[Predictors of severe course of new coronavirus infection (COVID-19): study design].

AIM: To identify predictors of the severe course of a new coronavirus infection. MATERIALS AND METHODS: A retrospective analysis of 120 clinical case histories of patients hospitalized in hospitals in Tyumen with a confirmed diagnosis of COVID-19 within one year (01.08.2020-01.08.2021) was carried out. The patients were divided into two groups: 1st - with a favorable outcome (n=96), 2nd - with an unfavorable (fatal) outcome (n=24). For a more complete analysis, scales for assessing the clinical condition of patients (SHOCK-COVID), severity assessment (NEWS2) were used. Information processing was carried out in the IBM.SPSS.Statistics-19 program (USA). RESULTS: As a result of the study, the median age for the 1st group was significantly lower (58 years) than for patients of the 2nd group (69 years; p=0.029). A certain set of laboratory parameters for group 2 patients deviate significantly from the reference values (C-reactive protein - CRP - 7.6 [4.7; 15.2] mg/dl, D-dimer - 1.89 [1.36; 5.3] mcg/ml, ferritin - 605 [446.7; 792] ng/ml). When analyzed in groups, taking into account the main markers of the severity of the disease, using the V.Yu. Mareev CCAS-COVID (Clinical Condition Assessment Scale) scale, for the 1st group, the sum of the set of parameters was 6 [2; 7] points, which corresponds to the average severity of coronavirus infection, for the 2nd group 13 [9; 16] points - severe course. For patients of the 2nd group, a significant increase in the indicators of an unfavorable prognosis was revealed in comparison with the 1st group. CONCLUSION: Thus, in this study, the level of CRP, ferritin, D-dimer, the percentage of lung tissue damage according to computed tomography results, SaO2 were significantly associated with an unfavorable prognosis.

Comparative Analysis of the Effects of Upconversion Nanoparticles on Normal and Tumor Brain Cells.

Glioma is the most aggressive type of brain tumors encountered in medical practice. The high frequency of diagnosed cases and risk of metastasis, the low efficiency of traditional therapy, and the usually unfavorable prognosis for patients dictate the need to develop alternative or combined approaches for an early diagnosis and treatment of this pathology. High expectations are placed on the use of upconversion nanoparticles (UCNPs). In this study, we have produced and characterized UCNPs doped with the rare-earth elements ytterbium and thulium. Our UCNPs had photoluminescence emission maxima in the visible and infrared spectral regions, which allow for deep optical imaging of tumor cells in the brain. Moreover, we evaluated the toxicity effects of our UCNPs on a normal brain and glioma cells. It was revealed that our UCNPs are non-toxic to glioma cells but have a moderate cytotoxic effect on primary neuronal cultures at high concentrations, a condition that is characterized by a decreased cellular viability and changes in the functional metabolic activity of neuron-glial networks. Despite the great potential associated with the use of these UCNPs as fluorescent markers, there is a need for further studies on the rate of the UCNPs accumulation and excretion in normal and tumor brain cells, and the use of their surface modifications in order to reduce their cytotoxic effects.

The Role of Brain-Derived Neurotrophic Factor and Glial Cell Line-Derived Neurotrophic Factor in Chronic Fetal Oxygen Deprivation.

The aim of the study was to define the role of brain-derived and glial cell line-derived neurotrophic factors (BDNF and GDNF) in realization of compensative and adaptive mechanisms of a neonatal organism to hypoxia. MATERIALS AND METHODS: The experiments in vivo have been carried out on pregnant C57BL/6 mice (n=36). Chronic hypobaric hypoxia has been modeled in different pregnancy trimesters. On gestation days E19-20, concentration of BDNF and GDNF in the blood of the pregnant females was determined by enzyme immunoassay. Further, the number of neonatal mice, their weight and body length parameters have been assessed.Parturient mothers (n=88) and their newborn babies followed up at the Clinic of Obstetrics and Gynecology of Pavlov University took part in the clinical investigations. Concentration of BDNF, GDNF, neuron-specific enolase (NSE), and hypoxia-inducible factor (HIF-1ß) in the fetal cord blood has been determined by ELISA. The obtained data were retrospectively compared with cardiotocography, dopplerometry, presence of meconium-stained amniotic fluid and the neonate state at birth, assessment according to the Apgar score, and the course of adaptation period. RESULTS: Chronic hypobaric hypoxia in pregnant mice in trimester I and II resulted in the significant decrease of BDNF and GDNF level, decrease in the number of embryos, and in significant changes in weight/height characteristics of the newborn pups.According to the clinical observations, an increased expression of the neurotrophic factors BDNF, GDNF provides protection to a neonate even if hypoxia factors are present and realized. A low content of BDNF and GDNF was observed in the group of infants with a high risk of developing unfavorable hypoxic damaging effects. CONCLUSION: The protective role of BDNF and GDNF in the regulation of fetal homeostasis in chronic hypoxia has been established experimentally and clinically.

Role of Neurotrophic Factors BDNF and GDNF in Nervous System Adaptation to the Influence of Ischemic Factors.

We developed a complex in vitro model of ischemic damage. Analysis of hippocampal cell viability in primary cultures after modeling of various stress factors revealed the features of action of the main pathological factors of ischemia. Neurotrophic factors BDNF and GDNF produced pronounced neuroprotective effect during modeling both the complex ischemic damage and its individual pathophysiological components. Neurotrophic factor GDNF produced the most pronounced protective effect.

[INTEGRATIVE MONITORING FOR INTRACEREBRAL COMPLICATIONS OF ISCHEMIC STROKE].

The severity of neurological deficit according to the NIHSS scale, for critical patients with an intracerebral complications of ischemic stroke (ICIS), corresponded to severe ischemic stroke in both the group of surviving patients (15,5±0,4 points) and the group of deceased patients from ICIS (16,1±0,6 points). At a time when the predictors of an unfavorable result of 21 critical patients with an ICIS were cerebral perfusion pressure <50 mm Hg. (p<0,05), cardiac index ˂1,8 L×min-1×m-2 (p<0,05), oxygen delivery index ˂280 mL×min-1×m-2 (p<0,05), plasma osmolality > 325 mmol×L-1 (p<0,05), progression of diastolic destabilization > 20% (p<0,05). The severity of systolic destabilization (SD) indicates the presence of systemic vasospasm and determines the need for the correction of hypertension. The achievement of hemodynamic autoregulation is characterized by the limits of normal hemodynamic stabilization (HS) values (0,636-0,599). Diastolic destabilization (DD) indicates a decrease in the pumping function of the heart, which requires immediate inotropic support.

Antioxidant Properties of Glial Cell-Derived Neurotrophic Factor (GDNF).

We propose an in vitro model of chronic oxidative stress based on the use of glucose oxidase. Oxidative stress modeling leads to a significant increase in the number of dead cells in culture. It was shown that the glial cell-derived neurotrophic factor exhibits a pronounced anti-oxidant effect. Preventive application of 1 ng/ml glial cell-derived neurotrophic factor significantly reduced the percentage of dead cells in culture.

Formation of Neural Networks in 3D Scaffolds Fabricated by Means of Laser Microstereolithography.

We developed and tested new 3D scaffolds for neurotransplantation. Scaffolds of predetermined architectonic were prepared using microstereolithography technique. Scaffolds were highly biocompatible with the nervous tissue cells. In vitro studies showed that the material of fabricated scaffolds is not toxic for dissociated brain cells and promotes the formation of functional neural networks in the matrix. These results demonstrate the possibility of fabrication of tissue-engineering constructs for neurotransplantation based on created scaffolds.

Antihypoxic and Neuroprotective Effects of Glial Cell-Derived Neurotrophic Factor (GDNF) in Cultures of Dissociated Hippocampal Cells under Conditions of Experimental Hypoxia.

We analyzed the effect of glial cell derived neurotrophic factor (GDNF) on changes in functional bioelectric and calcium activity in dissociated hippocampal cell cultures under conditions of modeled acute normobaric hypoxia in vitro. GDNF (1 ng/ml) partially neutralized the negative effects of hypoxia on cell survival and parameters of functional network activity. GDNF exhibited a pronounced anti-hypoxic effect.

[Compatibility of cells of the nervous system with structured biodegradable chitosan-based hydrogel matrices].

Hydrogel matrices for cell cultivation have been generated by two-photon laser polymerization of unsaturated chitosan derivatives and methacrylated hyaluronic acid. The adhesive and toxic properties of the matrices have been assessed, and the matrices have been shown to have a good compatibility with primary hippocampal cell cultures. The formation of morphologically normal neural networks by cells of the nervous system cultured on the surface of hydrogel matrices has been observed. The metabolic status of dissociated hippocampal cells cultured on the matrices was similar to that of the control cultures, as shown by the results of MTT reductase activity assay. Thus, matrices based on unsaturated polysaccharide derivatives crosslinked by laser irradiation showed good compatibility with differentiated cells of the nervous system and considerable potential for use in neurotransplantation.

[Dynamics of daily rhythm changes of arterial blood pressure in hypopinealism].

The article presents the original data on the character of the changes in arterial blood pressure (ABP) in rabbit with hypopinealism induced by long 24-hour lighting. In experimental animals registered leveling the daily rhythm of ABP primarily because of increase this value in dark time (night, evening) and formation of arterial hypertension by 'non-dipper".

[The results of the multicenter pharmaco-epidemiological observational project on the use of mydocalm in the treatment of pain syndromes with the muscle spasm].

The prospective multicenter open noncomparative pharmaco-epidemiological observational project on the use of mydocalm in real clinical practice has been completed in 2013. The project has been performed in 2090 clinical/rehabilitation settings in 284 cities of 13 countries using the results of 35,383 patients. The project aimed to assess the safety of treatment (percentage of patients with adverse-effects) and pain relieving efficacy as well as patient's satisfaction with the treatment. In total, 6603 (19%) adverse-effects were recorded. Their severity was evaluated as mild in 84,48%, no serious adverse-effects were noted. The high efficacy of mydocalm in the treatment of pain syndromes with the muscle spasm has been demonstrated. The high level of tolerability and absence of the clinically significant increase of adverse effects in the combination with nonsteroidal anti-inflammatory drugs have been confirmed.

[Genetic potential of local endemic forms of the pea (Pisum sativum L.) on the basis of nitrogen fixation and productivity].

Morphological and symbiotic traits were studied in local endemic forms of the pea originating from Egypt, Syria, Afghanistan, and Palestine. A number of endemic forms exceeded the zoned Druzhnaya variety of the fodder pea in productivity of the seeds in field and greenhouse experiments. In order to improve nodulation and nitrogen fixation, endemic forms were crossed with the supernodulating K301 mutant marked by the nod4 gene. Recurrent selection of lines up to F5,6 generations was conducted with an estimation of productivity, nodulation, and nitrogen fixation. The most promising recurrent lines with a high productivity, active nodulation, and high nitrogen fixation were obtained during the crossing of endemic forms with the recurrent line marked by the nod4 gene. The line was previously created during the crossing between the Druzhnaya variety and the supernodulating K301 mutant marked by the nod4 gene.

[Functional state of vision system under chronic mercury intoxication].

Examination of chronic mercury intoxication patients in distant (post-contact) period revealed marked vision disorders and inhibited neuro-conductivity--inhibited neuronal structures of retina and optic nerve.

[Study of dominant symbiotic mutants of pea Pisum sativum L].

Phenogenetic studies of four symbiotic hypernodulating mutants of pea (Pisum sativum L.) induced from seeds of cultivar Rodno by chemical mutagen EMS were conducted. All mutants have improved symbiotic traits, i.e., an increased number of root nitrogen fixating nodules and high activity of nitrogenase. Symbiotic traits were shown to be inherited dominantly. Mutants grown in the field or in a greenhouse showed superiority over the original cultivar in productivity. An important feature of hypernodulating mutants was found that is responsible for the appearance of high-height productive plants in F2 after crossing mutants and the original cultivar. Constant lines retaining the ability for high-level production up to the F5 generation were created based on individual plants.

[Expression of the symbiotic nod4 pea gene against various genotypic backgrounds].

Experiments on the effect of genotypic environment on the expression of the nod4 gene, responsible for supernodulation in pea, were performed. The genotypic background was found to affect the manifestation of both major symbiosis-related traits (number of nitrogen-fixing bacterial nodules and nitrogenase activity) and productivity-related traits (stem height, seed number, and seed weight), which form the pleiotropic complex of the mutant gene. Using recurrent selection, we developed supernodulating lines significantly exceeding the original mutant line and studied them up to generations F5-F6. Of special importance is the fact that these lines showed high levels of nodulation and nitrogen fixation. The results are discussed from the viewpoint of breeding.

[Disorders of mental function in patients with circulatory encephalopathy due to hypertension and atherosclerosis]. / Narusheniia nekotorykh psikhicheskikh funktsii u bol'nykh distsirkuliatornoi éntsefalopatiei, obuslovlennoi gipertonicheskoi bolezn'iu i aterosklerozom.

The authors described the dynamics of disorders of memory, attention and thinking in the course of treatment of patients with circulatory encephalopathy. It was shown that treatment resulted a prevailing regression of neurodynamic disorders of the higher psychic functions that was more productive at early stages of cerebrovascular insufficiency.

[Status of cerebral and central hemodynamics in patients with dyscirculatory encephalopathy]. / Sostoianie tserebral'noi i tsentral'noi gemodinamiki u bol'nykh distsirkuliatornoi éntsefalopatiei.

On the basis of radiocardiographic and radiocirculatory examination of the central and cerebral hemodynamics in 130 patients with dyscirculatory encephalopathy (DE) caused by essential hypertension and atherosclerosis, the authors have demonstrated that the development of DE is facilitated by disturbances of the central and peripheral hemodynamics. In turn, DE reduces the function of the autoregulatory mechanisms of the cerebral blood flow and leads to insufficiency of compensatory adaptive possibilities of the cardiovascular system. It is recommended that not only cerebral disorders but also the type (hyperkinetic, hypokinetic, eukinetic) of the blood circulation in these patients be taken into consideration in selecting the optimal method of treatment.

[Quantitative analysis of circulatory radiograms using computers]. / Kolichestvennyi analiz radiotsirkulogramm s ispol'zovaniem EVM.

A technique of quantitative RCG analysis is proposed and tested. It enables the unbiased evaluation of regional hemodynamics phases and of the relation between blood flow rate in arterial and venous beds. The technique is based on calculating the first derivative of the radiocirculogram. The specially developed program may be executed by the computer (ZBM EC).