Translational Medicine
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Background. Gene TTN associated with all types of cardiomyopathy, however its large size (294 b.p.) warrants a lot of individual unique genetic variants or variants with low frequency, that aggravates their interpretation. Besides that nowadays there is no data about spectrum of variants in this gene in healthy Russian population. Recognition frequency and spectrum of variants in gene TTN in healthy Russian population will allow us to use it for interpretation results of molecular genetic research for patients with different heart pathology, and define prognosis for different heart diseases.Objective. Recognize frequency and spectrum of single nucleotide and truncating variants in gene TTN in healthy Russian population and compare it with international data bases, and evaluate level of pathogenicity these variants and their distributing across titin structure.Design and methods. 192 men in age 55,8±6,6 years were tested with next-generation sequencing. Identified genetic variants were confirmed by Sanger sequencing. Results. Allele missense variant frequency (with frequency less than 0.1%) in TTN in healthy Russian population amount to 15.1 %, and truncating variants — 0.52 %. 37,9 % of them were variants of unknown significance, 62 % — likely-benign and 0.1 % — benign. There was no pathological and likely-pathological variants. Identified genetic variants distributed throughout the titin structure.Conclusion. Received result is congruent с international data bases and researches. Expended laboratory method (Next generation sequencing and confirmation with Sanger sequencing) can be used both in clinical practice, and in creating data bases of genetic variants in healthy Russian population.

Background. Biodegradable polymers are one of the most promising groups of materials suitable for creating tissue-engineered scaffolds. The high interest in biopolymers is associated with the possibility of creating scaffolds with desired properties, through the use of mixtures and copolymers. The determination of the key parameters of biocompatibility is the basic purpose for testing created materials.Objective. To perform the comparative in vitro study of biocompatibility properties of biopolymer scaffolds produced using polycaprolactone, polylactic acid, their mixtures and copolymers by electrospinning technology.Design and methods. The adhesion properties and cytotoxicity of scaffolds made from polycaprolactone, polylactic acid, copolymer of L- and D-isoforms of lactic acid, their mixtures and co-polymers with the addition of polyglycolic acid were investigated after scaffolds co-cultivation with human mesenchyme stem cells (MSC).Results. The largest number of spread spindle-shaped MSCs was on the surface of polymers containing polyglycolic acid. Besides, the cells on the surface of the copolymer with polyglycolic acid had the morphology closest to the control. The lowest number of living cells was found on the surface of polylactic acid scaffolds, and the highest on the surface of samples from of polycaprolactone and polylactic acid blend.Conclusion. Thus, all tested polymers had good adhesion properties in experiments with human mesenchyme stem cells were possessed by biodegradable polymers with the addition of polyglycolic acid. 

In transplantation, there has always been an acute problem of the discrepancy between the number of donor organs and the number of recipients, including donor hearts. There are various ways to increase the pool of donor organs, one of them is the use of asystolic or non-heart-beating donors. Due to poor myocardial tolerance of ischemia during the asystole period, as well as because of the difficulties in diagnosing cardiac diseases of the asystolic donor, which can be contraindication to transplantation. Therefore, an in-depth study of the state of the myocardium in asystolic donors is required. Currently, there is no generally accepted protocol for working with asystolic heart donors. This protocol should include methods of heart conditioning and assessing of myocardium state. For its development we need more experimental and preclinical studies. A protocol for such a study is proposed. The modeling of an asystolic donor using rats is described on the basis of experimental work carried out by a team of authors. The article describes the following technical aspects: anesthetic guidance, asystole detection criterion, maintaining the rat body temperature in accordance with the human body temperature during cardiac arrest, surgical aspects of performing the main experimental model. The Langendorff model of isolated cardiac perfusion was chosen as the main model for assessing the state of the myocardium of a small laboratory animal. Intra-left ventricular pressure, volume of coronary blood flow, heart rate and the presence of post-reperfusion arrhythmias were selected as criteria for assessing the state of donor hearts. Assessment of the volume of damage to the donor heart is carried out using triphenyltetrazolium chloride staining of the donor organ. 

Background. Application of a biomarker panel during the acute period of the ischemic stroke (IS) can contribute to a more accurate and prompter diagnostics and verification of the optimal approach to a patients’ management.Objective. We aimed to clarify values of neuron-specific enolase (NSE), glial fibrillar acidic protein (GFAP) and antibodies for NMDA receptor’s NR2-subunit (NR2-antibodies) in the acute period of IS, to compare with such values in patients without IS, to assess their relationship with severity of neurological deficit and short-term outcome and also to establish sensitivity and specificity of the biomarker panel.Design and methods. 63 patients with IS and 31 people (11 with chronic brain ischemia and 20 healthy individuals) as controls were included. Results. NSE and GFAP values in IS group exceeded reference values at the onset of disease, lowering significally by 10-14 day, while NR2-antibodies’ values were lower at the onset of the disease compared with controls, rising by 10-14 day. In patients with unfavourable short-term outcome higher levels of NSE, GFAP and NR2-antibodies were found. A panel of such biomarkers has higher sensitivity and specificity than each of them individually.Conclusion. Researched substances can be used in a biomarker panel for IS diagnostics, brain damage monitoring, patient’s condition evaluation and short outcome prognosing.

Background. The basis of pre-surgical neurophysiological examinations of patients with pharmaco-resistant structural epilepsy is the method of monitoring bioelectrical activity of the brain, video-electroencephalographic monitoring and, if indicated, long-term invasive monitoring.Objective. The goal of the study is to estimate the diagnostic efficacy of the methods used for monitoring of the brain bioelectric activity on the basis of longterm results of surgical treatment of patients with temporal structural pharmaco-resistant epilepsy.Design and methods. The study included 61 patients with temporal lobe pharmaco-resistant epilepsy, who were divided into two groups: performance of video-EEG monitoring only (33 patients) and the additional use of invasive monitoring for the localization of the epileptogenic zone (28 patients). Each group was divided into subgroups depending on the outcome of surgical treatment: patients, in whom seizures ceased (Engel 1) and patients in whom seizures persisted to some degree (Engel 2-3-4). Invasive monitoring with ictal event recording was chosen as the reference method to calculate diagnostic efficacy.Results. Invasive monitoring was performed as part of the pre-surgical evaluation of patients with temporal lobe pharmaco-resistant epilepsy with a higher sensitivity (72.7 %) and accuracy (82.4 %) than video-EEG monitoring (sensitivity 50 %, accuracy 45.9 %).Conclusion. In simple monofocal variants of structural epilepsy, video-EEG monitoring has a sufficient level of diagnostic efficiency. The phenomenon of neurophysiological phenotypes convergence is responsible for the reduced diagnostic efficacy of noninvasive and invasive monitoring.

Background: The relevance of the work lies in the search for new hemocontact drugs with hemocompatibility and a pronounced activation effect on the cellular and humoral blood systems for their possible use in clinical practice during low-volume hemoperfusion.The aim of this work was to assess the activation capabilities of three granular hemosorbents by the rate of adhesion of blood cellular elements to the surface of granules in vitro.Materials and methods. When using the method of low-volume hemoperfusion (LVH) in the clinic it is important to take into account the activation properties of solid-phase granular drugs. Blood-contact interaction was carried out in bench conditions with the use of donated blood in rotary mode. Blood samples were taken before the experiment and after 5, 20, 40 and 60 minutes. Changes in blood cell and subcellular populations were evaluated using the Sysmex XT 1800i hematological analyzer (26 parameters), which made it possible to indirectly judge the activation of blood cells. 30 experiments were conducted. To analyze the activation functions of the hemocontact preparations the speed-time adhesive profile of blood cells on the sorbent was used.Results. The effect of using the preparations Silochrome S-120 and SPS in comparison with SСT-6A HP as contact hemoactivators can be more pronounced, since the activation potential of these sorbents for blood cells is much higher. Silochrome S-120 has the highest activation capabilities compared to SPS and SKT-6A HP.Conclusion. Adhesion rate indicators can be indicators of the activation of blood cells upon contact with foreign surfaces and serve as a criterion for assessing the activation capabilities of these surfaces when using the LVH method in the clinic.

Background. Spastic diplegia (Little’s disease) is the most common form of infantile cerebral palsy (ICP), leading to persistent motor and functional impairments. One promising area of rehabilitation is a combination of physical therapy with methods of stimulation of various parts of the nervous system, among which functional electrical stimulation of muscles and nerves is the most prominent.Objective. To study structural changes of cerebral white matter conduction pathways in patients with spastic diplegia after translingual neurostimulation using magnetic resonance tractography.Materials and Methods. An open single center-controlled study was conducted. A total of 18 children were examined. All patients underwent comprehensive MRI in two time points, before and after a course of translingual neurostimulation, on a tomograph with magnetic field induction 3.0 Tesla, which included a traditional protocol in 3 mutually perpendicular planes), and diffusion-weighted imaging — DWI (Diffusion-Weight Imaging).Results. All patients after neurostimulation showed clinical improvement of movement coordination and decrease of muscle tone with formation of new motor skills, improvement of limb motor function. Statistically significant decrease of spasticity index was revealed up to 17% for arms and 23% for legs, improvement of motor skills on all three scales.Conclusion. Translingual neurostimulation allows to affect all components of motor activity, as a result of which neuroplasticity processes are activated and the brain of patients with spastic diplegia becomes more receptive to motor rehabilitation aimed at restoration of motor control and formation of new motor skills.

Background. Most complications of vascular access for hemodialysis require surgical treatment and if ineffective lead to fistula loss and depletion of the vascular resource for the new fistula creation.Objective. To identify complications of permanent vascular access for hemodialysis which require surgical treatment and evaluate its results using duplex scanning.Design and methods. Ultrasonography, clinical and laboratory examinations were performed in 550 patients undergoing hemodialysis.Results. Complications of vascular access for hemodialysis were detected in 154 (28.0 %) patients, surgical treatment was performed in 96 (62.3 %) patients. The main indications for surgical treatment were: significant stenosis, occlusive thrombosis, non-occlusive thrombosis in combination with significant vein stenosis, aneurysm with increased access flow, ischemic steal syndrome of the hand and pulsating hematoma. The analysis of surgical interventions showed that the creation of a new access was more often performed (41.7 %) compared to other types of fistula reconstructions which leads to a decrease in the number of vessels in the upper extremities that can be used to create access in the future.Conclusion. Duplex ultrasound allows diagnosing vascular access for hemodialysis complications and evaluating the results of their surgical treatment.

Background. The processes of inflammation and repair in the area of myocardial infarction (MI) are carried out and regulated by various populations of immune cells, including monocytes, lymphocytes, and NK-cells. The success of myocardial recovery after infarction and the risk of developing acute heart failure (AHF) depend on their adequate interaction. The presence of type 2 diabetes mellitus (T2DM), in which chronic low-gradient inflammation occurs, can affect the monocytic and lymphocytic response in MI, which may contribute to the development of AHF.Objective. to assess the features of monocytic and lymphocytic responses in patients with MI T2DM complicated by the development of AHF.Design and methods. The study included 121 patients with MI T2DM (38 of them with AHF). The control group included 59 patients without diabetes mellitus (including 13 patients with AHF). For all patients within 1 day, on days 3, 5 and 12 of MI, the total number of monocytes and lymphocytes, the monocytes-to-lymphocytes ratio (MLR), subpopulations of monocytes and T-lymphocytes with NK cells (T&NK-cells) were determined by flow cytometry.Results. In patients with T2DM, the number of monocytes of different subpopulations did not differ depending on the development of AHF. In patients without T2DM with MI, complicated by AHF, compared with patients without AHF, on day 3, the number of CD14(+)CD16(-)monocytes was higher: 1018 (824; 1144) vs 593 (557; 677) cells/μL, p <0,01, and on days 3 and 5, the number of CD16(+) T&NK-cells was lower: 122 (95; 275) cells/μL and 307 (220; 406) cells/μL, respectively (p = 0,03); (117 (61; 228) and 437 (408; 545) cells/μL, respectively, p < 0,01. On the 12th day of MI in patients with T2DM and AHF lymphocytes and CD16(+)T&NK-cells counts were lower in comparison with patients without AHF: 1856 (1245; 1975) cells/μL and 2294 (1827; 2625) cells/μL, respectively, p = 0,04; 268 (128; 315) cells/μL and 344 (226 ; 499) cells/ μL, respectively, p = 0,04.Conclusion. In patients with T2DM, the development of AHF is associated with a low number of lymphocytes in the absence of a pronounced monocytic response. In non-diabetic patients, the development of AHF is associated with an increase in CD16(-)monocytes and a lower number of CD16 (+) T&NК-cells.

Background. Electroencephalography is the main technique for assessing the functional state of the brain. Indications for EEG are diagnosis of paroxysmal states, prediction of the outcome of a pathological state, evaluation of bioelectrical activity if brain death is suspected. Up to 90 % of the native EEG in calm wakefulness in healthy individuals is occupied by “alpha activity”. In children in active wakefulness, the EEG pattern depends to a great extent on their age.Objective. The aim of the work was to assess EEG parameters in children aged 3–4 years in eyes-open resting state. Design and methods. 31 healthy participants aged 3–4 years were enrolled. EEG was registered for 30 minutes in a state of passive wakefulness in the supine position with open eyes. Average values of the power of the spectra for the alpha-rhythm, delta-rhythm and theta-rhythm in the frontal and temporal leads, as well as the ratio of the average power of alpha/theta and alpha/delta rhythms in the frontal and temporal leads were calculated.Results. Average power of the alpha-rhythm was significantly higher over the right frontal lobe than over the right frontal-temporal area, as well as average amplitude of it was significantly higher in F3-A1 than F7-A1, F4-A2 than F8-A2, which is associated with the articulatory praxis. Average alpha-rhythm power was significantly higher in T5-A1 than T3-A1 and T6-A2 than T4-A2, which corresponds to the recognition and naming of objects optically. Significant differences according to the total average power of the alpha- and theta-rhythms above the frontal and frontal-temporal regions reflect the relationship between the frontal cortex temporal lobes and the premotor zones, i.e. arcuate bundle, responsible for the “speech system”.Conclusion. The identified patterns can reflect the characteristics of the state of active wakefulness in a 3–4-year-old child and can be used for comparison in the future (both in the course of behavioral experiments and observation of patients with certain pathological processes).