Effect of colloidal magnetite (Fe3O4) nanoparticles on the electrical characteristics of the azolectin bilayer in a static inhomogeneous magnetic field.

This work is devoted to the study of the combined effects of applied magnetic field and MNPs on the electrical characteristics of bilayer lipid membranes. We present results of the study of electrical parameters of azolectin membranes in a static inhomogeneous magnetic field at the one-sided addition of positively charged quasi-spherical superparamagnetic magnetite nanoparticles with a diameter of about 4 nm. The magnet was located at different distances from the membrane, and the magnetic field attracted the nanoparticles to the membrane surface with different strengths. We observed three pronounced effects that depended on the external magnetic field. Firstly, after addition of nanoparticles in a magnetic field, the conductance of the membranes increased. A smooth increase in conductance was accompanied in some cases by the appearance of current jumps, which can be associated with the formation of through pores with a radius of no more than 1 nm. The conductance increased with increasing magnetic field gradient. Secondly, at zero command voltage, a negative current through the membrane was observed. Although our experiments did not allow us to unambiguously determine which particles create this current, we believe that this current is associated with the penetration of particles through the membrane. This effect intensified with increasing magnetic field gradient. Thirdly, we observed a sharp change in the nonlinear dependence of capacitance on voltage associated both with the change in the surface potential of the azolectin membrane and with the effect of MNP binding to the membrane surface on the apparent membrane capacitance.

First Observation of Neutral Bremsstrahlung Electroluminescence in Liquid Argon.

A recent discovery of additional mechanism of electroluminescence (EL) in noble gases due to the neutral bremsstrahlung (NBrS) effect led to a prediction that NBrS EL should be present in noble liquids as well. A theoretical model of NBrS EL in noble liquids was developed accordingly in the frameworks of Cohen-Lekner and Atrazhev. In this work, we confirm this prediction: For the first time, visible-range EL has been observed in liquid argon at electric fields reaching 90 kV/cm, using gas electron multiplier (GEM) and thick GEM structures. Absolute light yields of the EL were measured and found to be in excellent agreement with the theory, provided that the momentum-transfer cross section of electron scattering is used for calculation of the NBrS cross section (instead of the energy-transfer one).

[Clinical aspects of diagnosis and treatment of glossodynia in elderly and senile people.]

Glossodynia is a disease that is difficult to diagnose and treat. Persons of older age groups are in the most risk of its occurrence. This is due to the fact that its etiological factors are: age-related changes, general somatic diseases, usage of some pharmacological drugs, changes in the psycho-emotional background. Due to the similarity of the clinical picture of glossodynia with other diseases of the oral cavity, the doctor is required to be thoughtful when diagnosing and differentiating glossodynia. Clinical methods of examination are used, paying most attention to the anamnesis of life and disease, assessment of the personal and emotional sphere of the patient. Clinico-functional, clinico-instrumental, and laboratory methods of examination are also used. In the treatment of glossodynia, attention should be paid not only to the elimination of symptoms, but also to its prevention. The main efforts should be aimed at combating the main links of pathogenesis. Treatment should be comprehensive, differentiated and personalized. As a result of many researchers work, certain principles of diagnostics and treatment of glossodynia have been developed, which will be considered in our work.

A Complex of Pyrosequencing-Based Methods for Detection of Somatic Mutations in Codons 600 and 601 of the BRAF gene.

The aim of the study is to develop methods for the differentiation of mutations in the BRAF codon 600 and to increase the sensitivity of the K601E mutation detection. Materials and Methods: The nucleotide sequence of the BRAF codons 592-602 was identified using the PyroMark Q24 genetic analysis system. The mutations search in codon 600 was conducted using the 600-S primer in line with the following order of adding nucleotides: GCTGTCАTCTGCTAGCTAGAC (corresponding to nucleotides 1799-1786). The K601E mutation was detected using the 601-S primer in line with the following order of nucleotide addition: GCTACTCACTGTAG (corresponding to nucleotides 1801-1793). The analytical characteristics of the proposed methods for somatic mutations' detection were determined using dilutions of plasmid DNA samples containing the BRAF gene region without mutations or with one of the following mutations: V600E, V600R, V600K, V600M, and K601E. Validation was performed on 132 samples of biological material obtained from the thyroid nodules. Results: The developed methods allow to determine 2% of the V600E or V600M mutations, 1% of the V600K and V600R mutations, and 3% of the K601E mutations in samples with high DNA concentration; it is also possible to confidently detect at least 5% of the mutant allele for all mutations in low concentration samples (less than 500 copies/PCR). During biological material testing, 53 samples with the V600E mutation were detected; the proportion of the mutant allele was 4.9-50.0%. Conclusion: A complex of methods for determination of the nucleotide sequence of the BRAF codons 592-601 and the algorithm for testing samples and analyzing mutations in the BRAF codons 600-601 was developed. The method provides sufficient sensitivity to detect frequent mutations in codons 600 and 601 and allows them to be precisely differentiated.

Differences in Fatty Acid Composition between Orb-Weaver Spiders Inhabiting a Riparian Zone and a Steppe Are Associated with the Consumption of Different Chironomid Taxa.

Amphibiotic insects, chironomids of the genera Glyptotendipes and Chironomus, which emerged from saline Lake Shira, differed in composition and content of fatty acids, including the essential eicosapentaenoic acid (20:5n-3, EPA), and upon flying out they were concentrated in different territories, the riparian zone and remote arid steppe zone, respectively. Potential consumers of chironomids adults, the orb-weaver spiders Larinoides suspicax, which inhabited both zones, also differed in fatty acid composition. The main difference in their biochemical composition was a significantly higher level of EPA in spiders from the riparian zone that likely to be explained by consumption of the Glyptotendipes adults enriched in this fatty acid and concentrated only within this zone. The higher level of EPA, which is deficient in terrestrial ecosystems, in orb-weaver spiders from the riparian zone of the saline lake may potentially promote a successful survival of the consumers in the arid landscape.

[Mechanisms for the Development of Blood Pressure Variability and the Potential of Antihypertensive Drugs in Their Correction].

Blood pressure variability (BPV) is the fluctuations of blood pressure over a certain period of time under the influence of various factors. The issue of increased BPV is of particular clinical importance due to high predictive value of this parameter as a risk factor for fatal and non-fatal cardiovascular, cerebrovascular and renal events. It is proved that in the BPV increasing, the key role is played by impairments in arterial baroreflexes, which, in turn, are mediated by increased vascular stiffness, impact of angiotensin II and the sympathetic nervous system, endothelial dysfunction, nitric oxide deficiency and aging, including the vascular aging. Antihypertensive drugs that targeting largest amount of pathophysiological mechanisms in BPV increasing have a most advantages in correcting excessive pressure fluctuations. In this regard such drugs are perindopril and amlodipine, which can eliminate almost the entire spectrum of increased BPV causes and, therefore, optimally reduce the cardiovascular risk.

Macroscopic and microscopic fluorescence spectroscopy of colorectal benign and malignant lesions - diagnostically important features.

Fluorescence spectroscopy is a sensitive, fast and non-invasive tool for a diagnostics of cancerous gastrointestinal lesions. It could be applied for in situ detection of tumours during primary endoscopic observations or as add-on measurement modality during microscopic observations of tissue histology slides for their initial or retrospective diagnosis. Therefore, we are looking for diagnostically important features of normal and cancerous tissue areas in a broad spectral range for gastrointestinal tissues ex vivo using two steady-state macroscopic fluorescent spectroscopic modalities and by confocal fluorescent microscopic detection. Results obtained from autofluorescence spectroscopy of benign and malignant lower part gastrointestinal tract (GIT) lesions from freshly excised tissues during surgical removal of the lesions in 18 patients (22 lesions), were compared with the spectral measurements obtained during confocal fluorescent microscopy observations of unstained tissue slides using 405 nm excitation. Excitation-emission matrices (EEMs) were used for ex vivo measurements with applied excitation in 280-440 nm spectral region and emission observed between 300 and 700 nm. Synchronous fluorescence spectroscopy (SFS) approach was also applied to improve the spectral resolution of the observed complex emission spectra. Specific fluorescent features observed, related to presence of structural proteins, co-enzymes and endogenous porphyrins in the tissues investigated, allow discriminating normal mucosa from benign polyps and malignant carcinoma lesions with diagnostic accuracy up to 94.4%.

[Single Pill Indapamide and Perindopril Arginine Combination: Optimal Coupling of Vascular Protection and Hemodynamic Risk Factors Reduction in Patients with Essential Arterial Hypertension].

OBJECTIVE: to investigate the impact of indapamide / perindopril single-pill combination (I / P SPC) on arterial stiffness parameters, blood pressure (BP) level and BP variability (BPV) in middle-aged patients with stage II grade 1-2 essential arterial hypertension (EAH). Materials and methods. We retrospectively formed a group of patients with stage II grade 1-2 EAH who had not previously received regular antihypertensive therapy (AHT) (n=52, mean age 52.9±6.0 years). All patients were treated with I / P SPC and all of them achieved target office BP level (less than 140 / 90 mm Hg). After 12 weeks of follow-up (from the time of reaching the target BP) assessment of AHT effectiveness (general clinical data, ambulatory blood pressure monitoring [ABPM], volume sphygmography, echocardiography), and vascular stiffness evaluation were performed. RESULTS: At the end of follow-up office systolic BP (SBP), diastolic BP (DBP), pulse BP, day-time, night-time and 24­hour SBP and DBP significantly (p<0.001 for all) decreased. According to the ABPM data day-time, nighttime, and 24­hour systolic BPV significantly decreased (p=0.029, p=0.006 and p<0.001, respectively); day-time and 24­hour diastolic BPV also significantly decreased (p=0.001 and p<0.001, respectively). Day-night standard deviation (SDdn) significantly decreased too (p=0.002 and p<0.001, respectively). Volumetric sphygmography showed significant decrease of right cardio-ankle vascular index (CAVI) (from 8.20±1.29 to 7.58±1.44, p=0.001) and of left CAVI (from 8.13±1.40 to 7.46±1.43, p<0.001), as well as reduction of the number o f patients with a right- and / or left-CAVI >9.0 (from 32.7 to 11.5 %, p=0.018). According to assessment of arterial stiffness using the Vasotens24 software package, the arterial stiffness index (ASI) significantly (p<0.001) decreased from 153.5±29.9 to 138.3±20.0 (by -9.2±13.1 %). Transthoracic echocardiography data demonstrated significant decrease (p<0.001) in effective arterial elastance (from 1.82±0.43 to 1.58±0.36 mm Hg; by -11.85±16.29 %) and significant (p<0.001) increase in the arterial compliance - from 1.27±0.34 to 1.54±0.38 mm Hg / ml (+26.95±38.06 %). CONCLUSION: In AHT naive patients 40-65 years old with stage II grade 1-2 EAH therapy with I / P SPC provided effective 24­hour BP control, reduced BPV and improved arterial stiffness parameters.

[Cognitive functions, emotional status, MRI measurements in treatment-naïve middle-aged patients with uncomplicated essential arterial hypertension]. / Kognitivnye funktsii, émotsional'nyi status i pokazateli magnitno-rezonansnoi tomografii u nelechenykh patsientov srednego vozrasta s neoslozhnennoi arterial'noi gipertenziei.

AIM: To study cognitive functions, anxiety and depression levels, 24-hour blood pressure (BP) profile, cerebral blood flow (CBF) perfusion in treatment-naive middle-aged patients with uncomplicated essential arterial hypertension (EAH) depending on the white matter hyperintensities (WMH) burden. MATERIAL AND METHODS: Forty-one hypertensive patients (mean age 46.2±4.6 years) and 41 healthy volunteers (mean age 50.3±6.7 years) were enrolled to the study. All subjects underwent brain MRI (MAGNETOM Skyra 3.0T, T1, T2 FSE, T2 FLAIR, T1 MPRAGE, ASL), Montreal cognitive assessment (MoCa), 10-word learning task, verbal fluency test, trail making test, Stroop color and word test, anxiety and depression assessment with Hamilton rating scales, 24-hour blood pressure monitoring (ABPM). RESULTS: WMH were found in 22 (53.7%) hypertensive patients and in 3 (7.3%) healthy volunteers (p=0.0002). Hypertensive patients had the significantly lower CBF compared to controls (p<0.001). CONCLUSION: WMH were identified in treatment-naive middle-aged patients with uncomplicated mild to moderate EAH. There was an association between WMH and lower CBF in the cortical plate of frontal lobes, SBP variability and worse cognition. Cerebral hypoperfusion can cause cognitive impairment even in the earliest stages of EAH, which increases due to emotional disorders.

[Day-by Day Blood Pressure Variability: Methodological Aspects, Prognostic Value, Effects of Antihypertensive Therapy].

In this article we present problems of prognostic value of day-by-day blood pressure (BP) variability, its role in development and progression of damage of target organs in arterial hypertension, and impact on risk of cardiovascular, cerebral-vascular complications, and mortality. We also discuss methodological aspects of assessment of day-by-day BP variability. The article contains literature data on effects of antihypertensive therapy on variability of home BP, and consideration of evidence base of possibilities of the fixed amlodipine/perindopril combination for lowering day-by-day BP variability.

[Blood Pressure Variability. Visit-to-Visit Blood Pressure Variability].

The article is devoted to the modern state of the problem of blood pressure variability (BPV). Along with discussion of classification and methods of diagnosis it contains data on prognostic value of visit-to-visit BPV. We have also reviewed effect on BPV of various regimens of antihypertensive therapy and presented evidence base supporting ability of amlodipine/perindopril fixed dose combination to lower visit-to-visit BPV.

[24­Hour Arterial Pressure Variability: Prognostic Significance, Methods of Evaluation, Effect of Antihypertensive Therapy].

We discuss in this article problems of prognostic significance of 24­hour arterial pressure variability (24hAPV), as well as the role of 24hAPV in development and progression of various target organs damage by arterial hypertension. We also present literature data on impact of various regimens of antihypertensive therapy on 24hAPV, and on ability of fixed-dose perindopril/amlodipine to lower 24­hAPV.

[A change in adrenal responsiveness in sotalol-treated patients with paroxysmal atrial fibrillation depending on autonomic nervous system tone].

AIM: To evaluate the efficacy of sotalol depending on the magnitude of changes in adrenal responsiveness and autonomic nervous system tone in patients with paroxysmal atrial fibrillation (AF). SUBJECTS AND METHODS: Twenty-six patients with paroxysmal AF in the presence of coronary heart disease (CHD) and hypertension were examined. Sinus rhythm variability and sympathicotonic and vagotonic disorders were studied in patients with paroxysmal AF before and during sotalol treatment. A commercial Beta-ARM-Agat kit was used to estimate the adrenal responsiveness of erythrocyte membranes (ß-APM), which can judge the body's individual sensitivity to ß-adrenoblockers. RESULTS: Sotalol used in the average therapeutic doses of 160-240 mg did not reduce ejection fraction or increase atrioventricular conduction up to abnormal values. In patients with borderline and mild hypertension, the drug lowered blood pressure statistically significantly (p=0.01) and was well tolerated. The drug increased the sensitivity of ß-adrenoblockers in patients with adrenergic AF. CONCLUSION: The effect of sotalol on the autonomic nervous system manifested in the higher power of a high-frequency spectral component of heart rate variability than in that of a low-frequency one. Long-term sotalol administration significantly reduced ß-APM, increasing the sensitivity of adrenoceptors.

FOR EXTRAINTESTINAL MANIFESTATIONS OF INFLAMMATORY BOWEL DISEASE IN CHILDREN.

Inflammatory bowel disease (IBD) are systemic diseases with different intestinal and extra-intestinal manifestations (ElM). This fact can determin an examination plan and the disease course and prognosis. Up to 8.4% of children with IBD have ELM like the first symptom of the disease. The range of ElM of iBD in children is differ from that one of adult patients: rarer arthropathy and arthritis, skin and liver diseases, an extremely rare eye disease. The physical development disorder is a typical children's manifestation of the IBD, the "failure of the weight curve" is an early symptom of the IBD debut (82% of examined children), especially ulcerative colitis. The article discusses the clinical features and therapy of the most frequent extraintestinal manifestations of IBD in children: skin, mucous, eye diseases, axial and peripheral arthropathies, primary scierosing cholangitis, physical, sexual development disorders, decreased bone mineral density. Most often, we observed patients with arthritis and primary scierosing cholangitis - up to 12.5% of patients with active disease. A growth failure was observed in 20% of children with IBD debut, and remained in 9.7% children despite adequate anti-inflammatory therapy. Decreased bone mineral density in children with IBD observed in 30% cases (ISCD-recommendations). Extraintestinal manifestations are very important to make the early diagnosis of IBD without any intestinal symptoms. The pediatrician can suspect a systemic diseases course. ElMs adversely impact upon patientsquality of life and some can be life-threatening.

[THE IMPLEMENTATION OF "EFFECTIVE CONTRACT" EXEMPLIFIED BY THE MEDICAL CENTER OF YAKUTSK].

The article considers issue of implementation of employment agreement by way of effective contract exemplified by the Yakutsk medical center of the Republic Sakha (Yakutia). The new job descriptions, criteria of effectiveness, ratings of implementation of functions of medical job position were developed. At that, mechanisms of registration and implementation of social guarantees in respect of health workers were proposed.

GASTROESOPHAGEAL REFLUX DISEASE IN ASSOCIATION WITH LIPID-METABOLIC INDICATORS AT THE YAKUTSK.

AIM: To estimate interrelations of gastroesophageal reflux disease with lipid-metabolic indicators at the Yakutsk. MATERIALS AND METHODS: A one-stage investigation of 100 patients of the Yakut nationality with gastroesophageal reflux disease (GERD) is carried out. For estimating the association of GERD clinical symptoms with lipid-metabolic indicators a method of binary logistical regress with compulsory inclusion of predictors has been used. RESULTS: According to results of the comparison most statistically significant distinctions of metabolic indicators are revealed at GERD esophageal (eructation) and extra-esophageal symptoms (night cough), dyspepsia (distention, epigastric heaviness), as well as snoring. Logistical regression analysis has confirmed interrelation of clinical symptoms with lipid-metabolic indicators, as waist circumference, a level of arterial pressure and blood lipid (triglycerides, lipoprotein cholesterol of low and high density). CONCLUSIONS: Thus, the estimation of interrelation of GERD clinical symptoms with MS criteria at the Yakutsk has revealed the influence of MS components, especially abdominal adiposity, arterial hypertension and triglycerides on the development of dyspepsic symptoms (distention, epigastric heaviness), GERD esophageal (eructation) and extra-esophageal manifestations (night cough).

FEATURES OF CLINICAL-FUNCTIONAL MANIFESTATIONS OF CHRONIC OBSTRUCTIVE LUNG DISEASE IN COMBINATION WITH METABOLIC SYNDROME IN ETHNIC GROUPS OF THE YAKUTS AND THE RUSSIANS.

AIM: Studying features of clinical-functional manifestations of chronic obstructive lung disease in the combination with metabolic syndrome in the Yakut ethnic group. MATERIALS AND METHODS: The basic group consisted of 39 patients of Yakut nationality with chronic obstructive lung disease (COLD) in the combination with metabolic syndrome (MS), middle age of them being 53.4 ± 1.17 years. The comparison group comprised 40 patients of Russian nationality with COLD and MS with middle age 53.1 ± 1.21 years. Features of clinical manifestations and respiratory functions are studied. RESULTS: Cough and sputum were noted in dynamics for 3 years by 64.1% of Yakut patients and 85% of the Russians, p = 0.033; the intensity of cough was marked at 30% of patients of Russian nationality and 15.4% of patients of the Yakut nationality, p = 0.01 6. The morning sputum and daily sputum within 3 months a year at the Russians in comparison with the Yakuts was marked in 95 % vs 74,4 %, p = 0.011; 80.0% vs 56.4% p = 0.024, accordingly. According to Medical Research Council (mMRC) Dyspnea Scale (Mahler et al., 1985) dyspnea has been 2.2 ± 0.09 points atthe Yakuts vs 2.7 ± 0.09 points at Russian, p = 0.002. At patients of the Yakut nationality more often exacerbations were registered 2 times a year (53.8%), at patients of Russian nationality noted 3 times a year (55%). Respiratory function manifestations have been at patients of the Yakut nationality with COLD and MS, in comparison with similar Russian patients: forced expiratory volume for a first second (FEV,) - 64,0+2,30 % vs 56,8?2,69 %, p = 0,026; forced vital capacity of lungs (FVC) - 65,0?2,45 vs 65,0?3,70, p = 0.733; FEV1/FVCL ratio being 102.5 ± 2.81 vs 87.3 ± 3.30, p = 0.000, accordingly. CONCLUSIONS: Regardless of ethnicity the phenotype "D" has higher prevalence rate of clinical phenotype COLD in the combination with metabolic syndrome, thus at the Russians the clinical COLD is characterized by severe clinical manifestations in comparison with theYakuts, and also in both ethnic groups expiratory dysfunctions in the form of decreasing FEV1, decreasing FVC and increases of ratio FEV1/FVC > 70% are marked.

[Medical and Dosimetric Register of the Siberian Group of Chemical Enterprises Personnel--the Basis for the Evaluation of Chronic, Radiation Exposure Effects].

The characteristic of medical and dosimetric register database of Siberian Group of Chemical Enterprises personnel is represented. This characteristic includes the description of the database structure, main sources of information, quantitative composition of the cohort under study, methods of evaluation of the external and internal irradiation doses, modern data on cancer incidence and reasons of death. The database is the basis for estimating the risk of the cancer and non-cancer effects after a long-term radiation exposure and dependence of "dose-response" at different levels: from population and group to cell and molecular. Now the database of register contains the information about more than 66,500 employees at the Siberian Group of Chemical Enterprises, about 22,000 of whom were exposed to external irradiation and more than 7500 employees--to internal irradiation. The register is the information resource of a large biological material bank. Using this bank, the research of chronic radiation exposure genetic effects and markers of individual radio sensitivity is performed.

[Manifestations of polymorphism of ß1-adrenoreceptors in patients with newly diagnosed cardiac rhythm disorders].

Individual peculiarities of the receptor apparatus of cardiomyocytes may determine pathological features of heart activity and susceptibility to pharmaceuticals. The possible role of beta-adrenoreceptor polymorphism in the development of cardiac rhythm disturbances is assessed by PCR. Special attention is given to A145G polymorphism of the ADRB1 gene in 127 patients with primary cardiac rhythm disorders. It was shown that AJ45G polymorphism (Ser49Gly) at DNA sites encoding for the amino acid sequence of beta-1 adrenoreceptors can influence the development of sex-specific cardiac rhythm disorders.

[Tertiary syphilis of the pancreas and liver in 82-year-old patient: case study].

It has been described a clinical case of late diagnosis of syphilis of the pancreas and liver of elderly patients. Two years before that it was wrongly diagnosed with cancer of the pancreas with liver metastases, and the patient was operated on with the imposition of cholecystostomy. It was conducted appropriate therapy and reconstructive surgery after verification of the diagnosis of syphilis of the pancreas and liver.