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The article (the third one of authors cycle of historical studies of medication supply and pharmaceutical business) examines period of economic renaissance of the Russian pharmaceutical market in the first years of third millennium. The state of market according data of Russian analytical agencies, medical periodicals and recollections of participants is considered. The article consists of three reports. In the first report the issue was the “field players” of pharmaceutical market, and in the second one - all the personnel serving market game, making it possible, their reflections on their new, post-Soviet experience of life in private business.

Nirmatrelvir is an antiviral drug that, in combination with ritonavir, is an effective agent for the etiotropic therapy of patients with mild to moderate COVID-19.The aim of the study was to evaluate bioequivalence of the generic drug nirmatrelvir Аrpaxel in combination with ritonavir and the original drug Paxlovid, which is a combination of nirmatrelvir/ritonavir, in a single dose administration to healthy volunteers.Materials and methods. This research was an open-label, randomized, two-period crossover bioequivalence study. It included 2 periods, in each of which the volunteers received either a test drug (nirmatrelvir at the dose of 300 mg) in combination with ritonavir (100 mg), or a reference drug (a combination of nirmatrelvir 300 mg and ritonavir 100 mg), given as a single dose. A wash-out period between each of the administrations was 7 days. The blood sampling to determine the concentration of nirmatrelvir was carried out in the range from 0 to 36 h in each of the study periods. A nirmatrelvir concentration was determined by a validated HPLC-MS/MS method with a lower quantitation limit of 10 ng/mL. Bioequivalence was assessed by comparing 90% confidence intervals (CIs) for the ratio of geometric means of AUC(0–16) and Cmax of the test drug and reference drugs with the established equivalence limits of 80.00–125.00%.Results. In the study were included 68 healthy volunteers, 67 participants of which were included in the bioequivalence population. The pharmacokinetic parameters of the drugs were comparable to each other. The 90% confidence interval for the ratio of the geometric mean of the maximum drug concentration in the blood plasma and the area under the pharmacokinetic curve «concentration-time» from zero to the last blood draw within 36 hours of nirmatrelvir was 87.26–100.83 and 93.27–103.74%, which meets the criteria for assessing bioequivalence. The test drugs were well tolerated by the volunteers. The incidence of adverse events was similar for the test and reference drugs. No serious adverse events were recorded during the entire study.Conclusion. As a result of this study, bioequivalence of the test and reference drugs has been established.

Molnupiravir is one of the drugs for the etiotropic therapy of a new coronavirus infection COVID-19. It has confirmed its clinical efficacy in the treatment of patients with mild and moderate COVID-19, including those who are at high risk of progressing to severe disease.The aim of the study was to evaluate bioequivalence of the generic drug molnupiravir ALARIO-TL and the original drug Lagevrio with a single oral administration in healthy volunteers.Materials and methods. This bioequivalence study was an open, randomized, two-period crossover study. In each of the two periods, volunteers received a single dose of the test drug, or reference drug molnupiravir, in the form of capsules at the dose of 200 mg. The washout period between the doses was 3 days. To determine pharmacokinetic (PK) parameters and bioequivalence, the concentration the concentration of N-hydrozycytidine (NHC), the main molnupiravir metabolit in the blood plasma of volunteers was evaluated. The blood plasma sampling was carried out in the range from 0 to 16 hours in each of the study periods. Bioequivalence was assessed by comparing 90% confidence intervals (CIs) for the ratio of geometric means of AUC(0–16) and Cmax of the test drug and reference drugs with the established equivalence limits of 80.00 – 125.00%.Results. A total of 28 healthy male volunteers were included in the study. According to the results of the statistical analysis, after the administration of the test and reference drugs, the 90% CIs for the ratio of the geometric means of AUC (0–16) and Cmax were 96.31% – 113.64% and 91.37% – 114.8%, respectively. These intervals fit within the established limits of 80.00–125.00%, which confirms the bioequivalence of the drugs. When comparing the frequency of the individual adverse events registration, no significant differences were found out after the administration of the test and reference drugs.Conclusion. Based on the results of this study, it can be concluded that the test and reference drugs of molnupiravir are bioequivalent. In addition, the data obtained indicate that the drugs have similar safety profiles.

High-fat diet (HFD) for 28 wk leads to type 2 diabetes mellitus (T2DM) phenotype, concomitant with increased plasma soluble prorenin receptor (sPRR), nondipping blood pressure, and vascular stiffness in male mice. HFD-fed female mice exhibiting a preserved cardiometabolic phenotype until ovariectomy revealed increased plasma sPRR and blood pressure. Plasma sPRR may indicate the status of systemic renin-angiotensin-aldosterone system (RAAS) activation and the onset of vascular complications during T2DM in a sex-dependent manner.

A Blockchain-based decentralized cab aggregator system that aims to revolutionize the traditional ride-hailing industry. The system leverages the transparency and security features of blockchain technology to create a thrustless environment where riders and drivers can connect without the need for intermediaries. The decentralized platform also eliminates the problem of surge pricing and ensures that drivers are paid fairly. In addition, the use of smart contracts ensures that all parties fulfil their obligations, thereby reducing the risk of fraud and disputes. The project promises to create a more equitable and efficient cab aggregation system that benefits all stakeholders involved.

We present a rare clinical observation of an 11-year-old boy who, as a result of a fall from a height, received a severe combined injury of the chest, abdomen, retroperitoneal space, which was accompanied by a contusion of the lungs with hydrothorax, contusion of the right kidney, pancreas and duodenal rupture with the development of traumatic shock of the III degree, bile peritonitis. It required emergency surgery, intensive care and was combined with the patient’s chronic reflux esophagitis with esophageal stenosis, erosive gastritis, duodenitis. The development of stenosis of the esophagus may have had a post-traumatic character.

The article refl ects the results of a study of the infl uence of adverse environmental factors on the formation of pathology of the biliary system in children of the Krasnodar Territory living in ecologically unfavorable territories.The purpose of the work is to study the features of clinical manifestations of diseases of the biliary system in children living in ecologically unfavorable territories of the Krasnodar Territory. 683 children aged 7–17 years were examined on the basis of the DDC DKKB of Krasnodar.In the course of the study, the clinical features of various forms of dysfunctional disorders, prevalence and morbidity in relation to the level of environmental pollution were studied according to the method of V. A. Shashel and co-authors. The regularities of the prevalence of diseases of the digestive tract depending on the level of pollution have been revealed.

Summary Post- COVID syndrome refers to the long-term consequences of a new coronavirus infection COVID-19, which includes a set of symptoms that develop or persist after COVID-19. Symptoms of gastrointestinal disorders in post- COVID syndrome, due to chronic infl ammation, the consequences of organ damage, prolonged hospitalization, social isolation, and other causes, can be persistent and require a multidisciplinary approach. The presented clinical practice guidelines consider the main preventive and therapeutic and diagnostic approaches to the management of patients with gastroenterological manifestations of postCOVID syndrome. The Guidelines were approved by the 17th National Congress of Internal Medicine and the 25th Congress of Gastroenterological Scientifi c Society of Russia.

Aims. The study of clinical and diagnostic features of the course of chronic gastroduodenitis in children, taking into account the types of constitution (somatotypes), the impact of these features on the course of the disease and the treatment.Materials and methods. We studied 250 patients with a diagnosis of “Chronic gastroduodenitis” aged 4 to 17 years, with morphological changes in the mucous membrane of the stomach and duodenum, corresponding to the criteria for gastroduodenitis, as well as contamination with the H. pylori bacterium. An assessment was made of the age, gender composition, types of constitution according to the classifi cation of M. V. Chernorutsky (based on the Pignet index). Clinical- anamnestic and laboratory- instrumental features of the course of chronic gastroduodenitis in one or another somatotype were noted. The analysis and assessment of the infl uence of the constitutional specifi city of the patient on the course of the disease and the results of treatment was carried out.Results and conclusion. It was revealed that the presence of an asthenic type of constitution predisposes to the frequent development of chronic gastroduodenitis in children, but a milder course with the development of superfi cial gastroduodenitis, in contrast to normosthenic and hypersthenic types, prone to the development of hypertrophic and erosive gastroduodenitis. It was noted that in asthenics and normosthenics, the success of eradication anti- Helicobacter therapy is signifi cantly higher than in hypersthenics.

In article, the technological effect of oil production increase by the inverted nine-point development system into a single-row system transformation is quantified. The anticipatory watering of the production wells located on the same row with the injection wells in the direction of regional stress in the inverted nine-point development system implemented at the oil facility BP14 object is shown. The effect of anticipatory watering is explained by the formation and growth of auto-hydraulic fractures on injection wells. With the effect and in order to increase the watering implementation coefficient the program of transferring highly watered and idle production wells to injection was started at the aim to form the single-row development system directed along the lineregional stress. Analysis of the ten-year project implementation actual results showed that the system transformation on BP14 object will increase the cumulative oil production on nearby 20 % on the latest stage of development.

Nowadays, People share their opinions through social media. This information may be informative or non-informative. To filtering the informative information from the social media plays a challenging issue. Nevertheless, in social media especially when a disaster been occurs the peoples will interact more on that particular disaster event. They share their opinion through some textual information such as tweets or posts. In this work, we are proposing a generalized approach for categorizing the informative and non-informative on twitter media. We collected the seven natural disaster events from the crisisNLP. These datasets are different disaster events which contains the people’s opinions on that specific event. We preprocess the information which converts the tweet information into machine understandable vectors. These vectors been processed by the different machine learning algorithms. We consider the individual performance of each ML algorithm on different disaster datasets upon chosen the best five algorithms for voting techniques. We tested the performance with matrices such as accuracy, precision, recall and f1-score. We compared our results with existing models in which our proposed model performed better than other existing state of art models.

Kole lands are one of the biggest saline, humid tropical wetland ecosystems. It spreads across Thrissur and Malappuram districts of Kerala state. They serve as a water storage structure during rainy season. After rains, the stored water is dewatered and circulated in various Kole padasekarams and channels to cultivate paddy. However, the problem is the lack of a proper water management plan resulting in crop loss. The current study is conducted in the Perumpadappu block of Ponnani Kole lands in Malappuram district. In this study, both GIS and Remote sensing technology have been collaborated to plan the crop calendar. The cropping calendar of Ponnai Kole was developed mainly for 37 Kole padashekharams of Perumpadappu block. Data about elevation, transportation, irrigation, weather and soil were collected to arrive at the crop calendar. Together, by adopting participatory rural appraisal methods and local knowledge were integrated. The final crop calendar was wetted with farmers and experts.

According to the results of the analysis of scientific and methodical literature, it was established that the existing system of individual physical training of future officers needs a scientifically based transformation in accordance with today's requirements. The main goal of the study is to determine the essence and structure of the formation of physical readiness of future officers of the National Guard of Ukraine (NGU) in the system of individual physical training with the accented use of modern readiness technologies. As a result of a theoretical study, we determined the essence and structure of the formation of physical readiness of future officers of the NGU in the system of individual physical training with an emphasis on the use of modern readiness technology – personal multi-vector education, which is formed through an accented and targeted pedagogical influence on the formation of the future officer's readiness to defend Ukraine, performance of assigned tasks in various conditions of service and combat activity, which require a high level of development of physical qualities, as well as military-applied skills and provides a combination of his knowledge: about the content and structure of future military professional activity; forms and methods of organizing physical training in subordinate units, as well as the requirements of this activity to the level of physical readiness of the subordinate personnel, individual level of physical and special physical readiness, formed key competences of the future military professional activity with the opportunities and needs formed and realized by him in the process of development.

Introduction. Assessment of the state of the hemostasis system in cardioanesthesiology is carried out both clinically and using standard laboratory tests — thromboelastography (TEG), rotational thromboelastometry (ROTEM), or a combination of both. Both TEG and ROTEM are designed to detect disorders in the hemostasis system in real time. Aim – to evaluate the informativeness of ROTEM performed at the stage of cardiopulmonary bypass (CPB) before neutralization of heparin with protamine and to study the prognostic value of this study in assessing the risk of postoperative bleeding during cardiac surgery with a high risk of bleeding. Materials and methods. The assessment of the diagnostic significance of ROTEM studies at the CPB stage is based on the observation of 31 patients operated on from July to October 2018. The median age of these patients was 55 years (31–72 years). The criteria for inclusion of patients in the study were the performance of planned cardiac surgery with a high risk of bleeding: operations on the aorta, combined operations (coronary bypass surgery and/or surgery on the valve(s), multivalve correction), including repeated. Methods of descriptive statistics, correlation and comparative analyses, and ROC-analysis were used to assess the diagnostic and prognostic capabilities of ROTEM research during CPB against the back=-ground of high doses of heparin. Results. A statistically significant linear correlation was noted between A5 and MCF indicators in EXTEM, FIBTEM and PLTEM tests performed both during and after CPB. The results obtained indicate that determining the cause of bleeding and deciding on the choice of therapy is possible significantly earlier than the MCF indicator is determined, namely 5 minutes after the start of blood clotting in the ROTEM study. The informative value of ROTEM studies performed during CPB is shown, however, when interpreting the results, it is necessary to focus not only on the reference intervals, but also on the obtained cut-off levels for ROTEM parameters during CPB for early detection of hypofibrinogenemia or thrombocytopenia after CPB. Conclusion. ROTEM performed with the use of high doses of heparin during CPB is informative for the choice of pathogenetically justified therapy for possible bleeding.

The analysis of scientific-methodical and special literature (results of monitoring Internet sources) on the problems of improving technical skill of qualified weightlifters shows that the problem of studying the spatio-temporal characteristics of competitive exercises of athleyes at the main stages of multi-year improvement remains relevant for coaches and weightlifting specialists. The purpose of the work is the study of individual and group models of the kinematics of the technique of competitive exercise (velocity of the projectile in different phases of motor action) of weightlifters in the process of effective competitive activity. During of research and analytical work, the following methods were used: the study of scientific and methodological literature, Internet resources, pedagogical observations, video recordings of competitions, biomechanical analysis of the structure of the movement of the barbell, methods of mathematical statistics. As a result of the research, we analyzed the individual and group models of the kinematics of the snatch and clean and jerk (first phase of C&J) in qualified weightlifters from different countries of the world (winners and medalists of the Olympic Games, world and continental championships). It has been proven that the efficiency of the technique of performing competitive exercises of qualified weightlifters in characteristics by the appropriate use of spatio-temporal characteristics of projectile movement in various phases of the movement structure of the «athlete-barbell». The cited research materials show that there are certain differences in the technique of performing competitive exercises in qualified weightlifters of different genders and groups of weight categories regarding the speed characteristics of moving the bar up. It has been confirmed that the of fictiveness of the technique of movement the barbell by qualified weightlifters is determined by the requirements of the sport – to lift the barbell of maximum weight up witching the space-time characteristics and aria footprint.

Relevance. The Sverdlovsk district is a tense natural focus for Lyme borreliosis (LB) with a constantly recorded incidence that exceeds these indicators in the Russian Federation and the Ural Federal region several times. LB is registered on 56 of 59 administrative territories of the district. Currently, the count of LB in the Russian Federation includes both infections caused by Borrelia burgdorferi sensu lato group Borrelia and infections caused by Borrelia miyamotoi sensu lato group Borrelia.Aim. To characterize the epidemic process of LB in the territory of the Sverdlovsk district over a 20-year period (2002–2021).Materials and methods. The paper uses data from federal and regional statistical observations, reporting materials of the Department of Rospotrebnadzor in the Sverdlovsk district for 2002–2021, methods of statistical analysis.Results and discussion. During the follow–up period (2002–2021), the incidence rate of BL in the Sverdlovsk district exceeded the average long-term level in the Russian Federation by almost 3 times, and in the Ural Federal region – by 1.8 times. Among the mechanisms and ways of transmission of LB pathogens, the vector-borne mechanism dominated (84.5%), the share of the unidentified pathway was 15.4%, alimentary (when using raw goat's milk) – 0.1%. The duration of the epidemic season for LB in the district was 10 months (from March to December) with a peak incidence in June. Cases of LB were registered among people of different ages, with a predominance in the group of 60 years and older (39.1%). An analysis of the distribution of people with LB by social composition showed that pensioners prevailed among them – 36.3%, officials made up 27.8%, unemployed – 14.1%. Among the cases, a high proportion of schoolchildren and children under 7 years old were noted. It was found that erythematous and non-erythematous forms of LB are registered in the district, with a predominance of erythematous (64.5%). The main etiological agent of the erythematous form is Borrelia garinii, while the non-erythematous form is Borrelia miyamotoi and B. garinii. In the general structure of morbidity, the number of cases of LB is largely determined by the city inhabitants (92.9%). There were no fatal outcomes in LB in the territory of the district during the studied period.Conclusions. Due to the lack of vaccination of LB worldwide, the only strategy to reduce the incidence of LB is non-specific prevention and timely diagnosis of the disease, including data from epidemiological history, clinical and laboratory diagnostics. The long-term clinical and epidemiological and laboratory studies conducted by us in the Sverdlovsk district allowed us to characterize the main manifestations of the epidemic process of LB and to improve the diagnosis of the disease.

Relevance. Elderly people have become the fastest growing segment of the global population over the past few decades. The number of people over the working age in Russia, and with them citizens living in closed long-term care facilities (CLTFS), is growing. Residents of these organizations belong to the risk group, and CLTFS have a number of characteristics that turn these institutions into a unique environment for the spread of infectious diseases.Aims. To analyze the CLTFS residents infectious morbidity in the "pre-covid stage" (according to literature sources). A scientific review of research in Russian and English using information portals and platforms has been carried out eLIBRARY. ru , Web of Science, PubMed, Google Academy and Scopus for the period 1981-2022. The search was carried out by keywords. Information about the most frequent infectious diseases affecting residents of closed long-term care institutions was the criterion for inclusion in the sample of publications. Out of 16171 initially identified articles, 61 publications were selected after initial analysis.Conclusions. According to various estimates, the leading infectious diseases in CLTFS were: acute respiratory infections, pneumonia, urinary tract infections, skin and mucous infections, acute intestinal infections. The article describes pathogens and their prevalence in CLTFS including pathogens with multiple drug resistance (MDR), describes the resistance of bacteria to antimicrobial drugs formation problem in these organizations, as well as development of certain diseases risk factors. Studies conducted in various CLTFS in Europe, Russia, the USA, and Asia indicate a high prevalence of infectious diseases among their residents, high colonization of residents with antimicrobial-resistant pathogens, as well as the infection transmission probability from the CLTFS and its spread to other long-term care institutions and medical and preventive organizations.

Relevance. The identification of determinants of the human genome, such as single nucleotide polymorphisms (SNPs), in association with various disease patterns, including infectious diseases, is one of the most actively developing areas of scientific research in the world.. Hepatitis C (HC), which remains a serious global health problem, belongs to the number of infections that attract the attention of specialists.Aims. Determination of genetic markers of hepatitis C virus (HCV) natural elimination and assessment of their role as a monitoring parameter of the epidemiological surveillance system.Materials and methods. The study included 660 people divided into 2 groups: persons with chronic HC (CHC) and blood donors (indicator group of the healthy population). In the studied groups, the following SNPs were typed: rs1143634, rs1143627 (IL-1B); rs4251961, rs419598 (IL1RN); rs1800795 (IL6); rs1800896 (IL-10); rs4986790 (TLR4); rs4374383 (MERTK). The associative relationship between SNPs and CHC alleles was identified using logistic regression analysis within four models (codominant, dominant, recessive, and overdominant). Additionally, the significance of polymorphisms at the intragenic and intergenic levels was assessed using modern bioinformatic resources in the field of functional genomics.Results. In this study, genotypes associated with the natural elimination of HCV were identified. Paired combinations of IL 1RA/IL-1B genotypes associated with the probability of the formation of CHC have been established. It is shown that synonymous SNPs can be associated with any characteristics of the pathological process, which can be explained by disequilibrium in coupling with functionally significant alleles of other genetic loci.Conclusion. The detection of the association of SNPs with clinical manifestations of the pathological process is not final and requires further study taking into account ONP coupling groups.

Relevance. Despite the ongoing program of mass vaccination of tick-borne encephalitis (TBE) for more than 20 years in the Sverdlovsk district, the incidence rate of TBE continues to exceed the average in Russia and the Ural Federal region.Aim. To analyze the main indicators of the manifestation of the epidemic process of TBE in the territory of the Sverdlovsk district under the conditions of planned vaccination over a 20-year period (2002–2021).Materials and methods. The article uses data from federal and regional statistical observations, reporting materials of the Department of Rospotrebnadzor in the Sverdlovsk district for 2002-2021, methods of statistical analysis.Results and discussion. During the study period (2002-2021), 3861 cases of TBE were registered in the Sverdlovsk district, while the highest incidence rate was detected in 2005 – 10.1 per 100 thousand population, and the lowest in 2020 – 1.0 per 100 thousand population. The share of the vector-borne mechanism was 78.4%, the unidentified path – 20.1%, alimentary – 1.5%. Analysis of the seasonal distribution of cases of TBE showed that the incidence is recorded from April to November. Cases of TBE were recorded in all age groups, including the child population. Most often, people aged 60 years old and older (24.6%) were ill with TBE. Among the children's population, the largest share fell on children aged 7–14 years (5.4%). Men of working age prevailed among the patients (66.0%). TBE was mainly registered among the unvaccinated population (81.5%) with a predominance of urban (86.1%). Officials predominated among the sick persons – 29.8%, pensioners made up 22.3%, unemployed – 19.8%. Persons whose work is professionally connected with the forest made up only 0.6%. The ongoing program of mass vaccination of TBE has led to a decrease in the proportion of severe and moderate forms of diseases (focal – 9.8% and meningeal – 24.0%) and an increase in the proportion of febrile (33.8%) and atypical forms (32.4%). Deaths during the studied period were recorded mainly among the adult unvaccinated population.Conclusions. The Sverdlovsk district continues to be a tense natural focus of TBE with a constantly recorded incidence among contingents of different age and social groups. In the absence of highly effective etiotropic drugs for the treatment of TBE, the only strategy for reducing the incidence of TBE, the development of severe forms and deaths in the territory of the Sverdlovsk district is mass vaccination of the population.

The Brown Plant Hopper (BPH), Nilaparvata lugens (Homoptera: Delphacidae) is one of the most destructive insect pests causing significant yield loss in most of the rice cultivars of Asia. Marker-assisted backcrossing is used to introgress the genes for BPH resistance in which the selection of donor parents to confer durable resistance and validation of the presence of genes is a prerequisite. Jyothi the most popular, widely cultivated rice variety in Kerala is screened along with four parental lines viz., PTB33 (Variety released from RARS, Pattambi), IRRI introgressed lines- IR65482-7-216-1-2, IR7103-121-15-B, and a breeding line RP2068-13-5-8 for validating the presence of genes Bph3, BPH18, Bph20, and Bph21 using SSR markers. Parental polymorphism was shown for markers specific to Bph3, BPH18, and Bph20. Besides this, cluster analysis using the UPGMA method produced 4 clusters. The variety ‘PTB33’ was obtained in a separate cluster which can be attributed to its resistant character against BPH and can be considered as a potential donor. The IRRI introgressed lines- IR65482-7-216-1-2, IR7103-121-15-B, and the breeding line RP2068-13-5-8 can also be well utilized as donors by proper standardized BPH screening tests for confirming the phenotypic expression of BPH resistance.

The authors describe a clinical case of successful treatment of a patient with an ischiorectal abscess complicated by extensive purulentnecrotic phlegmon on the anterior abdominal wall and right thigh. Topical negative pressure wound technique (NPWT) was used. Its combination with surgical debridement and rational systemic antibiotic therapy has been shown to contribute to successful treatment of this life-threatening pathology.

Introduction. The material presents the results of the study of the effectiveness of the drug Ethylmethylhydroxypyridine malate in patients with long COVID, based on the dynamics of clinical manifestations and metabolomic parameters responsible for the level of oxidative stress. Aim. Evaluation of efficacy and registration of adverse reactions of ethylmethylhydroxypyridine malate administration to decrease oxidative stress level and reduce symptoms of asthenia and cognitive disorders in patients with long COVID. Materials and methods. 24 patients diagnosed with U09.9 “Condition after COVID-19 unspecified” were included in a non-randomized controlled prospective study, Patients were divided into 2 groups of 12 each. The experimental group received Ethylmethylhydroxypyridine malate tablets chewable 100 mg in a dosage of 400 mg/day. Clinical assessment by scales (mMRC dyspnea scale; 6-minute walk test (6MWT); MFI-20 subjective asthenia assessment scale; Montreal Cognitive Assessment Scale (MoCA); Barthel Baseline Functional Activity Rating Scale), and determination of metabolomic parameters were performed on days 1 and 14–18 of the study. Results. Use of the drug ethylmethylhydroxypyridine malate in patients with long COVID, led to a decrease in the level of oxidative stress, and normalization of mitochondrial function, as well as more pronounced improvements of the clinical picture. According to the scale of evaluation of asthenia (MFI-20) in the group of patients who received ethylmethylhydroxypyridine malate improvement of 21% was noted, in the control group improvement of 13% was noted. According to cognitive impairment assessment scale (MoCA), the drug group showed 20% improvement, while the control group showed 12,5% improvement. Conclusion. The drug ethylmethylhydroxypyridine malate tablets chewable 100 mg in a dosage of 400 mg/day demonstrates clinical efficacy characterized by, among other things, a decrease in oxidative stress, as well as clinical safety due to the absence of development of adverse reactions in patients with long COVID.

The present character association study aims to understand the correlation between morphological, physiological and yield traits of rice genotypes under water stress and non-stress conditions, so as to identify the differentially expressing traits under both the conditions. Such differentially expressed traits with positive influence on yield can serve as selection criteria for selection of stress tolerant plants. The experiment was carried out using randomized complete block design with three replications at the department of plant breeding and genetics, college of agriculture, Kerala Agricultural University between December 2021 and March 2022. Sixteen characters pertaining to morphological, physiological and yield of three rice genotypes were recorded under reproductive stage water stress and non-stress conditions. The intensity of trait correlations varied significantly under drought and non-drought conditions. The results of correlation studies indicate positive and significant correlation of grain yield with number of tillers, 1000 grain weight, photosynthetic rate, inter cellular CO2 content and water use efficiency under well-watered condition and of these, 1000 grain weight, and inter cellular CO2 content had significant positive influence on grain yield under drought stress. Principal component analysis results indicated two principal components i.e., PC1 and PC2 accounted for 70.5% and 29.5% of the total variation in grain yield under drought and 89% and 11% respectively under non drought conditions. Correlation and principal component analysis concluded that plants with higher grain weight along with improved high internal carbon dioxide content in leaves can be selected for attaining high yield potential under drought and non-drought conditions and will serve as climate adaptive crops under varying soil moisture levels.

Background. Enteroatmospheric fistulas (EAF) that occur during the use of the “open abdomen” surgical tactics are a complex surgical pathology with a high mortality rate.The aim. To assess the effectiveness of treatment of various forms of enteroatmospheric fistulas in patients with postoperative peritonitis using vacuum aspiration technology.Methods. We assessed the results of the surgical treatment of 46 patients with EAF in the late course of postoperative peritonitis (PP). Three clinical and morphological groups were distinguished: group 1 (n = 24) – EAF in small wounds of the anterior abdominal wall; group 2 (n = 15) – EAF opening into limited cavities; group 3 (n = 7) – EAF opening into laparostoma wounds. In group 1, a fistula was formed using continuous aspiration devices or VAC systems. In group 2, we used continuous aspiration of intestinal contents from the cavity. In group 3, laparostoma was treated using vacuum devices with isolation of the intestinal fistula and simulation of a floating enterostoma.Results. Group 3 of patients with EAF was characterized by a high flow rate (1224.2 ± 210.3 ml), duration of treatment (87.3 ± 12.5 day), extensive laparostoma (335.4 ± 14.3 сm2), high mortality rate (57.1 %). The best results of treatment were obtained in groups 1 and 2. The flow rate was 675.8 ± 154.3 and 541.3 ± 114.1 ml, the duration of treatment was 2 or 3 times less (37.7 ± 6.1 and 26.4 ± 5.2 days), the mortality rate was 8.3 % and 6.7 % respectively.Conclusion. EAF that occur when using the “open abdomen” surgical tactics due to the impossibility of their isolation in extensive wounds of the anterior abdominal wall are complicated clinical and morphological forms. For their treatment, it is advisable to use VAC systems, aimed at the treatment of both the anterior abdominal wall wound itself and the intestinal fistula opening into it for its gradual extraterritorialization by modeling a floating enterostoma in a vacuum device.

The article presents a review of the main circadian mechanisms regulating carbohydrate metabolism and their role in maintenance of energy homeostasis; the molecular genetic structure of the circadian system is also discussed. The role of adipose tissue and other organs and systems in the maintenance of circadian rhythm of carbohydrate metabolism, both in health and in obesity and diabetes, is highlighted. Particular attention is paid to diurnal rhythms of endocrine factors responsible for metabolic patterns of hormones such as cortisol, growth hormone and melatonin. Gender differences in the circadian regulation of energy and carbohydrate metabolism are also discussed, as well as their changes in different age periods. Article provides detailed review of the mechanisms of glucose utilization, reactivity of the pancreatic islets and peripheral insulin sensitivity shifts at different time periods of the day in people with normal body weight, android and gynoid types of obesity, both in women and men. Protective factors of energy metabolism circadian regulation structure preventing the development of diabetes mellitus and cardiovascular disease in individuals with so-called “metabolically healthy” obesity type are discussed. Article provides a review of various pathways of circadian rhythm disturbances, mechanisms of their development, as well as exogenous and endogenous factors leading to carbohydrate metabolic circadian rhythm misalignment, such as shift work, untiming of natural and artificial lighting, jet lags, sleep disorders. Represented data contribute to a new look at the pathogenesis of obesity and carbohydrate metabolism disorders in various types of obesity in men and women, that provides basis for searching for new effective methods of prevention and treatment of these conditions, elaboration of evidence-based diets and physical activity recommendations, as well as approaches to their medical treatment.

Whey proteins perform important biological functions. They can also be a source of numerous natural bioactive peptides that have a positive effect on various physiological systems of the body. For research and usage of this phenomenon, the question of these proteins isolating with saving of their structure and biological functions is relevant. Considering the significant difference in molecular weights, gel filtration is a promising method. The purpose of the study was the fractionation of milk whey proteins using gel filtration with a combination of different dextran gels. We used in the work milk whey proteins after isoelectric precipitation of casein and isolation of low molecular weight peptides by gel filtration on Sephadex G-25. The first gel filtration of the whey protein preparation was performed on a column with Sephadex G-150. For further fractionation were used three sectors from the first two chromatographic peaks obtained by gel filtration on Sephadex G-150. The first peak contains high molecular fractions of proteins eluting with a volume close to the free volume of the chromatographic column. The second asymmetric peak consists mainly of β-lactoglobulin and α-lactalbumin mixture. The third peak includes low molecular weight polypeptides and peptides that are not fixed in a polyacrylamide gel. The combined chromatographic fractions of three sectors from the first two chromatographic peaks were re-fractionated on a G-100 column. Electrophoretic analysis of chromatographic fractions after repeated chromatography of milk whey proteins confirmed the feasibility of choosing a certain sequence of sephadex. At the same time, the yield of β-lactoglobulin fraction increases by 12 ± 1 %, and α-lactalbumin by 9 ± 1 % compared to the results obtained by repeated gel filtration on one Sephadex (G-100). The degree of purification of β-lactoglobulin and α-lactalbumin, according to the densitometry, was 93 ± 5 % and 77 ± 4 %, respectively.

Objective. To evaluate the effectiveness of upadacitinib for improving the quality of life and correcting psycho-emotional disorders in patients with eczema.Material and methods. The study included 64 patients with eczema (mean age 58.5 ± 3.4 years, men – 43, women – 21), randomized into two groups. Patients of group 1 (n = 33) received basic drug therapy (BDT), group 2 (n = 31) – in addition to BDT, the Janus kinase 1 inhibitor upadacitinib (UPA) 15 mg per day for 2 months. The values of the patients' dermatological symptom scale index (DISS), Dermatology Life Quality Index (DLQI), anxiety, depression, functional state of patients on the WAM (wellbeing, activity, mood) scale were evaluated in dynamics after 2 months after the start of treatment.Results. In the BDT group, the value of DISS in patients after 2 months from the start of treatment decreased by 1.33 times, while in the UPA + BMT group it decreased by 2.17 times. In the BDT group, the DLQI index decreased by 1.26 times, while in the UPA + BDT group – by 1.66 times. The level of anxiety in patients in the BDT group decreased by 1.34 times, in the UPA + BDT group – by 1.64 times. The level of depression in the BDT group decreased by 1.22 times, in the UPA + BDT group – by 1.67 times. Indicators of the functional state of the WAN scale in patients with BMT increased only by 1.06, 1.03, 1.05 times, and in the UPA + BMT group, respectively, 1.4, 1.5, 1.6 times.Conclusions. BDT, while improving the clinical status of patients, at the same time has an insufficient corrective effect on the severity of anxiety, depression, WAM indicators and a reduced quality of life. Additional appointment of upadacitinib to patients was accompanied by a more pronounced positive effect on the levels of anxiety, depression, indicators of the functional state of patients, which contributed to an improvement in the quality of life compared to the results of BDT.

Aim To evaluate the frequency and structure of lipid-lowering therapy and of achieving the goal of low-density lipoprotein cholesterol (LDL-C) in patients with very high cardiovascular risk (CVR) who were monitored at the outpatient stage. Material and methods A retrospective snapshot analysis was performed by continuous sampling method for 136 medical records of outpatient patients (71 men, 65 women) aged 42 to 91 years [median, 68 years; 25th and 75th percentiles (59; 78)].Results 134 (98,53 %) patients took statins; 8 (5.88 %) patients took a combination of statin and ezetimibe; 2 (1.47 %) patients took proprotein convertase subtilisin/kexin type 9 enzyme inhibitors (PCSK9): 2 (1.47 %) patients took evolocumab and 1 (0.74%) of 2 PCSK9-treated patients took a combination of PCSK9 inhibitor and statin. Atorvastatin at a dose of 20 (20; 40) mg as recommended at the hospital was the most frequently prescribed statin. 5 (3.68%) patients achieved the goal LDL-C of ≤1.4 mmol/l.Conclusion Statins prevail in the structure of lipid-lowering therapy in patients with very high CVR. The frequency of combination therapy (statin/ezetimibe, 5.88%; PCSK9 inhibitor/statin, 0.74%) and PCSK9 inhibitors was noted to be low. Only 3.68% of patients achieved the goal LDL-C during the lipid-lowering treatment.

Relevance. Against the background of stress and high physiological load, cows experience a lack of energy, the need for which increases many times over in comparison with the dry period, in connection with this, their body is forced to use the reserves of adipose tissue. It is important to timely prevent and monitor the status of cows during the transition period.Methods. The methodology of the work was to study the effectiveness of the use of immunostimulating drugs PS-2, Prevention-N-E and PDE + E-selen. For scientific research, 4 groups of down-calving cows of the Holsteinized Black-and-White breed were selected, 10 animals each. Dry cows of the 1st and 2nd experimental groups received PS-2 and Prevention-N-E intramuscularly at a dose of 10.0 ml three times (40, 20 and 10 days before calving), animals of the 3rd experimental group were injected subcutaneously with tissue preparation PDE (denatured emulsified placenta) at a dose of 20.0 ml and intramuscularly — with a complex mineral and vitamin preparation E-selen at a dose of 10.0 ml 20 days before calving. Biological preparations were not used in animals of the control group.Results. An analysis was made of the prevalence of postpartum metabolic disorders: clinically pronounced hypocalcemia was observed in 5.9% of the newly-calved cows, ketosis — in 11.6%, subclinical hypocalcemia — in 17.7%, and a latent form of ketosis — in 22.7%. Biological preparations PS-2 and Prevention-N-E have a corrective effect on the synthesis of aminotransferases, mineral and carbohydrate metabolism, digestibility of macronutrients, against which background the number of newly-calved cows with subclinical forms of ketosis and hypocalcemia is reduced by 2 times.

Relevance. In modern conditions of industrial poultry farming, technological methods in many respects do not correspond to the biological needs of the bird's body. A high concentration of poultry in limited areas, year-round stay in enclosed spaces in cages leads to negative consequences. Under the influence of unfavorable factors, nonspecific resistance and immunobiological reactivity of the organism decrease. Therefore, at present, the issues of implementing the reproductive qualities and productivity of poultry through the directed impact of biologically active substances are of particular relevance.Methods. The methodology of the work was to study the effectiveness of the use of immunostimulating drugs PS-7 and Prevention-N-C for actualization of the productive and reproductive qualities of hens of the parent flock of the Hubbard F-15 cross. The objects of research were hens of the parent flock of broilers of the French cross Hubbard F-15. In the scientific and economic experiment, according to the principle of analogue groups, three groups of birds were formed with 150 heads each: one control and two experimental groups. Chickens of the 1st experimental group at the age of 21–23 weeks were fed with water three times with an interval of 7 days the biopreparation PS-7 at a dose of 0.1 ml/kg of body weight, chickens of the 2nd experimental group — Prevention-N-C at the same dose and timing.Results. It was found that the use of tested preparations based on the polysaccharide complex of Saccharomyces cerevisiae cells and benzimedazole contributed to an earlier peak of egg production (by 2.0 and 3.0 weeks), increased egg yield on the initial laying hen (by 5.1 and 6.6%) and the average laying hen (by 2.8 and 2.0%), gross egg production (by 1,365 and 1,770 eggs) and livability (by 2.0 and 4.0%). The use of the tested preparations contributed to the improvement of the morphological parameters of eggs and, as a result, the withdrawal of chickens by 0.8 and 2.0%.

The purpose of this work is to realize the productive qualities of young pigs by increasing the effectiveness of specific prevention of infectious diseases. The object of the study was 45 pigs of the Landrace breed from 14 to 171 days of age, divided according to the principle of pairs of analogues into 3 groups of 15 heads. The animals of the 1st experimental group were injected with the immunotropic drug PigStim-V in a dose of 1.0 ml per head twice at the age of 14 and 21 days in order to stimulate nonspecific resistance of the body and increase the effectiveness of specific prevention of infectious diseases intramuscularly at the age of 14 and 21 days. Moreover, the second injection was carried out simultaneously with immunization against type 2 porcine circovirus infection. The tested immunotropic drug PigStim-V was administered to animals of the 2nd experimental group once, at a dose of 1.0 ml per head at the age of 21 days simultaneously with a commercial vaccine against porcine circovirus. Animals of the 3rd group served as biological control. The results of the study confirm the effectiveness of the use of the immunotropic drug PigStim-V as an adjuvant in the vaccination of pigs. Both single and double intramuscular injection of PigStim-V increases the titer of specific antibodies against porcine circovirus infection and against α, β and ε toxins of the microorganism Clostridium perfringens, prevents and increases the effectiveness of therapy of diseases of non-infectious etiology, stimulates growth. A more pronounced positive effect is observed with the double administration of an immunotropic drug.

Obtaining livestock products from healthy livestock is the main goal of the entire livestock industry. The intensification of animal husbandry is accompanied by the active introduction of modern technologies for keeping, feeding and exploitation. Against the background of technological stress factors in cattle, there is a decrease in the duration of productive use, which is due to high morbidity against the background of a decrease in the immune response. The economic losses associated with postpartum illness are forcing professionals to make more informed decisions about prevention and treatment.It is for this reason that the purpose of our study was to study the spread of postpartum diseases in highly productive cows and the prevention of metabolic disorders in newborn cows with PS-2, Prevention-N-E and PDE with E-selenium.In the course of the analysis of morbidity, it was revealed that after calving cows, obstetric and gynecological pathologies are most often recorded: mastitis (26.5%), endometritis (24.5%), subinvolution of the uterus (24.15%), retention of the placenta (7.15%), ovarian diseases (17.45%). Against the background of inaccuracies in feeding during the transition period, the animals have a deficiency of calcium, glucose, phosphorus, as well as an excess of reference values in terms of aminotransferase metabolism. Against the background of immunocorrection of the body in cows of 1,2 and 3 experimental groups, an increase in the level of calcium, in contrast to the control, is noted by 0.22 mmol / l - PS-2, 0.27 - Prevention-NE and 0.24 mmol / l - PDE+ E-selenium. Similar dynamics was observed in the level of glucose in the blood of cows of the experimental groups, exceeding the control values by 22-38%.The use of PS-2, Prevention-N-E and PDE with E-selenium made it possible to reduce the risk of latent ketosis and hypocalcemia by 2 times, compared with animals that did not receive prophylaxis.The obtained results of biochemical studies prove the stimulating effect of biological products on the mineral metabolism of the body and the absorption of macronutrients.

The composition and morphology of a ceramic material based on magnesium oxide and their influence on its thermophysical and physico-mechanical properties are studied. It is established that when using different initial precursors, the matrix component has the same morphological features and is a cubic magnesium oxide. The dependences of physical and mechanical properties on the type of material and the method of molding were studied on experimental samples. Ill. 3. Ref. 23.

Purpose. To solve the problem of the allocation of contact vertical normal tensions along the sole of a rigid round stamp, located in an elastic isotropic half-space at a certain depth h  0. To compare the obtained solution with the well-known classical result for h = 0, to check the obtained results for adequacy. Methodology. Based on the analysis of the decision on the stress-strain state of the base, inside which there is a vertical arbitrary load distributed over the area of the circle, the necessary formulas are obtained to solve the problem. An algorithm for constructing an approximate solution has been developed, the essence of which is to use a combination of the boundary element method and the iteration process by S.N.Klepikov. For a number of depths, approximate solutions of the considered problem are obtained. Findings. The proposed algorithm for the approximate solution of the problem of indenting a round rigid stamp into the upper boundary of an elastic isotropic half-space has good agreement with the exact solution and can be used to solve contact problems. The outlines of the contact stress diagrams depend on the depth at which they are determined – the greater the depth, the flatter the outlines of the diagrams are, while starting from a certain depth, the diagrams of contact stresses practically coincide. The greater the depth is at which the stamp is located, the more force must be applied to obtain equal displacements of the stamp. Originality. The obtained research results significantly expand the possibilities of solving various problems of soil mechanics and foundation engineering, make it possible to obtain absolutely new results. In particular, a clear dependence of the contact stresses along the sole of a rigid round stamp on the depth at which it is located was identified. In addition, the presented data allow us to designate an absolutely new direction in the calculation of the foundations of ground anchors, namely, the calculation of their deformations. Practical value. For engineering practice, it is important that the greater the value of Poisson’s ratio of the base is, the greater the contact stresses are, other things being equal.

Background. Interleukin (IL) 6 plays an important role in the pathogenesis of comorbid rheumatoid arthritis (RA) depression, and IL-6 inhibitors (i) used to treat RA patients may have an antidepressant effect.Objective – to evaluate the effectiveness of Russian iIL-6 olokizumab (OKZ) in reducing symptoms of depression in patients with moderate/high RA activity.Material and methods. To date, 49 RA patients have been included, of which 43 (87.7%) are women, with an average age of 47.8±12.8 years; with a predominant high activity of RA according to DAS28 (CRP) indices (89.8%), SDAI (79.6%) and CDAI (75.5%) and inefficacy of stable 12-week therapy of сDMARDs. In all patients, a psychiatrist, in accordance with ICD-10, diagnosed depression (chronic or recurrent) of varying severity during a semi-structured interview. At week 0, all patients were randomized by the method of sequential numbers in a ratio of 1:1:1 to one of the 3 study groups: group 1 – cDMARDs+OKZ 64 mg subcutaneously once every 4 weeks (n=18); group 2 – cDMARDs+OKZ 64 mg subcutaneously once every 4 weeks + psychopharmacotherapy (PPT) (n=26); group 3 – cDMARDs+PPT (n=5). The duration of the study is 24 weeks. The dynamics of depression severity was assessed on the PHQ-9, MADRS scales; anxiety – HAM-A; experimental psychological projective techniques were also used.Results. After 12 and 24 weeks of therapy, there was a significant decrease in the severity of depression and anxiety in all groups of patients. However, the difference between the final and initial values of all scales was statistically significantly greater (pPHQ-9 24–0 =–6.75±3.91; ΔMADRS 24–0 =–22.5±4.83; ΔHAM-A 24-0 =–14.6±5.37) and cDMARDs+PPT (ΔPHQ-9 24–0 =–15.5±3.53; ΔMADRS 24–0 =–25.0±1.41; ΔHAM-A 24-0 =–18.5±3.53), compared with the cDMARDs+OKZ group (ΔPHQ-9 24–0 =–4.00±3.89; ΔMADRS 24-0 =–5.75±8.29; ΔHAM-A 24–0 =–8.50±8.21). According to a semi-structured interview with a psychiatrist and design experimental psychological techniques, the proportion of patients without depression after 24 weeks of therapy was significantly higher in the groups of patients receiving PPT: 90% in the group of cDMARDs+OKZ+PPT and 100% – cDMARDs+PPT, as opposed to 25% in the group of cDMARDs+OKZ. OKZ therapy contributed to the normalization of night sleep but did not lead to a decrease in the frequency and severity of cognitive disorders (CD).Conclusions. OKZ has an antidepressant effect in RA patients, leads to a decrease in the frequency of sleep disorders, but a com[1]plete regression of depression symptoms is possible because of the appointment of OKZ without PPT only in 25% of RA patients, mainly in patients with mild depression. Optimal for the complete regression of depression, anxiety and a decrease in the frequency and severity of CD is a combination of OKZ and PPT.

The objective: to study the epidemiology and incidence of XDR tuberculosis given the updated definition.Subjects and Methods. The results of replies to the specialized inquiry by the Russian Ministry of Health about results of microbiological diagnostics and MTB drug susceptibility tests were studied. To assess the incidence of pre-extensive drug resistance, general population data were used, and for extensive drug resistance, data from 8 regions of Russia were used.Results. The incidence of pre-extensive drug resistance was 39,1% [95% CI 38,4–39,8] among tuberculosis cases with rifampicin resistance including 26,8% in new cases [95% CI 25,8–27,9]; among all cases receiving treatment for whom DST results were available, it made 20,2%, including primary resistance in 9,7%. The incidence of XDR among cases with pre-extensive drug resistance was 3,0% [95% uncertainty interval 1,8–5,3] for all cases, including primary resistance in 1,6% [95% uncertainty interval 0,2–5,7].Conclusion. Despite the low incidence of pre-extensive drug resistance, it is expected to increase primarily due to growing resistance to fluoroquinolones. Resistance to innovative drugs, in particular XDR, is not yet a serious problem.

Ayurveda has its own unique principles in understanding a disease by its preventive and therapeutic viewpoints. So that Nasya ‟being prime therapy for maintaining the health of Urdhvajatru”, because the only Karma, which finds a place in simple references like “Dinacharya” and the most sophisticated places like Panchakarma. Nose is highly vascular structure and its mucous membrane provides good absorbing surface. Hence, Siddha Sneha on their administration spread along the nasal mucous membrane. An active principle along with Sneha gets absorbed inside the olfactory and respiratory mucosa and from there it is carried to different places. Sneha provides nourishment to nasal structures and other Shirogata organs also. The networks of nasal blood and lymph vessels have many communications with those of sub-Dural and sub arachnoid spaces. This fact is one of the important factors contributing to the extension mentioned drugs from the nose into cranial cavity. Myeline sheath is the first covering of the nerve fibre which is composed of lipid material blood- brain barrier is highly permeable for lipid substances, and substances which are fat soluble. Therefore, these substances can easily passthrough blood brain barrier and exert their action. The lipid contains of p tail may pass through blood-brain barrier easily dure to its transport, some of the active principles may reach up to certain levels in the nervous system to exert their Vataghna property.