Effect of colloidal magnetite (Fe3O4) nanoparticles on the electrical characteristics of the azolectin bilayer in a static inhomogeneous magnetic field.

This work is devoted to the study of the combined effects of applied magnetic field and MNPs on the electrical characteristics of bilayer lipid membranes. We present results of the study of electrical parameters of azolectin membranes in a static inhomogeneous magnetic field at the one-sided addition of positively charged quasi-spherical superparamagnetic magnetite nanoparticles with a diameter of about 4 nm. The magnet was located at different distances from the membrane, and the magnetic field attracted the nanoparticles to the membrane surface with different strengths. We observed three pronounced effects that depended on the external magnetic field. Firstly, after addition of nanoparticles in a magnetic field, the conductance of the membranes increased. A smooth increase in conductance was accompanied in some cases by the appearance of current jumps, which can be associated with the formation of through pores with a radius of no more than 1 nm. The conductance increased with increasing magnetic field gradient. Secondly, at zero command voltage, a negative current through the membrane was observed. Although our experiments did not allow us to unambiguously determine which particles create this current, we believe that this current is associated with the penetration of particles through the membrane. This effect intensified with increasing magnetic field gradient. Thirdly, we observed a sharp change in the nonlinear dependence of capacitance on voltage associated both with the change in the surface potential of the azolectin membrane and with the effect of MNP binding to the membrane surface on the apparent membrane capacitance.

Conjugates of 3,5-Bis(arylidene)-4-piperidone and Sesquiterpene Lactones Have an Antitumor Effect via Resetting the Metabolic Phenotype of Cancer Cells.

In recent years, researchers have often encountered the significance of the aberrant metabolism of tumor cells in the pathogenesis of malignant neoplasms. This phenomenon, known as the Warburg effect, provides a number of advantages in the survival of neoplastic cells, and its application is considered a potential strategy in the search for antitumor agents. With the aim of developing a promising platform for designing antitumor therapeutics, we synthesized a library of conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones. To gain insight into the determinants of the biological activity of the prepared compounds, we showed that the conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones, which are cytotoxic agents, demonstrate selective activity toward a number of tumor cell lines with glycolysis-inhibiting ability. Moreover, the results of molecular and in silico screening allowed us to identify these compounds as potential inhibitors of the pyruvate kinase M2 oncoprotein, which is the rate-determining enzyme of glycolysis. Thus, the results of our work indicate that the synthesized conjugates of 3,5-bis(arylidene)-4-piperidone and sesquiterpene lactones can be considered a promising platform for designing selective cytotoxic agents against the glycolysis process, which opens new possibilities for researchers involved in the search for antitumor therapeutics among compounds containing piperidone platforms.

[Psychopathology of depressive-delusional states with religious content]. / Psikhopatologicheskie osobennosti depressivno-bredovykh sostoyanii s religioznym soderzhaniem.

OBJECTIVE: Identification of psychopathological characteristics of depressive-delusional states with religious content, development of a typology, determination of formation features, nosological assessment. MATERIAL AND METHODS: A total of 79 patients (47 female, 32 male, mean age 27±6.5 years) with depressive-delusional states with religious content within the affective and schizophrenia spectrum disorders were studied. Clinical-psychopathological, psychometric (PANSS, HDRS, S. Huber CRS) and statistical methods were used. RESULTS: Based on the psychopathological structure, specific mechanisms of development of delusions and themes of the religious experiences, three types of depressive-delusional states were identified: type 1 - with a predominance of depressive delusions congruent with affect and delusional ideas of guilt, sinfulness, abandonment of God (14 patients, 17.7%; 6 women, 8 men; mean age 28±4.5 years; HDRS score 33±5.6, the total PANSS score 71±5.3, the PANSS positive subscale score 15.8±3.7); type 2 - with the addition of incongruent delusional constructs, persecutory disorders and acute sensory delusions to the existing depressive religious delusion, with the phenomenon of confessional ambivalence (27 patients, 34.2%; 16 women, 11 men; mean age at attack manifestation 25±9 years; HDRS score 29.6±4.4, the total PANSS score 87±6.2, the PANSS positive subscale score 23.5±4.2); type 3 - depressive-paranoid states with a predominance of Kandinsky-Clerambault syndrome of religious content (38 cases, 48.1%; 20 women, 18 men; mean age at attack manifestation 23.4±2.5 years; HDRS score 32.7±3.7, the total PANSS score 102±7.3, the PANSS positive subscale score 32.5±4.5). CONCLUSION: The study of depressive-delusional states with religious content has shown their clinical-psychopathological heterogeneity. The religious experiences served as a pathoplastic factor, which essentially modified the clinical-psychopathological picture of the disease due to presence of the specific religious phenomena. The identified types of depressive-delusional disorders with religious content had different diagnostic value.

Behavioral performance and microglial status in mice after moderate dose of proton irradiation.

Cognitive impairment is a remote effect of gamma radiation treatment of malignancies. The major part of the studies on the effect of proton irradiation (a promising alternative in the treatment of radio-resistant tumors and tumors located close to critical organs) on the cognitive abilities of laboratory animals and their relation to morphological changes in the brain is rather contradictory. The aim of this study was to investigate cognitive functions and the dynamics of changes in morphological parameters of hippocampal microglial cells after 7.5 Gy of proton irradiation. Two months after the cranial irradiation, 8- to 9-week-old male SHK mice were tested for total activity, spatial learning, as well as long- and short-term hippocampus-dependent memory. To estimate the morphological parameters of microglia, brain slices of control and irradiated animals each with different time after proton irradiation (24 h, 7 days, 1 month) were stained for microglial marker Iba-1. No changes in behavior or deficits in short-term and long-term hippocampus-dependent memory were found, but an impairment of episodic memory was observed. A change in the morphology of hippocampal microglial cells, which is characteristic of the transition of cells to an activated state, was detected. One day after proton exposure in the brain tissue, a slight decrease in cell density was observed, which was restored to the control level by the 30th day after treatment. The results obtained may be promising with regard to the future use of using high doses of protons per fraction in the irradiation of tumors.

Female and Male Phenotypes of Iron Deficiency in CHF. Additional analysis of the «The Prevalence of Iron Deficiency in Patients With Chronic Heart Failure in the Russian Federation (J-CHF-RF)¼ study.

Aim    To evaluate the incidence of iron deficiency (ID) in men and women with chronic heart failure (CHF) and to compare clinical and functional indexes in patient with and without ID depending on the gender.Material and methods    An additional analysis of the study "Prevalence of Iron Deficiency in Patients With Chronic Heart Failure in the Russian Federation (ID-CHF-RF)" was performed. The study included 498 (198 women, 300 men) patients with CHF, in whom, in addition to iron metabolism, the quality of life and exercise tolerance (ET) were studied. 97 % of patients were enrolled during their stay in a hospital. ID was defined in consistency with the European Society of Cardiology (ESC) Guidelines. Also, and additional analysis was performed according to ID criteria validated by the morphological picture of the bone marrow.Results    ID was detected in 174 (87.9 %) women and 239 (79.8 %) men (p=0.028) according to the ESC criteria, and in 154 (77.8 %) women and 217 (72.3 %) men (p=0.208) according to the criteria validated by the morphological picture of the bone marrow. Men with ID were older and had more severe CHF. They more frequently had HF functional class (FC) III and IV (63.4 % vs. 43.3 % in men without ID); higher concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and lower ET. HF FC III increased the probability of ID presence 3.4 times (p=0.02) and the probability of HF FC IV 13.7 times (p=0.003). This clinical picture was characteristic of men when either method of determining ID was used. In women, ID was not associated with more severe CHF.Conclusion    Based on the presented analysis, it is possible to characterize the male and female ID phenotypes. The male ID phenotype is associated with more severe CHF, low ET, and poor quality of life. In females of the study cohort, ID was not associated with either the severity of CHF or with ET.

Growth Induction of Solid Ehrlich Ascitic Carcinoma in Mice after Proton Irradiation of Tumor Cells Ex Vivo.

This study presents data on the growth rate and frequency of induction of the solid form of Ehrlich's ascites carcinoma (EAC) in mice in the short and long term after inoculation of ascitic cells irradiated ex vivo with a proton beam in the dose range of 30-150 Gy. It was shown that the growth rate of solid tumors after inoculation of irradiated cells ex vivo coincided with the growth of tumors in the control group. The frequency of tumor induction in mice after inoculation of EAC cells irradiated at a dose of 30 Gy was 80%, 60 Gy-60%, 90 Gy-25%, and 120 Gy-10%; at irradiation at a dose of 150 Gy, no tumors appeared during the entire observation period. Thus, we determined the dose of proton radiation required to eliminate tumor cells and/or signaling factors that can lead to the induction of tumor growth of EAC in mice.

Different effects of two Poloxamers (L61 and F68) on the conductance of bilayer lipid membranes.

The integral conductance of planar lipid bilayer membranes in the presence of two Poloxamers (Pluronics) L61 and F68 with the same lengths of hydrophobic poly(propylene oxide) blocks and the different lengths of hydrophilic poly(ethylene oxide) blocks increases with an increase in the concentration of both Pluronics; however, the shape of the conductance-concentration curves is super linear for L61 and sublinear for F68. In the presence of both Pluronics, rare discrete current jumps are observed against the background of continuous current. At high concentrations, the I-V curves of membranes with both L61 and F68 became nonlinear at sufficiently low voltages but differed significantly. At voltages greater than 50 mV, the conductance of membranes with L61 increased sharply and quantized jumps were observed toward higher conductance, which could be interpreted as the appearance of additional pores. On the contrary, the conductance of membranes with F68 decreased and quantized jumps to lower conductance were observed, which could be interpreted as blocking of already existing pores. We attributed the differences in the conductance-concentration and I-V curves of these two Pluronics to their different effects on the dynamics of membrane hydration and, accordingly, on the probability of formation of conducting pores.

Anti-tumor Effect of High Doses of Carbon Ions and X-Rays during Irradiation of Ehrlich Ascites Carcinoma Cells Ex Vivo.

The effect of carbon ions (12C) with the energy of 400 MeV/nucleon on the dynamics of induction and growth rate of solid tumors in mice under irradiation of Ehrlich ascites carcinoma cells (EAC) ex vivo at doses of 5-30 Gy relative to the action of equally effective doses of X-ray radiation was studied. The dynamics of tumor induction under the action of 12C and X-rays had a similar character and depended on the dose during 3 months of observation. The value of the latent period, both when irradiating cells with 12C and X-ray, increased with increasing dose, and the interval for tumor induction decreased. The rate of tumor growth after ex vivo irradiation of EAC cells was independent of either dose or type of radiation. The dose at which EAC tumors are not induced within 90 days was 30 Gy for carbon ions and 60 Gy for X-rays. The value of the relative biological effectiveness of carbon ions, calculated from an equally effective dose of 50% probability of tumors, was 2.59.

The Effect of Xylazine/Zoletil Anesthesia on the Radiosensitivity of Mice under Total Irradiation with X-Rays, Protons, and Carbon Ions.

The effect of xylazine-zoletyl anesthesia on the radiosensitivity of mice irradiated with protons, carbon ions in two regions of the Bragg curve, and X-ray radiation was studied according to the criteria of 30-day survival, dynamics of death, and the average life span of dead mice. The maximum effect of anesthesia by 3.3 times was observed by a decrease in the death of animals during irradiation with carbon ions at the Bragg peak; in the case of irradiation before the peak, the effect was 1.2 times. In the case of proton irradiation at the Bragg peak, the protective effect of anesthesia by a factor of 1.7 was observed only at a dose of 8.5 Gy. When mice were irradiated with X-rays in the dose range of 6.0-8.5 Gy, the anesthesia effect coefficient was 1.7-2. According to the 30-day survival method, it was shown that the use of a xylazine-zoletil mixture significantly changes the radiosensitivity of mice depending on the radiation dose and the radiation source quality.

[Pharmacological modulation of wound healing in glaucoma surgery]. / Farmakoterapevticheskie podkhody k upravleniyu reparativnymi protsessami v khirurgii glaukomy.

Despite the well-known effectiveness of pharmacological glaucoma therapy, surgical approach remains one of the main treatment options for some forms and stages of the disease. The long-term success of glaucoma surgery depends on the intensity of local wound healing processes at the surgical site. The most common way to influence healing processes in surgical treatment of glaucoma is the use of antimetabolites. However, given the high risk of serious complications associated with their use, the search for new drugs devoid of these disadvantages continues. The aim of this review is to describe the efficacy and safety of both currently used and upcoming pharmacological ways to influence the wound healing process after glaucoma surgery in order to improve the stability of hypotensive effect.

[Prevalence of overweight and obesity in children].

The growing prevalence of overweight and obesity is an urgent problem not only in adults but also in children in both developed and developing countries. The purpose of this study was to analyze the prevalence of overweight and obesity and other forms of nutritional disorders in Russian children. Material and methods. The nutritional status of 17 329 children aged 2-18 years was assessed on the basis of anthropometric data, obtained by the Federal State Statistics Service during the "Sample Survey of the Population's Diet" in 2018. The prevalence of various forms of malnutrition was assessed by the Z-score categories: underweight, stunted growth (short stature), thinness, overweight, obesity. Results. Population mean and median values of Z-scores in all sex-age groups do not exceed ±0.5 in relation to WHO standards, which indicates the applicability of the standards to assessing the nutritional status of Russian children population. High body weight (WAZ>2) occurs in 7.6% of children, underweight in 2.6%. The incidence of short stature in boys and girls is 7.0 and 6.8%, respectively. The prevalence of overweight and obesity in boys is 20.4 and 10.4%, respectively, while in girls, 15.4 and 7.6%. In general, in the population of children 2-18 years old, the prevalence of overweight is 18%, and obesity is 9.1%. The index of malnutrition, including the sum of the frequency of various combinations of low Z-scores (<-2), characterizing underweight, short stature, thinness, and their combinations was 8.0%. The multilevel logistic regression showed that overweight and obesity inversely depend on age; the risk of developing these conditions is lower in the city, but higher in male children compared to female children. Conclusion. The population of children 2-18 years old in the Russian Federation is characterized by a low incidence of forms of malnutrition, such as underweight and thinness. However, the prevalence of overweight and obesity is higher than in European countries.

[Iron deficiency in Russia heart failure patients. Observational cross-sectional multicenter study].

Aim    To evaluate the prevalence of iron deficiency (ID) in Russian patients with heart failure (HF).Material and methods    Iron metabolism variables were studied in 498 (198 women, 300 men) patients with HF. Data were evaluated at admission for HF (97 %) or during an outpatient visit (3 %). ID was determined according to the European Society of Cardiology Guidelines.Results    83.1 % of patients had ID; only 43.5 % of patients with ID had anemia. Patients with ID were older: 70.0 [63.0;79.0] vs. 66.0 years [57.0;75.2] (p=0.009). The number of patients with ID increased in parallel with the increase in HF functional class (FC). Among patients with ID, fewer people were past or current alcohol users (p=0.002), and a greater number of patients had atrial fibrillation (60.1 vs. 45.2 %, p=0.016). A multiple logistic regression showed that more severe HF (HF FC) was associated with a higher incidence of ID detection, whereas past alcohol use was associated with less pronounced ID. An increase in N-terminal pro-brain natriuretic peptide (NT-proBNP) by 100 pg/ml was associated with an increased likelihood of ID (odds ratio, 1.006, 95 % confidence interval: 1.002-1.011, p=0.0152).Conclusion    The incidence rate of HF patients is high in the Russian Federation (83.1 %). Only 43.5 % of these patients had anemia. The prevalence of ID in the study population increased with increases in HF FC and NT-proBNP.

[Satisfaction with the quality of medical care of the mentally ill patients and its determining factors]. / Udovletvorennost' kachestvom meditsinskoi pomoshchi psikhicheski bol'nykh i faktory, ee opredelyayushchie.

OBJECTIVE: To study satisfaction with treatment as a predictor of compliance in patients with mental disorders prone to committing socially dangerous acts (SDA). MATERIAL AND METHODS: The study included 83 patients of a psycho-neurological institution prone to commit SDA. The comparison group consisted of 88 mental patients who were not inclined to commit SDA. The material was collected using the method of anonymous survey according to the «Questionnaire for the Study of Satisfaction of the Population with Inpatient Medical Care¼. To interpret the data, quantitative and qualitative indicators were calculated. RESULTS: Satisfaction with treatment in consumers of psychiatric services is high, reaching 96.4% (n=80) in the main group and 97.7% (n=86) in the comparison group. Doctors' knowledge (95.2%, n=79 and 97.7%, n=86) and the level of trust in them (86.8%, n=72 and 90.9%, n=80) received the highest share of positive assessments by the patients. However, patients who are prone to commit SDA rate lower both medical care in general (68.7%, n=57 vs. 90.9%, n=80) and its individual parameters. Thus, 71.1% (n=59) believe that the doctor does not perceive them as an independent person, does not devote enough time to them (41%, n=34). In the comparison group, there are fewer such answers (11.4%, n=10; 4.5%, n=4). Patients highly (89.2%, n=74 and 94.3%, n=83) rate the living conditions in the hospital.The perceived quality of medical care is influenced by three groups of factors: the characteristics of consumers of medical services, the possibilities for using health services, the assessed and perceived need for medical services. Equally important is the study of contextual factors in the use of mental health services. CONCLUSION: The formation of a trusting relationship between the patient and the doctor and ensuring the latter maintain medical secrecy contributes to strengthening social interaction and, as a result, reducing the feeling of coercion, increasing internal motivation and satisfaction with the quality of treatment.

Epidemiology of atrial fibrillation in a representative sample of the European part of the Russian Federation. Analysis of EPOCH-CHF study.

Aim    To study true prevalence of atrial fibrillation (AF) in a representative sample from the European part of the Russian Federation; to describe characteristics of patients with AF; and to provide the frequency of anticoagulant treatment.Material and methods    Cross-sectional data of the EPOCH epidemiological study (2017) were used. Data were collected in 8 constituent entities of the Russian Federation; the sample size was 11 453 people. The sample included all respondents who had given their consent for participation and were older than 10 years. Statistical tests were performed in the R system for statistical data analysis.Results    The prevalence of AF in the representative sample from the European part of the Russian Federation was 2.04 %. The AF prevalence increased with age and reached a maximum value of 9.6% in the age group of 80 to 89 years. The AF prevalence among females was 1.5 times higher than among men. With age standardization, the AF prevalence was 18.95 and 21.33 per 1,000 people for men and women, respectively. The AF prevalence increased in the presence of concurrent cardiovascular diseases (CVDs) or diabetes mellitus as well as with an increased number of comorbidities in the same person and reached 70.3 and 60.0 % in patients with 4 and 5 comorbidities, respectively. Patients with AF had a greater number of comorbidities and higher CHA2DS2VASc scores (5.0 vs. 2.0, p<0.001) compared to patients with CVDs without AF. Only 22.6 % of patients with CVD and AF took anticoagulants. Only 23.9% of patients with absolute indications for the anticoagulant treatment received anticoagulants.Conclusion    The AF prevalence in the European part of the Russian Federation was 2.04 %; it increased with age and in patients with concurrent CVDs or diabetes mellitus. Most of AF patients (93.2 %) required a mandatory treatment with oral anticoagulants.

Radioprotective Effect of Nanocerium by Irradiation of Mice with Carbon Ions in Medium and Lethal Doses.

The data of the study of the radioprotective properties of nanocerium (nCeO2) after total irradiation of mice with carbon ions in medium and lethal doses according to the micronucleus test and the criterion of 30-day survival are presented. A significant protective effect of nCeO2 upon irradiation at medium doses was observed at per os administration for 5 days before irradiation (that is, at long-term prophylactic use). Mouse survival data showed no protective effect of per os administration of nCeO2 in contrast to the micronucleus test results. After injections of both nCeO2 and saline solution 24 h before or immediately after irradiation, the radioprotective effect was detected using both methods. The data obtained revealed the dependence of the observed effects on the mode and time of nCeO2 administration, the influence of the solvent, the level of doses and the quality of radiation, as well as demonstrated the possibility of using nanocerium preparations to protect organisms from radiation with high LET values and the importance of further studies of the radioprotective properties of new nanomaterials.

Low-Intensity Femtosecond Radiation Activates the Natural Defenses of Mice in vivo.

The possibility of induction of cytogenetic damage in the bone marrow, changes in the cellularity of lymphoid organs and blood composition in mice irradiated with low-intensity femtosecond laser radiation at a power flux density of 5.1, 10.4, and 52 mJ/cm2 (0.5 mW for 5, 10, and 50 s) in vivo was shown. Using the radiation adaptive response test (0.1 Gy + 1.5 Gy), it was found that, when mice were exposed to femtosecond laser radiation in high doses, the body's natural defenses were activated in the same narrow range of energy flux density (2-16 mJ/cm2) as in the case of X-ray irradiation in a dose of 0.1 Gy (4 mJ/cm2). The data obtained suggest a similar mechanism of activation of the body's natural defense upon exposure to low doses of both ionizing and non-ionizing radiation.

Adaptive Role of Cell Death in Yeast Communities Stressed with Macrolide Antifungals.

Microorganisms cooperate with each other to protect themselves from environmental stressors. An extreme case of such cooperation is regulated cell death for the benefit of other cells. Dying cells can provide surviving cells with nutrients or induce their stress response by transmitting an alarm signal; however, the role of dead cells in microbial communities is unclear. Here, we searched for types of stressors the protection from which can be achieved by death of a subpopulation of cells. Thus, we compared the survival of Saccharomyces cerevisiae cells upon exposure to various stressors in the presence of additionally supplemented living versus dead cells. We found that dead cells contribute to yeast community resistance against macrolide antifungals (e.g., amphotericin B [AmB] and filipin) to a greater extent than living cells. Dead yeast cells absorbed more macrolide filipin than control cells because they exposed intracellular sterol-rich membranes. We also showed that, upon the addition of lethal concentrations of AmB, supplementation with AmB-sensitive cells but not with AmB-resistant cells enabled the survival of wild-type cells. Together, our data suggest that cell-to-cell heterogeneity in sensitivity to AmB can be an adaptive mechanism helping yeast communities to resist macrolides, which are naturally occurring antifungal agents. IMPORTANCE Eukaryotic microorganisms harbor elements of programmed cell death (PCD) mechanisms that are homologous to the PCD of multicellular metazoa. However, it is still debated whether microbial PCD has an adaptive role or whether the processes of cell death are an aimless operation in self-regulating molecular mechanisms. Here, we demonstrated that dying yeast cells provide an instant benefit for their community by absorbing macrolides, which are bacterium-derived antifungals. Our results illustrate the principle that the death of a microorganism can contribute to the survival of its kin and suggest that early plasma membrane permeabilization improves community-level protection. The latter makes a striking contrast to the manifestations of apoptosis in higher eukaryotes, the process by which plasma membranes maintain integrity.

[REASONS FOR CITIZENS TO APPLY FOR PAID MEDICAL SERVICES ACCORDING TO SOCIOLOGICAL SURVEYS OF THE POPULATION].

An actual characteristic of the processes taking place in the Russian healthcare, especially during the ongoing transformation of the state healthcare system aimed at building a patient-oriented healthcare model, is the analysis of the reasons why citizens prefer medical care provided for a fee. The purpose of the study is to study the main reasons for the treatment of the population of the city of Moscow for medical services provided for a fee and their comparison with the reasons for applying for paid medical services (PMU) in other regions of the Russian Federation.The main materials of the study were the data of a sociological survey of visitors to the capital's medical organizations about the reasons for the population's application for obtaining PMU, as well as the results of sociological surveys on this topic in other regions of the Russian Federation. As a result, not only the main reasons for applying for medical services on a paid basis were identified, but also regional peculiarities of the prevalence of PMU.

Assessment of the Relative Biological Efficiency of Pencil Beam Scanning of Protons in Mice in Vivo.

The effect of proton pencil beam scanning in the dose range of 4.5-15 Gy on the radiosensitivity of mice under irradiation in two regions of the Bragg curve was studied according to the criteria of 30-day survival, dynamics of death, and average lifespan of mice. The relative biological effectiveness (RBE) value of protons relative to X-ray radiation before and at the Bragg peak determined by the LD50/30 index was 0.86 and 0.94, respectively, and by the criterion of 30-day survival at a dose of 6.5 Gy it was 0.83 and 0.84, respectively. With similar RBE values for protons in different regions of the Bragg curve, significant differences in the dynamics of the course of radiation sickness were revealed, which indicates different damage to critical systems and organs of animals and the induction of compensatory mechanisms involved in the formation of stress responses at the organismal level.