[A tool to assess functional communication skills and its correspondence with traditional language testing in patients with brain tumors]. / Instrument izmereniya funktsional'nykh kommunikativnykh navykov i sopostavlenie ego s traditsionnym rechevym testirovaniem u patsientov s opukholyami golovnogo mozga.

OBJECTIVE: To identify the relationship between speech impairment as measured by the Russian Aphasia Test (RAT) and functional communication as assessed by the Communicative Effectiveness Index (CETI). MATERIAL AND METHODS: RAT and CETI were administered to 87 patients at two time points, before surgery and in 3 months after brain tumor resection surgery. RESULTS: There were significant correlations between CETI and the total scores on RAT subtests for speech comprehension and production before surgery but not in the follow-up period. CONCLUSION: The present research is the first to present the Russian version of CETI and to confirm the relationship between speech disorders measured by the comprehensive standardized battery for evaluating speech function RAT and functional communication as measured by CETI.

[Enteral nutrition in postoperative rehabilitation after reconstructive esophageal and gastric surgery]. / Rol' enteral'nogo pitaniya v reabilitatsii patsientov posle rekonstruktivnykh vmeshatel'stv na pishchevode i zheludke.

OBJECTIVE: To investigate enteral nutrition as a component of postoperative rehabilitation after reconstructive esophageal and gastric surgeries. MATERIAL AND METHODS: The study included 217 patients who underwent reconstructive esophageal and gastric surgeries between 2010 and 2020. In the main group (n=121), patients underwent postoperative enhanced recovery program (ERAS). Early enteral feeding including micro-jejunostomy and early oral feeding was essential for postoperative management. The control group included 96 patients who were treated in traditional fashion. The primary endpoint was length of hospital-stay (LOS) and ICU-stay. Restoration of gastrointestinal function (peristalsis, stool, oral nutrition), anastomotic leakage rate and other complications comprised secondary endpoints. RESULTS: Both groups did not differ by sex, age, body mass index, diagnosis and comorbidities. There was significant reduction in postoperative LOS in the ERAS group (14 (12; 15.8) and 9 (6.3; 12) days, p<0.0001). In the same group, we observed less in ICU-stay (4.7 (3.6; 5.6) and to 3.5 (2; 4) days, p<0.001), earlier recovery of peristalsis and X-ray control of anastomosis in patients with and without anastomotic leakage. Incidence of respiratory complications was lower in the ERAS group (p=0.034). Overall postoperative morbidity and mortality were similar. CONCLUSION: Early enteral and oral feeding after esophageal and gastric reconstructive surgery reduces hospital-stay and accelerates postoperative rehabilitation.

Multiple Sclerosis Is Associated with Immunoglobulin Germline Gene Variation of Transitional B Cells.

The regulatory functions of the B-cell compartment play an important role in the development and suppression of the immune response. Disruption of their anti-inflammatory functions may lead to the acceleration of immunopathological processes, and to autoimmune diseases, in particular. Unfortunately, the exact mechanism underlying the functioning and development of regulatory B cells (Breg) has not yet been fully elucidated. Almost nothing is known about their specificity and the structure of their B-cell receptors (BCRs). In this research, we analyzed the BCR repertoire of the transitional Breg (tBreg) subpopulation with the CD19+CD24highCD38high phenotype in patients with multiple sclerosis (MS), using next-generation sequencing (NGS). We show, for the first time, that the immunoglobulin germline distribution in the tBreg subpopulation is different between MS patients and healthy donors. The registered variation was more significant in patients with a more severe form of the disease, highly active MS (HAMS), compared to those with benign MS (BMS). Our data suggest that during MS development, deviations in the immunoglobulin Breg repertoire occur already at the early stage of B-cell maturation, namely at the stage of tBregs: between immature B cells in the bone marrow and mature peripheral B cells.

Differential Diagnostics of Active Progressing Multiple Sclerosis Using a Fluorescent Biomarker with Resonance Energy Transfer.

Previous data showed that myelin-reactive autoantibodies found in patients with multiple sclerosis and mice with experimental autoimmune encephalomyelitis recognize and hydrolyze various fragments of myelin basic protein (MBP). Moreover, antibody-mediated cleavage of the encephalithogenic fragment MBP81-103 flanked with two fluorescent proteins can serve as a new biomarker of multiple sclerosis. Here we describe creation of the next generation of this biomarker based on antibody-dependent degradation of a new chemically synthesized fluorescent substrate with resonance energy transfer that contains fluorophore Cy5 and quencher QXL680 separated by MBP81-99 protein (Cy5-MBP81-99-QXL680). This substrate is degraded during incubation with purified antibodies and B cells from patients with multiple sclerosis, but not healthy volunteers.

[A case of subtentorial progressive multifocal leucoencephalopathy in a patient treated with natalizumab]. / Sluchai razvitiia progressiruiushchei mul'tifokal'noi leikoéntsefalopatii subtentorial'noi lokalizatsii na fone terapii natalizumabom.

This paper presents a case report of subtentorial progressive multifocal leukoencephalopathy (PML) in a 26-year-old female patient treated with natalizumab. The evolution of clinical features, neuroimaging data and treatment as well as the development of immune reconstitution inflammatory syndrome (IRIS) are described. This case emphasizes the importance to keep accurately the risk management plan during natalizumab treatment. This includes performing MRI scans in order to detect changes typical for PML at the earliest (preclinical) stage in time.

Grey and white matter substrates of action naming.

Despite a persistent interest in verb processing, data on the neural underpinnings of verb retrieval are fragmentary. The present study is the first to analyze the contributions of both grey and white matter damage affecting verb retrieval through action naming in stroke. We used voxel-based lesion-symptom mapping (VLSM) with an action naming task in 40 left-hemisphere stroke patients. Within the grey matter, we revealed the critical involvement of the left precentral and inferior frontal gyri, insula, and parts of basal ganglia. An overlay of white matter tract probability masks on the VLSM lesion map revealed involvement of left-hemisphere long and short association tracts with terminations in the frontal areas; and several projection tracts. The involvement of these structures is interpreted in the light of existing picture naming models, semantic control processes, and the embodiment cognition framework. Our results stress the importance of both cortico-cortical and cortico-subcortical networks of language processing.

Neural mechanisms of two different verbal working memory tasks: A VLSM study.

Currently, a distributed bilateral network of frontal-parietal areas is regarded as the neural substrate of working memory (WM), with the verbal WM network being more left-lateralized. This conclusion is based primarily on functional magnetic resonance imaging (fMRI) data that provides correlational evidence for brain regions involved in a task. However, fMRI cannot differentiate the areas that are fundamentally required for performing a task. These data can only come from brain-injured individuals who fail the task after the loss of specific brain areas. In addition to the lack of complimentary data, is the issue of the variety in the WM tasks used to assess verbal WM. When different tasks are assumed to measure the same behavior, this may mask the contributions of different brain regions. Here, we investigated the neural substrate of WM by using voxel-based lesion symptom mapping (VLSM) in 49 individuals with stroke-induced left hemisphere brain injuries. These participants completed two different verbal WM tasks: complex listening span and a word 2-back task. Behavioral results indicated that the two tasks were only slightly related, while the VLSM analysis revealed different critical regions associated with each task. Specifically, significant detriments in performance on the complex span task were found with lesions in the inferior frontal gyrus, while for the 2-back task, significant deficits were seen after injury to the superior and middle temporal gyri. Thus, the two tasks depend on the structural integrity of different, non-overlapping frontal and temporal brain regions, suggesting distinct neural and cognitive mechanisms triggered by the two tasks: rehearsal and cue-dependent selection in the complex span task, versus updating/auditory recognition in the 2-back task. These findings call into question the common practice of using these two tasks interchangeably in verbal WM research and undermine the legitimacy of aggregating data from studies with different WM tasks. Thus, the present study points out the importance of lesion studies in complementing functional neuroimaging findings and highlights the need to consider task demands in neuroimaging and neuropsychological investigations of WM.

[Generation of Superoxide Radicals by Complex III in Heart Mitochondria and Antioxidant Effect of Dinitrosyl Iron Complexes at Different Partial Pressure of Oxygen].

The EPR spin-trapping technique and EPR-oximetry were used to study generation of superoxide radicals in heart mitochondria isolated from Wistar rats under conditions of variable oxygen concentration. Lithium phthalocyanine and TEMPONE-15N-D16 were chosen to determine oxygen content in a gas-permeable capillary tube containing mitochondria. TIRON was used as a spin trap. We investigated the influence of different oxygen concentrations in incubation mixture and demonstrated that heart mitochondria can generate superoxide in complex III at different partial pressure of oxygen as well as under the conditions of deep hypoxia (< 5% O2). Dinitrosyl iron complexes with glutathione (the pharmaceutical drug "Oxacom") exerted an antioxidant effect, regardless of the value of the partial pressure of oxygen, but the magnitude and kinetic characteristics of the effect depended on the concentration of the drug.

Diagnostic transcranial magnetic stimulation as a prognostic tool in children with acute transverse myelitis.

STUDY DESIGN: We performed transcranial magnetic stimulation (TMS) in children with sequelae of acute transverse myelitis. Single-pulse TMS protocol was implemented. Twenty controls and 24 patients with myelitis were enrolled. TMS was performed on 12-24 day after the onset of the first symptoms, average on 16th day. OBJECTIVES: The objective of our study was to evaluate motor pathways in children with viral myelitis using the TMS technique. SETTING: All investigations were performed in Scientific Research Institute for Children's Infections, Russia. RESULTS: There were statistically significant differences between the groups on central motor conduction time and motor evoked potential (MEPs) amplitudes. MEP thresholds were elevated, and MEP shape was abnormal in 96% of patients with myelitis (n=23). Three neurophysiologic patterns were observed: the presence of both cortical and spinal MEP, the absence of cortical MEP with the spinal MEP present and the total absence of both cortical and spinal MEP. Last finding was associated with paraplegia, resistant to any sort of treatment. CONCLUSION: Thus, myelitis in 96% of the cases causes neurophysiologic changes, which may be detected by TMS; the method may be used as a predicting tool.

Role of Chlamydia in Multiple Sclerosis.

Chlamydia and antibodies to them were detected by serological, molecular biological, and culture methods in the sera and cerebrospinal fluid of patients with multiple sclerosis and in the reference groups of subjects without neurological diseases. Correlations between the agent presence in the biological fluids of patients and clinical characteristics of the disease were analyzed. C. pneumoniae were more incident in the biological liquids of patients with multiple sclerosis than in healthy volunteers. On the other hand, the incidence of the agent in the patients was not high and its presence did not correlate with the clinical manifestations. C. trachomatis was equally rare in the patients and volunteers. The studies indicated the existence of a group of patients infected by C. pneumoniae in the cohort of patients with multiple sclerosis, but the impact of this agent for the disease course remains unclear.

[Comparative study of carbon nanotubes and polymer composites with silver as sorbents of the influenza A and B viruses].

The comparative examination of the interaction of the influenza A and B viruses and fragments of DNA with the carbon nanotubes--composites of polyaniline (PANI) nanotubes and granules containing Ag and without Ag was performed. The increased absorption of the allantois viruses and DNA was demonstrated in composites with Ag. The influence of temperature in the range of 4-36 degrees C was not found to be essential. The intensive absorption took place within the first 15 min of the contact with the sorbents. In total, the properties of the composites of PANI nanotubes + Ag 30% are the most promising for the influenza viruses and DNA absorption in water solutions.

[FMRI study of visual task switching in healthy individuals].

The present study was aimed, first, at developing a visual switching task for fMRI research and, second, at identification of the brain regions involved in task switching. Forty eight healthy individuals (from 21 to 56 years of age) participated in the study. The designed visual switching task was relatively short, it consisted of an easy stimulus set and involved a simple condition, in which participants had to shift their attention between two task conditions (classifying figures according to their form or number). Thus, this developed testing procedure can further be used to assess special populations, including patients with brain damage who cannot do monotonous tasks for a long period of time and have language impairments. The results of this testing technique revealed that task switching is carried out by an interconnected neuronal network, consisting of dorsolateral prefrontal cortex, inferior parietal area, secondary visual area, supplementary motor area and cerebellum cortex of both hemispheres.

[Internal carotid artery dissection as a cause of severe ischemic stroke with lethal outcome]. / Dissektsiya vnutrennei sonnoi arterii kak prichina tyazhelogo ishemicheskogo insul'ta s letal'nym iskhodom.

We present a medical history of a 30-year old male patient with fatal ischemic stroke, resulting from the right internal carotid artery (ICA) dissection provoked by repeated head tilts and verified by magnetic resonance imaging and pathomorphological examination. At admission, the high level of creatine phosphokinase (5284 un/ml, normal level<171) in the blood was found, the coagulation parameters were normal. Autopsy revealed intramural hematoma (IMH), which was located between the media and adventitia of the arterial wall, began at 3 cm above the common carotid artery bifurcation and extended to the base of the skull. The lumen of the ICA at the level of the IMG and intracranial parts as well as of the middle cerebral artery was occluded by the thrombus. The histological examination of the right ICA wall found splitting, thinning, fragmentation, disrupters of internal elastic membrane, severe media fibrosis, myocyte necrosis at the site of the dissection with the surrounding leukocyte infiltration, as well as lymphocytic infiltrates, clusters of eosinophils in adventitia. Similar changes, except myocyte necrosis, were also found in intact (non-dissected) brain supplying arteries. In general, they were similar to those in fibromuscular dysplasia (FMD). Histochemical and electron microscopic studies of skeletal muscles showed signs of mitochondrial cytopathy. The authors discuss the relationship between the dissection, FMD and mitochondrial pathology.

[Sex Differences in Visual Task Switching (an fMRI Study)].

Executive functions are an important ability of human brain to program, regulate and control various cognitive processes; one of these processes is the voluntary task switching. However, the sex differences in this process are poorly studied. In our study, these differences were investigated in 70 healthy subjects (36 men and 34 women) aged 21-48 years by means of functional magnetic resonance imaging (fMRI) and neuropsychological examination. During the fM RI study, the subjects had to shift their attention between two tasks (classifying figures according to their form or number). During neuropsychological examination, the subjects completed a series of visual attention, task switching and memory tests. The results of fMRI study showed that visual task switching in women is carried out by a neuronal network, consisting of dorsolateral prefrontal cortex, inferior parietal areas, secondary visual areas of both hemispheres and cerebellum cortex. Task switching in men involved the same areas and, in addition, right supplementary motor area, right insula and left thalamus. As compared with women, the rate of activation of prefrontal cortex, left parietal lobe and right insula in men was significantly higher. The results of neuropsychological tests showed that men completed the tasks with attention switching, searching and arranging of stimuli significantly slower than women. The data demonstrate the differences in the organization of task switching processes in men and women.

Processing lexical ambiguity in sentential context: Eye-tracking data from brain-damaged and non-brain-damaged individuals.

The purpose of the present study was to identify general and syndrome-specific deficits in the lexical processing of individuals with non-fluent and fluent aphasia compared to individuals without cognitive, neurological or language impairments. The time course of lexical access, as well as lexical selection and integration was studied using a visual-world paradigm in three groups of Russian speakers: 36 individuals in the control group, 15 individuals with non-fluent aphasia and eight individuals with fluent aphasia. Participants listened to temporarily ambiguous sentences wherein the context biased the interpretation of an ambiguous word toward one of its two meanings. In half of the experimental sentences, a reanalysis was needed upon encountering the disambiguating phrase. The effect of the length of the intervening material between the ambiguous word and the disambiguation point was additionally monitored. All groups of participants showed intact lexical access under slowed speech rate, but non-fluent participants experienced difficulties with timely activation of multiple referents. At later stages of lexical processing, they additionally demonstrated a specific impairment of reanalysis. The deficit in participants with fluent aphasia was not focalized at any specific stage of lexical processing. Rather, the breakdown of lexical processes in fluent aphasia was likely related to difficulties with the inhibition of irrelevant lexical activation, which is further supported by the finding that increased phonological distance between the ambiguous word and ambiguity resolution was influential to the offline performance in this group.

CETP gene polymorphism in the caucasian population of West Siberia and in groups contrast by total serum cholesterol levels.

TaqIB polymorphism of the gene encoding cholesterol ester transporting protein (CETP) was analyzed in the Caucasian population of West Siberia and in groups contrast by total serum cholesterol content. The patients were selected for the study from the main sample of HAPIEE project (9600 examined subjects aged 45-69 years, 50% men). Analysis was carried out in 293 patients with high levels of total cholesterol (>300 mg/dl), 293 patients with normal and low levels of total cholesterol (<200 mg/dl), and 265 patients represented the population sample (mean level of total cholesterol 235.8±43.9 mg/dl). The frequencies of B1B1, B1B2, and B2B2 genotypes in the population were 27.5, 54.8, and 17.7%, respectively. The incidence of allele B2 was 45.1, 45.2, and 50.2% in the population and in groups with normal and high total cholesterol levels, respectively (p>0.05). Associations of CETP gene TaqIB (rs708272) polymorphism with HDL cholesterol levels was detected in groups with high and low total cholesterol levels (p=0.014 and p=0.008). CETP gene TaqIB polymorphism B2B2 genotype was associated with high level of HDL cholesterol and a more favorable lipid profile.

[The chylomicronemia under interpretation of the results of detection of lipid profile of blood].

The lipid profile of blood of several population screenings was studied in the framework of the international project HAPIEE. The sampling consisted of 9357 patients aged from 45 to 69 years. All participants of the study were notified in advance about blood sampling on an empty stomach for analysis. The blood serum was not totally clear and triglycerides concentration of 2.65 mmol/l in 16% of cases. The examined patients approved in 3.5% that blood was not taken on an empty stomach. The diabetes mellitus was diagnosed in 1.6% of patients. Among the rest 10.9% of patients with blood samples not totally clear half of them had concentration of glucose in blood higher than 5.5 mmol/l. Some of them probably came to screening not on an empty stomach and did not approve it. The epidemiologic studies require a strict regulation of daytime of food intake prior to blood sampling for analysis. The degree of blood clearness and blood glucose concentrations are to be regulated to and in some case the analysis is to be repeated.

Effects of simvaglyzin and atorvaglyzin on the expression of 3-hydroxy-3-methyl-glutaryl-CoA reductase in rat liver.

Activity and levels of protein and mRNA of 3-hydroxy-3-methyl-glutaryl-CoA reductase were estimated in rat liver after the administration of atorvastatin and simvastatin and their complexes with glycyrrhizic acid (atorvaglyzin and simvaglyzin). The amount of 3-hydroxy-3-methyl-glutaryl-CoA reductase protein in rats decreased by 13 and 25% (p<0.05) 24 h after treatment with atorvaglyzin and simvaglyzin, respectively. Activity of this enzyme decreased by 46% in rats treated with atorvaglyzin. The amount of messenger RNA in these groups significantly increased as compared to control group (untreated animals).

[Paramagnetic calcium melanins].

Treatment of catechol, pyrogallol, DOPA, dopamine, norepinephrine, and natural polyhydroxy-1,4-naphthoquinone echinochrome by aqueous solution of potassium superoxide (KO2) in the presence of CaCl2 leads to the formation of water-insoluble dark pigments with stable paramagnetic properties ("calcium melanins"). In control experiments in the same procedure without Ca2+, the pigments were not formed. EPR spectra of the calcium melanins had little difference from each other and from known melanins in shape, line width, and the g factor about 2,004. Addition of EDTA water solution to dried paramagnetic pigments leads to their fast dissolving and disappearing of EPR signal. Formation of similar polymers is also observed during autoxidation of o-diphenols in Ca(2+)-containing alkaline buffer solution, however, this process takes a few days instead of few seconds in the presence of KO2. Thus, calcium (and other divalent cation M2+) can consider as a key structural element in formation of M(2+)-catecholate paramagnetic Polymer. We assume the existence of two types of paramagnetic centers in melanin-like polymer: M(2+)-stabilized o-semiquinone radical or bi-radical complex containing o-semiquinone and superoxide anion radicals, stabilized by M2+.

[Biomarkers in multiple sclerosis (a review and experimental data)].

Identification of biomarkers in multiple sclerosis is a very complex problem, and intensive work is being made in this field for the last decades. The importance of establishing biomarkers of multiple sclerosis is related to the high disease heterogeneity and lack of characteristic symptoms that leads to diagnostic, prognostic challenges and difficulties in making decisions about therapy. In this paper, we review the most important biomarkers and discuss their diagnostic and prognostic value. Experimental results on neurofilament heavy chains and antibodies to sulfatide in multiple sclerosis are presented.