[Changes the level of differentiating growth factor - GDF 15 in patients with sleep apnea syndrome after aPAP-therapy: pilot study]. / Izmenenie urovnya differentsirovochnogo faktora rosta ­ GDF 15 u patsientov s sindromom apnoe sna na fone aPAP-terapii: pilotnoe issledovanie.

OBJECTIVE: Comparative assessment of the level of differentiating growth factor 15 (GDF 15 ) against the background of a 6-month course of respiratory support in the mode of automatic positive pressure in the airways therapy (aPAP therapy) in patients with obstructive sleep apnea syndrome (OSA). MATERIAL AND METHODS: 59 men participated in the study, the average age was 51.9±2.4 years. The main group (MG1) consisted of 30 patients with a verified diagnosis of moderate OSA. 29 men of comparable age and body weight made up the control group (CG) without an objectively confirmed diagnosis of OSA. After the stage of introduction into the study, the type of respiratory support with individual pressure settings was selected for patients with MG1. After 6 months of aPAP therapy with high compliance (at least 85%), the same patients who made up MG2 after treatment underwent repeated polysomnography (PSG) and the GDF 15 content was evaluated. Methods: questionnaire, examination, polysomnography, enzyme immunoassay of blood serum to determine the content of GDF 15. RESULTS: A 6-month course of aPAP therapy with a high degree of compliance significantly improved the sleep structure and breathing pattern: the representation of NREM 3 increased from 79.2±15.6 to 102.6±21.6 minutes and the REM phase from 56.9± 13.6 to 115.6±26.8. Episodes of apnea were eliminated - apnea-hypopnea index decreased from 21.1 [17.3; 39.1] to 2.5 [1.8; 4.6] and the average values of SaO2 increased from 85.9% to 91.5%. At the same time, a statistically significant excess of GDF 15 was revealed in MG1 - 20.4 [14.16; 31.71] and MG2 - 17.2 [13.63; 24.44]) in comparison with CG - 13.65 [10.7; 17.09]. Despite the lack of statistical significance, a change in the level of GDF 15 was revealed in the form of a decrease in its concentration after a 6-month course of aPAP therapy. CONCLUSION: A 6-month course of aPAP therapy made it possible to eliminate intermittent nocturnal hypoxia and improve sleep structure in patients with OSA, as well as reduce the content of GDF 15 protein in blood serum in patients with OSA. However, the tendency to decrease the content of this protein, despite the lack of statistical reliability, confirms the effectiveness of OSA therapy and the possibility of preventing early and pathological aging from the standpoint of somnology and molecular biogerontology.

[Reconstruction of total portosystemic shunt into selective portosystemic shunt in a child]. / Rekonstruktsiya total'nogo portosistemnogo shunta v selektivnyi portosistemnyi shunt u rebenka.

To date, side-to-side splenorenal shunt (SRS) and its analogues (splenosuprarenal shunts (SSRS)) are mainly used for portal hypertension. These are total portosystemic shunts characterized by total blood shunt from portal vein into inferior vena cava. The latter is fraught with a significant risk of complications such as pulmonary hypertension, decreased portal liver perfusion, liver failure and hepatic encephalopathy. Prevention of these complications is still an urgent problem in modern surgery. However, we proposed a new method of treatment, i.e. reconstruction of SRS and SSRS into selective shunt. This procedure was performed in 37 patients after 2020. We present laparoscopic reconstruction in an 11-year-old girl with portal hypertension and signs of hepatic encephalopathy identified after previous SSRS.

The State of the LPO-AOD System and the Relative Length of Telomeric Repeats in the Chromosomes of Blood Leukocytes in Obstructive Sleep Apnea Syndrome.

We analyzed the relative length of telomeric repeats in peripheral blood leukocytes and indicators of oxidative stress in 32 men (mean age 51.2±3.1 years) with obstructive sleep apnea syndrome (OSAS). The control group consisted of volunteers without OSAS. The relative length of telomeres was determined in a DNA sample isolated from venous whole blood samples. The length of telomeric repeats of chromosomes was determined using quantitative real-time PCR (3 times for each DNA sample); albumin served as an internal control. The intensity of LPO processes and antioxidant protection was assessed by conventional spectrophotometric methods. It was found that in patients with OSAS, the relative length of telomeric repeats was lower by 48%, the levels of substrates and products of LPO were higher (double bonds and diene conjugates by 34 and 19%, respectively), and antioxidant protection indicators were lower (concentrations of fat-soluble vitamins α-tocopherol and retinol by 18 and 19.3%, respectively, total antioxidant activity by 32.9%) than in volunteers of the control group. Thus, we can conclude that the nucleotide sequences are reduced in patients with OSAS under conditions of intensified free radical oxidation.

[Activity of the telomerase complex before and after CPAP therapy in patients with obstructive sleep apnea syndrome]. / Aktivnost' telomeraznogo kompleksa na fone SIPAP-terapii u patsientov s sindromom obstruktivnogo apnoe sna.

OBJECTIVE: To evaluate changes in the activity of the telomerase complex in patients with obstructive sleep apnea (OSA) before and after continuous positive airway pressure (CPAP) therapy. MATERIAL AND METHODS: In accordance with the objectives of the stages of the study of telomers-telomerase relationships, we maintained the unified design of the study described earlier. The main group 1 (MG1), n=35, consisted of men, aged 53.4 [45.5-60.1] years with characteristic complaints indicating of OSA. The main group 2 (MG2) included the same patients before and after 6 months of CPAP therapy. Blood sampling was performed after the first diagnostic polysomnography (PSG) and after 6 months of CPAP in the morning after the second PSG. The control group (CG) consisted of 26 men, comparable in age and the presence of chronic diseases. Questionnaire, PSG and blood sampling were conducted in CG as well. All participants signed an informed consent. RESULTS: As a result of the STOP-BANG questionnaire conducted before PSG, all patients in the MG1 had scores from 5 to 8. The scores on the Epworth scale were more than 5 points. In the MG2 apnea-hypopnea index decreased from 20.1 to 6.4 ev/hour, the desaturation index decreased from 15.6 to 7.1 ev/hour after 6 months of CPAP. Statistically significant differences in changes in the activity of the telomerase complex were revealed, which after treatment significantly exceed the values of these indicators before treatment. So, telomerase reverse transcriptase value was 0.04 (0.009; 0.06) in the MG1, after treatment it was 0.07 (0.06; 0.09) in the MG2 and 0.134 (0.009; 0.18) in the CG. Telomerase RNA subunit TER1 values were 0.06 (0.03; 0.09), 0.07 (0.05; 0.09) and 0.136 (0.04; 0.17), respectively. However, despite the activation of the telomerase complex during CPAP therapy in patients with OSA, in the CG its activity is significantly higher in comparison with the MG1 and MG2. CONCLUSION: In OSA accompanied by intermittent hypoxia, a decrease in the activity of the telomerase complex was shown. Elimination of nocturnal hypoxia and improvement of breathing during sleep is accompanied by an increase in the activity of the components of the telomerase complex.

IgG Stimulates the Formation of Neutrophil Extracellular Traps and Modifies Their Structure.

We studied the neutrophils and monocytes obtained from 37 patients with various inflammatory diseases such as psoriasis, acute infectious process in the abdominal cavity (acute appendicitis/abscess of the abdominal cavity, and acute cholecystitis), acute pancreatitis, and post-COVID syndrome after mild COVID infection. The number and the morphological structure of neutrophil extracellular traps (NET) as well as the effect of IgG on NET were examined. NET were visualized and counted by fluorescence microscopy with fluorescent dye SYBR Green. All the studied types of inflammation were accompanied by spontaneous formation of NET. After application of IgG, the number of NET doubled, their size increased, and transformation of net-like traps into the cloud forms was observed. The clouds form structure of the network is not capable of capturing pathogens with subsequent retraction, the products of its enzymatic degradation can be the factors of secondary alteration. The study results demonstrate a previously unknown mechanism of infection resistance.

Analysis of the boundary integral equation for the growth of a parabolic/paraboloidal dendrite with convection.

The growth of a parabolic/paraboloidal dendrite streamlined by viscous and potential flows in an undercooled one-component melt is analyzed using the boundary integral equation. The total melt undercooling is found as a function of the Péclet, Reynolds, and Prandtl numbers in two- and three-dimensional cases. The solution obtained coincides with the modified Ivantsov solution known from previous theories of crystal growth. Varying Péclet and Reynolds numbers we show that the melt undercooling practically coincides in cases of viscous and potential flows for a small Prandtl number, which is typical for metals. In cases of water solutions and non-metallic alloys, the Prandtl number is not small enough and the melt undercooling is substantially different for viscous and potential flows. In other words, a simpler potential flow hydrodynamic model can be used instead of a more complicated viscous flow model when studying the solidification of undercooled metals with convection.

Dendrite tips as elliptical paraboloids.

This review article summarizes current theories of the steady-state growth mode of dendrites in the form of elliptical paraboloids. The shape of dendrite tips is analyzed, temperature and solute concentration distributions are described in its vicinity, and a solution of the hydrodynamic problem of a viscous incompressible fluid flowing against a dendrite tip is developed. A significant difference in analytical solutions describing a dendrite tip as an elliptic paraboloid as compared to an axisymmetric morphology is shown. The system of nonlinear equations for determining the stationary velocity of dendrite growth and the radii of curvature of the dendrite tip along the major and minor axis of the ellipse, respectively, is derived. The developed theory is compared with experimental data on the growth of ice crystals consisting of D2O or H2O.

Dendritic growth of ice crystals: a test of theory with experiments.

Motivated by an important application of dendritic crystals in the form of an elliptical paraboloid, which widely spread in nature (ice crystals), we develop here the selection theory of their stable growth mode. This theory enables us to separately define the tip velocity of dendrites and their tip diameter as functions of the melt undercooling. This, in turn, makes it possible to judge the microstructure of the material obtained as a result of the crystallization process. So, in the first instance, the steady-state analytical solution that describes the growth of such dendrites in undercooled one-component liquids is found. Then a system of equations consisting of the selection criterion and the undercooling balance that describes a stable growth mode of elliptical dendrites is formulated and analyzed. Three parametric solutions of this system are deduced in an explicit form. Our calculations based on these solutions demonstrate that the theoretical predictions are in good agreement with experimental data for ice dendrites growing at small undercoolings in pure water.

[Efficiency of minilaparotomy in the treatment of choledochal malformation in children]. / Otsenka effektivnosti mini-laparotomii pri lechenii mal'formatsii obshchego zhelchnogo protoka u detei.

OBJECTIVE: To evaluate an effectiveness of minilaparotomy in the treatment of choledochal malformation (CM) in children. MATERIAL AND METHODS: The study included children with CM who underwent surgery from January 2010 to May 2020. All patients were divided into 3 groups depending on surgical approach: minilaparotomy (ML), laparoscopy (LS) and laparotomy (LT). We analyzed surgery time, early postoperative outcomes and cosmetic results. RESULTS: There were 99 patients with CM for 10 years. ML was performed in 39 patients, LS - in 51 patients, and LT - in 9 patients. Significantly (p-value <0.001, Kruskal-Wallis test with Dunn paired comparison test, p<0.05) less surgery time was observed in ML group. According to Clavien-Dindo classification of surgical complications, we found a significant prevalence of complications in the LS group (p - 0.018, Kruskal-Wallis test). Moreover, LS was characterized by insignificant (p>0.05) predominance of the most severe complications requiring multiple redo surgeries. CONCLUSION: Currently, open surgery is a "gold standard" in the treatment of children with CM. LS is not preferred in children with CM. ML ensures favorable early outcomes in children with CM.

The role of presepsin in the diagnosis and assessment of severity of sepsis and severe pneumonia.

AIM: The aim of this study was to evaluate marker of inflammation presepsin to improve diagnosis of severe pneumonia, sepsis. MATERIALS AND METHODS: 75 patients with pneumonia, sepsis, other inflammatory diseases aged from 17 to 78 years were examined. These patients have been investigated for the level of the presepsin. Presepsin level was quantified on immunohemilyuministsentny analyzer Pathfast (Mitsubishi Chemical Medience Corporation, Japan) in pg/ml. All patients had obtained an antibacterial therapy in other health care organizations before entering the hospital. RESULTS: Рresepsin at the general group of patients with pneumogenic sepsis was 3196.9±1202.16 pg/mL (n=14, x̅±m), with abdominal sepsis - 2506.7±448.32 pg/mL (n=28), with other inflammatory diseases - 671.6±124.55 pg/mL (n=11). Рresepsin of patients with pneumogenic sepsis was 1125.3±240.59 pg/mL (n=3), presepsin of patients with severe pneumonia was - 362.6±76.29 pg/mL (n=13, р<0.05), non-severe pneumonia - 157.3±33.02 pg/mL (n=9, р<0.05). CONCLUSION: The high level of presepsin is an indication of an active infectious disease and reflects the severity of the pneumonia and development of sepsis. Keeping a high level against the backdrop of earlier presepsin ongoing antibiotic therapy is an indication of their lack of effectiveness. A significant variability of presepsin should be taken into account.

[Laparoscopic decompression of celiac trunk in children]. / Laparoskopicheskaia dekompressiia chrevnogo stvola pri kompressionnom stenoze u detei.

MATERIAL AND METHODS: For the period 2013-2016 four patients were treated at the Filatov Children's City Clinical Hospital #13. There were 2 children aged 14 years and 2 children aged 17 years. All patients have been diagnosed via anamnesis, complaints, pulse-wave doppler sonography, contrast-enhanced MDCT and angiography. After comprehensive examination 3 patients underwent laparoscopic decompression of celiac trunk. In all cases celiac trunk compression was predominantly caused by median arcuate ligament of the diaphragm combined with neurofibrotic tissue of celiac plexus. RESULTS: All patients were discharged after laparoscopic decompression of celiac trunk. Intra- and postoperative complications, as well as cases of conversion were absent. Mean time of surgery was 65 minutes. In all cases postoperative period was smooth (4 days on the average). Two patients underwent follow-up examination in long-term postoperative period: pulse-wave doppler sonography, contrast-enhanced MDCT and angiography. In both cases reduced severity, incidence and duration of pain syndrome were observed. CONCLUSION: Clinical examples show some problems in diagnosis and treatment of compressive stenosis of celiac trunk due to rarity of pathology especially in childhood. Nevertheless, combination of abdominal ischemia and celiac trunk stenosis confirmed by instrumental diagnosis is indication for surgical treatment.

[Extract of Hirudo medicinalis leeches: biogenic substance for the creation of effective drugs].

Investigations of the extract of medicinal leech Girulux established parameters that enable one to verify the authenticity of related drugs using the characteristics of their UV spectra the and anticoagulant and antithrombin activity. The limits of pH must range from 5.5 to 7.5. Pilot-scale series of medical leech extract are in compliance with terms of "microbiological purity" quality characteristics. The natural storage has been used to assess the temporal stability of leech extract. The obtained characteristics showed that the activity of extract was retained after 3-year storage.

The late phase of post-stroke neurorepair in aged rats is reflected by MRI-based measures.

Non-invasive criteria determining the progress of brain healing are especially important in aging, providing a case-specific therapeutic strategy in populations with dysregulated neurorepair mechanisms. We hypothesized that temporal evolution of magnetic resonance imaging (MRI) of T2 tissue relaxation values correlate with neurological severity scores (NS), and provide a robust indicator of healing in the aging brain after stroke. Pre-treatment of aged rats with brain-only proton irradiation was undertaken to pre-condition the inflammatory system. Irradiation was performed 10days prior to right middle cerebral artery occlusion (MCAO) for 50min (MCAO+Rad). Control rats included naïve (no ischemia, no radiation), irradiated-only (Rad), irradiated ischemic, or ischemic-only (MCAO). MRI and NS were obtained at 3, 14 and 28days post-stroke. At 28days post-stroke, immunofluorescence for visualizing blood vessels (Von Willebrand factor; vWF), neurons (neuronal nuclear antigen; NeuN), astrocytes (glial fibrillary acidic protein; GFAP), activated microglia/macrophages (ionized calcium-binding adapter molecule 1, Iba1), T-lymphocytes (CD3), phagocytes (ED1) and apoptotic cells (caspase-3) was assessed. We found a positive T2-NS correlation in irradiated, ischemic rats that corresponded to late-stage brain recovery. Late-stage brain recovery was characterized by improved neovascularization, formation of glio-vascular complexes (visualized by GFAP/vWF) and enhanced neuronal viability (by NeuN/caspase-3) in the peri-lesional zone. The immune response plateaued at the late stage of repair as evidenced by significantly decreased expression (41.7%) and distribution of phagocytes (phagocytic rim decreased 44.6%). We also found reduced infiltration of T-lymphocytes (CD3) in the brain and normalization of blood lymphocytes. The observed T2-NS correlations may provide a simple MRI-based criterion for recognition of regenerative brain transformation in aged patients following stroke. Selective activation of innate immunity and accelerated transition from pro-inflammatory to pro-healing macrophage phenotypes induced by localized brain irradiation is a potential mechanism for enhancing repair ability in the elderly.

Novel mitochondria-targeted compounds composed of natural constituents: conjugates of plant alkaloids berberine and palmatine with plastoquinone.

Novel mitochondria-targeted compounds composed entirely of natural constituents have been synthesized and tested in model lipid membranes, in isolated mitochondria, and in living human cells in culture. Berberine and palmatine, penetrating cations of plant origin, were conjugated by nonyloxycarbonylmethyl residue with the plant electron carrier and antioxidant plastoquinone. These conjugates (SkQBerb, SkQPalm) and their analogs lacking the plastoquinol moiety (C10Berb and C10Palm) penetrated across planar bilayer phospholipid membrane in their cationic forms and accumulated in isolated mitochondria or in mitochondria in living human cells in culture. Reduced forms of SkQBerb and SkQPalm inhibited lipid peroxidation in isolated mitochondria at nanomolar concentrations. In isolated mitochondria and in living cells, the berberine and palmatine moieties were not reduced, so antioxidant activity belonged exclusively to the plastoquinol moiety. In human fibroblasts, nanomolar SkQBerb and SkQPalm prevented fragmentation of mitochondria and apoptosis induced by exogenous hydrogen peroxide. At higher concentrations, conjugates of berberine and palmatine induced proton transport mediated by free fatty acids both in model and in mitochondrial membrane. In mitochondria this process was facilitated by the adenine nucleotide carrier. As an example of application of the novel mitochondria-targeted antioxidants SkQBerb and SkQPalm to studies of signal transduction, we discuss induction of cell cycle arrest, differentiation, and morphological normalization of some tumor cells. We suggest that production of oxygen radicals in mitochondria is necessary for growth factors-MAP-kinase signaling, which supports proliferation and transformed phenotype.

[Computed tomographic findings in patients with chronic pulmonary obstruction and diabetes mellitus].

The study included 40 patients aged 33-71 years with chronic pulmonary obstruction (CPO) and diabetes mellitus (DM). They were examined by multilayer CT with detailed analysis of parenchymal tissues. The main microvascular changes in lung parenchyma included dilation, focal opacity (2-5 mm), and beaded vessels. In patients with isolated CPO, these changes were less pronounced than in those with combined pathology. All patients presented with bronchial deformities, bronchoectasia, emphysema, and cysts. Microvascular pathology in lung parenchyma appears to be a manifestation of universal diabetic microangiopathy responsible for the unfavourable development of CHD in DM patients.

Speech disorders in right-hemisphere stroke.

Clinical practice shows that right-hemisphere cerebral strokes are often accompanied by one speech disorder or another. The aim of the present work was to analyze published data addressing speech disorders in right-sided strokes. Questions of the lateralization of speech functions are discussed, with particular reference to the role of the right hemisphere in speech activity and the structure of speech pathology in right-hemisphere foci. Clinical variants of speech disorders, such as aphasia, dysprosody, dysarthria, mutism, and stutter are discussed in detail. Types of speech disorders are also discussed, along with the possible mechanisms of their formation depending on the locations of lesions in the axis of the brain (cortex, subcortical structures, stem, cerebellum) and focus size.

Exposure to 56Fe-particle radiation accelerates electrophysiological alterations in the hippocampus of APP23 transgenic mice.

Abstract An unavoidable complication of space travel is exposure to high-charge, high-energy (HZE) particles. In animal studies, exposure of the CNS to HZE-particle radiation leads to neurological alterations similar to those seen in aging or Alzheimer's disease. In this study we examined whether HZE-particle radiation accelerated the age-related neuronal dysfunction that was previously described in transgenic mice overexpressing human amyloid precursor protein (APP). These APP23 transgenic mice exhibit age-related behavioral abnormalities and deficits in synaptic transmission. We exposed 7-week-old APP23 transgenic males to brain-only (56)Fe-particle radiation (600 MeV/nucleon; 1, 2, 4 Gy) and recorded synaptic transmission in hippocampal slices at 2, 6, 9, 14 and 18-24 months. We stimulated Schaeffer collaterals and recorded field excitatory postsynaptic potentials (fEPSP) and population spikes (PS) in CA1 neurons. Radiation accelerated the onset of age-related fEPSP decrements recorded at the PS threshold from 14 months of age to 9 months and reduced synaptic efficacy. At 9 months, radiation also reduced PS amplitudes. At 6 months, we observed a temporary deficit in paired-pulse inhibition of the PS at 2 Gy. Radiation did not significantly affect survival of APP23 transgenic mice. We conclude that irradiation of the brain with HZE particles accelerates Alzheimer's disease-related neurological deficits.

[The comparative analysis of high-risk behaviour related to HIV infection in users of psychoactive drugs with stimulating action and opioids].

To study clinical and psychological characteristics associated with high-risk behaviour related to HIV infection in 2006-2007 years, we examined 68 patients with psychoactive drugs (with stimulating action) and opioids (heroin) dependencies. Patients were stratified into 2 groups: users of psychoactive drugs (UPS)--34 patients and opioid users (OU)--34. Behavior of UPS differed from that of OU by using more drug injections per day although the former used syringes of other users less often. Therefore, the risk of being infected was lower in the UPS group compared to the OU group. The evaluation of the risk through sexual transmission did not reveal significant between-group differences.

Radiation exposure prior to ischemia decreases lesion volume, brain edema and cell death.

PURPOSE: To investigate the neuronal response to ischemic injury following exposure to whole brain proton irradiation. METHODS: Brain only proton irradiation (8 Gy, 250 MeV) was performed ten days prior to middle cerebral artery occlusion (MCAO) in 1 year old male Sprague Dawley rats. MCAO was induced in two animal groups: proton irradiated (MCAO + Rad) and MCAO only. Magnetic resonance imaging (MRI) and quantitative analysis were performed prior to and 2 days after irradiation, and then 2, 14 and 28 days after MCAO. After the last imaging time point animals were sacrificed and TUNEL staining was performed on 4% paraformaldehyde - fixed brain sections. RESULTS: Neuroimaging demonstrated a reduction in ischemic lesion volume in the MCAO + Rad group compared with MCAO alone. Neurological deficits did not differ between ischemia groups. Interestingly, there was a 34% decrease in the number of TUNEL-positive cells in MCAO + Rad brains compared to MCAO alone. CONCLUSION: Our results suggest that radiation treatment reduces brain edema, ischemic lesion volume and peri-ischemic apoptosis. The underlying mechanisms are currently unknown and additional studies will elucidate the significance of these results.

[Speech disorders in right-sided brain stroke].

The clinical picture revealed that right-sided brain stroke is often accompanied by some speech disturbances. The present paper aims at the analysis of literature devoted to speech disturbances in right-sided brain stroke. The paper addresses issues on lateralization of speech functions, in particular the role of the right hemisphere in speech activity and structure of speech pathology in right hemispheric foci are specified. Such clinical variants of speech disturbances as aphasia, disprosodia, dysartria, mutism and stammering are analyzed in depth. Types of speech disorders as well as possible mechanisms of their formation in dependence of the lesion localization on the brain axis (cortex, subcortical structures, stem, cerebellum) and size of brain lesion are reviewed.