Features of osseous regeneration and informative value of subchondral remodeling markers in early signs of primary gonarthrosis.

Subchondral remodeling is an important pathogenic mechanism in primary gonarthrosis progress. The role of altered metabolism of osseous tissue in early signs of articular pathology remains vague, and the informative value of biochemical markers is discussible. Our research involved 103 patients (64 women and 39 men) with 0-I gonarthrosis stages and 103 healthy individuals (72 women and 28 men) of 36 to 50 years old. We measured osteocalcin, pyridinoline, type I collagen telopeptides, vitamin B metabolites, cartilage oligomeric matrix protein concentrations, determined the activity of bone alkaline phosphatase, and diagnostic significance of the markers with the ROC curve. We found the increase (p<0.0001) in bone alkaline phosphatase, type I collagen telopeptides, cartilage oligomeric matrix protein concentrations as well as osteocalcin (p<0.0002) in 0-I gonarthrosis stages as compared to the controls. The ROC curve featured 98.1 and 79.6 percent sensitivity and specificity of type I collagen telopeptides; 80.6 and 52.4 percent of osteocalcin; 99.0 and 78.6 percent of pyridinoline, respectively. These findings suggest the significant role of subchondral remodeling in the pathogenesis of early gonarthrosis stages. Pyridinoline and type I collagen telopeptides are the most informative osseous markers detectable in the serum of patients with early gonarthrosis.

Erratum: Final Results of the OPERA Experiment on ν_{τ} Appearance in the CNGS Neutrino Beam [Phys. Rev. Lett. 120, 211801 (2018)].

This corrects the article DOI: 10.1103/PhysRevLett.120.211801.

Final Results of the OPERA Experiment on ν_{τ} Appearance in the CNGS Neutrino Beam.

The OPERA experiment was designed to study ν_{µ}→ν_{τ} oscillations in the appearance mode in the CERN to Gran Sasso Neutrino beam (CNGS). In this Letter, we report the final analysis of the full data sample collected between 2008 and 2012, corresponding to 17.97×10^{19} protons on target. Selection criteria looser than in previous analyses have produced ten ν_{τ} candidate events, thus reducing the statistical uncertainty in the measurement of the oscillation parameters and of ν_{τ} properties. A multivariate approach for event identification has been applied to the candidate events and the discovery of ν_{τ} appearance is confirmed with an improved significance level of 6.1σ. |Δm_{32}^{2}| has been measured, in appearance mode, with an accuracy of 20%. The measurement of the ν_{τ} charged-current cross section, for the first time with a negligible contamination from ν[over ¯]_{τ}, and the first direct evidence for the ν_{τ} lepton number are also reported.

AMG 151 (ARRY-403), a novel glucokinase activator, decreases fasting and postprandial glycaemia in patients with type 2 diabetes.

Phase I studies have shown that AMG 151 activates glucokinase, a key enzyme in glucose homeostasis. The present randomized, placebo-controlled phase IIa study evaluated the dose-effect relationship of the glucokinase activator AMG 151 relative to placebo on fasting plasma glucose (FPG) in 236 patients (33-35 patients per arm) with type 2 diabetes treated with metformin. Patients received oral AMG 151 at 50, 100 or 200 mg twice daily, AMG 151 at 100, 200 or 400 mg once daily or matching placebo for 28 days. A significant linear dose-effect trend was observed with the twice-daily regimen (p = 0.004) for change in FPG to day 28. No trend was observed with the once-daily regimen. A higher incidence of hypoglycaemia and hypertriglyceridaemia was observed with AMG 151 administration. AMG 151 significantly reduced FPG when administered twice daily but not when administered once daily in patients with type 2 diabetes treated with metformin.

[Enhanced Resistance of Pea Plants to Oxidative: Stress Caused by Paraquat during Colonization by Aerobic Methylobacteria].

The influence of colonization of the pea (Pisum sativum L.) by aerobic methylobacteria of five different species (Methylophilus flavus Ship, Methylobacterium extorquens G10, Methylobacillus arboreus Iva, Methylopila musalis MUSA, Methylopila turkiensis Sidel) on plant resistance to paraquat-induced stresses has been studied. The normal conditions of pea colonization by methylobacteria were characterized by a decrease in the activity of antioxidant enzymes (superoxide dismutase, catalase, and peroxidases) and in the concentrations of endogenous H2O2, proline, and malonic dialdehyde, which is a product of lipid peroxidation and indicator of damage to plant cell membranes, and an increase in the activity of the photosynthetic apparatus (the content of chlorophylls a, b and carotenoids). In the presence of paraquat, the colonized plants had higher activities of antioxidant enzymes, stable photosynthetic indices, and a less intensive accumulation of the products of lipid peroxidation as compared to noncolonized plants. Thus, colonization by methylobacteria considerably increased the adaptive protection of pea plants to the paraquat-induced oxidative stress.

[The cytoprotective drug rebamipide in therapy for inflammatory and erosive-ulcerative lesions of the gastrointestinal tract]. / Tsitoprotektor rebamipid v terapii vospalitel'nykh i erozivno-yazvennykh porazhenii zheludochno-kishechnogo trakta.

Rebamipide is a cytoprotесtive drug that stimulates the generation of endogenous prostaglandins in the gastric and small intestinal mucosa and accelerates the healing of erosions and ulcers caused by Helicobacter pylori infection and NSAID administration. The major properties of rebamipide include stimulation of prostaglandins and synthesis of muсus glycoproteins, inhibition of reactive oxygen species, inflammatory cytokines, and chemokines, and suppression of neutrophil activation. This paper shows the ability of rebamipide to enhance the efficiency of therapy for Helicobacter pylori-induced infection, to reduce inflammation, including that after infection eradication, to accelerate ulcer healing, and to prevent the progression of preneoplastic lesions.

Discovery of τ Neutrino Appearance in the CNGS Neutrino Beam with the OPERA Experiment.

The OPERA experiment was designed to search for ν_{µ}→ν_{τ} oscillations in appearance mode, i.e., by detecting the τ leptons produced in charged current ν_{τ} interactions. The experiment took data from 2008 to 2012 in the CERN Neutrinos to Gran Sasso beam. The observation of the ν_{µ}→ν_{τ} appearance, achieved with four candidate events in a subsample of the data, was previously reported. In this Letter, a fifth ν_{τ} candidate event, found in an enlarged data sample, is described. Together with a further reduction of the expected background, the candidate events detected so far allow us to assess the discovery of ν_{µ}→ν_{τ} oscillations in appearance mode with a significance larger than 5σ.

[DNA CONTENT IN INDIVIDUAL CHROMOSOMES OF NORMAL CHINESE HAMSTER KARYOTYPE AND CHROMOSOMES OF CONSTANT HAMSTER CELL LINES CHL V-79 RJK AND Vebr-5].

Using cytometry and an microfluorimetry, we have determined the genome size in Chinese hamster Cricetulus griseus, as well as absolute and relative DNA content of its individual chromosomes and of chromosomes in the transformed Chinese hamster cell lines V-79 RJK and Vebr-5 after prolonged cultivation. It has been shown that the genome size in male and female Chinese hamster is 6.660 and 6.746 pg, respectively. Absolute content of chromosomal DNA of both studied cell lines differed significantly from the content of the corresponding chromosomal DNA of the Chinese hamster normal karyotype. During long-term cellular cultivation, changes in the DNA content of certain chromosomes in both cell lines (generally upward) reached 20-25 %. The level of DNA amplification in the p-arm of chromosome Z6, registered at the beginning of the experiment, in the course of further cellular cultivation (over 20 years) remained stable. The data obtained allow us to conclude that the malignant transformation of cells and subsequent adaptation to the conditions in vitro leads to a profound restructuring of its genome, which affects almost all chromosomes.

[Disorders of gut microflora in the pathogenesis of liver cirrhosis and complications of portal hypertension].

A total of 85 patients with alcoholic and viral cirrhosis were included in study to assess the prevalence of dysbiosis and its relationship with the severity of disease, and with development of dyspeptic disorders. Intestinal bacterial over-growth was measured by means of a lactulose breath test, fecal flora was cultured under aerobic and anaerobic conditions. Intestinal bacterial overgrowth and colon dysbiosis were determined in 82.4% of patients with equal prevalence in alcoholic and viral cirrhosis. Intestinal dysbiosis was found to be risk factor of increasing cirrhosis severity and liver dysfunction, as well as development of complications of portal hypertension. It was documented, that intestinal dyspepsia syndrome in cirrhotic patients is strongly associated with the presence of gut microflora disorders.

[DNA image-fluorimetry of individual human chromosomes].

Mucrofluorimetric method for the determination of DNA content in individual human chromosomes has been developed. The method is based on a preliminary identification of chromosomes with Hoechst 33258, followed by staining of the chromosomes with Feulgen reaction using Schiffs reagent type ethidium bromide-SO2, then measuring the fluorescence intensity of the chromosomes using an image analyzer. The method allows to determine the DNA content of individual chromosomes with accuracy up to 4.5 fg. DNA content of individual human chromosomes, their p-and q-arms as well as homologous chromosomes were measured using the developed method. It has been shown that the DNA content in the chromosomes of normal human karyotype is unstable. Fluctuations in the DNA content in some chromosomes can vary 35-40 fg.

Measurement of the velocity of neutrinos from the CNGS beam with the large volume detector.

We report the measurement of the time of flight of ∼17 GeV ν(µ) on the CNGS baseline (732 km) with the Large Volume Detector (LVD) at the Gran Sasso Laboratory. The CERN-SPS accelerator has been operated from May 10th to May 24th 2012, with a tightly bunched-beam structure to allow the velocity of neutrinos to be accurately measured on an event-by-event basis. LVD has detected 48 neutrino events, associated with the beam, with a high absolute time accuracy. These events allow us to establish the following limit on the difference between the neutrino speed and the light velocity: -3.8 × 10(-6) < (v(ν)-c)/c < 3.1 × 10(-6) (at 99% C.L.). This value is an order of magnitude lower than previous direct measurements.

OPERA tau neutrino charged current interactions.

The OPERA experiment was designed to discover the vτ appearance in a vµ beam, due to neutrino oscillations. The detector, located in the underground Gran Sasso Laboratory, consisted of a nuclear photographic emulsion/lead target with a mass of about 1.25 kt, complemented by electronic detectors. It was exposed from 2008 to 2012 to the CNGS beam: an almost pure vµ beam with a baseline of 730 km, collecting a total of 1.8·1020 protons on target. The OPERA Collaboration eventually assessed the discovery of vµâ†’vτ oscillations with a statistical significance of 6.1 σ by observing ten vτ CC interaction candidates. These events have been published on the Open Data Portal at CERN. This paper provides a detailed description of the vτ data sample to make it usable by the whole community.

[Meteospazmil for correction of motor disorders in functional colon diseases].

This article describes meteospazmil clinical effectiveness in problem of abdominal pain syndrome and flatulence reduction at IBS and gastrointestinal diseases that are attended with secondary colon motor disorders.

[The use of bismuth tripotassium dicitrate (De-Nol), a promising line of pathogenetic therapy for irritated bowel syndrome with diarrhea].

The aim of the study was to assess the expediency of prescription and efficiency of bismuth tri-potassium di-citrate in different therapeutic schemes for the management of irritable bowel syndrome (IBS) dominated by diarrhea. The open prospective study of de-nol efficacy and safety included 30 patients with this disorder allocated to 2 groups. Patients of the main group (n=20) were given 120 mg of de-nol thrice daily in combination with meteospasmyl (a spasmolytic and antifoaming agent). Control patients (n=10) received aluminium phosphate with meteospasmyl (1 capsule thrice daily). Duration of the treatment was 3 weeks. Therapeutic efficiency was assessed from the dynamics of abdominal pain syndrome, stool frequency, properties of faeces, results of their microscopic and microbiological studies, lactulose breath hydrogen test, rectoromanoscopy with rectal mucosal biopsy, and hepatic biochemical test. Before the study, all patients had abdominal pain, diarrhea, meteorism, altered composition of fecal bacteria, their excessive growth in the intestines, and morphological signs of chronic inflammation. Bacterial activity was recorded in 80 and 40% of the patients of the respective groups. By the end of therapy, abdominal pain was eliminated in 90 and 60%, meteorism was absent in 80 and 40%, diarrhea in 75 and 50%, excessive bacterial growth in small intestine in 75 and 30%, changes of fecal microflora persisted in 20 and 70%, histological signs of active mucosal inflammation remained in 40 and 85.7% of the patients of the main and control groups respectively. It is concluded that all patients with irritable bowel syndrome and diarrhea show altered composition of intestinal microflora, morphological signs of moderate chronic inflammation of intestinal mucosa. Most of them have apparent bacterial activity. Treatment with de-nol and spasmolytics for 3 weeks effectively eliminated clinical manifestations of the disease, restored normal composition of intestinal microflora, normalized faeces properties, and resolved active inflammation.

Biodiversity of aerobic methylobacteria associated with the phyllosphere of the southern Moscow Oblast.

During the summer period (15­25°C), 34 strains of methylotrophic bacteria associated with different species of herbs, shrub, and trees in Pushchino (Moscow oblast, Russia) were isolated on the medium with methanol. Predominance of pink-colored Methylobacterium strains in the phyllosphere of many plants was confirmed by microscopy, enumeration of the colonies from grass leaves, and sequencing of the 16S rRNA genes. Colorless and yellow-pigmented methylotrophs belonged to the genera Methylophilus, Methylobacillus, Hansschlegelia, Methylopila, Xanthobacter, and Paracoccus. All isolates were able to synthesize plant hormones auxins from L-tryptophan (5−50 µg/mL) and are probably plant symbionts.

A novel Delftia plant symbiont capable of autotrophic methylotrophy.

A facultative methylotrophic bacterium, strain Lp-1, which was isolated from root nodules of lupine (Lupinus polyphyllus L.) on the medium with methanol as a carbon and energy source, exhibited high similarity of the 16S rRNA gene sequences to Delftia strains (94‒99.9%). The cells of Delftia sp. Lp-1 were motile gram-negative rods dividing by binary fission. Predominant fatty acids were C16:0 (34.2%), C16:1ω9 (14.5%), and C18:1ω7c (17.3%). Phosphatidylethanolamine, phosphatidylcholine, and phosphatidylglycerol were the dominant phospholipids. Q8 was the major ubiquinone. Optimal growth occurred at 24‒26°C and pH 7.1‒7.3; growth was inhibited by 1% NaCl. The organism oxidized methanol with the classical methanol dehydrogenase and used the ribulose bisphosphate pathway of C1 metabolism. Analysis of translated amino acid sequence of the large subunit of the MxaF methanol dehydrogenase revealed 85.5‒94% similarity to the sequences of such autotrophic methylotrophs of the class Alphaproteobacteria as Angulomicrobium, Starkeya, and Ancylobacter, indicating the possible acquisition of the mxaF gene via horizontal gene transfer. Delftia sp. Lp-1 (VKM B-3039, DSM 24446), the first methylotrophic member of the genus Delftia, was shown to be a plant symbiont, stimulating plant growth and morphogenesis, increasing the level of photosynthetic pigments and specific leaf weight. It possesses the nifH gene of nitrogen fixation, is capable of phosphate solubilization, synthesis of auxins and siderophores, and is antagonistic to plant pathogenic fungi and bacilli.

[Effects of probiotic bifiform on efficacy of Helicobacter pylori infection treatment].

AIM: To study effects of the probiotic bifiform on efficacy of Helicobacter pylori (HP) eradication in patients with chronic gastritis and ulcer disease. MATERIAL AND METHODS: A total of 98 patients with verified HP infection were divided into two groups. The study group received a week three-component anti-HP therapy+a probiotic. The control group received the same treatment without the probiotic. All the patients were tested for HP before the treatment and one month after the end of the treatment. Cell composition of duodenal mucosa (DM), tissue proinflammatory cytokines, secretory immunoglobulin A (sIgA) in coprofiltrates, serum IgA, IgM, IgG, phagocytic parameters and copromicrobiology were studied. RESULTS: HP eradication rate in the study group was higher than in the control group (89.1 vs 63.5, respectively, p < 0.05). After the treatment, patients of the study group had lower rates of side effects, impaired intestinal biocenosis, tissue cytokines levels but higher concentration of plasmatic cells in CO and cIgA in coprofiltrates. CONCLUSION: The addition of probiotic bifiform to the standard three-component antihelicobacter scheme of the treatment raises its efficacy and is promising treatment of HP. Mechanisms of a potentiating action of the probiotic are related to enhancement of antibacterial activity of local immune reactions.

[Osteogenesis in healthy children and in children with growth retardation depending on body constitution]. / Konstitutsional'naia obuslovlennost' tempov osteogeneza u zdorovukh detei i ego osobennosti u detei s zaderzhkoi rosta.

Somatometric and radiographic study of bones of the hand and of the distal forearm was performed in 258 healthy children and adolescents (148 boys and 110 girls) aged 11-17 years and in 115 children (84 boys and 31 girl) aged 13-16 years which were under the observation due to growth retardation. It was shown that within the groups of the same age children with various somatometric characteristics possessed different levels of skeletal (and therefore, biological) maturity. In the group of healthy children, different variants of skeletal maturation were established, which corresponded to the constitutionally stipulated rates of somatic development including accelerated, average and retarded. In children with growth retardation, the third (retarded) variant of somatic development rate was prevalent, which was also found in the group of healthy children and was accompanied with its peculiar osteogenesis characteristics. In the other cases, when such abnormalities of skeletal maturation as asymmetry in the appearance of ossification centers and synostoses as well as the presence of pseudoepiphyses, were observed, growth retardation could be caused by some endocrine pathology. Thus, the radiographic study enables the differentiated approach to the evaluation of the morphological status of children and adolescents and permits to avoid the unjustified administration of hormonal treatment.

[Effect of multiple exposure to stress on the lysosomal system of neutrophilic leukocytes]. / Vliianie mnogokratnogo stressornogo vozdeistvii na lizosomal'nyi apparat neitrofil'nykh leikotsitov.

The lysosomes of neutrophils and system influenced by the Hageman factor were shown to take part in adaptation of the body to manyfold stress. The data obtained show that manyfold stress (immobilization) led to adaptation of the neutrophil lysosomes so as no need occurred in the lysosome enzymes to take part in the humoral regulation.

[Pantothenate metabolism in the rat liver and its regulation]. / Obmen pantotenata v pecheni krys i ego reguliatsiia.

Pantothenate, penetrating the liver tissue after intraperitoneal administration into young rats at a dose 100 mumole/kg was metabolized to unidentified substances within 15-30 min without accumulation of 4-phosphopantothenate. Within subsequent 2-4 hrs period pantothenate, 4-phosphopantothenate, CoA and considerably higher amounts of the unidentified metabolites (apparently symmetric and mixed (disulphides) were simultaneously accumulated in liver tissue; the latter substances determined the subsequent prolonged and essential elevation in content of CoA in the liver tissue. The phase dynamics of accumulation in liver tissue of the administered pantothenate is due to its recirculation from intestine and to alteration in the activity of pantothenate metabolizing enzymes, particularly those, which catalyze the reactions of thiodisulphide metabolism.