An Individualized Approach to Skin Conductance Assessment during Execution of Tasks of Different Complexities.

Researchers use different approaches to analyze changes in skin conductance. At the same time, individual differences observed in both the initial values of skin conductance and response to stimuli do not allow comparing the responses of different subjects to the same impact. An individualized approach to the assessment of psycho-emotional stress has been developed using the real-time skin conductance index during continuous performance of a task with different levels of complexity. The participants, 18 second-year students at the actors' high school, performed a simple task (expressive reading aloud of a simple text) and a difficult task (expressive reading aloud of the text inverted 180°). During the task, the skin conductance in the participants was continuously recorded. We revealed a change in the parameters of skin conductivity depending on the complexity of the task, both in comparison with resting state (baseline) and with simple and complex stages of the study. However, the individual skin conduction curves in the subjects differed greatly. A method for assessing the individual differences in parameters of skin conductance was proposed based on ranking by categories of values during continuous performance of tasks with different levels of complexity. This method allows comparing the levels of cognitive load in participants with different initial levels of skin conductance due to transition from the absolute to relative values at time intervals that are important for the researcher.

Parameters of Cell Death and Proliferation of Prostate Cancer Cells with Altered Expression of Myosin 1C Isoforms.

Myosin 1C is a monomeric myosin motor with a truncated tail domain. Such motors are referred as slow "tension sensors." Three isoforms of myosin 1C differ in short N-termed amino acid sequences, the functional differences between isoforms have not been elucidated. Myosin 1C isoform A was described as a diagnostic marker for prostate cancer, but its role in tumor transformation remains unknown. Based on data on the functions of myosin 1C, we hypothesized the potential role of myosin 1C isoforms in maintaining the tumor phenotype of prostate cancer cells. In our work, we showed that a decrease in the expression level of myosin 1C isoform C leads to an increase in the proliferative activity of prostate tumor cells.

Mesenchymal stem cells lose the senescent phenotype under 3D cultivation.

BACKGROUND: Three-dimensional (3D) cell culture is widely used in various fields of cell biology. In comparison to conventional two-dimensional (2D) cell culture, 3D cell culture facilitates a more accurate replication of the in vivo microenvironment, which is essential for obtaining more relevant results. The application of 3D cell culture techniques in regenerative medicine, particularly in mesenchymal stem cell (MSC)-based research, has been extensively studied. Many of these studies focus on the enhanced paracrine activity of MSCs cultured in 3D environments. However, few focus on the cellular processes that occur during 3D cultivation. METHODS: In this work, we studied the changes occurring within 3D-cultured MSCs (3D-MSCs). Specifically, we examined the expression of numerous senescent-associated markers, the actin cytoskeleton structure, the architecture of the Golgi apparatus and the localization of mTOR, one of the main positive regulators of replicative senescence. In addition, we assessed whether the selective elimination of senescent cells occurs upon 3D culturing by using cell sorting based on autofluorescence. RESULTS: Our findings indicate that 3D-MSCs were able to lose replicative senescence markers under 3D cell culture conditions. We observed changes in actin cytoskeleton structure, Golgi apparatus architecture and revealed that 3D cultivation leads to the nuclear localization of mTOR, resulting in a decrease in its active cytoplasmic form. Additionally, our findings provide evidence that 3D cell culture promotes the phenotypic reversion of senescent cell phenotype rather than their removal from the bulk population. CONCLUSION: These novel insights into the biology of 3D-MSCs can be applied to research in regenerative medicine to overcome replicative senescence and MSC heterogeneity as they often pose significant concerns regarding safety and effectiveness for therapeutic purposes.

Inside and outside of virus-like particles HBc and HBc/4M2e: A comprehensive study of the structure.

Hepatitis B virus core antigen (HBc) with the insertion of four external domains of the influenza A M2 protein (HBc/4M2e) form virus-like particles whose structure was studied using a combination of molecular modeling and cryo-electron microscopy (cryo-EM). It was also shown that self-assembling of the particles occurs inside bacterial cells, but despite the big inner volume of the core shell particle, purified HBc/4M2e contain an insignificant amount of bacterial proteins. It was shown that a fragment of the M2e corresponding to 4M2e insertion is prone to formation of amyloid-like fibrils. However, as the part of the immunodominant loop, M2e insertion does not show a tendency to intermolecular interaction. A full-atomic HBc-4M2e model with the resolution of about 3 Å (3.13 Å for particles of Т = 4 symmetry, 3.7 Å for particles of Т = 3 symmetry) was obtained by molecular modeling methods based on cryo-EM data.

Stabilometric Biofeedback Training in Cognitive and Affective Function Improvement. Contribution of the Russian Scientific School. Part II.

This review is the second part of the critical analysis of recent papers of Russian and other authors devoted to the study of the stabilometric parameters in postural control biofeedback training and rehabilitation, associated with psychological functions. The review presents the studies of postural control features in chronic pain syndrome, chronic fatigue syndrome, Parkinson's disease, multiple sclerosis, and depression. The leading role of Russian researchers in the development and application of stabilometric biofeedback in the training of optimal functioning, rehabilitation, and correction of neurological disorders is noted. The paradigm of stabilometric biofeedback training of the cognitive and affective functions is offered.

The Impact of Hypoglycemic Therapy on the Prognosis for Acute Coronary Syndrome in Patients with Type 2 Diabetes.

The article discusses particular circumstances of acute coronary syndrome (ACS) in patients with type 2 diabetes (T2D). In addition, the available literature data and clinical guidelines reflecting the role of hypoglycemic therapy as a cardioprotection factor in ACS are analyzed. The article considers possible protective molecular mechanisms of various groups of drugs in ischemic cardiomyocytes.

Psychophysiological Indicators of Postural Control. Contribution of the Russian Scientific School. Part I.

This article aimed to systematically review the published results of studies of psychophysiological mechanisms of posture maintenance and identify the key factors that influence the effectiveness of postural control. The recommendations of "Preferred Reporting Elements for Systematic Reviews and Meta-Analyzes" (PRISMA) were followed for the review. The results were classified, taking into account the target psychophysiological mechanisms and factors affecting postural control. The article presents the theoretical and empirical results of the Russian scientific school of research on the role of support afferentation in the sensorimotor mechanisms of cognitive and postural functions. Due to the limited number of randomized studies found, it was impossible to make meta-analytic comparisons, so the literature analysis was carried out only qualitatively. Meanwhile, our systematic review provides promising information about possible relationships between stabilometric and psychological indicators of postural control, which have theoretical significance and application in the correction and training of posture control. However, more thorough research is needed to overcome the methodological shortcomings that we have encountered in our qualitative analysis.

[Atrial fibrillation and cognitive impairment: features of the relationship, developmental and prevention mechanisms].

The article discusses the development of cognitive deficit in patients with atrial fibrillation (AF) and provides data on mechanisms of the development of cognitive disorders in AF. Under discussion are a possibility of reducing the risk of cognitive disorders with the anticoagulant therapy for prevention of stroke in AF and different properties of different anticoagulants, which may be important for patients. Thus, patients with cognitive disorders are more prone to missing the dose, which may entail serious, possibly fatal consequences. Therefore, the convenience of dosing may be essential. The drug rivaroxaban that has once-a-day dosing schedule and a calendar package, may help the patient better adhere to the doctor's recommendations. Therefore, rivaroxaban may help improving the compliance, which is the major condition for comprehensive, necessary protection of an elderly patient with AF, including the protection, with high safety, from stroke, from the risk of coronary complications, and from the impairment of kidney function.

Disruption of the pro-inflammatory, anti-inflammatory cytokines and tight junction proteins expression, associated with changes of the composition of the gut microbiota in patients with irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a pathologic condition characterized by changes in gut microbiome composition, low-grade inflammation, and disruption of intestinal wall permeability. The interaction between the gut microbiome and the disease manifestation remains unclear. The changing of tight junction proteins and cytokines expression throughout the gastrointestinal tract in IBS patients has not been studied yet. AIM OF THE STUDY: To assess the changes of gut microbiome composition, tight junction proteins, and cytokines expression of intestinal mucosa from the duodenum to the distal part of the colon in IBS patients and healthy volunteers. METHODS: In 31 IBS patients (16 patients with IBS-D; 15 patients with IBS-C) and 10 healthy volunteers the expression of CLD-2, CLD-3, CLD-5, IL-2, IL-10, and TNF-α in mucosal biopsy specimens was determined by morphological and immune-histochemical methods. The qualitative and quantitative composition of the intestinal microbiota was assessed based on 16S rRNA gene sequencing in both groups of patients. RESULTS: The expression of IL-2 and TNF-α was significantly increased in IBS patients compared with the controls (p<0.001), with a gradual increase from the duodenum to the sigmoid colon. The expression of IL-10, CLD-3, and CLD-5 in mucosal biopsy specimens of these patients was lower than in the control group (p<0.001). Increased ratios of Bacteroidetes and decreased ratios of Firmicutes were noted in IBS patients compared to healthy volunteers (p<0.05). CONCLUSION: IBS patients have impaired gut permeability and persisting low-grade inflammation throughout the gastrointestinal tract. Changes in the gut microbiota may support or exacerbate these changes.

Dragendorff's reagent: Historical perspectives and current status of a versatile reagent introduced over 150 years ago at the University of Dorpat, Tartu, Estonia.

The well-known Dragendorff's reagent (DR) was introduced by an Estonian-German Professor Johann Georg Noel Dragendorff (1836-1898) in the middle of the 19th century (1866). Dragendorff, who was a full-time professor in pharmacy at the university of Dorpat (Tartu) used his reagent originally for the rapid screening of herbal products to find traces of alkaloids. DR is a solution of potassium bismuth iodide composing of basic bismuth nitrate (Bi(NO3)3), tartaric acid, and potassium iodide (KI), and when contact with alkaloids DR produces an orange or orange red precipitate. In this review article, we make a short historical overview on the biography and scientific research work of Professor Dragendorff at the University of Dorpat. The chemistry, method of preparation, mechanism of action, and practical uses of DR in various disciplines in various European countries including the Baltic countries (Estonia, Latvia, Lithuania), Finland, Ukraine, Moldova, and in Asia (Vietnam), are also discussed. Over several decades, DR and its modifications have found uses in many new applications and disciplines, and a number of commercial DRs are also currently available on the market. Today, DR is used for example in the production of surfactants, where non-ionic surfactant is precipitated in water solution with modified DR (KBiI4+BaCl2+glacial acetic acid). Total six different potassium iodobismuthate (DR) solutions are also presented in the European Pharmacopoeia. In conclusion, DR (after more than 150 years of its invention in Estonia) has still an important role in pharmaceutical and related sciences all over the world.

Influence of the Linking Order of Fragments of HA2 and M2e of the influenza A Virus to Flagellin on the Properties of Recombinant Proteins.

The ectodomain of the M2 protein (M2e) and the conserved fragment of the second subunit of hemagglutinin (HA2) are promising candidates for broadly protective vaccines. In this paper, we report on the design of chimeric constructs with differing orders of linkage of four tandem copies of M2e and the conserved fragment of HA2 (76-130) from phylogenetic group II influenza A viruses to the C-terminus of flagellin. The 3D-structure of two chimeric proteins showed that interior location of the M2e tandem copies (Flg-4M2e-HA2) provides partial α-helix formation nontypical of native M2e on the virion surface. The C-terminal position of the M2e tandem copies (Flg-HA2-4M2e) largely retained its native M2e conformation. These conformational differences in the structure of the two chimeric proteins were shown to affect their immunogenic properties. Different antibody levels induced by the chimeric proteins were detected. The protein Flg-HA2-4M2e was more immunogenic as compared to Flg-4M2e-HA2, with the former offering full protection to mice against a lethal challenge. We obtained evidence suggesting that the order of linkage of target antigens in a fusion protein may influence the 3D conformation of the chimeric construct, which leads to changes in immunogenicity and protective potency.

CROSS-PROTECTIVE PROPERTIES OF AN INFLUENZA VACCINE BASED ON HBC4M2E RECOMBINANT PROTEIN.

One of the main problems in the area of influenza prophylaxis and pandemic prevention is the development of cross-reactive vaccines, i.e. vaccines directed against all subtypes of human influenza viruses. Such vaccines are being developed in many countries for more than 10 years. A number of vaccines are presently undergoing clinical trials. We created Uniflu candidate vaccine based on recombinant HBc4M2e protein consisting of 4 tandem-connected copies of the highly conserved ectodomain of M2 protein of the influenza A virus. These 4 copies were genetically fused to the carrier protein, namely hepatitis B core antigen. Commercially available Derinat was used as adjuvant in the candidate vaccine. Preclinical studies on laboratory animals (mice, ferrets) demonstrated that immunization with Uniflu leads to significantly higher level of specific immunoglobulins in the blood and bronchoalveolar lavages. Moreover, it produces immunoglobulins belonging to subtype IgG2a that is the most important mediator of antibody-dependent cytotoxicity. The vaccine under review stimulates the proliferation of T-lymphocytes, as well as the formation of CD4+ and CD8+ T-cells synthesizing ɣ-IFN. When infected with the lethal doses (5 LD50) of influenza A viruses of the subtypes H1N1, H2N2, H3N2, and H1N1pdm09, immunized animals typically developed mild form of illness. This kept them alive in 90-100% of cases, which demonstrated almost complete protection from death. Replication of the virus in the lungs of immunized mice was reduced by 1.8-4.8 log10. High immunogenicity of the vaccine, and reduced clinical symptoms following experimental infection, were demonstrated in ferrets as well. The developed recombinant vaccine Uniflu has high specific activity and cross-protection. Uniflu can be proposed as pre-pandemic vaccine, provided that it passes clinical trials.

[Management of patients with isolated aortic stenosis considering negative prognostic factors].

BACKGROUND: Aortic stenosis (AS) is the most common valve defect in developed countries; its prevalence increases with age of the population. The most frequent cause for isolated AS in adults is calcification of normal tricuspid or congenital bicuspid aortic valve (AV). The only effective treatment of AS is aortic valve replacement (AVR). Major negative prognostic factors include low LV ejection fraction (EF), age older than 70, female gender, and comorbidities such as renal dysfunction, chronic obstructive pulmonary disease, and neural disorders. AIM: To study negative prognostic factors influencing outcomes of treatment for AS and to determine possibilities for managing AS patients taking into account these factors. MATERIALS AND METHODS: 120 medical records of patients who had undergone AVR for isolated AS (76 women and 44 men aged 45 to 81) were studied retrospectively, and 50 patients were examined in a late post-AV period (26 women aged 67.5 (65.0-72.0) at the time of surgery, 24 men aged 63.0 (57.0-68.0) at the time of surgery), and 84 unoperated patients (51 women and 33 men). RESULTS: Perioperative death rate was 8.76 %, 11 of 120 patients, 3 men (6.8 % of operated men) and 8 women (10.5 % of all operated women). The deceased patients aged 70 or older whereas perioperative death rate of patients younger than 70 was zero (Pχ 2 =0.004). Despite a relatively high perioperative risk, late survival of patients older than 70 who had undergone AVR was substantially and statistically significantly higher than that of unoperated AS patients. In elderly patients who died during the perioperative period of AVR, the history of valve defect was longer, and a part of the patients who did not survive AVR could have been operated at age younger than 70. Unoperated AS patients with a small LV cavity, severe LV hypertrophy, and LV EF >70 % were suggested to be isolated into a special group of risk with a special strategy for cardiosurgical treatment.

Control of autoresonance in mechanical and physical models.

Autoresonant energy transfer has been considered as one of the most effective methods of excitation and control of high-energy oscillations for a broad range of physical and engineering systems. Nonlinear time-invariant feedback control provides effective self-tuning and self-adaptation mechanisms targeted at preserving resonance oscillations under variations of the system parameters but its implementation may become extremely complicated. A large class of systems can avoid nonlinear feedback, still producing the required state due to time-variant feed-forward frequency control. This type of control in oscillator arrays employs an intrinsic property of a nonlinear oscillator to vary both its amplitude and the frequency when the driving frequency changes. This paper presents a survey of recently published and new results studying possibilities and limitations of time-variant frequency control in nonlinear oscillator arrays.This article is part of the themed issue 'Horizons of cybernetical physics'.

[Humoral regulation of nutritional status in children].

The purpose of the research was the investigation of the characteristics of insulin resistance, levels of adipokines, myokines and collagen metabolites type I in children in orphanages and social rehabilitation centers (SRC). The study involved 69 children aged 7-12 years. The first group consisted of 20 children from SRC, the second - 16 children living in orphanages, control group included 33 children (1-2 health groups) from wealthy families. The average length of stay of children in SRP was 1.0 (0.5-2.5) month, in orphanages - 38 (22-44) months. The groups were comparable in age and sex. Anthropometric indices were determined, in blood serum glucose concentration was measured by glucose oxidase method, blood serum level of insulin, cortisol, leptin, adiponectin, resistin, apelin, myostatin, collagen metabolites were determined by ELISA. Children from orphanages and SRC had significantly lower anthropometric indices in comparison with the control group. Particularly low parameters were observed in children from SRP, which in growth, body weight, chest circumference and body mass index significantly lagged behind the control group peers. The children from SRP as compared with the control group revealed higher insulin resistance index (3.33±0.49 vs 2.29±0.29, p<0.05) and cortisol level (405.21±38.21 vs 313.08±25.97 nmol/l, p>0.05). There were changes (p<0.05) in blood serum content of adipokines - reduced leptin level (5.35±1.55 vs 14.00±3.10 ng/ml) and increased apelin level (4.07±0.82 vs 2.19±0.41 ng/ml), as well as higher levels (p<0.05) of myostatin (183.95±16.3 vs 116.4±9.4 ng/ml) and C-terminal telopeptide of type I collagen (1.11±0.11 vs 0.72±0.08 ng/ml). The children in orphanages compared with the control group had lower levels of insulin (5.04±0.69 vs 11.3±1.12 µIU/ml), high insulin sensitivity - HOMA-IR was 1.01±0.16. The children in orphanages have even more pronounced reduction in leptin concentration (2.69±0.4 ng/ml), a decrease of resistin (4.99±0.32 vs 7.16±0.70 ng/ml, p<0.05), increased concentration (p<0.05) of apelin (3.53±0.67 ng/ml), myostatin (181.17±10.2 ng/ml) and C-terminal telopeptide of type I collagen (2.70±0.22 ng/ml). Features of hormone and cytokine regulation of metabolism make it particularly urgent to prevent disorders of eating behavior and to promote a healthy lifestyle among children left without parental care.

NEUROPHYSIOLOGICAL STATE OF HUMANS IN LONG-DURATION ISOLATION.

During the 520-d imitation of isolation and confinementin a long-duration exploration mission, the neuroufunctional state of 6 crewmembers was studied by synchronous registration of cerebral electrical (EEG) and energy (permanent potential level (PPL)) activities of the brain. Two baseline investigations predicted high adaptability of all crew members and low probability of depletion of the adaptation reserve in the experiment. During isolation, dynamics of neurofunctional correlates of the cerebral activity was generally proportionate to the factors the crewmembers were affected by. Events epochal to the crew gave rise to physiological reactions both of the metabolic and electrical activity of the brain. On week 54, crew physiological adaptation to the experimental environment was manifested by decreases in PPL without interhemispheric asymmetry and absolute a-power. All through the experiment none of the crew members showed signs of a distinct stress-reaction (a-activity asymmetry with a significant PPL decrease) supporting our prediction of low probability of adaptation reserve depletion in participants in the 520-day isolation and confinement study.

[EEG-parameters dynamic during relaxation (frequencies analysis)].

The aim of this study was to analyze the wide frequency range of EEG-parameters to estimate a possible functional importance of different EEG-components to reach the relaxation state. Sixty five subjects 17 to 20 years old were involved in the investigation. The relaxation session with monopolar EEG-registration and autonomic parameters recording was conducted to each subject. Significant changes in all analyzed EEG-bands were observed during relaxation. Two types of changes of EEG-coherence were distinguished by wakefulness-relaxation shift of state, and correlation of the type of dynamic with LF/HF ratio were discovered.

[Immunogenicity of recombinant proteins including ectodomain of M2 influenza virus A].

Two recombinant proteins with three copies of the ectodomain of the conserved influenza protein M2 (M2e) of influenza viruses were developed: A (H1N1)pdm09, A/Kurgan/05/05 (H5N1), and M2e consensus sequence of the human influenza A virus (H1N1, H2N2, H3N2) based on flagellin and core antigen of hepatitis B (HBc). The first recombinant protein comprised flagellin fused to three tandem copies of M2e, the second preparation was based on non-covalent interaction between M2e peptides and HBc. The immunogenicity of two preparations was comparatively tested. A covalent linkage of flagellin with M2e significant increased the immunogenicity of the target antigen compared with non-covalent interaction M2e and HBc. Flagellin as a protein carrier of M2e induced mainly IgG1 subclass, whereas HBc stimulated more balanced Th1/Th2 response. Our study showed a decrease in the viral titers in lung tissues of immunized mice after lethal challenge of A/PR/8/34 (H1N1). The study revealed a possibility to obtain a vaccine preparation with equal immunogenicity both against human influenza viruses and highly pathogenic avian influenza viruses.

Reproduction-related effects of green alga Coccomyxa sp. infestation in the horse mussel Modiolus modiolus.

The effects of Coccomyxa sp. infestation on the reproductive characteristics of the horse mussel Modiolus modiolus from the north-western Pacific (Peter the Great Bay, Sea of Japan) are demonstrated in this study. The mussels were collected monthly from May to September of 2009, and the prevalence of females and males with green tissues was 39% and 47%, respectively. Overall, the green alga infection caused a mild effect on gametogenesis in the horse mussel. The dynamics of gonad development in the healthy and infected mussels during the study period was generally similar, with the spawning being partial and occurring from the beginning of June to the first half of September; total spawning was recorded at the end of this period. However, several negative reproduction-related effects of the green alga infestation were observed, i.e., general gonadal underdevelopment, which was apparent from significant decrease in the acinus areas of the ovaries and testes and an increase in the connective tissue layer between the acini, a delay in some stages of the reproductive cycle and production of decreased number of spermatozoa and large vitellogenic oocytes, especially in the early spawning period (June). All of these results suggest a reduced reproductive output for the infected mussels.

Defining the optimal lymphadenectomy cut-off value in epithelial ovarian cancer staging surgery utilizing a mathematical model of validation.

OBJECTIVE: Since 1985 International Federation of Gynecology and Obstetrics includes pelvic and aortic lymphadenectomy as part of the surgical staging in epithelial ovarian cancer (EOC). There is no consensus on the overall number of nodes needed in a systematic lymphadenectomy. The aim of this study is to calculate the optimal cut-off value using a mathematical modeling approach. METHODS: Data was collected retrospectively, from 1996 to 2000, of 120 consecutive Mayo Clinic patients with EOC and positive nodes. All patients was underwent pelvic and/or aortic lymphadnectomy during surgical staging. To mathematically predict the probability of a positive node in EOC patients we used a predictive mathematical model (PMM). The mathematical analysis consisted: creation of a new PMM according to our purposes, application of PMM to describe the experimental data in order to build the polynomial regression curves in each lymphatic area and determine the optimal point for each curve. RESULTS: The mean number of lymph nodes and metastatic nodes removed were 35 and 7.8, respectively; the mean percentage of positive nodes was 28.3%. The optimal point of each fitting curves were: 7 nodes for unilateral aortic nodal sampling (at least 3 infrarenal or 5 inframesenteric) and 15 nodes for unilateral pelvic lymphadenectomy (at least 5 external iliac). CONCLUSIONS: We can mathematically predict the probability to obtain a positive node in EOC surgical staging. Our results have shown the need to obtain at least 22 lymph nodes between pelvic and aortic lymphadenectomy.