[WORLD EXPERIENCE: HOW THE DEVELOPMENT OF THE PRINCIPLES OF ACADEMICIAN OF THE ACADEMY OF MEDICAL SCIENCES OF THE USSR N. A. SEMASHKO HELPED ICELAND TO CREATE ONE OF THE MOST EFFECTIVE HEALTHCARE SYSTEMS IN THE WORLD. PART 1. HISTORICAL OVERVIEW].

Annotation. The review article is devoted to the healthcare system of Iceland, which demonstrates some of the best indicators of public health in the world at relatively low costs for a developed European country. The successful experience of Icelandic healthcare is important for Russia, on the one hand, due to the proximity of this country to many Russian regions in terms of climatic and geographical location, demography and territorial development. On the other hand, the success of Iceland's healthcare is closely linked to the development of a model, in many ways similar to the Soviet model of Nikolai Semashko, which Russia has abandoned. The authors believe that Iceland's experience can be used in the modernization of regional healthcare systems in Eastern Siberia, the Far East and the Arctic, as well as Russian healthcare in general.

[WORLD EXPERIENCE: HOW THE DEVELOPMENT OF THE PRINCIPLES OF ACADEMICIAN OF THE ACADEMY OF MEDICAL SCIENCES OF THE USSR N. A. SEMASHKO HELPED ICELAND TO CREATE ONE OF THE MOST EFFECTIVE HEALTHCARE SYSTEMS IN THE WORLD. PART 2. PRINCIPLES FUNCTIONING OF THE ICELANDIC HEALTH SYSTEM].

Annotation. The review article is devoted to the healthcare system of Iceland, which demonstrates some of the best indicators of public health in the world at relatively low costs for a developed European country. The successful experience of Icelandic healthcare is important for Russia, on the one hand, due to the proximity of this country to many Russian regions in terms of climatic and geographical location, demography and territorial development. On the other hand, the success of Iceland's healthcare is closely linked to the development of a model, in many ways similar to the Soviet model of Nikolai Semashko, which Russia has abandoned. The authors believe that Iceland's experience can be used in the modernization of regional healthcare systems in Eastern Siberia, the Far East and the Arctic, as well as Russian healthcare in general.

[Features of the course of COVID-19 in patients with type 2 diabetes mellitus].

AIM: To identify the features of the course of COVID-19 in patients with type 2 diabetes mellitus (T2DM), depending on the intake of hypoglycemic therapy at the prehospital stage, in conjunction with the functional state of the kidneys. MATERIALS AND METHODS: A retrospective analysis of 291 case histories of patients with COVID-19 and T2DM hospitalized in the infection department of Semashko Regional Clinical Hospital from January to December 2021, including the main clinical and laboratory parameters. Results. Among hospitalized patients with COVID-19, patients with T2DM had a higher mortality rate. An analysis of the case histories of deceased patients with COVID-19 and T2DM showed that at admission, body mass index (BMI), C-reactive protein, and creatinine were higher than those of survivors and amounted to BMI - 33 [30; 39] and 33 [28; 36] kg/m3; p=0.039, C-reactive protein - 77 [47.5; 106.0] and 57 [27.0; 89.0] mg/l; p=0.015, in terms of creatinine level - 89 [70.0; 144.0] and 82 [66.0; 101.0] µmol/l; p=0.039, respectively. It was found that in the second week of hospitalization in the group of deceased patients with COVID-19 and T2DM, the creatinine level was statistically significantly higher than in surviving patients and amounted to 94.5 [71.5; 141.0] and 72.5 [57.0; 88.0] µmol/L; p<0.001, respectively. The probability of death in hospitalized patients with type 2 COVID-19 and T2DM depended on BMI and creatinine levels at the second week of hospitalization. Patients with prehospital correction of hyperglycemia dipeptidyl peptidase-4 inhibitors (iDPP-4)/ glucagon-like peptide-1 receptor agonists (agGLP-1)/ sodium-glucose co-transporter 2 inhibitors (iSGLT-2) had significantly lower creatinine levels at week 2 of hospitalization. CONCLUSION: In patients with moderate to severe COVID-19 with concomitant T2DM, special attention should be paid to the combination of high BMI and creatinine in the second week of hospitalization, which is a prognostically unfavorable predictor of death in such patients.

DRUG DEVELOPMENT BY IN SILICO METHODS.

Multicenter studies of the last decade have confirmed the direct relationship between the spatial structure of drug compounds and their biological activity. Aim - the relevance of this topic, on the one hand, is explained by the rapid development of new technologies, on the other hand, by a large number of researches works devoted to the study of the influence of stereoisomeric factors on the therapeutic effect and side effects of drugs. In recent decades, computational approaches have been used to reveal the relationship between the biological properties of substances and their structure and to quantitatively describe this relationship. Quantitative Structure - Activity Relationships (QSAR) is widely used in modern drug chemistry. In combination with molecular modeling techniques, this trend has been commonly referred to as in silico methods, which implies a preliminary search for drugs by computer only, prior to experimental screening. Hundreds of QSAR and molecular modeling programs have been developed around the world: dozens of specialized scientific journals are published dedicated to computer-based methods of searching for biologically active substances. Thousands of articles have been published demonstrating the results of successful application of QSAR methods in the search for new biologically active substances. There are currently more than 101 million known organic compounds in the world, and the known number of biological activities exceeds 25,000, so global experimental testing of all substances is impossible. Thus, the use of in silico methods to search for drugs, in particular, for the preliminary selection of unpromising compounds is super relevant.

Influence of hepatic neoplasia on life expectancy in dogs.

BACKGROUND AND AIM: The present study investigated the influence of liver tumor structure on life expectancy in dogs. Diseases of the liver comprise 5-25% of all non-communicable diseases in dogs, and primary hepatic tumors account for 0.6-1.3% of tumors. This research aimed to study the post-operative life span of animals with primary or metastatic tumors of the liver. MATERIALS AND METHODS: During the study period, 7124 oncological operations were performed in our clinic. In total, 128 liver tumors were detected in live animals, while 323 were detected posthumously. Forty animals underwent surgery for various liver tumors. In dogs with primary liver tumors, the average age was 11.9 years and the average body weight was 15.5 kg, while in dogs with liver metastases, the mean age was 11.4 years and the average body weight was 24 kg. RESULTS: The ratio of males to females among dogs with primary liver tumors was about 1:1 (ten females and nine males), while that among dogs with metastatic liver damage was clearly predominantly female (14 females and two males) because females often undergo surgery for cancerous mammary glands or ovaries. CONCLUSION: The size of tumors and the number of affected lobes had a significant effect on the post-operative life span. With a tumor size of <5 cm and a lesion covering less than two lobes of the liver, life expectancy was significantly longer and the prognosis was more favorable. In cases of large tumors or those affecting more than two lobes, life expectancy was significantly reduced and the prognosis was cautious to unfavorable.

Features of formation of Yersinia enterocolitica biofilms.

AIM: The work aimed to study the morphology of colonies and their comparison by features of the formation of Yersinia enterocolitica biofilms. MATERIALS AND METHODS: Bacteria were cultured on a Yersinia Selective Agar medium ("CIN-agar") at 28°C for 24 h. The microorganisms were grown in meat-peptone broth with 1.0% glucose to measure the absolute values of the optical density of the culture. The optical density of the liquid was determined in a microplate photometric analyzer Immunochem-2100 (HTI, USA) at a wavelength of 490 nm. For the study of biofilms, the specimens were fixed for 3-5 h in pairs of 25.0% solution of glutaraldehyde (according to DV), and pairs of a 1.0% aqueous solution of osmic acid (OSO4) were used for contrasting for 2-3 min. The specimens were examined with stereoscopic microscopy "BIOMED MS-1 Stereo" (Russia) and scanning electron microscope "TM 3030 plus" (Holland). RESULTS: With stereoscopic microscopy of the colonies of Y. enterocolitica, the S-forms had an elevated intensely colored center, radial striation along the periphery, smooth edges, d ≤ 1.0 mm. R-form colonies had a dark color and a dry surface, were tuberous and had a dense center with a peripheral ridge, rugged edges, d ≥ 1.5 mm. The optical density of the Y. enterocolitica S-form showed that this type of microorganism belongs to the moderate producers of biofilms since the optical density of the sample (density of the sample - Ds) exceeded the optical density of control (density of the control - Dc) by 3 times. In Y. enterocolitic a R-form (D ≤ 0.197) weakly produced biofilms, the optical density of the sample exceeded the optical density of the control by <2 times. CONCLUSION: The ability to form biofilms, the variability of phenotypic features, and the multiplicity of virulence factors of bacteria significantly reduce the effectiveness of diagnostic studies. The development of accelerated methods of detection and differentiation of the virulent properties of pathogenic bacteria will allow scientifically to substantiate and develop a set of measures aimed at preventing animal diseases and obtaining safe livestock products to prevent human diseases. Thus, we need to pay attention to which forms of colonies do Y. enterocolitic a form on solid nutrient media: S- or R-forms. Through this study, we know that bacteria-forming S-shaped colonies are more capable of forming biofilms than R-forms. It means that they are more pathogenic and can cause persistent infections due to adhesion and biofilm formation.

[TESTING THE PROTECTIVE PROPERTIES OF ARGON DURING SUBACUTE EXPOSURE TO HYPOXIC HYPOXIA].

Previously it has been shown that argon has a stimulating effect on biological processes including, specifically, strong protective properties during exposure to acute (1-4 hrs.) hypoxic hypoxia. Experiments with animals under hypoxia gradually growing over 3 to 7 days may give insight into mechanisms of the argon protective action. Purpose of the work was to explore character and severity of developing disorders, to attempt their prognosis and to test potentiality of argon as a protector from the effects of subacute hypoxic exposure. In two series of experiments Wistar male rats were housed in pressure chambers with different rates of O2 reduction without argon and with argon in concentration of 32-38%. Oxygen reduction from 20.9 to 9.0% in 3 days led to the death of 50% animals. Oxygen reduction to 12.0% in 7 days and one day in low-oxygen atmosphere was harmless for animals. Argon in air makes the response to hypoxia almost twice as sharp on virtually every level (red blood system, physiological, morphological and biochemical shifts) validating the concept that argon acts as a stimulator. In context of the most critical processes of adaptation to hypoxia--activation of blood formation and lipid metabolism--this sharpening of the response results in depletion of body resources and instigates irreversible shifts.

[Hygienic education of servicemen under condition of tuberculosis hospital].

Hygienic education of servicemen under condition of tuberculosis hospital. TB patients need not only long-term complex specialized treatment in the hospital, but also the qualified psychological impact by medical personnel. To motivate patients to complete treatment and ensure proper awareness of the disease and its consequences it is required to organize hygienic education for patients. All health workers, especially nurses, have to participate in health education. The article shows the necessity to take into account psychological characteristics of patients with tuberculosis during the process of hygienic education of Recommendations on topics, methods and organization of activities of hygienic conditions in the education tuberculosis hospital are given.

[Posterior interosseous flap in pediatric hand reconstructions].

The results of hand reconstructions with posterior interosseous flap were studied in 10 children (4 males and 6 females) aged from 1 year to 13 years old. In 4 cases flap coverage was performed due to acquired posttraumatic hand deformity, in 6 cases reconstruction was assumed for congenital hand deformities. Combined procedures consisted of posterior interosseous flap coverage and other types of microsurgical reconstructions were suggested in all 10 patients. Preoperative color Doppler visualization of the posterior interosseous vessels was mandatory. All flaps were risen under 3.5-4.5X magnification. All flaps survived completely in 3 weeks postoperatively. There were not postoperative complications such as flap's arterial or venous insufficiency, deep infection, or posterior interosseous nerve palsy. Nearly whole group (9 of 10) of patients and/or their parents were satisfied with the esthetic view of the reconstructed hand and donor site of the forearm 1 year postoperatively.

[Effects of additional breathing resistance on oxygen consumption in healthy subjects].

Decrease of oxygen delivery is common in hypoxia. This is the reason of decrease of consumption (VO2) at Mammalia including human. Previously, we have described a hypoxic hypometabolism at 1/3 health persons breathing 17% O2 oxygen air. This light hypoxic (latent hypoxic) condition didn't issue hypoxia because of SpO2 had dropped from 97-98% to 95-96%. We hypothesized the existence of another reason for VO2 decrease. This is the ability of tissue to decrease oxygen consumption in human organism. Thus the hypometabolism maintains delivery/consumption O2 balance when respiratory center is informed by afferent receptors about potential threat of tissue hypoxia. The aim of this study was to investigate parameters of gas exchange in light mixed resistive load 0.4 cmH2O s L(-1). For compare it was used date obtained at ordinary mouthpiece with resistance less 0.1 cmH2O s L(-1). During the study 14 health subjects (6 men and 8 women) with the age ranging from 23 to 48 years were observed. Date showed a significant decrease in mean (SD) of VO2 at 9% and CO2 release (VCO2) at 10%. Value of SpO2 didn't change and remain 97.5%. The results suggest that hypometabolism may be a reaction prevented by disturbance O2 delivery/consumption for tissue of human organism.

Mechanism of suppression of phagocytic and metabolic activity of neutrophils and production of proinflammatory cytokines during chronic poisoning with organophosphorus compounds.

Experiments on albino outbred rats showed that chronic poisoning with organophosphorus compounds (Russian VX, and sarin) for 30 days in a total dose of 0.3 DL50 (0.01 DL50 daily) is followed by a decrease in phagocytic and metabolic activity of neutrophils. The reduction of functional activity of monocyte phagocytic system was stipulated by the stimulation of N-cholinergic receptors of these cells. These changes were accompanied by a decrease in blood concentration of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6).

[Peculiarities of pregnancy management after multiple stenting of coronary arteries].

This paper describes the strategy for pregnancy and labour management in women with the history of myocardial infarction after multiple stenting of coronary arteries using stents with cytostatic coating. The authors discuss a broad range of diseases underlying coronary lesions in young pregnant women receiving antiaggregation therapy. Neither multiple stenting nor intake of aspirin and ticlopid provoked teratogenic effect.

[The capnography parameters in healthy adults and patients with psychogenic dyspnea].

A comparison is made the end-tidal fractional concentration of carbon dioxide (FetCO2) and breathing frequency (f) obtained by capnography between 106 healthy persons (H-group) and 30 persons with a psychogenic dyspnea (P-group). The structure of a respiratory cycle was estimated by parameter R(CO2). It was calculated by relation of time of an exhalation to time of all respiratory cycle. Degree of "breath arrhythmia" was estimated by means of parameter CVR(CO2). It was the coefficient of variation (CV) for R(CO2) recorded during the 5-min capnography. The groups was differed for all parameters (p < 0.01), except for R(CO)2 (structures of a respiratory cycle). FetCO2 at H-group was 5.24 +/- 0.36%, at P-group 4.07 +/- 0.47. The breathing frequency at H-group was 14.3 +/- 3.7 br/min, at P-group 17.9 +/- 4.5 and CVR(CO2) at H-group was 8.9 +/- 2.7%, at P-group 12.7 +/- 3.1. We conclude that the most informative indicator of a psychogenic dyspnea is the complex of parameters taking into account all three characteristics of a pattern of breath: decrease FetCO2, increase f, and rhythm of breath.

[The variability of respiratory pattern and gas exchange].

It is known, that spectral analysis of heart rate and respiratory variability allows to find out the very low frequency (VLF) rhythm. However it is not known, it is necessary to carry this rhythm to what type of wave processes. The purpose of the present researches was to study the respiratory variability and the variability of gas exchange parameters. 10 healthy subjects have been surveyed. The pneumogramms within 30 minutes spent record, and then a method "breath-by-breath" within 30 minutes registered gas exchange parameters (Ve--lung ventilation, V(O2) -O2 consumption and other parameters). Fast Fourier transform method has found out two groups of the basic peaks. The first--in a range 0.2-0.3 Hz (a time cycle--3-5 s), that corresponds respiratory frequency which size at subjects varied from 12 to 20 per minute. The second--in a range 0.002-0.0075 Hz, that corresponds VLF diapason (a time cycle--1-3.5 minutes). At the analysis pneumogramms rhythms in the same ranges have been established. The carried out researches allow to draw a conclusion on steady character of wave process in a VLF-range. It can be carried to quasi-periodic oscillations type. First oscillator or respiratory frequency it is formed by means of mechanisms of chemoreception. Considering, that V(O2) and V(CO2) are function energy exchange, it is possible to believe, what exactly energy demand define the second oscillator.

[Tuberculosis morbidity among military personnel in modern conditions].

Among identified in the army for one year of active tuberculosis patients constitute 38.7% of the number of soldiers from young recruits, including 59.7% of infiltrative pulmonary tuberculosis. At the same time during the examination of these individuals revealed only about half of patients. Timely delivery of fluorographic examination recruitment plays a crucial role in preventing the spread of tuberculosis in the Armed Forces. From the military doctors need more work in groups at increased risk of tuberculosis, early identification of need in the dispensary dynamic observation and conducting a full range of therapeutic and preventive measures in foci of tuberculous infection.

[Problems of microbiological diagnosis of tuberculosis].

Objective methods of confirmation the diagnosis of tuberculosis are bacteriological (detection and isolation of Mycobacterium tuberculosis) and histological (detection of specific elements of granulomatous inflammation in the tissues). To improve the quality of microbiological examination of patients are needed equip clinical diagnostic laboratory fluorescent microscopes, modern flyuorohromnymi dyes and related training.

[Pharmacological correction of nonspecific resistance and production of proinflammatory cytokines during chronic intoxication with organophosphorus compound VX].

It is established in experiments on noninbred rats that the use of imunofan (20 mg/kg daily) and polyoxidonium (150 mg/kg daily) for 7 days on the background of chronic intoxication with organophosphorus agent VX (0.01 LD50, single daily treatment for 30 days) resulted in almost complete recovery of phagocytic-metabolic activity of neutrophils, the content of lysozyme, cationic protein of platelet, and levels of proinflammatory cytokines TNFa, IL-1b and IL-6 in the blood. The administration of T-activin (20 mg/kg daily for 7 days) restores these parameters insignificantly. The maximum overall stimulatory effect was produced by polyoxidonium, while the minimum effect was observed for T-activin.

[The increase of carbon dyoxidi production at hypoxia in health subjects].

Pulmonary gas exchange, SpO2 and heart rate at 15-min hypoxia (respiration by air with 0.17; 0.15 and 0.13 oxygen fractions) have been investigated in 24 health subjects. It has been established, results of the group analysis and the results of the individual analysis had been differed. Reaction on hypoxia at the group analysis had been found only at 0.13 02 fraction. It was only hyperventilation. The individual analysis had revealed 4 types of reaction on hypoxia already at 0.17 and 0.15 02 fractions: (1) hyperventilation, (2) decrease of oxygen consumption, (3) increase of ventilation effectiveness, (4) increase of CO2 production. The mechanisms of last reaction are unknown, but we supposed it was connected with anaerobic metabolism. The reactions were detected at light hypoxia (0.17 and 0.15 oxygen fractions) in 90% health subjects when SpO2 decreased to 87-93%. The increase ventilation has been detected at hypoxia within respiration 0.13 oxygen in 60% subjects when SpO2 decreased to 83-87%, while other reactions were nearly absent.

Mechanisms of immune status disorders in chronic ethanol intoxication.

Experiments of outbred albino rats showed that chronic ethanol intoxication (20 days, summary dose 5 LD(50)) inhibited immune reactions mainly mediated by Th1-cells, increased blood corticosterone concentration, reduced T-lymphocyte acetylcholinesterase activity, blood concentrations of IFN-γ, IL-2, IL-4, IL-10, and increased IL-6 level.