[The practice of stapes surgury in Russia]. / Praktika khirurgii stremeni v Rossii.

The aim of this study - to investigate the practice of stapes surgery in Russia using a special questionnaire (Appendix 1). Thirty-three questionnaires were sent to specialists dealing with stapes surgery in various Russian medical institutions. Responses were received from all ENT specialists, of whom 75.7% use stapedotomy as a technique. In most cases, colleagues perform more than 30 operations per year, there were also reports of performing about 100 operations per year and in one case 370 operations annually. 45.5% of respondents preferred a combination of general and local anesthesia for stapes surgery. According to the results of the survey, the titanium K-piston prosthesis is most frequently used. Analysis of the survey results showed that to date there is no unanimous opinion concerning some aspects of stapes surgery; however, in many issues the approaches of Russian surgeons coincide with the general world trends.

Chemical named entity recognition in the texts of scientific publications using the naïve Bayes classifier approach.

MOTIVATION: Application of chemical named entity recognition (CNER) algorithms allows retrieval of information from texts about chemical compound identifiers and creates associations with physical-chemical properties and biological activities. Scientific texts represent low-formalized sources of information. Most methods aimed at CNER are based on machine learning approaches, including conditional random fields and deep neural networks. In general, most machine learning approaches require either vector or sparse word representation of texts. Chemical named entities (CNEs) constitute only a small fraction of the whole text, and the datasets used for training are highly imbalanced. METHODS AND RESULTS: We propose a new method for extracting CNEs from texts based on the naïve Bayes classifier combined with specially developed filters. In contrast to the earlier developed CNER methods, our approach uses the representation of the data as a set of fragments of text (FoTs) with the subsequent preparati`on of a set of multi-n-grams (sequences from one to n symbols) for each FoT. Our approach may provide the recognition of novel CNEs. For CHEMDNER corpus, the values of the sensitivity (recall) was 0.95, precision was 0.74, specificity was 0.88, and balanced accuracy was 0.92 based on five-fold cross validation. We applied the developed algorithm to the extracted CNEs of potential Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) inhibitors. A set of CNEs corresponding to the chemical substances evaluated in the biochemical assays used for the discovery of Mpro inhibitors was retrieved. Manual analysis of the appropriate texts showed that CNEs of potential SARS-CoV-2 Mpro inhibitors were successfully identified by our method. CONCLUSION: The obtained results show that the proposed method can be used for filtering out words that are not related to CNEs; therefore, it can be successfully applied to the extraction of CNEs for the purposes of cheminformatics and medicinal chemistry.

[Combination of CT and MRT in the diagnostic of middle ear cholesteatoma. Fusion technology is precise localization tool]. / Sovmeshchenie rentgenovskoi komp'yuternoi i magnitno-rezonansnoi tomografii v diagnostike kholesteatomy srednego ukha. Tekhnologiya Fusion ­ instrument tochnoi lokalizatsii.

Computed tomography (CT) and magnetic resonance imaging (MRI) methods of the middle ear cholesteatoma diagnostic have its advantages and disadvantages. Fusion technology is a post-processing process of CT and MRI images. Its main advantage is the localization of MR-hyperintensive cholesteatoma within the bony anatomical structures obtained on CT, which provides the surgeon with important information both before planning the primary surgical intervention and during a second revision for recurrent cholesteatoma.

[Evaluation of the effectiveness of ultrasound shear elastography and liver steatometry].

Detection of liver fibrosis and steatosis at early stages is a difficult task for clinical practice, due to the lack of early signs in routine radiation diagnostics. AIM: To evaluate the efficacy of ultrasound shear elastography and ultrasound steatometry of the liver with the use of domestic ultrasonic diagnostic system Angiodin-Sono/N-Ultra. MATERIALS AND METHODS: 264 people held ultrasound elastography and ultrasound steatometry. 38 patients underwent percutaneous puncture liver biopsy and subsequent pathophysiological examination. RESULTS: High correlation of fibrosis obtained at the Angiodin-Sono/N-Ultra and the leading ultrasonic systems with shear elastography was revealed. Cross-sectional comparative analysis of elasticity with the results of liver steatometry was conducted. CONCLUSIONS: Results obtained in all groups correlate with the data obtained in studies on Fibroscan. When working with system Angiodin we got a simultaneous comparative analysis of elasticity with the results of liver steatosis. Results appear to be much more stable and compact than those obtained in studies on the Fibroscan. A new diagnostic criterion was revealed the phenomenon of independence of fibrosis and steatosis indices.

Higher Ca2+ -sensitivity of arterial contraction in 1-week-old rats is due to a greater Rho-kinase activity.

AIM: During early post-natal development, arterial contraction depends less on Ca2+ -signalling pathways but more on changes in Ca2+ -sensitivity compared to adult animals. Whether this difference is related to Rho-kinase, one of the major players affecting Ca2+ -sensitivity, is unknown for intact vessels. Thus, we tested the hypothesis that Rho-kinase critically contributes to the higher Ca2+ -sensitivity of contraction in intact arteries of 1-week-old rats. METHODS: We studied 1-week-old, 4- to 5-week-old and 10- to 12-week-old rats performing isometric myography, Ca2+ -fluorimetry and Western blotting using intact saphenous arteries and arterial pressure measurements under urethane anaesthesia. RESULTS: In 10- to 12-week-old rats, methoxamine (MX) produced vasoconstriction associated with an increase in [Ca2+ ]i and Ca2+ -sensitivity. In contrast, in 1-week-old rats these contractions were accompanied only by an increase in Ca2+ -sensitivity. All MX-induced effects were reduced by the Rho-kinase inhibitor Y-27632; this reduction was complete only in 1-week-old rats. The Rho-kinase specific site Thr855 on MYPT1 was increasingly phosphorylated by MX in vessels of 1-week-old, but not 10- to 12-week-old rats; this effect was also inhibited completely by Y-27632. The Rho-kinase inhibitor fasudil in a dose not affecting the pressor response to MX in 4- to 5-week-old rats reduced it considerably in 1-week-old rats. CONCLUSION: Our results suggest that the higher Ca2+ -sensitivity of arterial contraction in 1-week-old compared to 10- to 12-week-old rats is due to a greater Rho-kinase activity. Constitutively active Rho-kinase contributes to MX-induced contraction in 10- to 12-week-old rats. In 1-week-old rats, additional Rho-kinase activation is involved. This remodelling of the Rho-kinase pathway is associated with its increased contribution to adrenergic arterial pressure responses.

Voluntary exercise training restores anticontractile effect of NO in coronary arteries of adult rats with antenatal/early postnatal hypothyroidism.

INTRODUCTION: Our recent study showed that NO-mediated anticontractile effect of endothelium is absent in coronary arteries of adult rats, which suffered from antenatal/early postnatal hypothyroidism. This study tested the hypothesis that exercise training would improve such detrimental consequences of early thyroid deficiency. DESIGN AND METHODS: Wistar dams received propylthiouracil (PTU, 7 ppm) in drinking water during gestation and two weeks postpartum; control dams received tap water. Six-week-old male offspring of control (CON) and PTU dams was divided into sedentary (CON-Sed, n = 12; PTU-Sed, n = 10) and trained (CON-Tr, n = 12; PTU-Tr, n = 10) groups; the latter had 24-h access to running wheels. Eight weeks later coronary arteries were studied by wire myography. Anticontractile effect of NO was assessed by the effects of NOS inhibitor L-NNA on the basal tone and contractile response to U46619. Oxidative phosphorylation complexes and eNOS were estimated by Western blotting. RESULTS: T3/T4 and TSH levels (ELISA) were normalized in the progeny of PTU-treated dams at the age of 6 weeks and were not affected by training. Total running distance did not differ between CON-Tr and PTU-Tr. The contents of oxidative phosphorylation complexes were increased post-training in triceps brachii muscle from CON-Tr and PTU-Tr and in heart from PTU-Tr. Coronary arteries of PTU-Sed compared to CON-Sed demonstrated higher basal tone and contractile response to U46619, which were not further increased by L-NNA. The effects of L-NNA on the basal tone and contractile response to U46619 did not differ in CON-Tr and PTU-Tr groups, but were elevated in PTU-Tr compared to PTU-Sed group. PTU-Tr rats in comparison to PTU-Sed group had higher eNOS content in heart. Responses of coronary arteries to DEA/NO did not differ among all experimental groups. CONCLUSIONS: Long-lasting coronary endothelial dysfunction resulted from transient thyroid deficiency during the antenatal/early postnatal period can be corrected by voluntary exercise training.

[Computational prediction of human immunodeficiency resistance to reverse transcriptase inhibitors]. / Komp'iuternyi prognoz rezistentnosti virusa immunodefitsita cheloveka k ingibitoram obratnoi transkriptazy VICh.

Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS) and leads to over one million of deaths annually. Highly active antiretroviral treatment (HAART) is a gold standard in the HIV/AIDS therapy. Nucleoside and non-nucleoside inhibitors of HIV reverse transcriptase (RT) are important component of HAART, but their effect depends on the HIV susceptibility/resistance. HIV resistance mainly occurs due to mutations leading to conformational changes in the three-dimensional structure of HIV RT. The aim of our work was to develop and test a computational method for prediction of HIV resistance associated with the mutations in HIV RT. Earlier we have developed a method for prediction of HIV type 1 (HIV-1) resistance; it is based on the usage of position-specific descriptors. These descriptors are generated using the particular amino acid residue and its position; the position of certain residue is determined in a multiple alignment. The training set consisted of more than 1900 sequences of HIV RT from the Stanford HIV Drug Resistance database; for these HIV RT variants experimental data on their resistance to ten inhibitors are presented. Balanced accuracy of prediction varies from 80% to 99% depending on the method of classification (support vector machine, Naive Bayes, random forest, convolutional neural networks) and the drug, resistance to which is obtained. Maximal balanced accuracy was obtained for prediction of resistance to zidovudine, stavudine, didanosine and efavirenz by the random forest classifier. Average accuracy of prediction is 89%.

Integrated Assessment of Neurodynamic and Vegetative Indicators in Adolescents: Age- and Gender-Related Differences and Typological Features.

We examined schoolchildren aged 11-16 years (n = 930) and determined the features of neurodynamic and vegetative parameters associated with age and sex and the factors affectingthe psycho-physiological statusof adolescents. An analysis of the relationship of studied parameters in adolescents with different types of autonomic regulation showed thatthe evaluation of functional constitution has prognostic significance since it is indicative of the adaptation potential.

[CHANGES OF NORMALIZED SPECTRAL POWER OF ELECTROENCEPHALOGRAM RHYTHMS OF HARD-OF-HEARING CHILDREN AND TEENAGERS].

We showed that a cortical maturation rhythms of people with hard-of-hearing is the subject to the same laws as the background rhythm persons normally hear: with age on the background EEG in the people with hard-of-hearing is a gradual increase in α-rhythm, but still normalized spectral power of the α- rhythm on the background's EEG of teenagers with hard-of-hearing remains below the similar indicators adolescents normally, and greater representation of slow waves. It was found that the background's EEG of teenagers with hard-of-hearing observed moving focus of α-occipital activity in the parietal cortex, which is not observed in the hard-of-hearing children. It can be associated with an increased activity in the limbic system on the background of bark tone in the hard-of-hearing children.

[Population Dynamics of Cancer: a Model of Second Order Phase Transition].

The paper deals with an approach to the description of the age and temporal dynamics of cancer, based on the model describing the dynamics of the age of cancer as a second order phase transition. This approach is widely used for studying physical systems. This model of cancer development as second order phase transitions is in a good agreement with medical statistics. The cancer incidence dynamics is described only with two free parameters, easily verified according to statistics and well interpreted. The applicability of the second order phase transition model for description of a non-physical system defines the universal nature of the processes occurring during phase transitions.

[Gypsy moth Lymantria dispar L. in the South Urals: Patterns in population dynamics and modelling].

The analysis is conducted on population dynamics of gypsy moth from different habitats of the South Urals. The pattern of cyclic changes in population density is examined, the assessment of temporal conjugation in time series of gypsy moth population dynamics from separate habitats of the South Urals is carried out, the relationships between population density and weather conditions are studied. Based on the results obtained, a statistical model of gypsy moth population dynamics in the South Urals is designed, and estimations are given of regulatory and modifying factors effects on the population dynamics.

[THE INDICATORS OF GROWTH AND MYOGENESIS IN THE GLYCOLYTIC AND OXIDATIVE MUSCLES OF THE RAT AFTER INDIRECT ELECTROSTIMULATION].

A comparative analysis of the signaling pathways activity and gene expression in the red (RG) and white (WG) parts of the gastrocnemius muscle of rat after a series of short (1 s) tetanic contractions induced by motor nerve stimulation at a frequency of 100 Hz and with an amplitude that provides activation of all motor units of the muscle. WG compared to RG demonstrated a marked increase in the phosphorylation level of ERK1/2, although the increase in the phosphorylation of AMPK was not different in two muscles 2 h after the stimulation. Along with that, content of MyoD and myogenin mRNA in WG increased much higher than in RG, whereas the effect of stimulation on IGF-1, MaFbx and MuRF genes expression was weak and comparable in WG and RG. There was an increase of myostatin mRNA in RG. Thus, glycolytic muscle fibers of WG exhibit more pronounced regulatory shifts of hypertrophic character than oxidative muscle fibers of RG.

[Immunogenic properties of experimental production series of Staphylovac-2 vaccine].

AIM: Study experimental production series of Staphylovac-2 by accumulation of specific IgG and safety. MATERIALS AND METHODS: Experimental production samples of staphylococci vaccines were studied by the accumulation of specific IgG in sera of immunized BALB/c line mice in EIA. Safety was evaluated in tests of acute and chronic toxicity including pathomorphologic and histologic, hematologic and biochemical studies, studies of the effect on central nervous system. RESULTS: A statistically significant (2.6 - 3.0 times) increase of IgG levels in sera of immunized mice compared with control was noted. In the experiments studying acute and chronic toxicity the increase in body mass and mass of internal organs differed from data obtained from control animals at no observation periods. None of the studied methods of safety evaluation showed differences of the studied vaccine series from the control. CONCLUSION: The recommended dose for subcutaneous administration into human of 200 µg is experimentally justified and could be the basis for carrying out clinical studies of staphylococci vaccines in humans.

Trophic action of sympathetic nerves reduces arterial smooth muscle Ca(2+) sensitivity during early post-natal development in rats.

AIM: A decrease in the Ca(2+) sensitivity of smooth muscle contraction is a hallmark of functional remodelling of blood vessels during development. However, the responsible factors are largely unknown. Here, we tested the hypothesis that the post-natal decline of arterial Ca(2+) sensitivity is the result of trophic effects of sympathetic nerves. METHODS: Contractile responses, intracellular Ca(2+) levels and protein expression profiles were compared in saphenous arteries from young (1- and 2-week-old) and adult rats using wire myography, Ca(2+) fluorimetry and Western blotting respectively. RESULTS: We observed a lower Ca(2+) sensitivity of contractions induced by methoxamine, an agonist of α1 -adrenoceptors, and U46619, an agonist of thromboxane A2 receptors, in arteries from adult as compared to young animals. Post-natal maturation was associated with stronger expression of regulatory proteins mediating Ca(2+) -dependent contraction (myosin light chain kinase (MLCK), myosin targeting subunit (MYPT1) and h-caldesmon) and weaker expression of proteins regulating Ca(2+) -independent contraction (Rho kinase, extracellular-regulated kinases (ERK1/2) and mitogen-activated protein kinases p38 MAPK) in vessels from adult rats. To eliminate the trophic action of sympathetic nerves, we performed lumbar sympathectomy in adult rats. This resulted in higher Ca(2+) sensitivity of agonist-induced contractions in denervated as compared to control arteries. Furthermore, denervated arteries contained less MLCK, MYPT1 and h-caldesmon and more ERK1/2 and p38 MAPK. CONCLUSIONS: Sympathetic denervation reverses developmental changes both in Ca(2+) sensitivity and in the expression of regulatory proteins back to the early post-natal phenotype in the rat saphenous artery. We conclude that trophic effects of sympathetic nerves govern functional remodelling of arteries during early post-natal development.

Effects of continuous and intermittent aerobic exercise upon mRNA expression of metabolic genes in human skeletal muscle.

AIM: It is known that intermittent aerobic exercise training program is more efficient for the improvement of aerobic performance than continuous one but molecular mechanisms of such effects are purely understood. The aim of the present study was to compare gene expression of mitochondrial biogenesis regulators (peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), mitochondrial transcription factors A (TFAM) and B2 (TFB2M) and genes involved in exercise-induced catabolic events (forkhead box O1 (FOXO1) and Atrogin-1) in human skeletal muscle after single continuous (CE) and intermittent (IE) aerobic exercise sessions, equalized thoroughly in duration and mean power output. METHODS: Twelve physically active males performed CE (workload at lactate threshold [LT], 50 min) or IE ([3 min 81% LT+2 min 125% LT]x10). The biopsies were taken from m. vastus lateralis before and 1 h, 3 h, 5 h after the exercise. RESULTS: The IE induced a 2-fold greater increase of PGC-1α and TFAM gene expression after 3 h and 5 h of recovery than CE. The increments of Atrogin-1 mRNA abundance were observed 3 and 5 h after IE only. The increments in FOXO1 mRNA level were revealed 1 h and 3 h after the IE and 3 h after the CE. CONCLUSION: The results of the study suggest that higher potential of IE for the improvement of mitochondrial biogenesis than CE associated with more pronounced increase of PGC-1α and TFAM mRNA expression. Along with that, IE induces a higher increment of expression of FOXO1 and Atrogin-1 genes involved with exercise-induced catabolic events compared to CE.

[Functional alterations of the arterial vessels in experimental models of type 1 diabetes mellitus].

The review analyzws the literature on the pathological alterations of endothelium, smooth muscle and vasomotor innervation of arterial vessels in animal modes of type 1 diabetes mellitus. Particular attention is paid t the analysis of mechanisms of diabetic abnormalities in the light of modern knowledge on the functioning of the main components of the vascular wall.

[Study of protective activivty of "Staphylovac-2" vaccine].

AIM: Study the protective properties of "Staphylovac-2" vaccinie. MATERIALS AND METHODS: Samples of the vaccine manufactured by SPA "Microgen" based on the developed technology were studied in balb/c mice during 3- and 6-fold immunization schemes. Protective activity of the preparation was determined in experiments with active and passive protection during intraperitoneal infection, seeding of the causative agent from spleen and kidneys during intravenous infection, of animals. RESULTS: In experiments with active protection of mice for both 3- and 6-fold immunization schemes, a significant protective activity of the studied series was determined, compared with the control group of mice. Sera obtained after animal immunization (rabbits, mice) by staphylococcus vaccine had protective properties. A reduction of spleen and kidneys seeding by Staphylococcus aureus in immunized mice compared with the control group was detected in the model of generalized staphylococci infection. CONCLUSION: The preclinical studies carried out with the "Staphylovac-2" vaccine, developed baed on the complex of protective staplylococci antigens, have confirmed the high protective activity of the preparation.

[New antibiotics produced by Bacillus subtilis strains].

Two Bacillus subtilis strains isolated from the fruiting body of a basidiomycete fungus Pholiota squarrosa exhibited a broad range of antibacterial activity, including those against methicillin-resistant Staphylococcus aureus INA 00761 (MRSA) and Leuconostoc mes6nteroides VKPM B-4177 resistant to glycopep-> tide antibiotics, as well as antifungal activity. The strains were identified as belonging to the "B. subtilis" com- plex based on their morphological and physiological characteristics, as well as by sequencing of the 16S rRNA gene fragments. Both strains (INA 01085 and INA 01086) produced insignificant amounts of polyene antibiotics (hexaen and pentaen, respectively). Strain INA 01086 produced also a cyclic polypeptide antibiotic containing Asp, Gly, Leu, Pro, Tyr, Thr, Trp, and Phe, while the antibiotic of strain INA 01085 contained, apart from these, two unidentified nonproteinaceous amino acids. Both polypeptide antibiotics were new compounds efficient against gram-positive bacteria and able to override the natural bacterial antibiotic resistance.

[The early comprehensive rehabilitation of the children with perinatal pathology of the craniovertebral region and cerebrospinal neurological symptoms].

This paper is designed to report the results of a clinical study of the children presenting with neurologic pathology for the detection of the most common concomitant craniovertebral disorders. In addition, the experience of application of the methods for comprehensive rehabilitation is presented with special reference to remedial exercises, manual therapy, massage, and other physiotherapeutic procedures. Positive experience with the application of orthopedic devices is described including the Shants collars and corsets as well as the observance of the specific orthopedic locomotor regimen. These combined measures are designed to enhance the quality of life of the patients, correct their neurologic symptoms, and improve the compromised academic performance.