[Oxytocin genetic pathway (CD38) and SDQ psychosocial characteristics in adolescent schoolchildren]. / Geneticheskii put' oksitotsina (CD38) i psikhosotsial'nye kharakteristiki po oprosniku SDQ u shkol'nikov-podrostkov.

OBJECTIVE: To determine an effect of CD38 on the regulation of oxytocin (OT) production and to identify psychosocial characteristics according to the Strength and Difficulties Questionnaire (SDQ) in adolescent schoolchildren. MATERIAL AND METHODS: The study included 308 adolescents, aged 11-18 years, of an unbiased school sample from three large cities of Central Siberia (Krasnoyarsk, n=194; Abakan, n=76; Kyzyl, n=38). All participants were Russian. The ethnicity was determined by mother's descent. Psychological study using SDQ and analysis of gene polymorphisms in DNA from saliva samples were carried out. Genotyping was performed using TaqMan allele discrimination technology with TaqMan probes (DNA synthesis, Russia) using real-time polymerase chain reaction and Rotor-Gene 6000 (Corbett Life Science, Australia). Data were analyzed using Statistica v.10 software. RESULTS: In adolescence, the high activity of the OT pathway can cause a number of negative effects, such as emotional instability («Emotional problems¼ (p=0.048), «Goodman total score¼ (p=0.057), «Hyperactivity¼ (p=0.075). The differences are statistically significant (p≤0.05)) in young (11-14 years old) adolescent girls who carry the A allele for rs3796863 polymorphism. Similar gender differences are characteristic and have been described for other populations. The distribution of the CD38 rs3796863 genotypes was similar to that in Caucasians. In adolescence, OT production decreases in comparison with the prepubertal period, and there are gender differences in its concentration in biological liquids towards an increase in girls compared to boys. In addition, the medians of individual SDQ scales differed significantly between boys and girls in our sample. CONCLUSION: Our results support the hypothesis of excessive social sensitivity mediated by OT, which may lead to some gender- and age-dependent psychosocial problems.

[The relationship between internet addiction and sleep disorders in adolescents of Central Siberia in different types of consumed content]. / Vzaimosvyaz' internet-zavisimosti i narushenii sna u podrostkov Tsentral'noi Sibiri pri raznykh vidakh potreblyaemogo kontenta.

OBJECTIVE: To establish the relationship between disturbances of the regime and quality of night sleep and daytime sleepiness in adolescents from Central Siberia with internet addiction with different types of content consumed. MATERIAL AND METHODS: A single cross-sectional observational study of a school sample in three large cities in Siberia was performed. The study included 4615 schoolchildren aged 12-18 years (46.2% boys and 53.8% girls, average age 14.58±0.02 years). To identify Internet addiction and its types the following tests were used: the Chen scale (CIAS), adapted by V.L. Malygin and K.A. Feklisov; Russian-language versions of the Game Addiction Scale for Adolescents and the Social Media Disorder Scale. Questions from the Pittsburgh Sleep Quality Index (PSQI) were used to assess nighttime sleep. Daytime sleepiness was assessed by the Pediatric Daytime Sleepiness Scale (PDSS). RESULTS: Adolescents with Internet addiction are characterized by late going to bed (p<0.001), late awakening (p=0.016), a decrease in the duration of night sleep (p=0.004), an increase in the time to fall asleep and frequent nighttime awakenings (p=0.017), and more pronounced daytime sleepiness (p<0.001). CONCLUSION: Internet-addicted adolescents are characterized by significant disturbances in the quality of night sleep, which requires appropriate psychological and pedagogical correction.

Hepatocytic Apoptosis and Immune Dysfunction in Decompensation of Alcoholic Liver Cirrhosis with Different Grades of Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) of varying grades was assessed in 110 patients with alcoholic liver cirrhosis using the on-line CLIF-C ACLF Calculator ( www.efclif.com/scientific-activity/score-calculators/clif-c-aclf ); fragments of cytokeratin-18, TNFα, IL-1ß, IL-4, IL-6, and IL-8 were also assayed. As ACLF progressed from grade 0 to grade 3, the levels of cytokeratin-18 fragments, IL-6, and IL-8 significantly increased, while IL-4 decreased. TNFα peaked in ACLF grade 1, but decreased in grades 2 and 3. IL-1ß did not depend on the ACLF grade. Thus, hepatic damage and immune dysfunction are implicated in the progression of ACLF.

Role of Bacterial Infection in the Development of Acute Liver Failure in Patients with Decompensated Alcoholic Liver Cirrhosis.

We examined 74 patients with acute decompensation of alcoholic liver cirrhosis: 34 (45.9%) with bacterial infection (group 1) and 40 (54.1%) without bacterial infection (group 2). The degree and index of acute-on-chronic liver failure (ACLF) were determined using an on-line CLIF-C ACLF Calculator and the levels of cytokeratin-18 fragments, TNFα, IL-1ß, IL-4, IL-6, and IL-8. In group 1, AST, cytokeratin-18, TNFα, IL-1ß, IL-6, degree and score of ACLF were significantly higher than in group 2. ACLF developed in 18 (52.9%) patients in group 1 and in 11 (27.5%) (p<0.05) patients in group 2. Within 1 month, 10 (29.4%) patients of group 1 and 2 (5%) patients of group 2 died (p<0.05). Patients with bacterial infection showed a more severe course of alcoholic liver cirrhosis and ACLF than those without bacterial infection.

[The prevalence and mental comorbidity of internet-dependent behavior in adolescents of Central Siberia]. / Rasprostranennost' i psikhicheskaya komorbidnost' internet-zavisimogo povedeniya u podrostkov Tsentral'noi Sibiri.

OBJECTIVE: To study the prevalence of Internet addiction (IA) in adolescents in Central Siberia and the association of IA with mental health problems. MATERIAL AND METHODS: The study included 2950 adolescents (44.7% boys and 54.3% girls), aged 11-18 years (mean age 14.5±1.3). Younger adolescents (11-14 years old) accounted for 52.4%, senior ones (15-18 years old) did 47.6%. The Chen scale (CIAS) with a cutoff level of 65 points was used to evaluate IA. The overall CIAS value of 27-42 points was regarded to be adaptive Internet use (AIU); 43-64 points being non-adaptive Internet use (NIU); 65 points and above were considered to be IA. Mental health was assessed using SDQ, which includes five scales: 1) prosocial behavior; 2) emotional symptoms; 3) behavior problems; 4) hyperactivity; 5) peer problems. RESULTS: The prevalence of AIU is 50.3% (55.9% among boys and 45.6% among girls, p<0.01), NIU was found in 42.9% (38.9/46.3%, p<0.001), IA occurred in 6.8% (5.1/8.2%, p<0.001). The prevalence of IA among adolescents, aged 11-14 years old, was 5.9%, between the ages of 15-18 it was 7.8% (p=0.04). In the AIU group, emotional symptom** were observed in 5.1% of adolescents, behavior problems in 6.1%, hyperactivity in 3.6%; in the NIU group - in 14.9%, 11.7% and 9.4% of adolescents; in the IA group, there were 34%, 24% and 26% of adolescents, respectively. In terms of odds ratio (OR), the greatest effect size was observed for hyperactivity (OR=5.23, p<0.001) and emotional disorders (OR=4.85, p<0001). CONCLUSIONS: The prevalence of IA is 6.8%. IA is more common in girls and increases with age. IA is associated with mental health problems, the greatest effect size is observed for hyperactivity and emotional disorders. The incidence of psychopathological manifestations increases depending on the degree of impairment in network behavior.

[Hepatocellular damage and inflammation in various forms of alcoholic liver disease].

AIM: The aim of the study was to evaluate hepatocellular damage and immune inflammation in various forms of alcoholic liver disease (ALD). MATERIALS AND METHODS: 104 patients with ALD were examined: 15 (14.4%) with liver steatosis (LS), 19 (18.3%) with steatohepatitis and 70 (67.3%) with liver cirrhosis (LC); men 50 (48.1%), women 54 (51.9%); age 45.78.4 years. Traditional clinical, laboratory, instrumental studies were performed, the levels of fragments of cytokeratin-18 (FCK-18), cytokines IL-1, TNF-, IL-4, IL-6, IL-8 were determined by ELISA. The control group consisted of 39 healthy individuals: men 20 (51.2%), women 19 (48.7%), age 48.58.3 years. RESULTS: In LS, an increase in the level of FCK-18 was noted with normal aminotransferase activity, the content of TNF-, IL-6, IL-1, IL-8 increased and the level of IL-4 decreased compared to those in healthy individuals. In steatohepatitis, a triple increase in aminotransferases and FCK-18 was observed compared with LS, as well as an increase in the level of inflammatory mediators, to a greater extent IL-6, to a lesser extent IL-8, TNF-, a decrease in IL-4, IL-1 remained at the same level. In LC, there was a further increase in FCK-18, significantly more pronounced than an increase in AST, and the increase in cytokines continued to the same extent, the levels of IL-6 and IL-8, to a lesser extent IL-1 and TNF-, and the level of IL-4. CONCLUSION: With the progression of ALD from LS to steatohepatitis, hepatic cell damage was carried out by equally pronounced processes of hepatocyte necrosis and apoptosis, with the development of cirrhosis of the liver, parenchyma damage occurred mainly due to hepatocyte apoptosis. The immuno-inflammatory process progressively increased from the stage of LS to LC with IL-6 and IL-8 undergoing the greatest dynamics. FCK-18 can serve as a non-invasive marker of hepatic cell damage, and IL-6 and IL-8 markers of immune inflammation in ALD.

Predictors and consequences of declining insulin therapy by individuals with type 2 diabetes.

AIM: To determine the relationship between decline of insulin therapy by individuals with type 2 diabetes and subsequent blood glucose control. METHODS: We retrospectively studied adults with type 2 diabetes and suboptimal (HbA1c ≥ 53 mmol/mol [7.0%]) glycaemic control followed at two academic hospitals between 2000 and 2014 who were recommended insulin therapy. Decline of insulin therapy recommendations was identified using natural language processing of provider notes. Time to HbA1c < 53 mmol/mol (7.0%) served as the primary outcome. RESULTS: Of 5307 study participants, 2267 (42.7%) declined insulin therapy. Median time to HbA1c control in individuals who declined vs. started insulin therapy was 50 vs. 38 months, respectively (P < 0.001). In multivariable analysis, decline of insulin therapy was associated with hazard ratio for HbA1c control of 0.89 (95% CI 0.82 to 0.97; P = 0.008). Participants were more likely to accept insulin therapy recommendations if they had diabetes complications (OR 1.32; 95% CI 1.13 to 1.53; P < 0.001) or a higher HbA1c (OR 1.10; 95% CI 1.07 to 1.13; P < 0.001), and less likely if they were older (OR 0.81; 95% CI 0.76 to 0.86; P < 0.001) or were taking more non-insulin diabetes medications (OR 0.78; 95% CI 0.74 to 0.83; P < 0.001). CONCLUSIONS: Individuals with uncontrolled type 2 diabetes who declined insulin therapy subsequently had worse glycaemic control. These findings highlight the need to improve our understanding of the relationship of this common but poorly explored clinical phenomenon to blood glucose control and ultimately diabetes complications.

Nucleolar Methyltransferase Fibrillarin: Evolution of Structure and Functions.

Fibrillarin is one of the most studied nucleolar proteins. Its main functions are methylation and processing of pre-rRNA. Fibrillarin is a highly conserved protein; however, in the course of evolution from archaea to eukaryotes, it acquired an additional N-terminal glycine and arginine-rich (GAR) domain. In this review, we discuss the evolution of fibrillarin structure and its relation to the functions of the protein in prokaryotes and eukaryotes.

CHRONIC HEPATITIS WITH DOUBLE B/C INFECTION: VIROLOGICAL, CLINICAL, MORPHOLOGICAL CHARACTERISTICS.

AIM: To estimate the r, virological and clinical characteristics of chronic viral hepatitis (CVH) with double B/C infection. MATERIALS AND METHODS: We examined 282 patients with CVH. Genomes of hepatitis B virus (HBV) and hepatitis C virus (HCV) were studied by PCR in blood and liver (AmpliSens HBV and Amplisens HCV Russia), nuclear proteins (HBcorAg HBV and NS3 HCV) were determined by immunohistochemical method (Novocastra, UK), HBVgenome was sequenced by the Sanger method using ABI prism BigDye Terminator v3.1 kits and ABIPRISM 3100 analyzer (AppliedBiosystems, USA). Indices of histological activity (HAI), fibrosis, and portal vein (PV) congestion index (CI) were calculated by formula CI=SBB/LB V where S is P V cross section area in cm2 and LB V - linear blood flow velocity in cm/s (Vivid Pro- 7 apparatus, USA). RESULTS: CVH with double B/C infection was diagnosed in 85 (30.1%) patients including 44.7% with viral genomes and proteins in the live; 42.4% with HCVviremia, and 12.9% with HBJV/HCVviremia. Maximum CVH activity was documented in patients with latent HBV/HCVviremia (ALT 157.2±59.2 U/, HAI 11.6±1.3,fibrosis 2.8±0.7, C1 0.059±0.005); it was minimal inpatients.without viremia (Alt 76.25±63.0 U/I, HAI 6.7+-0.6,fibrosis 1.7±0.5, CI 0.042±0.001;p <0.05). Patients with latent HBV infection had precore/ore and pres/s mutations in HBVgenome and cytoplasmic localization ofHBcorAg. CONCLUSION: Double B/C infection was diagnosed in 30.1% of the patients with CVH dominated by HCV Patients with latent HBVhadprecore/ore and pres/s mutations. The highest intensity of hepatic cellular inflamation,fibrosis, and PV congestion was associated with HBV/HCV viremia and the lowest with intrahepatic localization of both viruses.

[DIAGNOSIS AND CLINICAL MANIFESTATIONS OF CIRRHOTIC CARDIOMYOPATHY].

UNLABELLED: The aim of the study was to determine the incidence of cirrhotic cardiomyopathy (CCMP), features of its recognition and clinical manifestations. MATERIALS AND METHODS: The study included 102 patients with alcoholic and viral liver cirrhosis (LC) without cardiovascular history, without viremia and signs of acute alcoholic hepatitis. Echocardiography, electrocardiography (ECG) and brain natriuretic hormone (proBNP) level were investigated in all patients. RESULTS: CCMP signs were detected in 65 (63.7%) of the 102 patients examined. All patients showed signs of electrophysiological myocardial abnormalities in ECG, signs of myocardial injury and the presence of heart failure in echocardiography, increase in proBNP. Interval QT length (0.4689 ± 0.012 s.) was significantly (p = 0.0461) higher than that of the control group. Violation of diastolic relaxation of the left ventricle was detected in 36 (55.6%) patients. The average level of proBNP was 540.85 ± 236.43 pg/ml, significantly different from the level of proBNP in healthy individuals--89.45 ± 26.43 pg/ml. The incidence of CCMP increased progressively with the severity of the Child-Pugh class and was 42.4% in patients of A class, 84.6% (p = 0.0132) in patients of B Class and 100% in patients of C class (p = 0.0219). The length of the QT interval, the proBNP level and frequency of diastolic dysfunction increased with increasing of liver cirrhosis severity. CONCLUSION: The frequency of detection of cirrhotic cardiomyopathy was 63.7%. More pronounced CCMP signs were observed in alcoholic liver cirrhosis than in viral. The frequency of detection and severity of cirrhotic cardiomyopathy progres sively increased with the severity of liver cirrhosis. Brain natriuretic peptide was the most sensitive indicator of myocardial damage in liver cirrhosis irrespective of its etiology.

A requirement for Nedd9 in luminal progenitor cells prior to mammary tumorigenesis in MMTV-HER2/ErbB2 mice.

Overexpression of the NEDD9/HEF1/Cas-L scaffolding protein is frequent, and drives invasion and metastasis in breast, head and neck, colorectal, melanoma, lung and other types of cancer. We have examined the consequences of genetic ablation of Nedd9 in the MMTV-HER2/ERBB2/neu mouse mammary tumor model. Unexpectedly, we found that only a limited effect on metastasis in MMTV-neu;Nedd9(-/-) mice compared with MMTV-neu;Nedd9(+/+) mice, but instead a dramatic reduction in tumor incidence (18 versus 80%), and a significantly increased latency until tumor appearance. Orthotopic reinjection and tail-vein injection of cells arising from tumors, coupled with in vivo analysis, indicated tumors arising in MMTV-neu;Nedd9(-/-) mice had undergone mutational selection that overcame the initial requirement for Nedd9. To better understand the defects in early tumor growth, we compared mammary progenitor cell pools from MMTV-neu;Nedd9(-/-) versus MMTV-neu;Nedd9(+/+) mice. The MMTV-neu;Nedd9(-/-) genotype selectively reduced both the number and colony-forming potential of mammary luminal epithelial progenitor cells, while not affecting basal epithelial progenitors. MMTV-neu;Nedd9(-/-) mammospheres had striking defects in morphology and cell polarity. All of these defects were seen predominantly in the context of the HER2/neu oncogene, and were not associated with randomization of the plane of mitotic division, but rather with depressed expression the cell attachment protein FAK, accompanied by increased sensitivity to small molecule inhibitors of FAK and SRC. Surprisingly, in spite of these significant differences, only minimal changes were observed in the gene expression profile of Nedd9(-/-) mice, indicating critical Nedd9-dependent differences in cell growth properties were mediated via post-transcriptional regulation of cell signaling. Coupled with emerging data indicating a role for NEDD9 in progenitor cell populations during the morphogenesis of other tissues, these results indicate a functional requirement for NEDD9 in the growth of mammary cancer progenitor cells.

[Evaluation of a long-term sensomotor deficit after neonatal rat brain ischemia/hypoxia].

The application of magnetic resonance imaging method showed that ischemia/hypoxia of the brain of neonatal rats made by the protocol suggested by Levine-Rice induces one-sided lesions in the areas of cerebral cortex, striatum and hippocampus. Unilateral ischemic injury leads to a long-term sensorimotor and behavioral distortions within 90-115 days after the operation which has been tested in animals by the battery of tests including Cylinder, Beam-walking, Staircase and Limb-placing test. Chosen battery of tests in combination with magnetic resonance imaging allows to reliably estimate the long-term sensorimotor recovery in adult animals suffered an injury in neonatal age.

[The role of interphase prenucleolar bodies in the recovery of the nucleolar structure after reversible hypotonic treatment].

Interphase prenucleolar bodies are globular structures which accumulate in large numbers in the nucleoplasm of cultivated cells after hypotonic treatment and subsequent return to isotonic conditions; detailed studies of the role of these structures in the recovery of the nucleolus have not yet been performed. The limited mobility of interphase pronucleoli within the nucleus has been demonstrated. Exchange of the major nucleolar protein B23 between prenucleolar bodies and the surrounding nucleoplasm, rather than stable binding of this protein to the prenucleolar bodies, has been demonstrated using fluorescence recovery after photobleaching method. Gradual accumulation of B23 in the recovering nucleolus with concomitant disappearance of prenucleolar bodies has been demonstrated.

[The role of different factors affecting the duodenum in chronic viral hepatitis B].

The aim of the present study was to determine the frequency and the character of duodenal lesions in patients with chronic viral hepatitis B (CVH-B), to elucidate the dependence of these parameters on the activity and duration of hepatitis, virulence, and portal blood flow. A total of 206 patients with CVH-B were examined. It was found that CVH-B was associated with the development of chronic duodenitis in 23.3% of the patients. Endoscopic studies revealed different degree of affection of duodenal mucosa. Superficial focal and moderately severe duodenitis occurred more frequently (in 33.3 and 37.5% of the patients) than manifest duodenitis (12.5%). Erosive duodenitis concomitant with Helicobacter pylori infection was diagnosed in 16.7% of the patients. The main factors contributing to the development of chronic duodenitis included viral infection, its intensity, duration of hepatitis, and disturbed portal circulation. Severity of duodenitis was closely related to the severity of CVH-B.

[The pancreatic lesions in chronic viral hepatitis B].

Sings of pancreas damage among 206 patients with chronic hepatitis B (CHB) appears in 45.1%: hyperamylasemia--in 18.9% patients, ultrasonography (USG) sings of pancreatic disorders--in 44.2%. Some parallelism was revealed between increasing of frequency and degree of pancreas damage and rising of CHB activity and viremia intensity. Pancreas USG can early revealed the symptoms of pancreas damage. Among all USG pancreas parameters in CHB changes of pancreas sound thickness appears more frequency, pancreas contours, sizes and structure changed more rarely.

The local anesthetic properties and toxicity of saxitonin homologues for rat sciatic nerve block in vivo.

BACKGROUND AND OBJECTIVES: Saxitoxin and its homologues are naturally occurring compounds that block the sodium channel with high potency. They have the potential for providing prolonged duration local anesthesia when coinjected with vasoconstrictors or conventional local anesthetics and are devoid of local neurotoxicity. Here, we compare sciatic nerve block with saxitoxin to those with neosaxitoxin, decarbamoyl saxitoxin, and tetrodotoxin (TTX), in a search for even safer compounds. METHODS: Rats received percutaneous sciatic nerve block with toxins. The compounds were compared in terms of lethality, onset and duration of action for thermal analgesia (hot-plate testing), and motor block (weight-bearing). Data were expressed as medians with 25th and 75th percentiles, and median effective concentrations were determined. RESULTS: The median concentrations at which analgesia of 60 minutes duration was achieved were neosaxitoxin, 34+/-2 micromol/L; saxitoxin, 58+/-3 micromol/L; TTX, 92+/-5 micromol/L; and decarbamoyl saxitoxin, 268+/-8 micromol/L. Similar trends were observed for other measures of effectiveness (block duration of 90 minutes, maximal block), and for lethality so that the therapeutic indices were similar. No toxin had a marked predominance of sensory or motor block. The potency of TTX was intermediate between those of the saxitoxins, and its therapeutic index was slightly better. No difference was observed in time to onset of nerve blockade among the toxins. CONCLUSIONS: Substitutions on the saxitoxin nucleus result in large differences in incidence and duration of block, and toxicity. The therapeutic indices of the saxitoxins are similar; that of TTX is slightly better.

Sciatic nerve blockade in infant, adolescent, and adult rats: a comparison of ropivacaine with bupivacaine.

BACKGROUND: Ropivacaine is a newly introduced local anesthetic. No data are available regarding its safety, efficacy, or sensory-selectivity in children. The sciatic block duration and systemic toxicity of bupivacaine and ropivacaine were compared among infant, adolescent, and adult rats. METHODS: Infant, adolescent, and adult rats received blocks with ropivacaine or bupivacaine. Nociceptive, proprioceptive, and motor blockade were assessed. Systemic effects (contralateral leg analgesia, seizures, respiratory distress, apnea) were quantified. Plasma local anesthetic concentrations were measured at terminal apnea. RESULTS: Nerve blockade for a given absolute dose lasted longer in infants than in older rats for both drugs. Block duration from ropivacaine generally was the same as or slightly shorter than bupivacaine. There was no difference in sensory-selectivity between the drugs. Doses required to induce all systemic toxicity indices were inversely related to age (e.g., the lethal dose in 50% of animals [LD50] of ropivacaine in infants is 155 mg/kg; in adults it is 54 mg/kg). All indices of toxicity occurred at higher doses per kilogram for ropivacaine than bupivacaine, at all ages (e.g., the LD50 of bupivacaine in infants is 92 mg/kg; in adults it is 30 mg/kg). Plasma concentrations at terminal apnea were higher for ropivacaine than for bupivacaine at all ages, and were higher in infants than in older rats. CONCLUSIONS: Ropivacaine resembles bupivacaine in its local anesthetic effects but has a greater margin of safety. For a given absolute dose, sciatic blockade in infant rats lasts longer than in adolescents or adults. Although the doses (in milligrams per kilogram) causing toxicity were much higher in infants than in adults, this probably does not correspond to a wider therapeutic index.