Giant oscillations of diffusion in ac-driven periodic systems.

We revisit the problem of diffusion in a driven system consisting of an inertial Brownian particle moving in a symmetric periodic potential and subjected to a symmetric time-periodic force. We reveal parameter domains in which diffusion is normal in the long time limit and exhibits intriguing giant damped quasiperiodic oscillations as a function of the external driving amplitude. As the mechanism behind this effect, we identify the corresponding oscillations of difference in the number of locked and running trajectories that carry the leading contribution to the diffusion coefficient. Our findings can be verified experimentally in a multitude of physical systems, including colloidal particles, Josephson junction, or cold atoms dwelling in optical lattices, to name only a few.

Mechanism of caspase-2 activation upon DNA damage.

The mechanism of caspase-2 activation in response to DNA damage was studied using human ovarian cancer cells Caov-4 treated with chemotherapeutic agent cisplatin. It was shown that mutations of the three cleavage sites of caspase-2 do not affect the assembly of the macromolecular complex of caspase-2 and its activation, but, conversely, stabilize this complex, most likely, via the inhibition of the dissociation of the active caspase-2.

[Radiological control of silvicultural production in Perm Krai].

Results of the studies carried out in 2009-2012 on the 137Cs content in edible fungi, berries and fruits of wild-growing bushes and the low shrubs growing in forest ecosystems of a number of regions of the Perm Krai are presented. It is shown that the activity of radio caesium in the studied samples does not exceed the maximal allowed levels approved in the Russian Federation.

[The concentration of procalcitonin in blood andi enteric exudation in patients at early post-operation period].

The study sampling included 46 patients operated on the occasion of acute surgical pathology of abdominal organs. The concentration of procalcitonin was analyzed at 2-3 days after operation in simultaneously obtained samples of blood serum and exudation of small intestine. The level of procalcitonin was analyzed using enzyme-linked immunosorbent assay with test-systems with sensitivity 0.01 ng/ml. The concentration of procalcitonin in content of small intestine was lower than in blood serum (p<0.001) and in most samples of enteric exudation (n=33) did not exceed 0.01 ng/ml. The analysis of correlation interdependences established that concentration of procalcitonin in intestinal exudation has no dependencies with its level in blood serum. The admixture of blood as a result of traumatization of mucous membrane under application of naso-jejunal probe is one of main causes of occurrence of procalcitonin in content of intestine.

[Caspase-2: what do we know today?].

Apoptosis (programmed cell death) is essential machinery for multicellular organisms. Apoptosis plays an important role in cell differentiation, damaged cell elimination and immune system homeostasis. This review is focused on various mechanisms of signal transduction through caspase-2 which believed to be one of the most enigmatical protease involved in apoptosis. Caspase-2 is activated upon stimulation by such agents as genotoxic stress, death receptors ligation, ER stress, metabolic changes, etc. In addition, caspase-2 may act as a tumor suppressor and has been implicated in cell response to oxidative stress and neurodegenerative progression during ischemic brain damage. Thus, variety of signal pathways triggered by caspase-2 place this protease apart from other members of the family and suggests a prominent role in apoptosis. Here, we analyse different functions of this unique caspase and discuss possible applications of accumulated knowledge in advanced oncology and medicine.

[The role of immunodeficiencies in development of complications during vaccination of children with BCG vaccine].

AIM: Study of the interrelation between the presence of immune deficiency and development of complications during vaccination of newborns with BCG vaccine. MATERIALS AND METHODS: In 24 children with complications of vaccine process in the form of cold abscess and lymphadenitis indicators of lymphocyte subpopulation levels were studied by flow cytofluorimetry on Beckman Coulter cytofluoriemter by using monoclonal antibodies with markers CD45+CD3+ - T-cell, CD45+CD3+CD4+ - T-helpers, CD45+CD3+CD8+ - T-supressors-cytotoxic killers, CD45+CD3 CD16+CD56+ - natural killers, CD45+CD3-CD19+ - B-lymphocytes. The level of IgG, IgA, IgM in sera was determined by immune diffusion method in agar by Mancini. RESULTS: In 4 children selective deficiency of IgA, in 5 - hyper-IgM syndrome was detected, which is an innate immunodeficiency and is characterized by the lack of sera IgA, reduction of IgG level and increase of IgM. In 9 children a reduction of CD16+ natural killer lymphocytes was detected, in some cases combined with a reduction of CD8+ T-supressors-cytotoxic killers. CONCLUSION: The reason of development of complications during BCG administration is the presence of immunodeficiency in children. In these children severe course of the vaccine process, presence of axillary lymphadenitis was observed, therapy of these children continued from 4 to 6 months.

[Cytogenetic profile in patients with primary myelodysplastic syndrome].

AIM: To analyze the prevalence of chromosome aberrations presented in the revised International Prognostic Scoring System (R-IPSS) in patients with de novo myelodysplastic syndrome (MDS). Subjects and methods. Chromosome aberrations were analyzed in 197 patients aged 14 to 86 years (median age 64 years) with de novo MDS. RESULTS: Karyotype abnormalities were revealed in 129 (65.5%) patients with de novo MDS. According to the IPSS criteria, the karyotypes found 52 (26.4%) patients were assigned to an intermediate prognostic group whereas in accordance with the R-IPSS guidelines, an intermediate karyotype group included chromosome abnormalities in 32 (16.2%) patients. Out of 5 R-IPSS prognostic types, the favorable karyotype group was the largest (48.2%). The very favorable and unfavorable karyotype groups comprised few patients with MDS: 3 and 3.6%, respectively. Despite the fact that it was not mentioned in the R-IPSS, a monosomal karyotype was verified in 24 (12.2%) patients There was a correlation of the (normal and complex) karyotype with bone marrow blast counts (r=0.469; p=0.000), but not with age. CONCLUSION: A variety of cytogenetic damages cannot identify the prognostic potential of all chromosome aberrations occurring in patients with MDS even if prognostic factors increased up to 5.

[Viral and drug-induced liver damage in children with tuberculosis: prevalence, clinical features].

UNLABELLED: THE AIM OF THE RESEARCH: Improving the effectiveness of diagnostics and treatment of viral and drug-induced lesions of the liver (DILL) at a tuberculosis in children by identifying the frequency of their distribution, peculiarities of diagnostics and clinics. MATERIALS AND METHODS: We examined 242 children in the age from 2 months to 17 years, the patients with different forms of tuberculosis. RESULTS: The prevalence of hepatitis in children with tuberculosis: B - 1,2%, C-0.4%, G - 4,6%, TT - 8,7%. DILL was diagnosed in 67.5% of children - TB patients, in 48% of the children with DILL an asymptomatic course of the disease was noted, however, in 54.4% of the children with DILL cytolitic syndrome was expressed (ALT> standards). CONCLUSION: The prevalence of viral hepatitis B and C among children with TB is low. The infection with viruses of hepatitis G and TT is more often, but has no significant impact as on the course of tuberculosis, and on the severity of the liver damage. Drug-induced liver damage is a dominant view of pathology of the liver in children - TB patients and is mostly asymptomatic, but with a pronounced cytolitic syndrome.

Temperature anomalies of oscillating diffusion in ac-driven periodic systems.

We analyze the impact of temperature on the diffusion coefficient of an inertial Brownian particle moving in a symmetric periodic potential and driven by a symmetric time-periodic force. Recent studies have revealed the low-friction regime in which the diffusion coefficient shows giant damped quasiperiodic oscillations as a function of the amplitude of the time-periodic force [I. G. Marchenko et al., Chaos 32, 113106 (2022)1054-150010.1063/5.0117902]. We find out that when temperature grows the diffusion coefficient increases at its minima; however, it decreases at the maxima within a finite temperature window. This curious behavior is explained in terms of the deterministic dynamics perturbed by thermal fluctuations and mean residence time of the particle in the locked and running trajectories. We demonstrate that temperature dependence of the diffusion coefficient can be accurately reconstructed from the stationary probability to occupy the running trajectories.

[Novel splicing isoform of actin-binding protein alpha-actinin 4 in epidermoid carcinoma cells A431].

Alpha-actinin 4 (ACTN4) belongs to actin binding proteins of the spectrin superfamily. Structural organisation of actin fibres and focal contacts is considered to be its primary function in a cell. Besides that, nucleocytoplasmic shuffling of ACTN4 and its involvement in nuclear processes were demonstrated. Lately, additional isoforms of ACTN4 resulted from an alternative splicing has been described in various cell types and malignant tumours. In this study, we present investigation of a novel ACTN4 isoform of 80 kDa. The isoform was found in human epidermoid carcinoma cells A431, and it was not detected in human skin fibroblasts, normal human keratinocytes and transformed human embryonic cells HEK293T. Analysis of ACTN4 mRNA in A431 cells showed the presence of a splice variant that lacked the exons 2-8. The deleted exons code two calponin homology domains responsible for ACTN4 binding to F-actin. Intracellular distribution of the described ACTN4 isoform (ACTN4ISO) overexpressed in HEK293T cells differed from that of the full size protein. In the cytoplasm, ACTN4ISO was allocated diffusively with no colocalisation with actin cytoskeleton structures. Intranuclear distribution of ACTN4ISO also differed from that of the full size ACTN4. Nevertheless, immunochemical analysis demonstrated possibility of ACTN4ISO to form heterodimers with the full size protein. Additional investigations of novel isoform interactions with ACTN4 protein partners might clarify its functional features in A431 cells.

[Age-specific characteristics of acute myeloid leukemia karyotype].

AIM: To study distribution of some karyotype variants among patients of different age with acute myeloid leukemia (AML). MATERIAL AND METHODS: Distribution of balanced, normal, unbalanced, complex and monosomic karyotype among 244 patients with de novo AML in age groups 16-20, 21-30, 31-40, 41-50, 51-60, 61 and older was analysed. RESULTS: There is difference in frequency of balanced and complex karyotype in patients under and over 60 years. Number of AML patients with balanced aberrations including favourable variants t(8;21), t(15;17) and inv(16) falls after 60 years of age (6.7% versus 15.0% in patients aged 16-20 years; p < 0.001), while a complex karyotype occurs more frequently in AML patients at the age of 61 and older (56.8% versus 2.7% in the group 16-20 years; p < 0.001). With age, more frequently detected is the most unfavourable monosomic karyotype with aberrations similar to those in myelodysplastic syndrome (57.1% in patients aged 16-60 years and in 80.0% in the group of 61 years of age and over). CONCLUSION: Age-specific karyotype features detected may be explained by different biological mechanisms involved in leukosogenesis in young and elderly AML patients.

Bedaquiline for multidrug-resistant TB in paediatric patients.

BACKGROUND: TMC207-C211 (NCT02354014) is a Phase 2, open-label, multicentre, single-arm study to evaluate pharmacokinetics, safety/tolerability, antimycobacterial activity and dose selection of bedaquiline (BDQ) in children (birth to <18 years) with multidrug-resistant-TB (MDR-TB).METHODS: Patients received 24 weeks' BDQ with an anti-MDR-TB background regimen (BR), followed by 96 weeks of safety follow-up. Results of the primary analysis are presented based on data up to 24 weeks for Cohort 1 (≥12-<18 years; approved adult tablet at the adult dosage) and Cohort 2 (≥5-<12 years; age-appropriate 20 mg tablet at half the adult dosage).RESULTS: Both cohorts had 15 patients, of whom respectively 53% and 40% of Cohort 1 and Cohort 2 children had confirmed/probable pulmonary MDR-TB. Most patients completed 24 weeks´ BDQ/BR treatment (Cohort 1: 93%; Cohort 2: 67%). Geometric mean BDQ area under the curve 168h values of 119,000 ng.h/mL (Cohort 1) and 118,000 ng.h/mL (Cohort 2) at Week 12 were within 60-140% (86,200-201,000 ng.h/mL) of adult target values. Few adverse event (AE) related discontinuations or serious AEs, and no QTcF >460 ms during BDQ/BR treatment or deaths occurred. Of MGIT-evaluable patients, 6/8 (75%) Cohort 1 and 3/3 (100%) Cohort 2 culture converted.CONCLUSION: In children and adolescents aged ≥5-<18 years with MDR-TB, including pre-extensively drug-resistant-TB (pre-XDR-TB) or XDR-TB, 24 weeks of BDQ provided a comparable pharmacokinetic and safety profile to adults.

[The nosological structure of congenital fetal malformations in Novosibirsk].

The authors comparatively studied the nosological structure of congenital malformations (CM) in 395 fetuses at 22-27 weeks post-conception age and the efficiency of prenatal diagnosis in Novosibirsk. They analyzed 227 and 168 autopsy protocols of fetuses with CM over the periods from 2000 to 2002 and from 2006 to 2008, respectively. In the nosological structure of mortality among low-weight fetuses, CM ranked third in 2000-2002 and second in 2006-2008. During all the observation periods, the structure of CM showed 4 major systemic CMs: multiple anomalies of development, the central nervous and urogenital systems, heart, and vessels; multiple CMs occupying a prominent place. There was a preponderance of hydrocephalus and spinal hernias among central nervous system CMs, that of hydronephrosis with megaureter among urogenital CMs, and that of ventricular septal defect among CMs of the heart and vessels. The efficiency of prenatal diagnosis in the above observation periods was 46-75%.

[A case of neonatal galactosemia].

The paper describes a rare case of hereditary thesaurismosis, galactosemia, in a full-term neonate girl aged 12 days with morphologically verified fetal giant-cell cholestatic hepatitis with the development of ascitis and jaundice.

[The nosological structure of mortality of low-weight fetuses in Novosibirsk].

The nosological structure of mortality was studied among low-weight fetuses, by analyzing 667 autopsy protocols over 2006-2008. There were 255 cases of spontaneous miscarriage and 412 cases of medically indicated abortion. Spontaneous and artificial abortions most frequently occur in repeated pregnant women at 26-27 weeks gestational age. In the nosological structure of fetal mortality, intrauterine fetal asphyxia was most commonly in spontaneous miscarriage; intrauterine pneumonias and generalized infection ranked second; in artificial abortion, the number of congenital malformations doubled and that of intrauterine fetal asphyxia reduced. In spontaneous and artificial abortions, the incidence of decompensated chronic placental insufficiency increased by twice.

[Investigation of FLT3-ITD and NPM1 mutations in patients with myelodysplastic syndrome and mixed myeloid diseases].

Two FLT3-ITD mutations, one FLT3-TKD) and five NPM1 mutations were detected in 7 patients with de novo myelodysplastic syndrome (MDS) out of 44 cases of MDS and MDS/mixed myeloid diseases. Expression of one of the three investigated mutations was identified: 4 in gene NPM1 (9.1%) and 2--FLT3-ITD (4.5%); simultaneous FLT3-ITD and NPM1 mutation--1 (2.3%); no progression in NPM1 within 9-20 months--3, although with chromosome 7 damage--2. It was suggested that NPM1 mutation without complex karyotype may serve as marker of relatively favorable course.

[FLT3 and NPM1 gene mutations in patients with acute myeloid leukemias and the impact of FLT3-ITD mutations on the survival of patients with a normal karyotype].

AIM: To estimate the extent of FLT3 and NPM1 gene mutations and the impact of mutations of FLT3-ITD on the survival of patients with acute myeloid leukemias (AML). MATERIALS AND METHODS: The nucleus-containing cells of bone marrow and blood were studied in 43 patients with AML. Polymerase chain reaction analysis of total genomic DNA was applied. RESULTS: Mutations of FLT3-ITD, FLT3-TDK, and the NPM1 gene were found in 16 (37.2%) patients. A total of 19 mutations were revealed. There were 8 mutations of FLT3-ITD, 5 of FLT3-TKD, and 6 in the NPM1 gene. Single damages to genes were detected in 13 patients: FLT3-ITD in 6 (13.9%), FLT3-TKD in 4 (9.3%), and NPM1 in 3 (7%). Three (7%) patients exhibited 2 mutations simultaneously: in the NPM1 and FLT3-ITD in 2 (4.7%) and in the NPM1 gene and FLT3-TKD in 1 (2.3%). In AML patients with a normal karyotype and the FLT3-ITD-/NPM1 and FLT3-ITD+/ NPM-T genotypes, median overall survival was 17.3 versus 8 months (p = 0.069); and event-free survival (EFS) was 11 versus 5 months (p = 0.026). Univariate analysis established the negative impact of FLT3-1TD mutation on EFS. CONCLUSION: The findings allow AML patients with a normal karyotype and the FLT3-ITD-/NPM-genotypes to be identified as a poor prognosis group.

[Development and use of a domestic test system for diagnosis of tuberculous infection on the basis of quantitative analysis of interferon-gamma induction in whole blood samples in vitro, by using specific recombinant antigens].

A test system was developed to detect tuberculous infection by qualitative analysis of interferon-gamma (IFN-gamma) in the plasma samples after 20-24-hour incubation of whole blood samples in the presence of Mycobacterium tuberculosis (MBT) antigens: tuberculin PPD and a mixture of the MBT-specific recombinant antigens ESAT-6 and CFP-10. The analysis used 3 test tubes each containing 1 ml of heparinized venous blood, one of which served as a control; the other two test tubes were employed to measure antigen-induced IFN-gamma production. Whether this test system might be used to determine primary tuberculous infection was studied in 277 children and adolescents. The threshold diagnostic IFN-gamma induction level determined in the test tube containing a mixture of the antigens ESAT-6 and CFP-10 was ascertained. Postvaccine allergy was detectable if there was IFN-gamma induction in the test tube containing tuberculin and if there was no diagnostic IFN-gamma level in that containing the antigens ESAT-6 and CFP-10. The diagnostic sensitivity of detection of primary tuberculous infection was 97.6% with 94.4% specificity, which enabled this condition to be differentiated from postvaccine allergy. The level of antigen-induced IFN-gamma may be lower in relatively disseminated forms of pulmonary tuberculosis.

[Analysis of nuclear protein complexes comprising alpha-actinin-4 by 2D-electrophoresis and mass-spectrometry].

Actin-binding protein alpha-actinin-4 is a member of spectrin super family. It is located in the cytoplasm and in the nucleus. However, nuclear functions of alpha-actinin-4 are still not clear. In this study, we analyzed composition of nuclear protein complexes associated with alpha-actinin-4 in A431 cells. Using 2D electrophoresis, we have determined that about 50 different proteins may be associated with nuclear alpha-actinin-4. Using mass-spectrometry, we analyzed major proteins of these complexes. beta-Actin, alpha- and beta-tubulins, ribonucleoprotein A2/B1, which regulates splicing and is associated with beta-actin, peroxiredoxin-1, which is involved in oxidative stress, and glycolytic enzyme D-3-phosphoglycerate dehydrogenase were identified by MALDI-TOF. Detection of these proteins in nuclear complexes with alpha-actinin-4 may suggest that alpha-actinin-4 is involved in transcription and splicing. Presence of beta-actin in the investigated complexes was confirmed by tandem mass-spectrometry (MALDI-TOF-TOF). Immunoprecipitation of nuclear proteins with antibodies against alpha-tubulin confirmed association of alpha-actinin-4 with alpha-tubulin in the protein complex. Nuclear alpha-actinin-4 constitutes of 105 KDa fullsize isoform and two truncated isoforms of 65 and 75 kDa, whereas only the truncated isoform have been found in nuclear complexes with alpha-tubulin. These data suggest that alpha-actinin-4 is associated with a number of different nuclear protein complexes which may carry out different functions in the cell nucleus.

[The specific features of tuberculosis in children and adolescents previously receiving chemoprophylaxis].

Examining 261 cases of active forms of tuberculosis in children and adolescents in the Samara Region in 1996 to 2004 indicated that 115 (44.1%) had earlier received chemoprophylaxis in the outpatient setting. The specific features of tuberculosis were revealed in this group of patients as compared with the children and adolescents who had never been treated with antituberculous drugs (n = 146): there was a predominance of preschool children; severe, disseminated forms of tuberculosis, detectable from complaints were observed less frequently; clinically cured pulmonary tuberculosis was more frequently characterized by residual posttuberculous changes. Outpatient chemoprophylaxis reduces the severity of the disease, but is not always effective in preventing tuberculosis.