Transcriptomic Analysis of DNA Repair Pathways in Human Non-Small Cell Lung Cancer Cells Surviving Multifraction X-Ray Irradiation.

Radioresistant sublines of non-small cell lung cancer cells differing in the p53 status were obtained: A549 (p53 wild type) and H1299 (p53 deficient). The exposure to ionizing radiation was carried out using a standard protocol developed on the basis of empirical clinical experience and consisting in exposure in a dose of 2 Gy once a day, 5 days a week up to total dose of 60 Gy. The cells survived after irradiation demonstrated reduced radiosensitivity, as well as changes in differential gene expression in comparison with parental cells. Some differences in the signaling pathways involved in DNA repair were revealed.

[Low doses of quetiapine (Seroquel) as an impulsivity corrector in patients with bipolar affective disorder in remission]. / Nizkie dozy kvetiapina (Serokvelya) v kachestve korrektora impul'sivnosti u patsientov s bipolyarnym affektivnym rasstroistvom v remissii.

OBJECTIVE: To evaluate the effectiveness of low doses (25-75 mg/day) of quetiapine (Seroquel) in patients with bipolar affective disorders in a euthymic state with signs of impaired impulse control. MATERIAL AND METHODS: The main criteria for patients' selection were as follows: both sex, diagnoses of bipolar affective disorders, remission (euthymic state), adult age (from 18 to 60 years old), stable basic therapy. The duration of the study was 6 weeks, a dose of quetiapine (Seroquel) varied from 25 to 75 mg. The examinations were carried out with the Barratt scale, computerized Go-No-Go and Balloon tests. RESULTS: The study group included 32 patients (11 men and 21 women), mean age 31.2±9.7 years (minimum 18, maximum 60 years). The changes in Barratt total score (p=0.000014, Wilcoxon test, effect size 0.48) and Balloon total earnings (p=0.03, Wilcoxon test, effect size 0.22) were statistically significant and reflected clinically significant improvement. The changes of the indices of the Go-No-Go test were not significant. The data of fMRI showed an increase in the connectivity of the cortex of the central and parietal tegmentum of the left hemisphere with other areas of the brain, which correlated with the changes in psychometric and test parameters. CONCLUSION: The results of the study showed that add-on of the low doses of quetiapine (Seroquel) significantly decreases impaired impulse control in remitted patients with bipolar affective disorders both in self-evaluation and in risk-taking experimental test. The drop of high level of impulsivity can improve the quality and stability of remission and reduce behavioral risks due to impaired impulse control.

[Antipsychotic selection strategies: the need for a holistic approach]. / Strategii vybora antipsikhoticheskoi terapii: neobkhodimost' kompleksnogo podkhoda.

OBJECTIVE: To describe the connections between strategies for antipsychotic prescribing and clinical, socio-psychological factors of treatment adherence in patients with psychotic disorders. MATERIAL AND METHODS: The study included 83 inpatients with schizophrenic spectrum disorders (F2x) - 67%, affective disorders (F3x) - 15%, neurotic and personality (F4x + F6x) - 9%, organic diseases of the central nervous system (F0x) - 9%. We used a visual analog scale for patients' subjective severity of their condition, locus control test, Internalized stigma of mental disorder scale (ISMI), Treatment motivation assessment questionnaire (TMAQ), and Medication Compliance Scale (MCS), which also includes BPRS, SANS, GAF scales. Dispersion analysis (p≤0.05), effect sizes calculation (Cohen's d/Cramer's V) were performed (ES). RESULTS: The options for prescribed antipsychotics did not depend on positive and negative symptoms, social maladjustment, suicidality, disease recurrence. The outpatient use of more than one antipsychotic was associated with socio-demographic differences in patients, high internality in life failures (ES=0.98), self-stigmatization (ES=0.94) due to the psychiatric stereotypes endorsement (ES=1.03), and social self-isolation (ES=1.08). Prescription of atypical antipsychotics during hospitalization was associated with subjectively less severe condition in patients (ES=0.7), their position of active cooperation with a doctor (ES=1.08), high internality of achievements (ES=0.99), lower psychiatric stereotypes endorsement (ES=1.19), social self-isolation (ES=1.58). Depot antipsychotic was predominantly an option for patients with secondary education (ES=0.34). CONCLUSION: Types and forms of antipsychotic treatment were associated not with clinical but with social and psychological patients' characteristics. The prescription of atypical antipsychotics, including depot forms, is specifically associated with not only treatment adherence, but with a favorable profile of patients' motivation for treatment.

Molecular Pathway Activation Markers Are Associated with Efficacy of Trastuzumab Therapy in Metastatic HER2-Positive Breast Cancer Better than Individual Gene Expression Levels.

Increased expression or amplification of HER2 receptor tyrosine kinase gene ERBB2 is well-known and widely used as a prognostic biomarker of breast cancer (BC) response to the targeted treatment with trastuzumab and its analogs. Considering that part of the BC patients overexpressing HER2 does not respond to trastuzumab, clinical trial NCT03521245 was initiated to identify additional gene expression and molecular pathway activation response biomarkers to trastuzumab treatment in HER2-positive BC. Using RNA sequencing gene expression in 23 formalin-fixed, paraffin embedded HER2 positive BC tissue blocks from patients who either responded or not responded to trastuzumab treatment was profiled. Differentially regulated genes and molecular pathways were identified in the groups of trastuzumab responders and non-responders. These results were next compared with the 42 previously published BC trastuzumab responder and non-responder RNA sequencing profiles from the clinical trials NCT00513292 and NCT00353483. No correlation was observed between the response status and the expression levels of ERBB2 gene in the HER2 positive BC samples. Analysis of the differentially expressed genes and molecular pathways in the combined dataset revealed 15/27 commonly up/down regulated genes and 15/25 pathways, respectively. However, only the intersection of molecular pathways upregulated in trastuzumab responders vs non-responders was statistically significantly enriched compared to the random expectation model. A classifier built using the most significantly upregulated molecular pathway - cAMP Pathway Protein Retention - demonstrated the best performance for prediction of the HER2 positive BC response to trastuzumab for both our experimental and previously reported data. This pathway also predicted time to recurrence in the combined dataset with Log-rank p-value 0.041.

Applicability of the Fokker-Planck equation to the description of diffusion effects on nucleation.

The nucleation of islands in a supersaturated solution of surface adatoms is considered taking into account the possibility of diffusion profile formation in the island vicinity. It is shown that the treatment of diffusion-controlled cluster growth in terms of the Fokker-Planck equation is justified only provided certain restrictions are satisfied. First of all, the standard requirement that diffusion profiles of adatoms quickly adjust themselves to the actual island sizes (adiabatic principle) can be realized only for sufficiently high island concentration. The adiabatic principle is essential for the probabilities of adatom attachment to and detachment from island edges to be independent of the adatom diffusion profile establishment kinetics, justifying the island nucleation treatment as the Markovian stochastic process. Second, it is shown that the commonly used definition of the "diffusion" coefficient in the Fokker-Planck equation in terms of adatom attachment and detachment rates is justified only provided the attachment and detachment are statistically independent, which is generally not the case for the diffusion-limited growth of islands. We suggest a particular way to define the attachment and detachment rates that allows us to satisfy this requirement as well. When applied to the problem of surface island nucleation, our treatment predicts the steady-state nucleation barrier, which coincides with the conventional thermodynamic expression, even though no thermodynamic equilibrium is assumed and the adatom diffusion is treated explicitly. The effect of adatom diffusional profiles on the nucleation rate preexponential factor is also discussed. Monte Carlo simulation is employed to analyze the applicability domain of the Fokker-Planck equation and the diffusion effect beyond it. It is demonstrated that a diffusional cloud is slowing down the nucleation process for a given monomer interaction with the nucleus edge.

[A role of motivation for treatment in the structure of compliance in psychopharmacologically treated patients].

OBJECTIVE: To reveal an impact of specific motivation structures on the compliance in psychiatric inpatients. MATERIAL AND METHODS: The Treatment Motivation Questionnaire and the Medication Compliance Scale have been administered to 104 patients, including 67 patients with schizophrenia and schizophrenia-spectrum disorders, 15 with affective disorders, 13 with personality and neurotic disorders and 9 with organic disorders, of the department of integrative pharmaco- and psychotherapy. RESULTS: A motivational mechanism based on the subjective suffering from disease plays a key role in the formation of overall score of compliance. Amotivation syndrome has a negative impact on the compliance. "Passive agreement" attitude to treatment corresponds to a deficiency in both patient and physician compliance subsystems along with a reduction in insight and cognitive functions in the patient's subsystem. Extreme external motivation for treatment correlates with insufficiently constructive support on the part of significant others in patient's environment subsystem resulting in the delay of internal motivation development. Extremely low scores based on understanding of disease character leads to the deficiency of medication compliance subsystem.

[The features of cardio-respiratory system and autonomic regulation in parasportsmen with spinal injury].

A comprehensive study of the functional state of basketball athletes in wheelchairs with spinal cord injuries in the T6-T10 and paraplegia (n = 9, mean age 26.6 +/- 1.7 years) was held. As a control, we used disability groups with a similar injury, leading an active life (n = 13, mean age 44.5 +/- 2.6 years), athletes ( = 14, mean age 24.6 +/- 1.3 years) and healthy physically active men (n = 15, the average age of 24.9 +/- 0.6 years). In the athletes in wheelchairs it was revealed an increase in the length of the body in a sitting position, the increase in tidal volume and increasing in the effectiveness of the functional respiratory tests. These changes in the state of the musculoskeletal system and autonomic systems to ensure physical activity classified as adaptive and due to sports training. In the state of the cardiovascular system and its autonomic regulation parasportsmen showed a reduction in trauma-induced increase in diastolic blood pressure and increase in the magnitude of arterial baroreflex sensitivity, decreased due to spinal injury. These data indicate availability of compensatory processes aimed at optimizing the cardiovascular system through the mechanisms of baroreflex regulation.

[Concentration of light hydrocarbons in exhaled air depending on the risk factors of metabolic disorder].

In this study we investigated the effect of risk factors of metabolic syndrome on the content of light hydrocarbons (C2-C3) in exhaled air. We used a gas chromatograph with a short multi-channel column. As a result, sex differences in concentrations of light hydrocarbons presented in exhaled air were found. In addition, such factors as smoking and diabetes mellitus type 2 in relatives reflect on the exhaled C2-C3 compounds only in women. But the overweight correlates with the exhaled acetone (C3) only in men. Thus, the fact that the metabolic changes caused by the presence of risk factors of metabolic syndrome lead to changes in gas composition of exhaled air and can be registered and used for early diagnosis has been ascertained.

[Expression of early developmental genes in vole Microtus rossiaemeridionalis].

The expression of genes Sox2, Klf4, Myc, Sall4, Gata6, Foxa2, Hnf4a, Cdx2, Esrrb, Hand1 in cultivated cells, embryos and organs of adult voles Microtus rossiaemeridionalis was studied. High resemblance of the expression patterns of these genes in the organs of adult voles, mice and humans was demonstrated. It was established that genes Gata6, Foxa2 and Hnf4a were specifically expressed in vole extraembryonic endoderm cells, while Cdx2 and Handl genes, in trophoblast stem cells. This shows that these genes can be used markers for corresponding vole cell lines. Indirect confirmation pointing to the fact that Oct4 gene is a marker gene for epiblast cells both in the vole and mouse was obtained.

Charge and charging of nanoparticles in a SiH4 rf-plasma.

Plasma-produced nanoparticles are of interest for many applications. They have very specific properties that can vary greatly from those in the atomic and bulk materials, including thermodynamic properties, such as a reduced melting temperature, and optical properties, such as blue-shifted blackbody radiation. Since a plasma is dominated by free electrons, charge related properties, like a reduced work function for electron attachment and increased work function for photo ionization, are of major importance. In situ detection of nanoparticles inside a plasma is difficult. Hence, indirect methods including changes in optical emission, plasma voltage and currents are used to study particle growth. Here, electron density measurements in the plasma are presented using an ultrafast microwave resonance technique (time resolution below 1 micros). This technique allows studying the charge and charging kinetics of nanoparticles within the initial milliseconds of their growth.

[The first successful bilateral lung transplantation in Russia].

Lung transplantation is one of the most difficult fields of contemporary transplantology. The operation was performed on a 53-year-old female who had been suffering from terminal stage COPD. The period of cold ischemia for the right and left lung was 1 hour 30 minutes and 2 hours 25 minutes respectively. The total operation time was 4 hours and 40 minutes. There were no surgical complications. There were no signs of transplant rejection 6 weeks after the operation. The considerable decrease in dispnea and increase in quality of life were registered during the follow-up. FEV1 was increased by 80% and 6 minute walk test distance was increased by 200 meters.

Effect of diffusion on nucleation of two-dimensional nanoislands.

Effect of diffusion on the steady-state nucleation of two-dimensional nanoislands is described analytically. New approach takes self-consistently into account coupling between the kinetics of adatoms near the island edge, their diffusion on the surface and annihilation at other islands. It was shown that due to this coupling the nucleation barrier can considerably differ from that predicted by the thermodynamics and can depend on the diffusion parameters of adatoms. This effect can be used for controlling of the kinetics of nanoisland nucleation.

Large Ground Level events in solar cycle 22 and some peculiarities of relativistic proton acceleration.

Some of the Ground Level Enhancements of Solar Cosmic Rays (SCR) recorded by neutron monitors during solar cycle 22 are analyzed. The events appeared in series, and their occurrence rate in 1989-1991 was a factor of 4 larger than the average value (approximately equal to 1/yr) for the total observation interval (since 1942). The events of Sept. 29 and Oct. 24, 1989 proved to be the more intensive. The analyzed events show no peculiarities as to the distribution of the T1/2 parameter, whereas the shape of the profile of some events is notable for a two peak structure. The latter implies the possibility of a two component SCR ejection from two different sources in the solar atmosphere. For the event of Sep. 29 we have estimated the ejection rigidity spectrum of protons to be D solar (R) = (1-2) 10(32)R(-2.9) Gv-1 at R greater than or equal to 1 Gv. As to its proton flux, this event proved to be by 1-2 orders less intensive than the well known event of Feb. 23 1956.

[Comparative study of lymph node gangliosides and blood serum of normal and T-lymphotrophic baboons]. / Sravnitel'noe izuchenie gangliozidov limfaticheskikh uzlov i syvorotki krovi pavianov-gamadrilov v norme i pri T-kletochnykh limfomakh.

The gangliosides from the lymph nodes and blood sera of normal and T-lymphomic baboons were studied. In lymph nodes the major gangliosides were identified as GM3 and GD3, those in blood sera--as GM3, GM1 and GD3. Gangliosides GM3 and GD3 contained N-acetyl as well as N-glycoloyl neuraminic acids. In gangliosides isolated from lymph nodes and blood sera of T-lymphomic baboons the levels of N-glycoloyl neuraminic acid markedly exceeded that in normal tissues. In tumour lymph nodes the GM3/GD3 ratio was shifted towards GD3.

Jet lag.

Jet lag is the loss of wellbeing associated with rapid travel across time zones. An understanding of its causes and the factors which influenced its severity may help in its prevention and management.

Human poisoning by ingestion of a sea hare (Dolabella auricularia).

A case-report of poisoning by ingestion of a sea hare, which is thought to be the first report of human poisoning, is presented. The clinical signs were mainly neurological with tremor, psychomotor over-activity, ataxia and muscle twitching being predominant. It is suggested that organic bromine compounds are responsible for the effects.