Transcription factor DREF regulates expression of the microRNA gene bantam in Drosophila melanogaster.

The bantam gene encodes a vital microRNA and has a complex expression pattern in various tissues at different stages of Drosophila development. This microRNA is involved in the control of normal development of the ocular and wing imaginal discs, the central nervous system, and also in maintaining the undifferentiated state of stem cells in the ovaries of adult females. At the cellular level, bantam stimulates cell proliferation and prevents apoptosis. The bantam gene is a target of several conserved signaling cascades, in particular, Hippo. At the moment, at least ten proteins are known to directly regulate the expression of this gene in different tissues of Drosophila. In this study, we found that the bantam regulatory region contains motifs characteristic of binding sites for DREF, a transcription factor that regulates the expression of Hippo cascade genes. Using transgenic lines containing a full-length bantam lethality-rescuing deletion fragment and a fragment with a disrupted DREF binding site, we show that these motifs are functionally significant because their disruption at the bantam locus reduces expression levels in the larvae and ovaries of homozygous flies, which correlates with reduced vitality and fertility. The effect of DREF binding to the promoter region of the bantam gene on its expression level suggests an additional level of complexity in the regulation of expression of this microRNA. A decrease in the number of eggs laid and a shortening of the reproductive period in females when the DREF binding site in the regulatory region of the bantam gene is disrupted suggests that, through bantam, DREF is also involved in the regulation of Drosophila oogenesis.

Effects of Age and Suntan on the Expression of Second Messenger Signaling Pathways of Necroptosis in Skin Cells during Facelifting Surgery.

We studied the effects of age and suntan on the expression of necroptosis signaling molecules (RIPK1, RIPK3, and MLKL kinases) and first TNF receptor (TNFR1) in isolated skin cells from women undergoing facelift surgery. In women above 50 years, the expression of the TNFR1, kinases RIPK1, RIPK3, and MLKL, the phosphorylated forms of these kinases was significantly (p<0.05) increased in comparison with the corresponding parameters in women under 30 years. The expression of all necroptosis proteins and TNFR1 in women with suntan was significantly (p<0.05) higher than in those without tan. Cells from the surgical material were incubated with TNFα to determine the level of induced necroptosis. In women aged >50 years and women with suntan, the expression of phosphorylated forms of kinases was significantly increased, which attested to necroptosis activation. This study allowed identifying the targets on skin cells for prevention of necrosis and inflammation after facelift surgery.

Three-dimensional modeling of intense unipolar THz pulses formation during their amplification in nonequilibrium extended Xe plasma channel.

We develop a three-dimensional (3D) fully self-consistent model for analysis of an ultrashort THz pulse propagation and amplification in a nonequilibrium plasma channel formed in xenon by a femtosecond UV laser pulse. The model is based on the self-consistent solution of a second order wave equation in the cylindrical geometry and the kinetic Boltzmann equation for the electron velocity distribution function (EVDF) at different points of the spatially inhomogeneous nonequilibrium plasma channel. We analyze the wide range of plasma and seed pulse parameters and reveal the optimal regimes for producing high intensity outgoing THz fields as well as highly unipolar THz pulses within the proposed mechanism. It is demonstrated that the process of EVDF relaxation in plasma limits the amplification of THz pulses at the level of ∼10^{7}W/cm^{2}. Both focusing features of nonequilibrium plasma and the possibility of producing THz pulses with a high degree of unipolarity are confirmed for the case of 3D geometry.

Unipolar terahertz pulse formation in a nonequilibrium plasma channel formed by an ultrashort uv laser pulse.

We perform an alternative approach to produce highly unipolar terahertz pulses. The idea is based on the nonuniform amplification of seed ultrashort carrier-envelope phase (CEP) pulses in nonequilibrium fast relaxing plasma of air or nitrogen. If the gain coefficient drops significantly within the duration of a one-cycle CEP pulse, it undergoes significant distortion where the leading edge of the pulse is amplified and the trailing tail of opposite polarity is absorbed. The obtained results involve a self-consistent solution of the second-order wave equation and kinetic Boltzmann equation for the electron velocity distribution function relaxation.

[Methodological issues of cognitive impairment studies in pediatric multiple sclerosis patients]. / Metodologicheskie problemy issledovaniia kognitivnykh narushenii u detei i podrostkov s rasseiannym sklerozom.

The article provides a review of the characteristics of cognitive impairment in multiple sclerosis (MS) and methods for its assessment in children. The features of the most frequently used neuropsychological batteries, with consideration of specifics of cognitive impairment in MS, and data on assessment of a state of cognitive functions obtained using neuropsychological tests are presented. The authors also discuss the issue of a long-term impact of the disease on a state of cognitive functions. Clinical factors, which can lead to cognitive impairment (type of multiple sclerosis, age at manifestation, number of relapses), are described.

Chemokine Expression in Neutrophils and Subcutaneous Adipose Tissue Cells Obtained during Abdominoplasty from Patients with Obesity and Normal Body Weight.

The study was aimed at assessing the role of chemokines in inflammatory changes in tissue following abdominoplasty. The levels of neutrophil-coupled chemokines and their receptors in the serum and blood cells, as well as in cells isolated from the subcutaneous adipose tissue sampled during abdominoplasty were compared in patients with obesity and normal body weight. The levels of chemokines CCL3, CCL3, and CCL5 in blood serum and expression of chemokine receptor CXCR2 and CXCR6 on blood neutrophils were significantly higher (p<0.05) in obese patients in comparison with patients with normal body weight. Elevated expression of chemokines CCL2, CCL3, CCL4, CCL5, CCL18, and CCL20 (p<0.05) was detected in subcutaneous adipose tissue cells isolated obese patients in comparisons with persons with normal body weight. These findings attest to favorable conditions for enhanced neutrophil migration to the adipose tissue in patients with obesity, which can promote leukocyte infiltration of the suture site after abdominoplasty and serves as additional risk factor for the development of postoperative complications associated with activity of neutrophil-derived proteolytic enzymes.

Impact of attributed audit on procedural performance in cardiac electrophysiology catheter laboratory.

PURPOSE: Audit has played a key role in monitoring and improving clinical practice. However, audit often fails to drive change as summative institutional data alone may be insufficient to do so. We hypothesised that the practice of attributed audit, wherein each individual's procedural performance is presented will have a greater impact on clinical practice. This hypothesis was tested in an observational study evaluating improvement in fluoroscopy times for AF ablation. METHODS: Retrospective analyses of fluoroscopy times in AF ablations at the Barts Heart Centre (BHC) from 2012-2017. Fluoroscopy times were compared pre- and post- the introduction of attributed audit in 2012 at St Bartholomew's Hospital (SBH). In order to test the hypothesis, this concept was introduced to a second group of experienced operators from the Heart Hospital (HH) as part of a merger of the two institutions in 2015 and change in fluoroscopy times recorded. RESULTS: A significant drop in fluoroscopy times (33.3 ± 9.14 to 8.95 ± 2.50, p < 0.0001) from 2012-2014 was noted after the introduction of attributed audit. At the time of merger, a significant difference in fluoroscopy times between operators from the two centres was seen in 2015. Each operator's procedural performance was shared openly at the audit meeting. Subsequent audits showed a steady decrease in fluoroscopy times for each operator with the fluoroscopy time (min, mean±SD) decreasing from 13.29 ± 7.3 in 2015 to 8.84 ± 4.8 (p < 0.0001) in 2017 across the entire group. CONCLUSIONS: Systematic improvement in fluoroscopy times for AF ablation procedures was noted byevaluating individual operators' performance. Attributing data to physicians in attributed audit can promptsignificant improvement and hence should be adopted in clinical practice.

[Corticosterone-induced changes in the inhibitory neurotransmission in hippocampal CA1 synapses depending on the activity of inhibitory synapses that express cannabinoid receptors]. / Vyzvannye kortikosteronom izmeneniia tormoznoi neirotransmissii v sinasakh zony SA1 gippokampa v zavisimosti ot aktivnosti ékspressiruiushchikh kannabinoidnye retseptory tormoznykh sinapsov.

AIM: To study an effect of corticosterone (100 nM) on spontaneous inhibitory postsynaptic currents (sIPSC) in pyramidal neurons of CA1 area and a role of inhibitory CB1-expressing synapses in the development of corticosterone-induced effects. MATERIAL AND METHODS: The experiments were performed on acute slices of the rat ventral hippocampus using whole-cell configuration of the patch-clamp technique. RESULTS AND CONCLUSION: The addition of corticosterone resulted in a small, but significant, increase in the frequency of sIPSCs during the first 10 minutes and then this parameter returned to the basal level. Corticosterone treatment resulted in a considerable decrease in the sIPSC amplitude 40 minutes after the beginning of treatment. The activation of CB1 receptors weakly affected sIPSC characteristics, however, the addition of corticosterone did not induce the rapid elevation in the sIPSC frequency, which occurred on the 10th minute in the control, as well as a decrease in the sIPSC amplitude, which was observed in the control on the 40th min after the beginning of corticosterone treatment. The data obtained suggest that both rapid and slow effects of corticosterone are associated with the activity of CB1-expressing inhibitory synapses of the hippocampus.

The molecular and genetic aspects of adolescent girls anomalous uterine bleeding: the role of endothelial dysfunction syndrome.

The objective of the study is to assess NOS3 and ESR1 gene polymorphism in adolescent girls born with low birth weight (LBW) and suffered by anomalous uterine bleeding (AUB). A total 95 adolescent girls were studied including 32 born with LBW and AUB; 36 girls with normal birth weight and AUB; and 27 healthy girls. Single allele gene polymorphism NOS3 786T > C, 894G > T, ESR1 351A > G and 397T > C was studied. The existence of polymorphous allele С gene NOS3 786Т > С (for homozygote OR = 2.03; 95% CI: 1.12-3.68; p = 0.04; for heterozygote OR = 1.68; 95% CI: 1.09-2.60; p = 0.046) and genotype Pvull-CC ESR1 (OR = 4.58; 95% CI: 0.97-21.68; p = 0.04) was detected in LBW girls with AUB. It was suggested that intrauterine programming of endothelial dysfunction syndrome could play a significant role in the development of AUB in adolescent girls born with LBW.

Corticosterone Induces Rapid Increase in the Amplitude of Inhibitory Response in Hippocampal Synapses with Asynchronous GABA Release.

Experiments were performed on cultured slices of rat ventral hippocampus. Using extracellular stimulation and patch clamp recording from pyramidal neurons in the hippocampal CA1 area, we studied characteristics of GABAergic synapse formed on these neurons by cholecystokinin-expressing interneurons. This synapse was characterized by asynchronous release of GABA and depolarization-induced suppression of inhibitory response. It was observed that administration of corticosterone increased the amplitude of evoked inhibitory postsynaptic currents in 5 minutes, but the paired ratio did not significantly change. Obtained data reflect that corticosterone can induce rapid genome-independent effects on inhibitory neurotransmission in one of hippocampal synapses.

Targeted mutagenesis of Drosophila RNaseZ gene by homologous recombination.

For the first time we used a homologous recombination method to obtain complete and precise deletion of Drosophila dRNaseZ gene. In the founder line of flies in which the RNaseZ sequence was replaced by attP site, the full-length sequence of the gene was reintegrated, and its functionality was shown. This approach will allow us to generate further gene mutations in different domains of dRNaseZ protein and discover a broad spectrum and uncover functions outside of tRNA processing.

ECTOPIC TETHERING OF THE CHROMATOR PROTEIN IN UASDBD(GAL4) SYSTEM AS APPROACH FOR STUDYING OF THE INSULATOR PROTEINS IN DROSOPHILA MELANOGASTER POLYTENE CHROMOSOMES.

Chromatin insulator proteins are one of the major components that determine the domain organization of the genome. According to the latest data, they can mark the boundaries of topological domains and prevent the spread of silent chromatin to adjacent areas. One approach to the analysis of the actions of these proteins is to use the ectopic involvement in the UAS>DBD(GAL4). The method allows to evaluate the effect of selected protein in chromatin organization, to establish its association with other insulator proteins and influence on the processes of transcription and replication. and influence the processes of transcription and replication. In this study, we have developed and tested the functionality of the system components in ectopic tethering of the Chromator (Chriz) to the region of intercalary heterochromatin 10A1-2. Preliminary data have been obtained showing that ectopically tethered Chromator to the band 10A1-2 can induce a partial decompactization of the band chromatin. Further use of this experimental model provides the opportunity to investigate the effect of insulator proteins on the chromatin structure.

[Clinical and gender characteristics of tobacco dependence in addiction psychiatrists]. / Klinicheskie i gendernye osobennosti tabachnoi zavisimosti u narkologov.

AIM: To study clinical and gender characteristics of tobacco dependence in addiction treatment specialists in comparison with physicians of other specialties. MATERIAL AND METHODS: A total of 21 addiction psychiatrists and 154 doctors of various therapeutic specialties were examined. All physicians were stratified into two groups and then each group was subdivided into male and female subgroups. A questionnaire developed by one of the authors and the Fagerström Test for Nicotine Dependence were used for standardization of the study. RESULTS AND CONCLUSION: In addiction psychiatrists, the prevalence of tobacco dependence among female addiction psychiatrists was higher than that of the female doctors of other specialties. Persistent smoking was formed earlier, and awareness of the urge to smoke appeared later compared to physicians of other specialties. The degree of tobacco dependence was higher in addiction psychiatrists of both genders. Affective component was dominated in the tobacco withdrawal syndrome in female addiction psychiatrists.

[THE SOCIAL PSYCHOLOGICAL ANALYSIS OF CONCEPTIONS CONCERNING OF ALCOHOL USING DURING PREGNANCY].

The article considers experience of application of focus-group technique for both analyzing social psychological conceptions about harm of alcohol consumption during pregnancy and development of prevention programs concerning fetal alcoholic syndrome, an incurable children disease developing because of mother's consumption of alcohol during her pregnancy. The development of preventive program is possible only on the basis the study results allowing getting reliable information about existing in different population groups (first of all in pregnant women, women of childbearing age and medical workers) attitudes concerning alcohol consumption during pregnancy and factors effecting decrease or stopping alcohol consumption by pregnant women as well. The study was carried out involving 7 focus groups: three with physicians (n=23) and four with women (n=23) and their husbands (n=5). The protocols of focus groups were analyzed using software A TLAS-ti 5.0. The most typical attitudes concerning alcohol consumption during pregnancy were established. It was discovered that neither women nor physicians have no essential knowledge about effect of alcohol on fetus and about fetal alcoholic syndrome.

Liposomes loaded with hydrophilic magnetite nanoparticles: Preparation and application as contrast agents for magnetic resonance imaging.

Magnetic fluid-loaded liposomes (MFLs) were fabricated using magnetite nanoparticles (MNPs) and natural phospholipids via the thin film hydration method followed by extrusion. The size distribution and composition of MFLs were studied using dynamic light scattering and spectrophotometry. The effective ranges of magnetite concentration in MNPs hydrosol and MFLs for contrasting at both T2 and T1 relaxation were determined. On T2 weighted images, the MFLs effectively increased the contrast if compared with MNPs hydrosol, while on T1 weighted images, MNPs hydrosol contrasting was more efficient than that of MFLs. In vivo magnetic resonance imaging (MRI) contrasting properties of MFLs and their effects on tumor and normal tissues morphology, were investigated in rats with transplanted renal cell carcinoma upon intratumoral administration of MFLs. No significant morphological changes in rat internal organs upon intratumoral injection of MFLs were detected, suggesting that the liposomes are relatively safe and can be used as the potential contrasting agents for MRI.

[Formation of Enterobacter cloacae resistance to disinfectants under the effect of bactericidal concentrations of quaternry ammonium compounds in the experiment].

AIM: Study the possibility of formation of induced resistance of purulent-septic infection (PSI) causative agents against disinfectants (DI) in bactericidal concentrations. MATERIALS AND METHODS: Daily exposure to bactericidal concentrations of preparations from the group of quaternary ammonium compounds (QAC) on Enterobacter cloacae strain that has incomplete sensitivity to the same disinfectants on the same test objects was carried out in experiments on test objects from wood and plastic. Exposure was carried out until the moment of transition from incomplete sensitivity to resistance. RESULTS: E. cloacae strain that initially had incomplete sensitivity to various disinfectants of the QAC group in antibacterial concentrations according to manuals acquires resistance on test objects from wood and plastic after 2 - 12 exposures to the preparations. CONCLUSION: The data obtained give evidence that the resistance of PSI causative agents to disinfectants can take place not only under the influence of low concentrations of the preparations but also during use of disinfectants at bactericidal concentrations.

[Sensitivity of nosocomial purulent-septic infection causative agents to disinfection agents and antibiotics].

AIM: Study the sensitivity of nosocomial purulent-septic infection (PSI) causative agents to disinfectants (DA) and antibiotics (AB). MATERIALS AND METHODS: Sensitivity to DA and AB of 209 PSI causative agent strains isolated from patients and the environment of 2 obstetric and 3 surgical hospitals was studied in 2009-2011. Sensitivity to DA of 94 strains and to AB of 189 strains of Pseudomonas aeruginosa isolated from patients with signs of PSI of reanimation and intensive therapy and surgical departments of a multi-field hospital was studied in 2012. Sensitivity to DA was determined on test-surfaces and in solution according to guidelines by V.V. Shkarin et al., 2010; sensitivity to AB - by disc-diffusion method. RESULTS: Among PSI causative agents resistant to DA the portion of poly-antibiotic resistant strains is higher than among microorganisms sensitive to DA, and among antibiotic resistant bacteria the number of strains resistant to DA is higher than among sensitive to antibiotics. The increase of resistance to DA and AB of P. aeruginosa strains is observed in parallel to the increase of volume of the antibacterial preparations used. CONCLUSION: The results obtained give evidence of the possibility of formation of combined (associated) resistance to DA and AB by nosocomial PSI causative agents against the background of increase of their consumption.

[Leukocyte elastase, alpha 1-proteinase inhibitor and C-reactive protein in patients with delayed negativation of serological reactions after treatment of early syphilis].

It was investigated the activity of leukocyte elastase, alpha 1-proteinase inhibitor and C-reactive protein in patients with delayed negativation of serological reactions after a treatment of syphilis. The patients were divided into three subgroups. The first subgroup consisted of patients who did not have the signs of non-specific immune system response. Second subgroup consisted of patients with clear signs of infection process. The patients this subgroup had elevated values of the contents of inflammatory mediators. The remaining patients with questionable results were attributed in the third subgroup. The obtained results can be of great value to determine further treatment strategy in patients with delayed negativation of serological reactions.

[Is resistance to disinfectants a mandatory feature of a hospital strain of causative agents of nosocomial purulent-septic infections?].

AIM: Evaluate resistance to working solutions of disinfectants by Staphylococcus haemolyticus and Klebsiella pneumoniae isolated from newborns and hospital environment objects of obstetric hospital during registration of group purulent-septic infections (PSI). MATERIALS AND METHODS: Analysis of 2 epidemic situations on PSI morbidity of newborns caused by S. haemolyticus and K. pneumoniae was carried out. Sensitivity to antibiotics of S. haemolyticus and K. pneumoniae strains isolated from newborns and hospital environment was studied by disc-diffusion method and genotyping of K. pneumoniae--by using polymerase chain reaction with universal primer M 13 (RAPD-PCR). Sensitivity of S. haemolyticus and K. pneumoniae to working solutions of disinfectants was determined on test-surfaces (glass, metal, plastic, wood, oilcloth). RESULTS: The detected identity of antibiotic phenotype of S. haemolyticus and K. pneumoniae strains as well as genotype of K. pneumoniae strains combined with registration of group PSI morbidity among newborns confirms that the circulating strains (clones) of the causative agents were hospital. S. haemolyticus and K. pneumoniae strains in most cases were sensitive to working solutions of disinfectants. CONCLUSION: Resistance of causative agents of nosocomial PSI to disinfectants is not an unconditional feature of a hospital strain, and concurrence of resistance profile of microorganisms to disinfectant preparations--a mandatory feature of the presence of epidemiologic connection between the diseased.