (36.4%), 3 (15.1%) in the main group. Glutathione status was determined by the content of reduced, oxidized glutathione and their ratio, glutathione peroxidase and glutathione reductase activities. The content of lipid peroxidation products was determined by the levels of diene conjugates and TBA-active products. RESULTS: PSQI was 3.81±1.30 points in the control and 8.88±3.12 points in the main group (p<0.001). There was an increase in the glutathione peroxidase activity (1349 [790.3; 2006] U/l, p=0.016) and oxidized glutathione level (2.17 [1.85; 2.33] mmol/l, p=0.048) in the main group compared with the control group (560 [438.1; 1462] U/l and 1.85 [1.53; 2.25] mmol/l, respectively). There were no statistically significant differences between the groups in the content of lipid peroxidation products such as diene conjugates and TBA-active products. CONCLUSION: The decrease of sleep quality in pregnant women is accompanied by changes in the glutathione component of antioxidant protection activation, which indicates the need to take measures to improve the sleep quality and correct the antioxidant status in these women.

[The successful use of Cytoflavin in the patient with postaveny syndrome]. / Uspeshnoe primenenie Tsitoflavina u patsientki s postkovidnym sindromom.

A clinical observation of the use of Cytoflavin according to a two-stage scheme (10.0 ml intravenously drip per 200 ml of 0.9% sodium chloride solution for 10 days, followed by a transition to a tablet form of 2 tablets 2 times/day for 25 days) in a patient with postcovid syndrome with pronounced vegetative and neurocognitive disorders. The effectiveness of therapy was confirmed by an improvement in heart rate variability and a decrease in the severity of depression, anxiety (on the HADS scale) and the level of autonomic dysfunction (on the COMPASS-31 scale). The significant changes in levels of fatigue (on a scale MFI) is not marked. The obtained results can serve as a basis for further research.

Recombinant Pneumolysin of Pneumococci Induces TLR4 Expression and Maturation of Dendritic Cells In Vitro.

Pneumolysin (Ply) is a target for the development of serotype-independent pneumococcal vaccines, an important condition for the efficacy of which is their ability to activate innate immunity with the subsequent formation of adaptive immunity. In this study, the ability of recombinant full-length Ply (rPly) of pneumococci to induce TLR expression and maturation of dendritic cells generated from mouse bone marrow was evaluated. It was shown that rPly in vitro increased the number of dendritic cells expressing Toll-like receptor 4 (TLR4) on the membrane. rPly caused maturation of dendritic cells generated from mouse bone marrow, which manifested in a decrease in the number of progenitor cells (CD34), an increase in the number of cells expressing the adhesion molecule CD38, costimulatory molecules CD80 and CD86, molecules of terminal differentiation of dendritic cells CD83, as well as molecules of antigenic presentation of the major histocompatibility complex class II.

[Morphological evaluation of orbital implants in postenucleation reconstruction (an experimental study)]. / Morfologicheskaya otsenka orbital'nykh implantatov v postenukleatsionnoi rekonstruktsii (eksperimental'noe issledovanie).

About 12 thousand surgeries for eyeball removal are performed every year in the Russian Federation. Formation of the supporting stump and implantation of the proper orbital implant is essential for successful cosmetic prosthesis. PURPOSE: Comparison of materials biocompatibility, design of different orbital implants and morphological condition of formed postenucleation stumps in an in vivo experiment. MATERIAL AND METHODS: In the course of the study 24 rabbits were operated, divided into three comparable groups. Enucleation with primary implantation of an orbital implant was performed in all subjects. The following implants were used: polymeric orbital implant - in the main (experimental) group, polytetrafluorethylene insertion implant - in the control group 1, and silicone endoprosthesis - in the control group 2. We assessed features of the implantation process, implant design, general condition of the operated animals, condition of the postenucleation stumps, passive motility of the stumps, and reaction of the surrounding tissues to the implants. RESULTS: Performed surgeries did not negatively affect the general condition of the rabbits, and there was no significant local tissue reaction to the implants. The structural and design features of the implants used in the main group were found to be more convenient for implantation, ensured stable fixation and position in the orbit. Postenucleation stump motility was comparable in all groups during the early postoperative period. This parameter decreased at later follow-up times mostly in the control group 2. When extracting the implants, it was revealed that in the main group it had secure fixation to the orbital tissues and stable position, did not cause abundant proliferation of connective tissue. Pathomorphological examination revealed that tissue reaction to the implants was less prominent and was reversed soon with fine connective tissue capsule formation in the main group and control group 2. In the control group 1 tissue reaction increased progressively, and capsule formation was delayed. CONCLUSION: Polymeric implant is the most suitable orbital implant for postenucleation orbital reconstruction.

Intravenouse immunoglobuline in dysautonomia.

Nowadays intravenous immunoglobulin (IVIg) treatment is considered to play a promising role in the autoimmune disease therapy. Despite its significant beneficial effects, the precise mechanism of action needs further studies, as well as recommended dosage in the treatment of autoimmune dysautonomia. In some diseases, like Guillain-Barre syndrome (GBS) and chronic inflammatory demyelinating neuropathy (CIDP), IVIg has a strong evidence that allows to recommend and prescribe the medication, while in other diseases only single case studies are available that requires further research. The review summarizes the currently available information on the effectiveness of IVIg in primary autoimmune neuropathies and neurological complications of systemic diseases, as well as side effects, features of clinical use with an emphasis on doses and treatment protocols in dysautonomia. Being safe and effective therapy, immunologic treatment is one of the most promising tools to achieve clinical remission of dysautonomia and good quality of life in autoimmune patients.

The effect of biodegradable silk fibroin-based scaffolds containing glial cell line-derived neurotrophic factor (GDNF) on the corneal regeneration process.

Corneal injury due to ocular trauma or infection is one of the most challenging vision impairing pathologies. The aim of the work was to study the effect of biodegradable silk fibroin-based scaffolds containing GDNF on the corneal regeneration process. During cultivate the highest keratocytes proliferative activity was registered with scaffolds containing 250 ng/ml and 500 ng/ml GDNF. In mice with an experimental model of epithelial-stromal damage to the cornea, silk fibroin-based scaffolds containing GDNF in various concentrations were used (in groups 1, 2 and 3 silk fibroin-based scaffolds containing GDNF in a concentration of 50 ng/ml, 250 ng/ml and 500 ng/ml, respectively; in group 4 - silk fibroin-based scaffolds without GDNF; in group 5 - a solution of GDNF with concentration of 500 ng/ml; group 6- control). The area of the corneal epithelial defect in groups 2, 3, and 5 was less than in the other groups. The most pronounced positive immunohistochemical reaction with antibodies to Bcl2, Bax, phosphoERK1/2 and phospho-JNK1/2, Ki67, Gap43 was observed in groups 2 and 3. Thus, silk fibroin-based scaffolds with GDNF stimulate the epithelialization process, proliferative activity of epithelial cells and keratocytes, accelerate the formation of the stromal nerve plexus and exhibit anti-apoptotic activity.

Visual Scale as a Non-Invasive Method for Evaluation of Risk and Severity of Coronary Atherosclerosis.

Aim      To evaluate quantitative and qualitative characteristics of atherosclerotic plaques (ASP) in carotid arteries (CA) and femoral arteries (FA) and to use these data for developing a visual scale (VS) for noninvasive diagnosis and determination of severity of coronary atherosclerosis.Material and methods  This study included 216 patients (115 men and 101 women) aged 24 to 87 years (mean age, 61.5±10.73 years). All patients underwent coronary angiography (CAG) for detecting and determining severity of CA atherosclerosis and duplex scanning (DS) for detecting atherosclerosis of CA and FA.Results Analysis of ultrasound parameters of ASP in CA and FA showed that the maximal ASP height, moderate stenosis and maximal stenosis of the arterial bed had higher predictive values than other ultrasound parameters. These parameters were used for forming diagnostic complexes, on the basis of which two individual VSs for CA and FA were developed. Based on the high prognostic value of both scales, they were combined into one that was named VSCOMB. A ROC analysis determined cut-off points of the VSCOMB for diagnosis of CA atherosclerosis of various severity. VSCOMB scores  >4 indicated pronounced CA atherosclerosis with sensitivity of 86.1 % and specificity of 87.5 % whereas VSCOMB scores  ≤4 excluded it. Thus, VSCOMB score 0-1 indicated the absence of CA atherosclerosis; score 2-4 indicated the presence of subclinical CA atherosclerosis; and score >4 indicated severe CA atherosclerosis.Conclusion      A VSCOMB was developed that includes a set of ultrasound parameters for CA and FA and is useful for noninvasive diagnosis of CA atherosclerosis of various severity. Simple and convenient use of VSCOMB allows it to be used at the screening stage to detect subclinical CA atherosclerosis and to prevent its progression.

New laboratory criteria of the autoimmune inflammation in pulmonary sarcoidosis and tuberculosis.

Sarcoidosis and tuberculosis have many clinical and laboratory similarities, which allowed researchers to assume the presence of common pathogenetic mechanisms in the development of both diseases. Recently, much attention has been paid to investigate the autoimmune origins in these pathologies. The aim of this study is to find out the characteristics of the autoinflammatory immune response in sarcoidosis and tuberculosis. In patients with sarcoidosis (n = 93), tuberculosis (n = 28), and in healthy donors (n = 40), the serum anti-MCV concentration was measured by ELISA, and B cell subpopulations were analyzed by flow cytometry. Based on the results obtained, the formula ([B-naïve%]\[B-memory%]) * ([B-CD38%] + [B-CD5%]) / [anti-MCV] was described. The increase in the calculated index by more than 5 units with a sensitivity of 80.00% and a specificity of 93.10% (AUC = 0.926) suggest the presence of the autoimmune component, which is more typical for sarcoidosis, rather than tuberculosis patients and may serve as a diagnostic criterion.

[Evolution of loss due to event of undetermined intent among the Moscow working-age population in the 2000s].

Accuracy of statistical registration of mortality in Russia, especially in times of crisis, is a pressing and relevant issue; this problem was challenging Moscow in the 2000s: until recently, the capital was a complete outsider in terms of accuracy of statistical registration of mortality. The purpose of the study was to identify peculiar features of evolution and the structure of mortality from an event of undetermined intent among Moscow working-age population in the 2000s against the background of the processes taking place in Russia. The article analyzes mortality from an event of undetermined intent among Moscow population of young and old working age in the 2000s, as well as its nosological aspects in 2011-2018, when certain events of undetermined intent were separated as individual nosological units. A sharp decline in indicators in 1999-2000 and their growth in 2015-2017 have been identified. It is shown that these shifts were due to all leading events of undetermined intent (falls/jumps from a high place, hanging/strangulation/suffocation, medicament, alcohol and drug poisoning as well as specified and unspecified events). As a result, the structure of mortality after 2015 has significantly changed due to a sharp increase in the significance of alcohol, medicament and especially drug poisoning. It should be emphasized that in the 2010s the significance of latent suicide in all age and gender groups of Moscow working-age population is significantly higher than in Russia.

[Optical coherence tomography and optical coherence tomography-angiography in the diagnosis of chiasmo-sellar region compression]. / Opticheskaya kogerentnaya tomografiya i opticheskaya kogerentnaya tomografiya-angiografiya v diagnostike kompressii khiazmal'no-sellyarnoi oblasti.

Preservation of visual functions in patients with chiasmo-sellar region compression (CSRC) is possible with early diagnosis and surgical decompression. PURPOSE: To analyze the parameters of optical coherence tomography (OCT) and optical coherence tomography-angiography (OCTA) in patients with CSRC. MATERIAL AND METHODS: The study included 10 patients (20 eyes) with CSRC, 15 healthy volunteers (30 eyes). OCT, OCTA was performed on Cirrus HD-OCT 5000 AngioPlex™ (Carl Zeiss Meditec, U.S.A.) with AngioVue system. RESULTS: Patients with CSRC were revealed to have decreased thickness of ILM-RPE in the nasal sector of outer circle (p<0.001) and average mGCIPL - total and for all six sectors (p<0.001), decreased RNFL in the inferior sector (p=0.017); decreased superficial vessel density (SVD) and perfusion density in the inner and outer circle areas and in all sectors of the ETDRS grid (p<0.001) except temporal; in the peripapillary area, decreased vessel perfusion density (VPD) in the inferior sector (p=0.025), capillary flux index (CFI) in all sectors (p<0.001; p=0.025 in the inferior sector). Informative diagnostic criteria included ILM-RPE in nasal sector of the outer circle (AUC=0.896); mGCIPL in the inferonasal sector (AUC=0.914), average (AUC=0.846), superior (AUC=0.829) and superonasal (AUC=0.846) sectors; average SVD (AUC=0.805) and SVD in the inner circle area (AUC=0.810); CFI in the inferior sector (AUC=0.806) with p<0.001. CONCLUSION: In CSRC, changes can be seen in OCT and OCTA parameters recorded in the macular and peripapillary regions before the changes in the central visual field. Informative diagnostic OCT and OCTA criteria can help diagnose the pathology early, expand the indications for decompression, and preserve the visual funcitons.

[Ultraviolet crosslinking in the treatment of keratoconus in patients with thin corneas]. / Ul'trafioletovyi krosslinking v lechenii keratokonusa pri sushchestvennom umen'shenii tolshchiny rogovitsy.

Corneal collagen cross-linking (CXL) is a procedure that aims to halt the progression of corneal ectasia in keratoconic eyes. It is achieved by inducing cross-links in the corneal stroma and extracellular matrix by exposing it to ultraviolet-A (370 nm) irradiation while it is filled with photosensitizer (riboflavin). According to the conventional protocol, the recommended de-epithelialized corneal thickness should be higher than 400 µm in order to avoid radiation damage to the corneal endothelium. However, in progressive keratoconus, corneal thickness is often close to or lower than this threshold of 400 µm, which limits the application of cross-linking for these patients. The present article reviews the different protocols of cross-linking for thin corneas, their advantages and disadvantages. At present, clinical research on modified cross-linking protocols is still limited due to the methodology and a low number of patients involved. Thus, comparative randomized controlled studies with long-term follow-up are necessary to confirm the safety and effectiveness of several CXL protocols and identify the most efficient one.

What Can We Learn about Aging and COVID-19 by Studying Mortality?

Promising ideas and directions for further research into biology of aging are discussed using analysis of the age-related kinetics of organisms' mortality. It is shown that the traditional evolutionary theory explaining aging by decreasing force of natural selection with age is not consistent with the data on age-related mortality kinetics. The hypothesis of multistage destruction of organisms with age, including the rate-limiting stage of transition to a state of non-specific vulnerability ("non-survivor"), is discussed. It is found that the effect of the COVID-19 coronavirus infection on mortality is not additive (as it was the case with the Spanish flu epidemic in 1918), but multiplicative (proportional) for ages over 65 years.

[Combined markers of initial stages of coronary atherosclerosis]. / Kombinirovannye markery nachal'noi stadii ateroskleroza koronarnykh arterii.

Abnormalities in energy metabolism and endothelial dysfunction contribute to signaling processes associated with atherogenesis. The goal of our study was to develop diagnostic tests based on endothelial functional markers and adiponectin to differentiate early stages of coronary lesions during atherogenesis. The cohort included male and female patients from 25 to 86 years of age. All subjects underwent coronary angiography and severity of coronary lesions was quantified by the Gensini score that assigns points depending on location and extent of the lesions. We have estimated associations between the Gensini score and some known primary and secondary diagnostic parameters and have found that the ratio of serum levels of adiponectin to endothelin strongly correlates with severity of coronary lesions and can be used for differentiation of male patients lacking coronary atherosclerosis (despite symptoms of ischemic heart disease) from patients that have severe coronary lesions. Predictive power of adiponectin to endothelin ratio did not depend on drug therapy.

[Modern state and prospects of the development of production of specialized foodstuffs for athletes].

Nutrition is a very important element in the training of athletes - both professionals and amateurs. Sports exercises accompanied by significant energy expenditure, hypoxia, large neuro-psychological stress that caused the body's increased need for energy and certain nutrients. It is almost impossible to provide athletes' needs through the regular diet, so during the training cycle they used specifically developed nutrition' systems. Modern methodology of athletes' nutrition makes provisions of using special diet, including not only conventional, but also fortified foods and dietary supplements, to compensate the comparative deficiency of any essential body' substratum and biologically active substances. Analytical researches indicate that lately generally in Russia, there is a tendency of increasing the number of people engaged in physical culture and sports, who needs specialized foodstuffs. Nowadays food and beverages intended for athletes of different specializations, widely represented in the Russian market, are mainly imported; the percentage of domestic specialized foodstuffs and beverages is small. In the last decade, native scientists developed a wide range of specialized foodstuffs for sportsmen's nutrition, that creates the prospect of the development of production of Russian foodstuffs with assured quality in order to achieve the best results in professional and amateur sports.

[Experimental and scientific formulation development of a specialized (sport) product, enriched with probiotic microorganisms].

The aim of the work is to scientifically justify the formulation of a probiotic food product for sports nutrition using a functional food ingredient. As a functional food ingredient, the association of probiotics (Lactobacillus and bifidobacteria) immobilized in a gel of biopolymers was studied. The main raw material used was cow's fat-free milk; as components that regulated the protein-carbohydrate composition of a multicomponent product, the whey protein isolate, natural honey and maltodextrin were chosen. A complex containing defibrated blood and an extract of reindeer antlers was used as an adaptogen of animal origin. In order to complement the qualitative and quantitative composition of vitamins and minerals, a premix containing 7 vitamins, calcium and iron was used. The process of obtaining a functional ingredient for fermenting a normalized mixture and enriching the product with viable probiotic cells is outlined. To protect them in the aggressive conditions of the technological process, as well as in the stomach and intestine, the process of immobilization by incorporating the association of probiotics into the gel of biopolymers was studied. The effectiveness of the delivery of the association of probiotic microorganisms immobilized in the gel of biopolymers was proved by carrying out studies in simulated conditions of the stomach and intestine. The functional food ingredient obtained experimentally was used for fermentation of a normalized mixture of components in the technology of a fermented (sour-milk) product for sport's nutrition.

Effects of Phenotype of Retinal Macrophages on the Features of Angiogenesis of Murine Retina.

The period of forming of superficial vascular plexus during physiological retinal angiogenesis was shorter in C57Bl/6 mice. Experiments on the model of oxygen-induced retinopathy showed that avascular and vascularized zones in BALB/c mice on day 17 are smaller than in C57Bl/6 mice are by 5 and 1.5 times, respectively. The obtained results confirmed the importance of phenotype of retinal macrophages in the regulation of processes of both physiological and pathological retinal angiogenesis.

[The application of lipoprint-system for analysis of sub-fractional spectrum of lipoproteins of blood serum.]

The lipoproteins of low and high density are presented by heterogeneous specter of particles differing by size, density, charge, composition and functional characteristics. The prevalence of small dense particles of lipoproteins of low and high density in blood plasma is associated with higher risk of development of coronary heart disease. The identification of subfractional spectrum of lipoproteins in clinical purposes is complicated because of requirement of expensive equipment and reagents and extended time of implementation. The lipoprint-system (Quantimetrix Lipoprint LDL/HDL System, USA) based on the vertical electrophoresis using 3% polyacrilamid gel, permits shortening time of sub-fractioning of lipoproteins up to three hours. In the spectrum of apoB-containing lipoproteins of very low density, intermediate density, C, B, A, lipoproteins of low density 1 and 2, small dense (lipoproteins of low density 3-7) are singled out. In the spectrum of lipoproteins of high density up to 10 sub-fractions associated in three groups and represented by large (lipoproteins of high density 1-3), intermediate (lipoproteins of high density 4-7) and small (lipoproteins of high density 8-10) particles are singled out. The article describes technique of identification of spectrum of particles of lipoproteins of low and high density in human blood serum. The conditions of implementation of experiments are presented. The advantages and limitations of technique are indicated. The number of examples of application of indices of sub-fractional spectrum of lipoproteins as additional markers of evaluation of aterogenity of lipid profile are presented. The conclusion is made concerning possibility of application of technique in clinical laboratory diagnostic.

[Combination of Visual and Metabolic Markers in Assessment of Probability of Presence and Severity of Atherosclerosis of Coronary Arteries].

AIM: to assess possibilities of the use of biochemical markers combined with data of methods of imaging of arterial atherosclerotic lesions for evaluation of risk of presence and severity of coronary atherosclerosis. MATERIALS AND METHODS: We enrolled into this study patients (n=205, 136 men, 69 women, age 33-85 years, 94% on statin therapy) who underwent coronary angiography and carotid artery ultrasound dopplerography. Examination included determination of parameters of lipid profile and carbohydrate metabolism, markers of inflammation and metabolism of visceral adipose tissue. The severity of carotid artery atherosclerosis was estimated using mean common carotid artery intima-media thickness and atherosclerotic plaques presence. Severity of coronary atherosclerosis was evaluated using Gensini score. RESULTS: We found association between a number of biomarkers and severity of coronary artery involvement. Presence of coronary atherosclerosis (Gensini score >0) was associated with male sex, carotid artery stenosis >45%, and adiponectin level <8.0 pg/ml. Overt coronary atherosclerosis (Gensini score more or equal 35) significantly correlated with intima-media thickness more or equal 0.9 mm, C-reactive protein level >3.0 mg/l and adiponectin level <8.0 pg/ml.

[Markers of visceral adipose tissue metabolic abnormalities in patients with coronary atherosclerosis in relation to the presence of type 2 diabetes mellitus]. / Markery narusheniya metabolizma vistseral'noi zhirovoi tkani u patsientov s koronarnym aterosklerozom v zavisimosti ot nalichiya sakharnogo diabeta 2-go tipa.

AIM: To assess the specific features of visceral adipose tissue metabolism in patients with coronary atherosclerosis, complicated or uncomplicated type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: A cohort of 429 patients (325 men and 104 women; mean age, 61.3±9.4 years) with coronary atherosclerosis who had been admitted to the National Research Centre for Preventive Medicine, Ministry of Health of Russia, to undergo coronarography (CG) and to receive high-tech treatments and met the criteria for being included in and excluded from this investigation, was examined. The Gensini scoring scale was used to estimate the magnitude of coronary atherosclerosis from CG RESULTS: Carotid artery duplex ultrasound scanning estimating the intima-media thickness was performed in 48% of the patients. DM was diagnosed from examination results (fasting plasma glucose ≥7.0 mmol/l and glycated hemoglobin >6.5%) and an endocrinologist's report. 94% of the patients took statins. RESULTS: Overall, 18% of the examinees had DM that was 2.5 times more common in the women than in the men (32.7 and 13.2%, respectively (p=0.000). The diabetic and non-diabetic patients showed no significant differences in age: 62.9±8.3 and 60.9±9.6 years, respectively (p=0.105). There were statistically significant differences in the magnitude of coronary artery atherosclerosis according to the Gensini scale in relation to the presence of T2DM; thus, the median Gensini score was 48 in the diabetic patients and 46 in the persons with no signs of the disease (Mann-Whitney test; p=0.03). Analysis of adipokine levels showed that the median leptin level was significantly higher than that in the male patients with T2DM than in the persons with no signs of the disease. In the patients with T2DM, the median adiponectin level turned out to be significantly lower in both men and women. CONCLUSION: The coronary atherosclerosis severity rated using the Gensini scale is shown to increase in the presence of T2DM. The probability of detecting obvious (>45%) carotid artery lesion is associated with the presence of DM in both men and women. The male patients with T2DM concurrent with coronary atherosclerosis are noted to have an elevated leptin level, but a lower adiponectin concentration was found in both the men and women.