[Genetic aspects of speech disorders in children]. / Geneticheskie aspekty narushenii rechi u detei.

Speech disorders still remains one of the cornerstones of pediatric neurology. Against the backdrop of gene diagnostic development, there are a huge amount of information about the role of genetic and chromosomal abnormalities in pathogenesis of speech disorders. In present article authors presenting an actual data on genetic basis of different types of speech disorders. Moreover, authors describing a clinical case of a patient with genetically determined developmental disorder, caused by KMT5B mutation validated by Sanger method.

[Uncommon variants of speech disorder in children: congenital bilateral perisylvian syndrome]. / Redkie varianty narusheniya rechi u detei: vrozhdennyi bilateral'nyi perisil'viarnyi sindrom.

This paper describes two cases of congenital bilateral perisylvian syndrome (CBPS), a rare disorder of late neuronal migration, which is characterized by language delay, intellectual disorders, epilepsy and bilateral perisylvian polymicrogyria. Pseudobulbar paralysis and orofacial muscles dyspraxia causing drooling and feeding difficulties are common for patients with CBPS. Communicational problems lead to low self-esteem and social maladaptation. Literature data regarding correlation between polymicrogyria topography and speech disorders and articulation impairment severity are presented. The results demonstrate the association of diffuse spreading of bilateral polymicrogyria and more severe speech disorders comparing to mild speech disorders in patients with more local polymicrogyria. Known etiology factors of this syndrome are bilateral cerebral hypoperfusion, brain damage while neuronal migration period, postmigrational vascular insults and gene mutations. Syndrome can be inherited in autosome dominant and X-linked manner. Speech apraxia with normal impressive speech, refractory epileptic seizures and status dysraphicus must be red flags for a physician regarding this syndrome. Overnight video-EEG monitoring and brain MRI confirm a thesis that this syndrome is underdiagnosed in everyday clinical practice.

Mechanism of the historical and the ongoing Vulcanian eruptions of Ebeko volcano, Northern Kuriles.

Ebeko is one of the most active volcanoes of the Kurile island arc, producing frequent mild Vulcanian explosions with eruption clouds up to 5 km high. The volcano poses a serious threat to the Severo-Kurilsk town with a population of around 2500 inhabitants, located at a distance of only 7 km on a fan of the volcano's laharic deposits. Here, we report an overview of the activity of the volcano in the 20th-21st centuries and the results of our geological and petrological investigations of the ongoing Vulcanian eruption that started in 2016. We have found that eruptions of Ebeko span a range of mechanisms from purely magmatic to phreatic/hydrothermal. Three of its historical eruptions (the 1934-1935, 1987-1991, and the 2016-ongoing) involved fresh magma, while during the others (1967-1971, 2009-2011) fresh magma was not erupted. Juvenile material of the ongoing eruption represents highly crystalline and highly viscous (more than 108 pa s) low-silica (56-58 wt% SiO2) andesite. Historical data and our observations of the ongoing eruption allowed us to suggest a functional model of the volcano where Vulcanian explosions are caused by shallow intrusions of small diapir-like batches of strongly crystallized and highly viscous andesitic magma ascending into water-saturated, hydrothermally altered rocks composing the volcano summit. We suggest that the diapir's ascent is governed by their positive buoyancy. Some of the diapirs reach and breach the ground surface producing magmatic eruptions of Ebeko, while the others are stuck at the shallow subsurface level and feed intensive hydrothermal activity as well as phreatic eruptions of the volcano. Positive buoyancy of the diapirs is too weak to allow them to extrude high above the ground surface to form lava domes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00445-020-01426-z.

A mini-review of X-ray photodynamic therapy (XPDT) nonoagent constituents' safety and relevant design considerations.

Conventional photodynamic therapy (PDT) has proved effective in the management of primary tumors and individual metastases. However, most cancer mortality arises from wide-spread multiple metastases. The latter has thus become the principal target in oncology, and X-ray induced photodynamic therapy (XPDT or PDTX) offers a great solution for adapting the PDT principle to deep tumors and scattered metastases. Developing agents capable of being excited by X-rays and emitting visible light to excite photosensitizers is based on challenging physical and chemical technologies, but there are fundamental biological limitations that are to be accounted for as well. In the present review, we have established eight major groups of safety determinants of NPs encompassing 22 parameters of clinical applicability of XPDT nanoparticulate formulations. Most, if not all, of these parameters can be accounted for and optimized during the design and development of novel XPDT nanoparticles.

[Neuroprotective mechanisms of the ubiquinol action in experimental focal ischemia]. / Issledovanie neiroprotektornykh mekhanizmov deistviia ubikhinola pri éksperimental'noi fokal'noi ishemii.

Ischemic stroke is one of the most socially important diseases characterized by impaired cerebral circulation with focal damage of the brain tissue and decreased functionality. Despite the successes of modern pharmacology, possibilities of pharmacotherapy for stroke remain limited, and the research for new drugs with neuroprotective effects that can prevent brain cell death is still relevant. In this study we have investigated the neuroprotective activity of ubiquinol as a part of an innovative form on a rat model of irreversible 24 h-cerebral ischemia with evaluation of the mechanisms of its neuroprotective effect. Ubiquinol (30 mg/kg), administered intravenously in the acute period of irreversible 24 h focal cerebral ischemia, had a direct neuroprotective effect, characterized by a decrease in the volume of brain tissue necrosis. The protective effect of ubiquinol is due to its ability to inhibit the development of oxidative stress by the direct anti-radical action, preventing the increase in the lipid hydroperoxide content in the brain tissue adjacent to the focus of necrosis, lowering the lipid oxidation rate in plasma against under conditions of increased total antioxidant activity in the brain and blood of experimental animals. In vitro experiments have shown the ability of ubiquinol to prevent cell death in primary culture of cerebral neurons of rat brain under 4 h oxygen/glucose deprivation followed by 20 h reoxygenation.

Metabolomic approach to search for fungal resistant forms of Aegilops tauschii Coss. from the VIR collection.

Broadening of the genetic diversity of donors of resistance to biotic environmental factors is a challenging problem concerning Triticum L., which can be solved by using wild relatives of wheat, in particular, Aegilops tauschii Coss., in breeding programs. This species, believed to be the donor of D genome of common wheat (T. aestivum L.), is a source of some traits important for breeding. This greatly facilitates the possibility of crossing Ae. tauschii with common wheat. Aegilops L. species are donors of effective genes for resistance to fungal diseases in wheat. For instance, genes that determine resistance to rust agents in common wheat were successfully introgressed from Ae. tauschii into the genome of T. aestivum L. The aim of our study was to identify differences in metabolomic profiles of Ae. tauschii forms (genotypes), resistant or susceptible to such fungal pathogens as Puccinia triticina f. sp. tritici and Erysiphe graminis f. sp. tritici. These indicators may be used as biochemical markers of resistance. A comparative analysis of groups of Ae. tauschii accessions showed that metabolomic profiles of the forms with or without resistance to fungal pathogens differed significantly in the contents of nonproteinogenic amino acids, polyols, phytosterols, acylglycerols, mono- and oligosaccharides, glycosides, phenolic compounds (hydroquinone, kempferol), etc. This fact was consistent with the previously obtained data on the relationship between Fusarium resistance in oats (Avena sativa L.) and certain components of the metabolomic profile, such as acylglycerols, nonproteinogenic amino acids, galactinol, etc. Thus, our studies once again confirmed the possibility and effectiveness of the use of metabolomic analysis for screening the genetic diversity of accessions in the VIR collection, of Ae. tauschii in particular, in order to identify forms with a set of compounds in their metabolomic profile, which characterize them as resistant. Ae. tauschii accessions with a high content of pipecolic acids, acylglycerols, galactinol, stigmasterol, glycerol, azelaic and pyrogallic acids, campesterol, hydroquinone, etc., can be used for creating wheat and triticale cultivars with high resistance to fungal pathogens causing powdery mildew, brown rust, and yellow rust.

The Gln3 Transcriptional Regulator of Saccharomyces cerevisiae Manifests Prion-Like Properties upon Overproduction.

Prions are proteins that can exist under the same conditions in two or more conformations, at least one of them is infectious. Usually, acquisition of infectious prion conformation is associated with the formation of amyloids - protein aggregates with a characteristic spatial structure. About 10 prions have been identified in the yeast Saccharomyces cerevisiae. The Gln3 protein, which is one of the key regulators of nitrogen metabolism in S. cerevisiae, contains an amyloidogenic region manifesting prion-like properties. The prion properties of the full-length Gln3 have not been studied. We have found that the amyloidogenic region of Gln3 acts as a template and initiates aggregation of the full-length Gln3 in the presence of the [PIN+] prion when Gln3 is overexpressed. Full-length Gln3 in its aggregated form manifests prion-like properties, including infectivity and dependence on the anti-prion agents; however, unlike other known yeast prions, prion-like state of Gln3 is observed only upon the protein overproduction. Here, we suggest the term "conditional prions" for proteins, whose prion state is maintained exclusively under non-physiological conditions.

Assessment of Oxidative Status of the Brain and Blood Plasma in Rats with Modeled Focal Cerebral Ischemia/Reperfusion Injury.

Parameters of the oxidative status of the brain and blood plasma were measured in rats 24 h after 1-h focal cerebral ischemia. In the brain of rats exposed to cerebral ischemia, activities of superoxide dismutase and catalase were elevated. Ischemia reduced the total antioxidant activity of the brain and the levels of malonic dialdehyde and protein carbonyl derivatives. In the blood plasma of experimental rats, superoxide dismutase activity and malonic dialdehyde level increased and total antioxidant activity decreased, i.e. the shifts were similar to those in the brain. The ischemia-induced changes in the brain and blood were not always co-directed.

[A neuroprotective action of carnosine in conditions of experimental focal cerebral ischemia-reperfusion]. / Neiroprotektivnoe deistvie karnozina v usloviiakh éksperimental'noi fokal'noi ishemii-reperfuzii golovnogo mozga.

AIM: To assess neuroprotective properties of preventive injections of carnosine in experimental focal cerebral ischemia in rats. MATERIAL AND METHODS: A focal ischemia in Wistar rats induced by the 60 min-occlusion of the middle cerebral artery with the following 24h-reperfusion was used. Animals received carnosine mixed with ration in daily dose of 150 mg/kg of body mass during 7 days before surgery. RESULTS AND CONCLUSION: Carnosine decreased the size of the lesion by 20%, neurological deficit by 43% with a simultaneous increase in the antioxidant status of blood plasma and brain tissue compared to the animals of the control group. The authors showed for the first time the neuroprotective effect of low dose of carnosine (150 mg/kg of body mass) mixed with ration used in preventive treatment courses in the experimental focal cerebral ischemia-reperfusion model.

Neuroprotective Effectiveness of Intravenous Ubiquinone in Rat Model of Irreversible Cerebral Ischemia.

The neuroprotective effect of ubiquinone (coenzyme Q10)was demonstrated on the rats model of ischemic stroke provoked by persistent 24-h occlusion of the middle cerebral artery. Coenzyme Q10 (30 mg/kg) was injected intravenously in 60 min after artery occlusion. Ubiquinone crossed the blood-brain barrier, accumulated in the brain, and produced a neuroprotective effect: it alleviated ischemia-induced neurological deficit and reduced the size of necrotic zone by 49% in comparison with rats receiving physiological saline.

[Intravenous injection of coenzyme Q10 increases its level in rat brain].

It is established that intravenous injection of solubilized coenzyme Q10 provides quick and lasting increase in its level in the brain as compared to control intact rats and those with cerebral ischemia. These new data provide a basis for studying the efficacy of coenzyme Q10 as a neuroprotective agent in ischemic stroke.

Propagation style controls lava-snow interactions.

Understanding interactions between volcanic eruptions and the cryosphere (a.k.a. glaciovolcanism) is important for climate reconstructions as well as for hazard mitigation at ice-clad volcanoes. Here we present unique field observations of interactions between snowpack and advancing basaltic lava flows during the 2012-13 eruption at Tolbachik volcano, Kamchatka, Russia. Our observations show that lava-snow heat transfer is slow, and that styles of lava propagation control snowpack responses. 'A'a and sheet lava flows advance in a rolling caterpillar-track motion on top of the rigid, snowpack substrate with minor lava-snow interaction. In contrast, pahoehoe lava propagates by inflation of lobes beneath/inside the snowpack, producing rigorous lava-snow interaction via meltwater percolation down into the incandescent lava causing production of voluminous steam, rapid surface cooling and thermal shock fragmentation. The textures produced by pahoehoe-snowpack interactions are distinctive and, where observed at other sites, can be used to infer syn-eruption seasonality and climatic conditions.

[Clinical effectiveness of cytoflavin inclusion in intensive care of patients with combined traumatic brain injury].

Autors determine the clinical effectiveness of including cytoflavin in intensive care of patients with severe combined traumatic brain injury. A prospective blind randomized controlled study was conducted on two groups involving 101 participants. In group I (58 patients), the intensive care was standard. In group II (43 patients), the intensive care included cytoflavin which was added beginning with the second day of the post-traumatic period. For this purpose, 10 ml of cytoflavin was dissolved in 200 ml of 10% aqueous solution of glucose and was administered intravenously at a speed of 140 drops (7 ml) per minute within 7 days. The use of cytoflavin in complex intensive care of severe combined traumatic brain injury within two days after injury (with the proper correction of blood circulation and respiration) reduced the number of multiple organ dysfunctions, the number is purulent-septic complications, the time of regress in multiple organ dysfunctions, and the reanimation period in intensive care department on the average by a factor of 1.4 - 1.6 (p < 0.005).

[New antioxidants as neuroprotective agents for the treatment of ischemic brain injury and neurodegenerative diseases].

Central nervous system disorders are the leading cause of mortality and disability in the world. Unfortunately, the possibility of pathogenetic therapy is limited and it is important to search for new drugs with neuroprotective mechanism of action. One of the most promising groups of drugs are antioxidants--substances that can neutralize free radicals and reduce oxidative stress. This review focuses on preclinical and clinical studies of new antioxidants.

[Efficiency of intensive care with cytoflavin in patients of advanced age in combined traumatic brain injury].

Research objective--determination of efficiency of intensive care with inclusion Cytoflavin in patients of old age in combined traumatic brain injury. A prospective controlled blind randomized study was conducted. In 1st group (21 people) the patients received a standard intensive care, in 2nd group (18 persons) Cytoflavin was included in complex intensive care. Using Cytoflavin starting from 2 days post-traumatic period (with the correction of blood circulation and respiration) had antioxidant and detoxification effects, contributed to the recovery rate of free radical and metabolic processes, reduced the degree of impairment in the structural-functional state of membranes and restored the conformational structure of membrane proteins in the earlier periods. Reduction in reactions of disadaptation led to regression of multiple organ dysfunctions, restoration the level of consciousness at an earlier date. The number of cases of severe respiratory distress syndrome decreased.

[Attention deficit hyperactivity syndrome: evolution, clinical presentations, treatment].

One-hundred and seven patients, aged 7-12 years, with attention deficit hyperactivity disorder (ADHD) were studied. All children were examined with psychoneurologist, additional methods included electroencephalography (EEG), ultrasound dopplerography of brachiocephalic vessels (USDG), rheoencephalography (REG), craniography and spondilography of the cervical spine. Perinatal adversities were recorded in 81.3% of children; pathological pregnancy (gestosis-26.6%, threat of miscarriage in 21.5%, treatment of latent urogenital infections -27.1% and others) and pathological deliveries (powerless labor-54.2%, asphyxia-21.5% etc) were also often observed; 43.9% of patients were discharged from the maternity hospital with diagnosis of hypoxic-traumatic CNS lesion. Mild mental retardation during the first year of life was reported in 41.1% of children, in 21.5% it remained for 3 years. The neurological study revealed coordination disturbances (31.8%), cervical insufficiency (67.9%), pyramidal insufficiency (33.6%). The changes correlating with perinatal pathology were shown by EEG, USDG and REG. Spondilography of the cervical spine confirmed the signs of the survived natal trauma in 45.8% of cases. All children received the complex therapy including drugs which improve the cerebral dynamics, nootropics, electrophoresis of spasmolytics in the cervical spine, psychotherapy sessions. Forty patients in addition received atomoxetine (strattera), the inhibitor of noradrenalin reuptake. The physician and parents as well reported the positive dynamics of patient's state as assessed the neurological status and performance on neuropsychological tests on attention concentration.

Activation of leptin expression by an inhibitor of carnitine palmitoyltransferase-1.

Leptin may regulate peripheral fatty acid oxidation and invoke a feedback mechanism that affects leptin expression in adipocytes. The objective of this study, therefore, was to determine whether inhibiting systemic fatty acid oxidation at the level of carnitine palmitoyltransferase-1 (CPT1) affects leptin expression. To accomplish this objective, fed or overnight fasted rats were treated with 2-tetradecylglycidic acid (TDGA), a specific, irreversible CPT1 inhibitor, and acute changes in rat epididymal leptin expression and serum leptin content were measured using Northern, RT-PCR, and radioimmunoassay analyses. Overnight fasting decreased both epididymal leptin mRNA content and serum leptin. Treating overnight fasted rats with TDGA increased both their epididymal leptin mRNA and their serum leptin significantly in a time- and concentration-dependent manner. TDGA affected neither epididymal leptin mRNA nor serum leptin in fed rats where systemic fatty acid oxidation is low. These results support the conclusion that CPT1-linked fatty acid oxidation is a key modulator of leptin expression in fasting rats.

[Use of T-activin and thymalin in the treatment of ophthalmic herpes]. / Primenenie taktivina i timalina pri lechenii oftal'mogerpesa.

Therapeutic efficacies of thymalin and T-activin were assessed in 80 patients with ophthalmic herpes. Thymic hormone preparations are recommended for the treatment of a protracted condition. To monitor the course of immunomodulating therapy, the neutrophil injury index and measurements of secretory IgA in the lacrimal fluid may be used, besides the routine tests.