Aberrant methylation of placental development genes in chorionic villi of spontaneous abortions with trisomy 16.

In humans, aneuploidy is incompatible with the birth of healthy children and mainly leads to the death of embryos in the early stages of development in the first trimester of pregnancy. Trisomy 16 is the most common aneuploidy among spontaneous abortions of the first trimester of pregnancy. However, the mechanisms leading to the death of embryos with trisomy 16 remain insufficiently investigated. One of these potential mechanisms is abnormal placental development, including aberrant remodeling of spiral arteries. Spiral artery remodeling involves the migration of trophoblast cells into the maternal spiral arteries, replacing their endothelium and remodeling to ensure a stable embryonic nutrition and oxygen supply. This is a complex process which depends on many factors from both the embryo and the mother. We analyzed the methylation level of seven genes (ADORA2B, NPR3, PRDM1, PSG2, PHTLH, SV2C, and TICAM2) involved in placental development in the chorionic villi of spontaneous abortions with trisomy 16 (n = 14), compared with spontaneous abortions with a normal karyotype (n = 31) and the control group of induced abortions (n = 10). To obtain sequencing libraries, targeted amplification of individual gene regions using designed oligonucleotide primers for bisulfite-converted DNA was used. The analysis was carried out using targeted bisulfite massive parallel sequencing. In the group of spontaneous abortions with trisomy 16, the level of methylation of the PRDM1 and PSG2 genes was significantly increased compared to induced abortions (p = 0.0004 and p = 0.0015, respectively). In the group of spontaneous abortions, there was no increase in the level of methylation of the PRDM1 and PSG2 genes, but the level of methylation of the ADORA2B gene was significantly increased compared to the induced abortions (p = 0.032). The results obtained indicate the potential mechanisms of the pathogenetic effect of trisomy 16 on the placental development with the participation of the studied genes.

Self-Similar Growth of Bose Stars.

We analytically solve the problem of Bose star growth in the bath of gravitationally interacting particles. We find that after nucleation of this object, the bath is described by a self-similar solution of the kinetic equation. Together with the conservation laws, this fixes mass evolution of the Bose star. Our theory explains, in particular, the slowdown of the star growth at a certain "core-halo" mass, but also predicts formation of heavier and lighter objects in magistral dark matter models. The developed "adiabatic" approach to self-similarity may be of interest for kinetic theory in general.

[Tractography in functional neuronavigation]. / Traktografiya v funktsional'noi neironavigatsii.

The review addresses the combined use of tractography and neuronavigation. Fundamentals of diffusion tensor imaging are given, technical aspects of fiber tracking in general and in depicting separate subcortical tracts are described. Main advantages of the method and possible causes of errors are highlighted. Precision assessment of this technology is given by comparing with results of subcortical neurostimulation. Surgical tactics is described depending on distance between the tumor and subcortical pathways.

Evaluation of the effectiveness of personalised therapy for the patients with irritable bowel syndrome.

Intestinal microbiota correction in the therapy of irritable bowel syndrome (IBS) is an important medical problem. We conducted a laboratory and pilot clinical trial to investigate the effect of autoprobiotic bacteria, indigenous bifidobacteria and enterococci isolated from faeces and grown on artificial media to use as personified food additives in IBS treatment. Convincing evidence of the clinical efficacy of autoprobiotic was demonstrated by the disappearance of dyspeptic symptoms. The microbiome of patients with IBS was compared to a group of healthy volunteers and changes in the microbiome after autoprobiotic use were detected by quantitative polymerase chain reaction and 16S rRNA metagenome analysis. The possibility of reducing opportunistic microorganisms in the treatment of IBS with autoprobiotics has been convincingly proven. The quantitative content of enterococci in the intestinal microbiota was higher in IBS patients than in healthy volunteers and increased after therapy. An increase in the relative abundance of genera Coprococcus, Blautia and a decrease in the relative abundance of Paraprevotella spp. were found at the end of therapy. A metabolome study which was performed by gas chromatography and mass spectrometry demonstrated an increase in the content of oxalic acid, a decrease of dodecanoate, lauric acid, and other metabolome components after taking autoprobiotics. Some of these parameters correlated with the relative abundances of Paraprevotella spp., Enterococcus spp., and Coprococcus spp. representative of the microbiome. Apparently, they reflected the peculiarities of metabolic compensation and changes in the microbiota. Therefore, the use of autoprobiotics for treatment of IBS may lead to a stable positive clinical effect, associated with compensatory changes in the intestinal microbiota, and accompanied by corresponding changes in metabolic processes in the organism.

Expression of the NUP153 and YWHAB genes from their canonical promoters and alternative promoters of the LINE-1 retrotransposon in the placenta of the first trimester of pregnancy.

The placenta has a unique hypomethylated genome. Due to this feature of the placenta, there is a potential possibility of using regulatory elements derived from retroviruses and retrotransposons, which are suppressed by DNA methylation in the adult body. In addition, there is an abnormal increase in the level of methylation of the LINE-1 retrotransposon in the chorionic trophoblast in spontaneous abortions with both normal karyotype and aneuploidy on different chromosomes, which may be associated with impaired gene transcription using LINE-1 regulatory elements. To date, 988 genes that can be expressed from alternative LINE-1 promoters have been identified. Using the STRING tool, genes (NUP153 and YWHAB) were selected, the products of which have significant functional relationships with proteins highly expressed in the placenta and involved in trophoblast differentiation. This study aimed to analyze the expression of the NUP153 and YWHAB genes, highly active in the placenta, from canonical and alternative LINE-1 promoters in the germinal part of the placenta of spontaneous and induced abortions. Gene expression analysis was performed using real-time PCR in chorionic villi and extraembryonic mesoderm of induced abortions (n = 10), adult lymphocytes (n = 10), spontaneous abortions with normal karyotype (n = 10), and with the most frequent aneuploidies in the first trimester of pregnancy (trisomy 16 (n = 8) and monosomy X (n = 6)). The LINE-1 methylation index was assessed in the chorionic villi of spontaneous abortions using targeted bisulfite massive parallel sequencing. The level of expression of both genes from canonical promoters was higher in blood lymphocytes than in placental tissues (p < 0.05). However, the expression level of the NUP153 gene from the alternative LINE-1 promoter was 17 times higher in chorionic villi and 23 times higher in extraembryonic mesoderm than in lymphocytes (p < 0.05). The expression level of NUP153 and YWHAB from canonical promoters was higher in the group of spontaneous abortions with monosomy X compared to all other groups (p <0.05). The LINE-1 methylation index negatively correlated with the level of gene expression from both canonical (NUP153 - R = -0.59, YWHAB - R = -0.52, p < 0.05) and alternative LINE-1 promoters (NUP153 - R = -0.46, YWHAB - R = -0.66, p < 0.05). Thus, the observed increase in the LINE-1 methylation index in the placenta of spontaneous abortions is associated with the level of expression of the NUP153 and YWHAB genes not only from alternative but also from canonical promoters, which can subsequently lead to negative consequences for normal embryogenesis.

CRISPR/Cas9 genome editing demonstrates functionality of the autoimmunity-associated SNP rs12946510.

Genome-wide association studies (GWAS) map genetic associations of complex traits with precision limited to a linkage disequilibrium group. To translate GWAS results into new understanding of disease mechanisms, individual causative polymorphisms and their target genes should be identified. CRISPR/Cas9 genome editing can be used to create isogenic cell lines bearing alternative genotypes of candidate single-nucleotide polymorphisms to test their causality and to reveal gene targets. An intergenic polymorphism rs12946510 is associated with multiple sclerosis, inflammatory bowel disease and asthma. We created sublines of the T-helper cell line bearing alternative genotypes of rs12946510 and showed that its risk ("T") allele is associated with lower expression of IKZF3 and ORMDL3 genes and reduced cell activation. Our editing procedure can become an effective tool for discovering new genes involved in pathogenesis of complex diseases.

[Treatment of attention deficit hyperactivity disorder in children: results of a multicenter, randomized, double-blind, placebo-controlled clinical trial]. / Terapiya sindroma defitsita vnimaniya s giperaktivnost'yu u detei: rezul'taty mnogotsentrovogo randomizirovannogo dvoinogo slepogo platsebo-kontroliruemogo klinicheskogo issledovaniya.

OBJECTIVE: Evaluation of the efficacy and safety of the new drug Prospekta in the treatment of attention deficit hyperactivity disorder (ADHD) in patients aged 7-12 years. MATERIAL AND METHODS: A multicenter (35 clinical centres) double-blind, placebo-controlled, randomized, parallel-group clinical trial enrolled 363 patients. The mean age was 9.3±1.7 years. Children of both sexes aged between 7 and 12 years with a diagnosis of ADHD confirmed by DSM-V diagnostic criteria were included in the study. Patients with a total score of 22 or more on the Attention Deficit Hyperactivity Disorder-Rating Scale-V (ADHD-RS-V) were included in the study. After randomisation, patients in group 1 received Prospekta, 1 tablet twice daily; patients in group 2 received placebo according to the study drug regimen. The primary efficacy criterion was the proportion of patients with a 25% or greater reduction in the overall ADHD-RS-V scale score after 8 weeks of treatment. As additional criteria for efficacy assessment were assessed: change of ADHD-RS-V total score from baseline after 8 weeks of treatment; Clinical Global Impression Efficacy Index (CGI-EI) score after 8 weeks of treatment; side effects. RESULTS: The proportion of patients with a 25% or more reduction in the ADHD-RS-V scale score after 8 weeks of treatment was 55.9% in the Prospekta group, and 43.3% in the placebo group (p=0.0199). There was a reduction of ADHD symptoms in the Prospekta group as a mean ADHD-RS-V score decreased by 10.2±7.7 (in the placebo group by 8.1±7.9); the difference between the mean ADHD-RS-V score reduction during Prospekta and placebo treatment was 2.09±7.81 (p=0.0096). Mean CGI-EI scores calculated on the basis of physician scores were different in the Prospekta group compared to the placebo group at 6.9±3.2 versus 8.0±3.1 (p=0.0012), indicating greater clinical efficacy of the study drug. The frequency of adverse events (AEs) did not differ significantly between the groups. There were a total of 66 AEs in 46 patients, including 31 AEs in 23 (13.2%) Prospekta group participants and 35 AEs in 23 (12.2%) placebo group participants (p=0.87). No cases of serious AEs were reported during the study. Prospekta is compatible with drugs used in pediatric practice. Prospekta did not cause an exciting effect and did not adversely affect the sleep of patients. CONCLUSION: The drug Prospekta is an effective and safe treatment for ADHD in patients 7-12 years old.

[Plant Genome Sequencing: Modern Technologies and Novel Opportunities for Breeding].

The investigation of plant genomes is of great importance for basic research and practical breeding. In 1977, F. Sanger proposed a DNA sequencing method, which allowed the complete sequences of a number of genomes to be determined. Then high-throughput and cost-effective next-generation/second-generation sequencing methods, producing up to billions of short reads, made it possible to sequence genomes of a significant number of species and provided a breakthrough in plant genetic studies. Finally, third-generation sequencing technologies allowed the determination of single-molecule sequences up to a million nucleotides in length, which is key for high-quality genome assemblies. An important task is to obtain a pan-genome, which includes an entire set of nucleotide sequences presented in various genotypes of the same species. The sequencing of plant genomes made it possible to assess intraspecific polymorphism, identify key genes influencing the formation of significant features, and develop molecular markers of economically valuable traits and this has become the basis for the development of marker-assisted and genomic selection. This review provides information on the latest advances in sequencing technologies and the assembly of plant genomes, as well as the opportunities that they open up for basic and applied works.

[Intraoperative brain shift in neuronavigation. Causes, clinical significance and solution of the problem]. / Intraoperatsionnoe smeshchenie mozga pri primenenii neironavigatsii. Prichiny, klinicheskaya znachimost' i puti resheniya problemy.

Intraoperative brain shift is the main cause of inaccurate navigation. This limits the use of both conventional and functional neuronavigation. Causes of brain shift are divided into surgical, pathophysiological and metabolic ones. Brain shift is usually unidirectional and directed towards gravitation. Brain dislocation depends on lesion size and its location. Shift is minimal in patients with tumors <20 ml and skull base neoplasms. Small craniotomy, retractor-free surgery and no ventriculostomy are valuable to reduce brain shift. Brain dislocation increases during surgery that's why marking of eloquent lesions at the beginning of surgery and primary resection near subcortical tracts minimize the risk of damage to conduction pathways. Augmented reality and manual shift of marked objects are the cornerstones of linear correction of brain shift in modern navigation systems. In case of nonlinear brain shift, sonography and intraoperative magnetic resonance imaging can clarify location of surgical target and cerebral structures.

Prompt gamma activation analysis for determining the elemental composition of archaeological ceramics.

The first experiments were carried out to study the elemental composition of archaeological ceramics using prompt gamma activation analysis (PGAA) at the pulsed reactor IBR-2, Frank Laboratory of Neutron Physics (FLNP) - Joint Institute for Nuclear Research (JINR). A radiation-resistant n-type High Purity Germanium (HPGe) detector was used to measure the radioactivity. The concentrations of 14 elements were determined namely; Al, C, Ca, Fe, Gd, H, K, Mn, Na, P, S, Si, Sm, and Ti. The obtained results were compared with those analyzed by other analytical techniques INAA (Instrumental Neutron Activation Analysis) and portable X-ray fluorescence (XRF) for the same archaeological batches. The results revealed a good agreement within a range of 1-30%. These insights will contribute to the discussion of improving the PGAA installation and automation of the data obtained, which in turn will improve the quality of analysis and increase the number of determined elements. In this work results are presented, and the analytical merits are compared.

[Intraoperative magnetic resonance imaging in surgery of brain gliomas]. / Intraoperatsionnaya magnitno-rezonansnaya tomografiya v khirurgii gliom bol'shikh polusharii.

Intraoperative magnetic resonance imaging (iMRI) is used in surgery of supratentorial gliomas to assess resection quality, as well as in neoplasm biopsy to control the needle position. Scanners coupled with operating table ensure fast intraoperative imaging, but they require the use of non-magnetic surgical tools. Surgery outside the scanner 5G line allows working with conventional instruments, but patient transportation takes time. Portable iMRI systems do not interfere with surgical workflow but these scanners have poor resolution. Positioning of MRI scanners in adjacent rooms allows imaging simultaneously for several surgeries. Low-field MRI scanners are effective for control of contrast-enhanced glioma resection quality. However, these scanners are less useful in demarcation of residual low-grade tumors. High-field MRI scanners have no similar disadvantage. These scanners ensure fast detection of residual gliomas of all types and functional imaging. Artifacts during iMRI are usually a result of iatrogenic traumatic brain injury and contrast agent leakage. Ways of their prevention are discussed in the review.

[Functional magnetic resonance imaging in neurosurgery]. / Funktsional'naya magnitno-rezonansnaya tomografiya v neirokhirurgii.

The study is a short review of articles concerning functional magnetic resonance imaging (fMRI) and its practical application in neurosurgery. Advantages and disadvantages of the methods are considered, the results of surgical treatment of patients using functional navigation are presented. Separate attention is paid to fMRI precision, a new resting-state method of visualization. Practical advices of fMRI application in neurooncology and surgery of arteriovenous malformations are given.

[Invasive EEG for temporal lobe epilepsy: selection of technique]. / Invazivnyi video-EEG monitoring pri visochnoi epilepsii: vybor metoda.

BACKGROUND: Non-invasive EEG reveals epileptogenic zone in 70% of patients. In other cases, invasive EEG monitoring is indicated. Various implantation strategies and techniques of intracranial EEG (icEEG) potentially provide different outcomes. Choosing the optimal icEEG technique may be challenging. OBJECTIVE: To analyze the results of icEEG in adults with temporal lobe epilepsy and to determine the algorithm for selection of optimal invasive EEG technique. MATERIAL AND METHODS: The study included 82 patients with temporal lobe epilepsy who underwent invasive EEG. Effectiveness of invasive EEG was determined by detection of epileptogenic zone and post-resection outcomes. Postoperative results were analyzed throughout more than 6-month follow-up period using the Engel grading system. Statistical analysis was conducted using the Fisher's exact test. RESULTS: Epileptogenic zone was revealed in 72 (88%) cases. Invasive EEG was supplemented by another modality in 3 (4%) patients. Mean follow-up period after resection was 17 months in 45 patients. Favorable outcomes were achieved in 31 (69%) cases. Statistical analysis showed that identification of epileptogenic zone depends existing of lesion and symptoms of seizures. Selection algorithm for optimal technique of invasive EEG was determined considering own results and literature data. CONCLUSION: Invasive EEG results and post-resection outcomes demonstrated favorable efficacy of original algorithm. The last one may be used in decision-making on optimal technique of invasive EEG in adults with temporal lobe epilepsy.

[Functional magnetic resonance imaging in neurosurgery]. / Funktsional'naya magnitno-rezonansnaya tomografiya v neirokhirurgii.

The review of publications on functional magnetic resonance imaging (fMRI) and its practical application in neurosurgery is presented. Advantages and disadvantages are selected taking pathogenesis into account. Results of surgical treatment with use of functional navigation are described. Separate attention is paid to fMRI precision by its comparing with direct cortical stimulation. New resting-state method of visualization is observed. Practical advices are given of fMRI application in neurooncology and surgery of arteriovenous malformations.

[Glutamine as a component of nutritional and metabolic therapy for surgical patients in ICU]. / Glutamin kak komponent nutritivno-metabolicheskoi terapii patsientov khirurgicheskogo profilya v usloviyakh ORIT.

Glutamine is the most abundant amino acid in the human body that is involved in various metabolic processes. The development of hypermetabolic and hypercatabolic syndrome that accompanies critical conditions of ICU patients is associated with a decrease in the concentration of glutamine, especially in the blood plasma and muscles. This process may last for quite a long time and lead to a number of complications up to a fatal outcome. This review was aimed to analyze clinical studies conducted over the past 20 years that demonstrate the effect of intravenous infusion of glutamine dipeptide as part of balanced parenteral nutrition on the perioperative period: the severity of inflammatory response; the state of the intestinal mucosa; the incidence and severity of complications; mortality; the duration of stay in the ICU and hospital in general, etc. The analysis was performed using systematic reviews and meta-analyses based on randomized double-blind, placebo-controlled trials in different countries selected in the main databases (PubMed, EMBASE, Web of Science, The Cochrane Library, etc.). Most of the reports state that the inclusion of glutamine dipeptide in nutritional and metabolic therapy (NMT) in surgical patients reduces the frequency and severity of infectious complications and mortality, reduces the length of stay in ICU and in hospital in general, improves the biochemical parameters that reflect the condition of patients, and reduces the treatment costs. Thus, the conducted systematic reviews and meta-analyses confirm that the use of the parenteral form of glutamine dipeptide (Dipeptiven 20%) as part of balanced standard parenteral nutrition (PN) is a clinically and pharmacoeconomically justified strategy of NMT in surgical ICU patients.

Artificial radio lighting with sources of microwave dynamic chaos.

Application of dynamic chaos for the illumination of the surrounding space by artificial incoherent sources of microwave radiation with the purpose of its subsequent observation using special receiving equipment is considered. An incoherent broadband microwave radiation field is provided by "radio light lamps" based on dynamic chaos generators. The radio light is received with specially designed sensitive elements that combine the properties of an envelope detector in communication systems and a radiometer. It is shown that with the help of directional antennas connected to these sensitive elements, it is possible to create receivers with spatial resolution for visualizing a part of the surrounding space in artificial radio light. Radio light images of a room have been obtained. The possibility to detect changes associated with the emergence of new objects on these images is demonstrated.

[Predict of metabolic stability of xenobiotics by the PASS and GUSAR programs]. / Prognoz metabolicheskoi stabil'nosti ksenobiotikov programmami PASS i GUSAR.

Metabolic stability refers to the susceptibility of compounds to the biotransformation; it is characterized by such pharmacokinetic parameters as half-life (T1/2) and clearance (CL). Generally, these parameters are estimated by in vitro assays, which are based on cells or subcellular fractions (mainly liver microsomal enzymes) and serve as models of the processes occurring in living organisms. Data obtained from the experiments are used to build QSAR (Quantitative Structure-Activity Relationship) models. More than 8000 compounds with known CL and/or T1/2 values obtained in vitro using human liver microsomes were selected from the freely available ChEMBL v.27 database. GUSAR (General Unrestricted Structure-Activity Relationships) and PASS (Prediction of Activity Spectra for Substances) softwares were used to make quantitative and classification models. The quality of the models was evaluated using 5-fold cross-validation. Compounds were subdivided into "stable" and "unstable" by means of the following threshold parameters: T1/2 = 30 minutes, CL = 20 ml/min/kg. The accuracy of the models ranged from 0.5 (calculated in 5-fold CV on the test set for the half-life prediction quantitative model) to 0.96 (calculated in 5-fold CV on the test set for the clearance prediction classification model).

[The last tsarist minister N. K. Kulchickiy (1856-1925): in between science and politics].

The article analyzes the scientific and political aspects of the biography of Nikolai Konstantinovich Kulchitsky (1856-1925). He was not only the last tsarist minister of education, but also the sole medico at this high position. The scientific achievements of professor histologist from Kharkov have proved to be in great demand in the XXI century not only in neuroendocrinology, but in oncology and pulmonology too. The authors analyzed the stages and conditions of the administrative career of the conservative Kulchitsky heading large educational districts during five years and two ministerial months in the beginning of 1917. He managed to do not a little for development of school hygiene and sanitation in the Kazan and Petrogad educational districts, including in conditions of the world war. The meaningful for the particular epoch the combination of medical and social aspects of activities of gifted researcher medico deserves a special attention and comprehensive study.

[Chronic spinal stimulation in treatment of lower limb critical ischaemia syndrome]. / Khronicheskaia spinal'naia stimuliatsiia v lechenii sindroma kriticheskoi ishemii nizhnikh konechnostei.

Obliterating peripheral artery disease is a commonly occurring pathological condition, most often resulting from an atherosclerotic lesion of vessels with progressive narrowing of their lumens. The consequences of decompensation of chronic arterial insufficiency such as ischaemic pain, claudication, and trophic impairments are in some instances difficult to treat, despite using multicomponent medicamentous therapy and/or performing revascularizing interventions. This article describes a clinical case report regarding the use of spinal stimulation in a patient presenting with stage IV chronic lower limb ischaemia according to the Fontaine classification. This is accompanied and followed by depicting the dynamics of the laboratory, instrumental, and clinical parameters over a two-year follow-up period. In order to explain the choice of the intervention and the causes of the described picture, discussed are the existing theories of the mechanisms of action of spinal stimulation. To this is added a literature review of using this method in treatment of lower limb critical ischaemia when performing reconstructive angiosurgical treatment is unavailable. Mention is also made of the incidence and types of probable complications, as well as possibilities and limitations of the method.