[Weather and climatic factors at the resort of the Southern coast of Crimea in the medical rehabilitation of patients with hypertension]. / Pogodno-klimaticheskie faktory na kurorte Yuzhnogo berega Kryma v meditsinskoi reabilitatsii patsientov s gipertonicheskoi bolezn'yu.

OBJECTIVE: To evaluate the effect of weather and climatic factors of the South Coast of Crimea (SCC) on the effectiveness of health resort medical rehabilitation (MR) of patients with arterial hypertension (AH). MATERIAL AND METHODS: One hundred and thirty-four patients with AH were examined. The effect of weather and climatic factors of the SCC was assessed using the methods of Modified Clinical Weather Pathogenicity Index (CWPI-M, developed at the I.M. Sechenov Institute) and assessment of medical rehabilitation according to International Classification of Functioning, Disability and Health (ICF) criteria. RESULTS: The regression equations for the change of ICF domains b2401, b420, b4301, b4552, d240 and the change of mean values of all domains depending on air temperature and humidity, wind velocity, amount of clouds, variability of air temperature, and atmospheric pressure were developed. The equations permit the generation of reliable rehabilitation prognosis for patients with AH for all terms of health resort care at the SCC. CONCLUSIONS: The use of CWPI-M makes it possible to form a rehabilitation prognosis for patients with AH based on certain ICF domains. The best rehabilitation prognosis for the SCC resorts is for the warm period of the year.

[Phenotypes of bronchial asthma during the health resort period and personalized programs of medical rehabilitation]. / Fenotipy bronkhial'noi astmy na sanatorno-kurortnom étape i personalizirovannye programmy meditsinskoi reabilitatsii.

INTRODUCTION: Bronchial asthma (BA) is a relevant social and medical problem in our country and around the world. Currently, phenotypes of the disease are distinguished. One of the original decisions in phenotypes distinguishing is the use of cluster analysis. However, the concept of BA phenotypes at the health resort period of rehabilitation has not yet been formed. AIM: To determine the BA phenotypes upon admission of patients to a health resort medical rehabilitation (HRMR) using cluster analysis and to offer personalized rehabilitation programs. MATERIAL AND METHODS: 518 patients with asthma who underwent HRMR on the southern coast of Crimea were examined. Each patient received clinical, functional and laboratory examination. HRMR included correction of long-term treatment according to the severity of asthma, climate therapy, respiratory therapy, educational programs, and physiotherapeutic procedures. We applied cluster analysis in order to identify BA phenotypes. Description statistics methods were used for phenotype-cluster characterization, comparative analysis - for determination of reliable phenotypic characteristics and relation of the effectiveness of HRMR and phenotypes. RESULTS: A model of three phenotype-clusters was developed. The first cluster included patients with BA of moderate severity, uncontrolled course, frequent exacerbations, history of atopy, a tendency to obesity, moderately reduced external respiration function, fixed airway obstruction, high adherence to long-term therapy with medium doses of inhaled glucocorticoids (ICS) combined with long-acting ß-2 agonists (LABA). Cluster 2 included patients with mild asthma, controlled or partially controlled course of the disease, with rare short exacerbations, late onset, preserved external respiration function and exercise tolerance, but low adherence to long-term therapy with medium and low doses of ICS. Cluster 3 included patients with moderate to severe BA, uncontrolled course, with early onset, frequent and prolonged exacerbations, severe symptoms, significantly reduced external respiration function with fixed obstruction, decreased exercise tolerance, but low adherence to long-term therapy (4th stage) with high doses of ICS in combination with LABA and long-acting anticholinergics. A close relationship was found between phenotypes-clusters and the achieved effects: a significant increase in the control of BA and a high efficiency of rehabilitation in patients of the 1st and especially 3rd clusters and low in the 2nd cluster. The optimal rehabilitation programs for each of the selected cluster phenotypes were determined. CONCLUSION: The cluster model developed with the help of artificial intelligence has demonstrated high prognostic value in the determination of the effectiveness and change of control over the course of asthma as a result of HRMR. Personalized HRMR programs are suggested.

[Robot-assisted and robotic systems used in dentistry]. / Robot-assistirovannye i robotizirovannye sistemy, primeniaemye v stomatologii.

In the present study, the role of robot-assistance in dentistry and the main ways of its further development are analyzed. The basic structures of mechatronic devices and the features of their application in dentistry were reviewed. A retro-prospective analysis of the structures of robotic and robot-assisted systems used in dental practice was carried out. The development of robot-assisted and robotic systems should include the improvement of methods of intraoperative imaging, diagnostic tools, the improvement of surgical instruments, as well as the emergence of new robotic developments.

[The Interaction of miRNA-5p and miRNA-3p with the mRNAs of Orthologous Genes].

miRNAs regulate the expression of many genes and are involved in the development of diseases. We studied miRNAs that interact partly or fully complementarily with the 5'UTR, CDS and 3'UTR of mRNAs of target genes. The MirTarget program used in this study allows for the discovery of miRNA binding sites (BS) in the entire nucleotide sequence of the mRNA and for determining the characteristics of the interactions of miRNAs with mRNAs. We identified five pairs of fully complementary BS for miR-127-5p and miR-127-3p, miR-136-5p and miR-136-3p, miR-431-5p and miR-431-3p, miR-432-5p and miR-432-3p, and miR-433-5p and miR-433-3p in the CDS of the human and animal mRNA of RTL1 gene. The fully complementary BS for miR-6720-5p, miR-6720-3p were identified in the CDS of the FOXF2 gene; BS for miR-3187-5p, miR-3187-3p were found in the CDS of the PLPPR3 gene; BS for miR-4665-5p, miR-4665-3p were found in the 5'UTR of the KIAA2026 gene; BS for miR-135a-5p, miR-135a-3p were found in the 3'UTR of the GLYCTK gene; BS for miR-7106-5p, miR-7106-3p were found in the 3'UTR of the CCDC42B gene. The miRNA-5p and miRNA-3p associated with the RTL1 gene have BS in the mRNAs of 32 target human genes. The miRNA-5p and miRNA-3p associated with the FOXF2, PLPPR3, KIAA2026, GLYCTK and CCDC42B genes have BS in the mRNAs of 27 target genes, involved in development of several diseases. Nucleotide sequences of miRNA-5p and miRNA-3p and BS are conserved over tens of millions of years of divergence of the studied animal species. Binding characteristics of miR-3120-3p and miR-3120-5p, miR-196b-3p and miR-196b-5p, miR-125a-3p and miR-125a-3p, let-7e-3p and let-7e-5p, miR-99b-3p in fully complementary BS of non-coding DMN3OS, HOXA10-AS, SPACA6P-AS genes have been established.

[Preclinical study of the new anti-influenza drug candidate AV0038 (ethyl 2-(dimethylaminomethyl)-5-hydroxy-1-methyl-6-(pyridin-3-yl)-1H-indole-3-carboxylate)].

In the framework of preclinical testing of AV0038, ethyl 2-(dimethylaminomethyl)-5-hydroxy-1-methyl-6-(pyridin-3-yl)-1H-indole-3-carboxylate, which showed high efficiency in the prevention and treatment of influenza A/Aichi/2/69 (H3N2) in mice, we have studied the drug solubility and stability in aqueous solutions, metabolic stability in human liver microsomes, stability in blood plasma of mice and humans, binding to plasma proteins of mice and humans, pharmacokinetics and bioavailability in mice, and the acute toxicity and the maximum tolerated dose. It is established that AV0038 has attractive pharmacological properties as anti-influenza drug candidate. The therapeutic doses of AV0038 do not cause acute toxicity in mice. It is expedient to continue preclinical investigations and study the drug metabolism, metabolites, and sub-chronic toxicity in test animals.

[Antiviral activity in vitro and pharmacokinetics of HCV entry inhibitor AVR560].

Several novel compounds were found to be potent inhibitors of the HCV (JFH-1 isolate) infection in vitro. Human serum did not significantly reduce antiviral activity of the lead compound, AVR560 (< 4-fold). The immunohistochemistry studies with the Huh7 cell line, infectable with the HCV (JFH-1 strain), demonstrated that AVR560 inhibited the early steps of viral infection and blocked the spread of the HCV infection in tissue culture. The cytotoxicity in Huh7 and Vero-76 cell lines was mild. AVR560 proved to be a specific HCV inhibitor and exhibited no activity against other flaviviruses such as yellow fever (strain 17D), West Nile (strain NY99), and dengue (New Guinea type 2) in in vitro infection experiments. AVR560 also did not inhibit any of the tested human CYP450 isozymes (3A4, 1A2, 2C19 and 2D6). In the pharmacokinetic studies in mice, rats and dogs, favorable pharmacokinetic profiles and good oral bioavailability were observed for AV560. Further pre-clinical studies with this novel HCV inhibitor are in progress.

[Preclinical study of AV0012 early stage inhibitor of hepatitis C virus infection: I. In vitro ADME and pharmacokinetics].

In vitro immunohistochemical investigations on the human hepatoma cell line (Huh7) infected with hepatitis C virus (HCV) strain JFH-1 showed that AV0012 compound blocks the early stages of viral infection. AV0012 also blocked viral infection spread in tissue culture through the secreted virus and through tight cell-to-cell contact. AV0012 is a specific inhibitor of HCV but not of related pestivirus, flaviviruses and other RNA-containing viruses such as bovine diarrhea (BVDV), Venezuelan equine encephalitis (strain TC-83), dengue type 2 (New Guinea), yellow fever (strain 17D), west Nile fever, parainfluenza (type 3) virus, RSV (strain A2), and Rhinovirus (type 2 strain HGP). It is established that human serum does not significantly affect the antiviral activity of AV0012 in vitro. The drug combination studies with AV0012 and interferon alpha 2a in vitro showed that the two inhibitors act additively, which makes possible the use of this combination in clinical tests. AV0012 is highly soluble and stable in aqueous solutions and murine blood plasma, has limited metabolic stability, low binding to human plasma proteins, high permeability through biological membranes, and only interacts with isoenzymes 2D6 and 3A4 of human cytochrome P450. In animal pharmacokinetic studies, AV0012 was rapidly absorbed into the blood stream upon oral administration, showed sufficiently long half-elimination times, and had high oral bioavailability that reached 92% in monkeys. Further preclinical development of AV0012 is in progress.

[Preclinical study of safety of the new pharmacological substance AV0012 to treat hepatitis C].

Pharmacological safety of a new type of HCV inhibitor, AV0012, was studied including acute, subchronic and chronic toxicity in mice, rats and monkeys. Genotoxicity was assessed using the Ames test and the chromosomal aberrations assay in the bone marrow cells of mice. It is established that AV0012 has low toxicity in SHK line mice, Wistar line rats, and monkey of Rhesus macaques species. Results obtained in the study of genetic toxicity showed that AV0012 exhibits no mutagenic activity. Data on general toxicity and mutagenicity discussed in this paper, together with data on 1 the pharmacological activity, pharmacokinetics, and metabolism published previously, allow us to consider AV0012 as a candidate drug for clinical research phase I.

[Experimental rationale of hand stabilization devices use by teeth preparation].

This paper compares two methods of teeth preparation - with or without mechanical hand stabilization device preventing accidental angular deviations of dental handpiece during preparation. The results of two experiment series showed decreased convergence of side walls of the prepared teeth in cases when mechanical hand stabilizer corresponding to the values recommended in literature. It is concluded that mechanical hand stabilization device is a useful tool for improving the quality of preparations.

[Epidemiological peculiarities of acute respiratory diseases and its prophylaxis in Internal Troops of the Ministry of Internal Affairs].

Acute respiratory diseases is the current problem of the medical service and command of Internal Troops of the Ministry of Internal Affairs. In recent years on the background of increase of contract servicemen the total rate of these infections decreased. However, rate of acute respiratory diseases in conscripts remains high and has a tendency to increase. Due to restricted possibilities of immunization in case of acute respiratory diseases it is necessary to improve the non-specific prophylaxis. The guaranty of sanitary-and-epidemiological safety may be active participation of military-and-professional society in realization of lifesaving measures and safety of military service.

[Features of surgical treatment of moderate ischemic mitral regurgitation in high risk patients].

The experience of surgical treatment of high risk group patients with ischemic mitral regurgitation of different degree of manifestations was analyzed. The basic approaches to the management and the choice of treatment strategy are reported in this article. The authors suggested the priority strategy on the background of completed investigation: 1) the performance of the annuloplasty on pressure ring in combination with coronary bypass surgery in surgical treatment of ischemic mitral regurgitation of Ill degree, as most effective kind of intervention; 2) the performance of operation of isolated coronary bypass surgery on working heart for high risk patients with the presence of moderate ischemic mitral regurgitation, that allows the significant improvement of indices of postoperative period and the decrease of evidence of mitral regurgitation at the expense of a salvage of myocardial contractility.

piRNAs may regulate expression of candidate genes of esophageal adenocarcinoma.

Elucidation of ways to regulate the expression of candidate cancer genes will contribute to the development of methods for cancer diagnosis and therapy. The aim of the present study was to show the role of piRNAs as efficient regulators of mRNA translation of esophageal adenocarcinoma (EAC) candidate genes. We used bioinformatic methods to study the interaction characteristics of up to 200 thousand piRNAs with mRNAs of 38 candidate EAC genes. The piRNAs capable of binding to mRNA of AR, BTG3, CD55, ERBB3, FKBP5, FOXP1, LEP, SEPP1, SMAD4, and TP53 genes with high free energy by the formation of hydrogen bonds between canonical (G-C, A-U) and noncanonical (G-U, A-C) piRNA and mRNA nucleotide pairs were revealed. The organization of piRNA binding sites (BSs) in the mRNA of candidate genes was found to overlap nucleotide sequences to form clusters. Clusters of piRNA BSs were detected in the 5'-untranslated region, coding domain sequence, and 3'-untranslated region of mRNA. Due to the formation of piRNA binding site clusters, compaction of BSs occurs and competition between piRNAs for binding to mRNA of candidate EAC genes occurs. Associations of piRNA and candidate genes were selected for use as markers for the diagnosis of EAC.

[Experience of left ventricular assist device "Incor" as "bridge to recovery" implantation in patients with end stage congestive heart failure].

Left ventricular assist device "Incor" ("Berlinhear", Germany) implantation experience in patient with ischemic cardiomiopathy and severe congestive heart failure is presented. Left ventricular assist device implantation was followed by coronary artery bypass grafting simultaneously. Total assist time was 211 days. Complications developed during assisting time are shown. After Left ventricular assist device explantation three chamber pacemaker was implanted as cardiac resynchronization therapy. Left ventricular end diastolic size decreased (from 78 to 70 mm), ejection fraction increased (from 19 to 35%) during assist time.

Physiological change in camel milk composition (Camelus dromedarius) 2: physico-chemical composition of colostrum.

Eleven samples of dromedary camel colostrum in Kazakhstan, which originated from one farm only, were collected to study the changes in the physico-chemical composition (total fat, total protein, iodine index, lactose, calcium, phosphorus, iron, vitamin C, urea, ammonia, density, Dornic acidity, pH, and skimmed dry matter) all along the first postpartum week. At that time, the fat matter decreased from 25.9% to 3.1% and protein from 17.2% to 4.2%, in contrast to vitamin C which increased. Minerals showed high variations with lower values the first day after parturition and variable changes up to the end of the week where the values were stabilized. The iron concentration decreased from the second day postpartum. No clear changes of the other parameters were observed, notably for the non-protein nitrogen (urea and ammonia).

[Substituted 2,3,4,5-tetrahydro-1H-gamma-carbolines: new antagonists of histamine H1 receptors].

The properties of 2,3,4,5-tetrahydro-1H-gamma-carbolines containing acid, ether, and amido-substituents, were assessed as potential antagonists of histamine H1 receptors (H1R), capable of blocking histamine-induced calcium fluxes in SK-N-SH cells. The structure--activity relationship for their antagonistic activity is discussed. Among the gamma-carbolines used in the study, the antihistamine activity considerably depends on the nature of substituents in positions 2, 5, and 8 of the heterocycle. The most active antagonist, ethyl 3-(2-methyl-8-fluoro-2,3,4,5-tetrahydro-1H-gamma-carboline-5-yl)propionate, with high affinity to the H1R (Ki = 6.5 nM), produces no adverse effects on motor activity of mice in doses 1-40 mg/kg, which shows the absence of a sedative effect.

[Toxicity of ethyl-3-(8-fluoro-2-methyl-2,3,4,5-tetrahydropyrido[4,3-b]indol-5-yl)-propionate dihydrochloride possessing antiallergic properties].

The toxicity of new gamma-carboline derivative [ethyl 3-(8-fluoro-2-methyl-2,3,4,5-tetrahydro-1H-gamma-carbolin-5-yl)-propionate dihydrochloride, CD-008-040] has been studied.

[Anti-allergic properties of a novel ethyl 3-(8-fluoro-2-methyl-2,3,4,5-tetrahydropyrido[4,3-b]indol-5-yl)propionate dihydrochloride].

The influence of ethyl-3-(8-fluoro-2-methyl-2,3,4,5-tetrahydro-1H-gamma-carboline-5-yl)propionate dihydrochloride belonging to the class of gamma-carbolines on the allergic reactions (inflammation and systemic anaphylaxis) has been studied on laboratory animals. It was established that the given substance administered in a dose of 5 - 20 mg/kg exhibits a pronounced antiallergic action. Unlike many other antihistamine drugs, this gamma-carboline derivative probably does not produce sedative effect.

[Exon-intron structure of genes of fungi genomes].

Objects of research--genes of A. fumigatus, C. glabrata, C. neoformans, D. hansenii, E. cuniculi, E. gossypii, K. lactis, M. grisea, N. crassa, S. cerevisiae, S. pombe, U. maydis and Y. lipolytica fungi genomes. Methods of research are computer calculation. The content of genes with exon-intron structure in fungi genomes are from 0.7 to 97.0%. The exon-intron gene structure was changed when the portion of genes with introns increased. In A. fumigatus, C. neoformans, M. grisea, N. crassa, S. pombe and U. maydis genomes that linear dependence between gene lengths, sum of exon lengths and intron number in genes was established.

[Variations of the length of exons and introns in human genome genes].

The exon-intron organization of genes of all human chromosomes was studied in relation to the density of gene distribution on DNA strands and on the number of introns in genes. The lengths of exons, introns and genes have been found to vary correlatively, and this correlation depends on the density of genes in human chromosomes. It has been established that genes with the exon-intron organization have similar tendencies of variation of the lengths of exons and introns with an increase in the number of introns.