[Assessment of systemic inflammation activity, myocardial structure and functional features, their relationship in patients with multiple myeloma, receiving bortezomib therapy].

AIM: To study the dynamics of calculated indices [neutrophil-lymphocyte ratio (NLR); systemic inflammation index (SIV)] and biomarkers of systemic inflammation [interleukin-1ß (IL-1ß); high-sensitivity C-reactive protein (hsCRP)], parameters of the structure-and-function state of the myocardium and intracardiac hemodynamics, and their relationship in patients newly diagnosed with multiple myeloma (MM) at the onset of the disease and after 6 courses of chemotherapy (CT) containing the proteasome inhibitor bortezomib. MATERIAL AND METHODS: This prospective study included 30 patients aged 63.8±10.0 years diagnosed with MM; 17 (56.7 %) of them were men. The following tests were performed for all patients: measurement of IL-1ß and hsCRP, calculation of the inflammation indexes NLR and SIV, transthoracic echocardiography before and after 6 courses of bortezomib-containing CT. At the time of study completion, 9 patients dropped out due to reasons not related to cardiovascular complications of CT. RESULTS: The antitumor therapy was associated with increases of immune-inflammation indexes: NLR increased from 1.54 [1.02; 1.83] to 2.9 [1.9; 4.35] (p=0.009) and SIV increased from 402.95 [230.5; 534.0] to 1102.2 [453.1; 1307.9] (р=0.014). IL-1ß increased from 5.15 [4.05; 5.77] to 6.22 [5.66; 6.52] pg/ml remaining within the reference range (p=0.142) whereas hsCRP decreased from 1.02 [0.02; 2.71] to 0.02 [0.02; 0.82] IU/l (p=0.138). Statistically significant changes in parameters of heart remodeling and clinical picture of cardiovascular complications were not observed. A correlation analysis showed significant inverse correlations of hsCRP with left ventricular ejection fraction (LV EF) (r= -0.557; p=0.003), the number of plasma cells (PC) with LV EF (r= -0.443; p=0.023), and a direct correlation of the number of PC with hsCRP (r=0.433; p=0.022). CONCLUSION: During the study, the accepted criteria for cardiotoxicity of bortezomib-containing chemotherapy in patients with MM, were not met. The identified correlations between the level of markers for acute inflammation, indexes of intracardiac hemodynamics, and the immediate MM substrate may indicate the role of chronic low-intensity inflammation in the pathogenesis of myocardial remodeling in patients with MM. This necessitates further studies on larger samples of patients to assess the prognostic significance.

Chronic, acute and protocol-dependent effects of exercise on psycho-physiological health during long-term isolation and confinement.

Exercise could prevent physical and psychological deteriorations, especially during pandemic times of lock-down scenarios and social isolation. But to meet both, the common exercise protocols require optimization based on holistic investigations and with respect to underlying processes. This study aimed to explore individual chronic and acute effects of continuous and interval running exercise on physical and cognitive performance, mood, and affect and underlying neurophysiological factors during a terrestrial simulated space mission. Six volunteers (three females) were isolated for 120 days. Accompanying exercise training consisted of a continuous and interval running protocol in a cross-over design. Incremental stage tests on a treadmill were done frequently to test physical performance. Actigraphy was used to monitor physical activity level. Cognitive performance, mood (MoodMeter®), affect (PANAS), brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), vascular-endothelial growth factor (VEGF), and saliva cortisol were investigated prior to, four times during, and after isolation, pre- and post-exercise on two separate days, respectively. As a chronic effect, physical performance increased (and IGF-1 tended) in the course of isolation and training until the end of isolation. Subjective mood and affect state, as well as cognitive performance, basal BDNF and VEGF levels, were well-preserved across the intervention. No acute effects of exercise were detected, besides slower reaction time after exercise in two out of nine cognitive tests, testing sensorimotor speed and memory of complex figures. Consistently higher basal IGF-1 concentrations and faster reaction time in the psychomotor vigilance test were found for the continuous compared to the interval running protocol. The results suggest that 120 days of isolation and confinement can be undergone without cognitive and mental deteriorations. Regular, individual aerobic running training supporting physical fitness is hypothesized to play an important role in this regard. Continuous running exercise seems to trigger higher IGF-1 levels and vigilance compared to interval running. Systematic and prolonged investigations and larger sample size are required to follow up on exercise-protocol specific differences in order to optimize the exercise intervention for long-term psycho-physiological health and well-being.

[Influence of N-alkynylaminosteroids on mitochondria function and autophagy in glioma cells]. / Vliianie N-alkinilaminosteroidov na funktsionirovanie mitokhondrii i protsessy autofagii v kletkakh gliomy.

In this work we examined the synthesized N-alkynyl-17-aminosteroids and N-alkynyl-20-aminosteroids (based on dehydroepiandrosterone and pregnenolone, respectively) for their effect on C6 rat glioma cell functions. At 10 µM, the compounds had an insignificant effect on C6 glioma mitochondrial membrane potential, but increased cell autophagy by 70-90%, comparable to the known autophagy inducer dexamethasone. Docking simulations predict a potential high-affinity interaction between N-alkynylaminosteroids and Keap1 and the Hedgehog pathway protein, Smoothened, which are involved in autophagy regulation. The possible mechanisms of observed processes are discussed.

[Endovascular treatment of women with pelvic varicose veins due to post-thrombotic iliac vein lesion]. / Éndovaskuliarnoe lechenie patsientok s varikoznoi bolezn'iu taza, obuslovlennoi posttromboticheskim porazheniem podvzdoshnykh ven.

BACKGROUND: Post-thrombotic iliac vein lesion is one of the causes of secondary pelvic varicose veins (PVV) in women. Endovascular treatment of this cohort of patients requires further studies. AIM: The study was undertaken to investigate the aspects of endovascular treatment of female patients diagnosed as having PVV secondary to post-thrombotic alterations of the iliac veins. PATIENTS AND METHODS: Presented herein are the results of diagnosis and treatment of nine women suffering from PVV in obstructive lesion of the iliac veins. All patients underwent phlebography with stenting of the iliac veins, followed by clinical and instrumental assessment of efficacy of treatment. RESULTS: The technical success rate of stenting amounted to 100%. In the early postoperative period thrombotic complications developed in two women and in the remote period in one. The operation was followed by a decrease in the intensity of PVV manifestations, as well as chronic venous insufficiency of the lower limbs, which was confirmed by clinical and instrumental methods of objectification and visualization. The composite index of quality of life was noted to decrease from 47±5.3 to 27.8±3.3 points (p<0.05). The median of the composite value of the Pelvic Venous Clinical Severity Score decreased by 8.6±1.8 points (p<0.05). The average value of the composite index of the Venous Clinical Severity Score (VCSS) diminished by 6.8±1.4 points (p<0.05) and that of the Villalta score by 8.3±1.6 points (p<0.05). CONCLUSION: Pelvic varicose veins appear to develop in two of three women after endured thrombosis. The experience with stenting of the iliac veins demonstrated good efficacy and safety. Efficiency of the intervention was determined by improved quality of life of the patients and positive dynamics of the clinical course of the disease.

[Method of determining disease severity in women with pelvic varicose veins]. / Sposob opredeleniia tiazhesti zabolevaniia u patsientok s varikoznoi bolezn'iu taza.

BACKGROUND: Using assessment scales in clinical and research practice is one of fundamental reference methods of evaluation in human pathological states. Pelvic vein varicosity is an independent nosological entity within the framework of chronic vein diseases. Currently, the clinical methods of assessment in the aspect of a patient-oriented approach in this type of disease are largely understudied and still not duly defined. AIM: The study was aimed at analyzing clinical outcomes of surgical treatment in the form of resection of the ovarian vein in female patients with pelvic varicose veins, based on the developed specialized scale of clinical assessment of disease severity. PATIENTS AND METHODS: We carried out an open prospective study of efficacy of resection of the ovarian vein in 37 women with pelvic varicose veins. The main criterion for assessment was a clinical method of determining manifestations of the disease by means of the Pelvic Venous Clinical Severity Score. RESULTS: According to the Pelvic Venous Clinical Severity Score, improvement of the condition was observed in 36 (97.3%) operated female patients and 1 (2.7%) woman turned out to have negative dynamics. The median of the composite score of the severity scale decreased form 11.78±5.06 points to 5.22±3.19 (p<0.05). The total positive gradient of the score amounted to 6.57±3 .65 points. A significant decrease in manifestations of severity was observed for 9 of the 10 clinical descriptors of the disease. CONCLUSION: The use of the suggested scale in practical assessment of the results made it possible to prove high efficacy of resection of the ovarian vein in women with pelvic varicose veins in the form of decreased intensity of the disease's symptomatology. The VCSS is an easy-to-fill-in tool, taking up little time, ensuring no influence of the physician's personality on the answers, presenting quantitative expression of therapeutic results.

[Ultrasonographic examination of major veins of lower limbs and pelvic veins in pregnant women]. / Ul'trazvukovoe issledovanie magistral'nykh ven nizhnikh konechnostei i ven taza u beremennykh zhenshchin.

The problem of chronic venous insufficiency in women during pregnancy is of current concern. A total of 115 pregnant women in the first, second and third trimesters of gestation were examined in a stage-wise manner. During the first stage we conducted a comprehensive clinical study with the obligatory consultation by the obstetrician-gynaecologist. At the second stage, all women were subjected to ultrasonographic examination of the venous system of both lower extremities and the small pelvis. Studying the diameters of the deep veins of the right and left lower limbs, as well as the paired veins of the small pelvis demonstrated no statistically significant differences, which made it possible to evaluate these parameters as a whole. In all pregnant women, the lumen of the examined vessels was uniform, with the veins being patent, compliant, stained on colour Doppler mapping. Respiration-synchronized, phasic blood flow was registered. In the course of the study it was revealed that the diameter of the veins of the lower limbs and small pelvis increased as gestation proceeded. The findings of ultrasonographic angioscanning showed that by the third trimester of pregnancy the diameter of the femoral vein was 1.5-fold larger and that of the popliteal vein was 1.4-fold larger. The diameter of the veins of the pampiniform plexus of the ovaries during gestation was noted to have increased 1.13-fold. This was accompanied and followed by deterioration of tonic-and-elastic properties of the venous wall and the development by the third trimester of valvular insufficiency with the emergence of venous congestion. Seventeen (16%) women were found to have varicose syndrome. The above mentioned alterations of venous haemodynamics appeared to lead to impairment of blood flow in the affected veins and to the emergence of thrombogenic zones in the valvular sinuses. Of the 115 women examined, 77 (67%) were found to have degree 1 sludge and 36 (31.3%) had degree 2 sludge, with the D-dimer level in these women having increased to 773.3±37.5 ng/ml. Degree 3 sludge was observed in 2 (1.7%) women previously operated on for acute venous thrombosis. Their D-dimer level amounted to 954.3±43.2 ng/ml. It was demonstrated that studying the valvular sinuses for detection of sludge during examination of pregnant women allowed obstetricians-gynaecologists and physicians of ultrasonographic diagnosis to form risk groups for the development of deep vein thrombosis and to timely take appropriate measures aimed at prevention of the pathology concerned.

[The application of the 'Biometriclal Dactylography 17.0' program complex for the digital interpretation of the finger dermatoglyphic features]. / Programmnyi kompleks 'Biometrical Dactylography 17.0' dlia tsifrovoi interpretatsii priznakov dermatoglifiki pal'tsev.

The objective of the present study was the development of the computer software for the scale-free interpretation of the finger dermatoglyphic features needed for the objective comprehensive evaluation of their principal characteristics in the digital terms. We have elaborated the program complex making it possible to address the following problems: thr formulation of the database of electronic copies of the finger print and toe print images in the family groups, the display of the finger print and toe print images on the screen, marking the points and lines for automated readout of digital angular and metric information or automated calculation of relative values, the formulation of the database of digital information about the papillary patterns on the fingers and toes in the family triplets (farther + mother + child) and its import into an Excel file.

Genetic Differentiation of the Steppe Field Mouse Sylvaemus witherbyi Populations: The Results of the Mitochondrial DNA Control Region Analysis.

The degree of genetic diversity of the steppe field mouse was estimated on the basis of the mtDNA control region variability data. Polymorphism of this mtDNA marker in S. witherbyi was more pronounced than previously assumed. The steppe field mouse population from the northern shore of Lake Manych-Gudilo includes several mitochondrial lines, which may be due to the existence of several migration flows to this area from Southwest Asia.

Memorization of Sequences of Movements of the Right or the Left Hand by Right- and Left-Handers: Vector Coding.

In order to test the hypothesis of hemisphere specialization for different types of information coding (the right hemisphere, for positional coding; the left one, for vector coding), we analyzed the errors of right and left-handers during a task involving the memorization of sequences of movements by the left or the right hand, which activates vector coding by changing the order of movements in memorized sequences. The task was first performed by the right or the left hand, then by the opposite hand. It was found that both'right- and left-handers use the information about the previous movements of the dominant hand, but not of the non-dom" inant one. After changing the hand, right-handers use the information about previous movements of the second hand, while left-handers do not. We compared our results with the data of previous experiments, in which positional coding was activated, and concluded that both right- and left-handers use vector coding for memorizing the sequences of their dominant hands and positional coding for memorizing the sequences of non-dominant hand. No similar patterns of errors were found between right- and left-handers after changing the hand, which suggests that in right- and left-handersthe skills are transferred in different ways depending on the type of coding.

[The point-digital interpretation and the choice of the dermatoglyphic patterns on human fingers for diagnostics of consanguineous relationship]. / Tochechno-tsifrovaya interpretatsiya i vybor priznakov dermatoglifiki pal'tsev dlya diagnostiki krovnogo rodstva.

The objective of the present study was the development of the point-digital model for the scaless interpretation of the dermatoglyphic papillary patterns on human fingers that would allow to comprehensively describe, in digital terms, the main characteristics of the traits and perform the quantitative assessment of the frequency of their inheritance. A specially developed computer program, D.glyphic. 7-14 was used to mark the dermatoglyphic patterns on the fingerprints obtained from 30 familial triplets (father + mother + child).The values of all the studied traits for kinship diagnostics were found by calculating the ratios of the sums of differences between the traits in the parent-parent pairs to those in the respective parent-child pairs. The algorithms for the point marking of the traits and reading out the digital information about them have been developed. The traditional dermatoglyphic patterns were selected and the novel ones applied for the use in the framework of the point-digital model for the interpretation of the for diagnostics of consanguineous relationship. The present experimental study has demonstrated the high level of inheritance of the selected traits and the possibility to develop the algorithms and computation techniques for the calculation of consanguineous relationship coefficients based on these traits.

[On the orientation of palmar whorl patterns]. / Ob orientatsii zavitkovykh uzorov ladoni.

The objective of the present work was to study the palmar whorl patterns for the inclusion them in the scope of dermatoglyphic signs along with the arc and loop patterns having a well apparent structural organization. For the first time in the history of domestic dermatoglyphic studies, we described the structure of palmar whorl patterns (based on the palmar prints obtained from 555 subjects) with respect to the surrounding tri-radii. Moreover, the role of their radiants in the formation of node orientation was considered. The analysis of the variants of palmar whorl patterns encountered in the study sample provided a basis for the elaboration of the rule for determining their orientation. Specifically, the orientation of the palmar whorl patterns can be found from the direction of the embracing radiants as in the loop or complex patterns.

Electromyographic evaluation of countermeasures during the terrestrial simulation of interplanetary spaceflight in Mars500 project.

The efficiency of six countermeasures (CM) for muscle atrophy was compared over 520 days of confinement during the terrestrial simulation of round space flight to Mars using surface electromyography (sEMG). Three of CM were cyclic exercises (a motor-driven and leg-driven treadmill, cycle ergometer), resistive exercises (the multifunctional dynamometer for space-MDS, and expanders), and vibration platform. Each of CM was applied for each crew member (n=6) once over the experiment, for 70 days in a row, in prescribed order. sEMG was collected during the "force step test" in which the subject voluntarily produced pressure by lower limb, with minimal force increment. The mean frequency (MNF) and average amplitude of sEMG were analyzed. The MNF of sEMG decreased from 104.3±4.2 to 95.3±2.9Hz (P<0.05) in the soleus muscle after 70 days of exercising on the leg-driven treadmill and after 35 days-on vibration platform. It can be caused by earlier (10-250ms) recruitment of the soleus in respect with the medial gastronemius on the leg-driven treadmill, while on the motor-driven treadmill synergists activated synchronously. In other lower leg muscles, MNF decreased from 180 to 200 to 165-180Hz after 70 days of resistive exercises on the MDS device. CM caused no effect on sEMG amplitude. In conclusion, (1) the leg-driven treadmill, the MDS and vibration platform significantly depressed MNF of sEMG of lower extremity muscles; (2) the leg-driven treadmill and vibration platform specifically affected the soleus muscle. Therefore, these CM can be recommended for a more extensive use on ISS board.

[Comparative Analisys of Efficacy of Countermeasure Provided by Different Modes of Locomotor Training in Space Flight.]

According to the results of the experiment performed on the ISS with participation of 15 Russian cosmonauts was fulfilled the comparative analysis of two models of preventive measures used by the Russian members of the long term space flight: the intense interval training in the aerobic-anaerobic zone power (recommended model) and the continuous low-intensity exercise in the aerobic zone energy power of the muscle activity. The interval trainings in the conditions of the space flight have provided the maintenance of the level of physical performance close to the preflight level; characterized by the maximum running speed, physiological value of work and lactate level after a standard load. The putative mechanisms of counteraction to adaptive remodeling of the propulsion system in zero gravity and enhanced understanding of the laws governing the interaction of the human body with the gravitational field of the Earth are described in the paper. The research results presented in the article show the high preventive efficacy of interval training compared with regular aerobic trainings, what is very important now in the time of searching of the means and methods of prevention of hypogravitation alterations during the interplanetary missions.

EFFECTIVENESS OF DIFFERENT TRAINING PROGRAMS FOR PHYSICAL PERFORMANCE MAINTENANCE IN THE CONDITION OF LOW MOTOR ACTIVITY.

Investigations made by the World Health Organization showed that lack. of physical activity and sedentary lifestyle are among ten major causes for death and disability. Typially, studies of the negative effects of reduced physical activity and their prevention face difficulties of providing standard conditions. These issues were obviated successfully in experiment MARS-500 on simulation of a space exploration mission. Human subjects were 6 men from Russia, France, Italy and China who spent 520 days in isolation. To prevent the negative effects of low physical activity, the volunteers performed resistive and cyclic exercises in different periods of isolation. The study was designed with two pauses in the training program. Physical performance was evaluated with an incremental loading test, maximal voluntary effort test (Russian-Austrian MDS resistive exercise system), and PWC-170 (bicycle ergometer). Level of physical performance of the subjects in this experiment never degraded to below baseline values. The proposed training system comprising different kinds of exercise ensured stability or improvement of subjects' physical performance as compared with baseline level.

LOCOMOTION STRATEGIES AND INTENSITY OF SUPPORT REACTIONS AS AN APPROACH TO INDIVIDUALIZATION OF COUNTERMEASURES AGAINST THE NEGATIVE EFFECTS OF MICROGRAVITY.

A search for optimal methods of planning cosmonaut's training is currently guided by the concept of the leading role of support afferentation in hypogravity-induced changes of locomotion. Support afferentation is dependent on the strength of support reactions (SR); in this connection, the investigation was aimed at analysis of the vertical component of maximal SR at identical speeds of different types of locomotion on motorized and nonmotorized treadmill in I g and micro-g. Minimal vertical components of maximal SR were, measured during walk on the motorized treadmill. Maximal vertical components of maximal SR were measured during run on the nonmotorized treadmill. This was observed regularly on ISS treadmill BD-2 outfitted with vibroisolation and a special training suit to produce axial loading. On the ground, the relationship was less regular. Considerable differences of individual locomotion strategies and maximal SR values imply that SR is a factor that must be taken into account when planning individual training programs for rnosmonaut on long-duration missions.

Russian Countermeasure Systems for Adverse Effects of Microgravity on Long-Duration ISS Flights.

INTRODUCTION: The system of countermeasures for the adverse effects of microgravity developed in the USSR supported the successful implementation of long-duration spaceflight (LDS) programs on the Salyut and Mir orbital stations and was subsequently adapted for flights on the International Space Station (ISS). From 2000 through 2010, crews completed 26 ISS flight increments ranging in duration from 140 to 216 d, with the participation of 27 Russian cosmonauts. These flights have made it possible to more precisely determine a crew-member's level of conditioning, better assess the advantages and disadvantages of training processes, and determine prospects for future developments.

The impact of long-term confinement and exercise on central and peripheral stress markers.

Long-term isolation has been reported to have impact on psycho-physiological performance in humans. As part of the 520 days isolation study (MARS500, n=6) from June 3rd 2010 to November 4th 2011, this study aimed to show that stress caused by isolation and confinement is mirrored in cortical activity and cortisol levels and that exercise is a valid countermeasure. Cortical activity was measured by electroencephalography (EEG) pre- and post-moderate exercise every two weeks, salivary cortisol was taken every 60 days. Data show a decrease of global cortical activity, in both alpha- and beta-activity (p<.05-p<.001), and an increase of salivary cortisol (p<.05-p<.001), during the isolation, indicating that isolation acts as a chronic stressor with impact on cortical activity and cortisol levels. Moderate exercise leads to an increase (p<.01) in cortical activity. Therefore, during long-term space missions the factor isolation must be kept in mind as the reduction of cortical activity and the heightened stress level could impair performance. However moderate exercise might be able to counteract this impairment.

[Urine protein profile in healthy people following locomotor loading with changing intensity].

The paper analyzes data on how physical exercise as a standard test of cosmonaut's performance, affects the renal function and urine protein profile. The investication involved 10 normal human subjects. Following exercise, rate of renal excretion of proteins increased. The occurrence of 4 proteins out of 9 in urine did not alter and of 2 (alpha-methylacyl coenzyme A racemase and cubilin) increased; occurrence of 3 proteins (kallikrein-1, osteopontin and vitamin K-dependent protein Z) decreased. Out of 24 proteins with molecular weights higher than albumin, 7 were detected in urine after exercise more frequently, 6 with same frequency as before the test and none less frequently which demonstrates lowered selectivity of the glomerular barrier during exercise.

Y-box binding protein 1 (YB-1) promotes detection of DNA bulky lesions by XPC-HR23B factor.

The nucleotide excision repair system (NER) is one of the main mechanisms protecting cellular DNA from lesions caused by such significant environmental factors as UV radiation, the influence of polycyclic aromatic hydrocarbons, and medical treatment by several antitumor drugs, e.g. cisplatin. One of the major NER components is XPC-HR23B, the key factor during the damage recognition step of repair. Binding of XPC-HR23B to DNA that contains different bulky lesions impairing the structure of DNA is the basis for the wide substrate specificity of this DNA repair pathway. The multifunctional protein YB-1 among other protein factors has high affinity towards damaged DNA. Involvement of YB-1 in the cellular response to genotoxic stress and its ability to interact with damaged DNA harboring lesions of various origins pinpoint its putative involvement as a modulatory factor in DNA damage recognition and verification steps of NER. In the present work, we assayed functional interactions of protein factors XPC-HR23B and YB-1 upon binding to DNA structures mimicking damaged DNA containing single bulky lesions, as substrates of NER, and bulky lesions combined with abasic sites as an example of clustered lesions. The results indicate that YB-1 and XPC-HR23B stimulate each other in binding to DNA containing a bulky or clustered lesion, which suggests the involvement of YB-1 in the regulation of DNA repair by the NER mechanism.

Phylogenetic relationships of intraspecific forms of the house mouse Mus musculus: Analysis of variability of the control region (D-loop) of mitochondrial DNA.

Analysis of the control region of mitochondrial DNA (mtDNA) or D-loop of 96 house mice (Mus musculus) from Russia, Moldova, Armenia, Azerbaijan, Kazakhstan, and Turkmenistan has been used to reconstruct the phylogenetic relationships and phylogeographic patterns of intraspecific forms. New data on the phylogenetic structure of the house mouse are presented. Three phylogroups can be reliably distinguished in the eastern part of the M. musculus species range, the first one mainly comprising the haplotypes of mice from Transcaucasia (Armenia); the second one, the haplotypes of mice from Kazakhstan; and the third one, the haplotypes of mice from Siberia and some other regions. The morphological subspecies M. m. wagneri and M. m. gansuensis have proved to be genetically heterogeneous and did not form discrete phylogroups in the phylogenetic tree.