[Sepsis biomarkers dynamics as an indicator of intensive care effectiveness]. / Dinamika biomarkerov sepsisa kak pokazatel' éffektivnosti intensivnoi terapii.

AIM: To evaluate dynamics of presepsin, procalcitonin and C-reactive protein in survived and dead patients with sepsis. MATERIAL AND METHODS: There were 41 patients with diagnosis of 'sepsis' ('Sepsis-3' concept) who were divided into 2 groups: survived patients with sepsis (21 people) - group 1, dead patients with sepsis (20 people) - group 2. All patients underwent generally accepted intensive therapy for sepsis. Besides conventional laboratory and instrumental examination, dynamics of presepsin, procalcitonin and C-reactive protein was assessed. RESULTS: Mean level of presepsin was 1718.00 and 3266.50 pg/ml in groups 1 and group 2, respectively. Half of the values was within (Me (25; 75) 1021.00-3231.00 pg/ml and 1618.50-7469.00 pg/ml in both groups, respectively. Mean level of procalcitonin was 0.995 and 4.465 ng/ml, respectively. Median (25; 75) was 0.49-4.44 ng/ml and 1,625-19.30 ng/ml, respectively. Mean level of C-reactive protein was 95.5 and 215.0 mg/L, respectively, median (25; 75) - 64.00-155.00 mg/L and 155.00-264.00 mg/L, respectively. Significant differences were determined for all variables (p-value 0.000008, 0.000242, 0.0000001 for presepsin, procalcitonin and C-reactive protein, respectively). CONCLUSION: The levels of C-reactive protein, procalcitonin and presepsin were significantly different in patients with sepsis followed by favorable and unfavorable clinical outcome. Unfavorable outcome was associated with increased levels of all biomarkers. Comprehensive assessment of all biological markers of sepsis is useful to assess an effectiveness of intensive therapy and to predict clinical outcome.

Formation free energies of point defects and thermal expansion of bcc U and Mo.

[Formula: see text]-U is a high temperature body-centred cubic (bcc) phase of uranium which is mechanically unstable at T = 0 K. The point defect properties in pure bcc uranium are not sufficiently well studied. In this work we use classical molecular dynamics simulations with the thermodynamic integration approach to calculate the formation free energies of vacancies and interstitials in bcc uranium and, for comparison, in bcc molybdenum. Contrary to the majority of other metals where the formation free energy is (much) higher for interstitials than for vacancies, our results show that in [Formula: see text]-uranium interstitials are the dominating type of defects in thermal equilibrium. We discuss the possible implications of this finding in the context of the thermal expansion data for [Formula: see text]-U that provide a certain supporting evidence.

Study of inelastic nuclear interactions of 400 GeV/c protons in bent silicon crystals for beam steering purposes.

Inelastic nuclear interaction probability of 400 GeV/c protons interacting with bent silicon crystals was investigated, in particular for both types of crystals installed at the CERN Large Hadron Collider for beam collimation purposes. In comparison to amorphous scattering interaction, in planar channeling this probability is ∼ 36 % for the quasi-mosaic type (planes (111)), and ∼ 27 % for the strip type (planes (110)). Moreover, the absolute inelastic nuclear interaction probability in the axial channeling orientation, along the ⟨ 110 ⟩ axis, was estimated for the first time, finding a value of 0.6 % for a crystal 2 mm long along the beam direction, with a bending angle of 55 µ rad. This value is more than two times lower with respect to the planar channeling orientation of the same crystal, and increases with the vertical angular misalignment. Finally, the correlation between the inelastic nuclear interaction probability in the planar channeling and the silicon crystal curvature is reported.

[The effect of ABCA1 rs2230806 common gene variant on plasma lipid levels in patients with dyslipidemia.]

The aim of this work was to assess the relationship of rs2230806 SNP of ABCA1 with lipid profile in patients with severe dyslipidemia. The study included 363 patients (42.8% of males), the average age was 48.7 years, 35.5% of patients received hypolipidemic drugs (mainly statins). Quantitative determination of total cholesterol (ТС) and triglycerides (TG) in fasting serum was carried out by a unified enzymatic method, and high density lipoproteins (HDL) - by a direct homogeneous method. Genotype according to the rs2230806 position in the ABCA1 gene was determined by polymerase chain reaction (PCR) «in real time¼ using adjacent samples and melting reaction products after PCR. The frequencies of alleles and genotypes of variant rs2230806 of ABCA1 gene in patients with dyslipidemia did not differ from those in the control group of healthy individuals (athletes). The levels of plasma lipids - TC, TG and HDL cholesterol, on average, in patients with dyslipidemia were 7.8±3,4, 3,4±6,5 and 1.29±0.4 mmol/l, respectively. Compared to different genotypes, the plasma lipid concentrations did not differ significantly, but the analysis of different inheritance models of the allelic variant studied showed a significant association with the level of TG in the additive model, in which each minor allele (a) further enhanced the effect on the level of plasma TG at 1.02 mmol/l (p=0.044). The results of this study demonstrate the effect of a common variant rs2230806 of the ABCA1 gene on the plasma TG level in patients with severe dyslipidemia.

[The positional isomers of palmitic and oleic triglycerides, lipolysis, conformation of apoB-100, formation of apoE/B-100 ligand and absorption of lipoproteins of very low density by insulin-dependent cells under action of statins.]

The study was carried out to trace back quantitative alterations of positional isomers, oleic and palmitic triglycerides and individual fatty acids in blood serum. After two weeks of taking of Simvastatin (40, 80 mg), analysis of blood serum established decreasing of content of Рhosphatidylcholine and more reliable decreasing of amount of non-etherized alcohol cholesterol. No alterations of content of particular fatty acids were detected. In apoB-100, Рhosphatidylcholine and non-etherized alcohol cholesterol form polar mono-layer; it covers mass of oleic and palmitic triglycerides that was bound by apoB-100 in oleic and palmitic lipoproteins of very low density disturbing bio-availability of substrate (oleic and palmitic triglycerides) for post-heparin lipase. This very pool of non-etherized alcohol cholesterol is inhibited by statins activating lipolysis in oleic and palmitic lipoproteins of very low density. In blood was detected amount of palmitic positional isomersin oleic and palmitic triglycerides (palmitoyl-palmitoyl-palmitate and palmitol-palmitoyl-oleate) and oleic positional isomers (oleyl-oleyl-palmitate and oleyl-oleyl-oleate). The significant difference was marked in content of positional isomers both of oleyl-oleyl-oleate and oleyl-oleyl-palmitate; their content is less in blood of patients of experimental group as compared with healthy people. In case of treatment with Simvastatin (40 mg) the level of palmitic positional isomers and palmitol-palmitoyloleate is decreased. In case of treatment with Simvastatin (80 mg) significant decreasing of positional isomers-palmitolpalmitoyl-oleate and oleyl-oleyl-palmitate as compared with data before treatment. The detection of content of positional isomers triglycerides permits: a) to characterize disorders of metabolism of palmitic fatty acid, oleic fatty acid, oleic and palmitic triglycerides and oleic and palmitic lipoproteins of very low density of the same name; b) to form individual diet therapy; c) to obtain objective information concerning compliance of prescribed recommendations b y patient. The basis of primary prevention of atherosclerosis and atheromatosis is in decreasing up to physiological level in food the content of longchained saturated fatty acids mainly palmitic acid.

Improving the performance of small amputations in complicated forms of diabetic foot.

The aim of the study was comparative assessment of the effectiveness of typical and atypical amputations at the level of footstep in patients with the most complicated course of the diabetic foot syndrome (DFS). The patients suffering from diabetes mellitus type 2 and purulo-necrotic complications of the DFS, treated in the surgical department of the № 1 Pirogov National Surgical and Medical Center of the Sankt Petersburg Clinical Complex were investigated. The study group included 68 patients who underwent atypical surgical interventions taking into account blood flow angiosomes of footstep tissues. Operative interventions at the level of footstep were carried out to 47 patients of the control group. Obligatory angiography was performed in all patients. Operative intervention was carried out under emergency conditions before conduction of angiography only to those patients who were admitted with acute purulent processes in the area of lower extremities. In all other cases individual peculiarities of blood circulation disorder in lower extremities determined the choice of tactics of operative treatment. In 76% and 46% correspondingly, for each group after angiography balloon angioplasty was carried out for reconstruction of the main blood flow. The average duration of the in-patient treatment in study group was 14,4±2,3. In the control group - 18,2±3,1. Conduction of post-operative angiography and when necessary angioplasty in the footstep tissues is prescribed before operative intervention to patients with purulo-necrotic complications of DFS. Application of the principle of angiosome blood flow based on the data of duplex sonography of arteries and angiography enables to choose the most rational tactics of the operative treatment. 3. Application of atypical technique of amputations in the area of footstep after postoperative complications enables to reduce the length of inpatient treatment and to improve postoperative mobility and ability for independent movement of patients.

[THE EFFECT OF SATINS: ACTIVATION OF LIPOLYSIS AND ABSORPTION BY INSULIN-DEPENDED CELLS LIPOPROTEINS OF VERY LOW DENSITY, INCREASING OF BIO-AVAILABILITY OF POLYENOIC FATTY ACIDS AND DECREASING OF CHOLESTEROL OF LIPOPROTEINS OF LOW DENSITY].

The Russian cardiologic R&D production complex of Minzdrav of Russia, 121552 Moscow, Russia The statins are synthetic xenobiotics alien to animal cells. They are unlikely capable to manifest pleiotropic effect. It is feasible to evaluate effect of statins by stages: a) initially a specific inhibition of synthesis of cholesterol alcohol; b) further indirect activation of hydrolysis of triglycerides in lipoproteins of very low density; c) nonspecific activation of cells' receptor absorption of palmitic and oleic lipoproteins of very low density and then d) linoleic and linolenic lipoproteins of low density with all polyenoic fatty acids. On balance, statins activate absorption ofpolyenoic fatty acids by cells. Just they manifest physiological, specific pleiotropic effect. The statins inhibit synthesis of pool of cholesterol alcohol-lipoproteins of very low density condensed between phosphatidylcholines in polar mono-layer phosphatidylcholines+cholesterol alcohol on surface oftriglycerides. The low permeability of mono-layer separates substrate-triglycerides in lipoproteins of very low density and post-heparin lipoprotein lipase in hydrophilic blood plasma. The higher is ratio cholesterol alcohol/phosphatidylcholines in mono-layer of lipoproteins of very low density the slower is lipolysis, formation of ligand lipoproteins of very low density and their absorption by cells under apoB-100-endocytosis. The statins normalize hyperlipemia by force of a) activation of absorption oflipoproteins of very low density by insulin-depended cells and b) activation of absorption of lipoproteins of low density by all cells, increasing of bio-availability of polyenoic fatty acids, activation of apoB-100-endocytosis. The limitation in food of content of palmitic saturated fatty acid and increasing of content of ω-3 polyenoic fatty acids improve "bio-availability" of polyenoic fatty acids and their absorption by cells and also decreases cholesterol alcohol/phosphatidylcholines and biological pleiotropic effect of essential polyenoic fatty acids. According our opinion, atherosclerosis is intracellular deficiency of polyenoic fatty acids. The value of cholesterol alcohol-lipoproteins of low density is equimolar to content of lipoproteins of low density in blood which under low bio-availability can't to absorb cells byforce of apoB-100-endocytosis.

Validation of a symptom-score questionnaire and long- term results of endoscopic dacryocystorhinostomy.

BACKGROUND: Endoscopic dacryocystorhinostomy (EN-DCR) is a commonly used procedure in the treatment of nasolacrimal duct obstruction (NLDO). However, there is no generally accepted disease-specific questionnaire for assessing outcomes. METHODOLOGY: We conducted a prospective study to initially validate a Nasolacrimal Duct Obstruction Symptom Score questionnaire(NLDO-SS) and to evaluate the long-term success of EN-DCR procedures. Seventy-six patients (86 eyes) were evaluated in follow-up visits at 1-8 years after EN-DCR. The patients completed the NLDO-SS questionnaire twice, first, at home and, second,after receiving information from the otorhinolaryngologist, during the visit. The surgical outcome was considered successful if the irrigation succeeded and if the patient symptoms were relieved as assessed with the NLDO-SS. RESULTS: The diagnostic accuracy of the NLDO-SS was 84%, sensitivity 82%, specificity 85%, positive predictive value 58%, negative predictive value 95%, odds ratio 26, risk ratio 11 and usefulness index 0.55. Cronbach's alpha was 0.85, and the test-retest reliability coefficient was 0.87. The long-term success rate after EN-DCR was 79%. CONCLUSION: The NLDO-SS iss a feasible clinical tool in assessing the success of EN-DCR. The success rate was found to decrease EN-DCR at long-term follow-up.

The impact of pharyngeal fat tissue on the pathogenesis of obstructive sleep apnea.

PURPOSE: Obesity is the most important risk factor for obstructive sleep apnea (OSA); however, the exact underlying mechanisms are still not fully understood. The aim of this study was to examine the morphology of upper airways in overweight habitual snorers and in mild OSA patients. Furthermore, the associations between weight loss, parapharyngeal fat pad area and OSA were assessed in a 1-year randomised, controlled follow-up study originally conducted to determine the effects of lifestyle changes with weight reduction as a treatment of OSA. METHODS: Thirty-six overweight adult patients with mild OSA [apnea-hypopnea index (AHI) 5-15 events/h] and 24 weight-matched habitual snorers (AHI < 5 events/h) were included in the study. All patients underwent nocturnal cardiorespiratory recordings and multislice computed tomography (CT) of parapharyngeal fat pad area, the smallest diameter and area in naso-, oro- and hypopharynx, the smallest diameter and area of the whole pharyngeal airway, the distance from the hyoid bone to the mandibular plane and to cervical tangent as well as the distance between mandibular symphysis and cervical spine. In addition, OSA patients were further randomised to receive either an active 1-year lifestyle intervention with an early weight loss programme or routine lifestyle counselling. After 1 year, the cardiorespiratory recordings and CT scans were repeated. RESULTS: The pharyngeal fat pad area was significantly larger, and the distance from the hyoid bone to cervical spine was longer in patients with OSA than in habitual snorers (p = 0.002 and p = 0.018, respectively). The multiple regression analysis showed that besides a large pharyngeal fat pad area and a long distance from the cervical spine to hyoid bone, also a short distance from the mandibular symphysis to cervical tangent increased a risk to OSA. During the 1-year follow-up in OSA patients, the pharyngeal fat pad area and AHI decreased significantly in the intervention group (p = 0.003 and p < 0.001, respectively). CONCLUSIONS: In the early stages of OSA, the pharyngeal fat pad seems to play an important role in the development of disease in overweight patients. Furthermore, weight reduction by lifestyle intervention-based programme reduces both central obesity and pharyngeal fat pads, resulting in an improvement of OSA.

Effect of iron oxidation state on the electrical conductivity of the Earth's lower mantle.

Iron can adopt different spin states in the lower mantle. Previous studies indicate that the dominant lower-mantle phase, magnesium silicate perovskite (which contains at least half of its iron as Fe(3+)), undergoes a Fe(3+) high-spin to low-spin transition that has been suggested to cause seismic velocity anomalies and a drop in laboratory-measured electrical conductivity. Here we apply a new synchrotron-based method of Mössbauer spectroscopy and show that Fe(3+) remains in the high-spin state in lower-mantle perovskite at conditions throughout the lower mantle. Electrical conductivity measurements show no conductivity drop in samples with high Fe(3+), suggesting that the conductivity drop observed previously on samples with high Fe(2+) is due to a transition of Fe(2+) to the intermediate-spin state. Correlation of transport and elastic properties of lower-mantle perovskite with electromagnetic and seismic data may provide a new probe of heterogeneity in the lower mantle.

First biological images with high-energy proton microscopy.

High-energy proton microscopy provides unique capabilities in penetrating radiography including the combination of high spatial resolution and field-of-view, dynamic range of density for measurements, and reconstructing density variations to less than 1% inside volumes and in situ environments. We have recently proposed to exploit this novel proton radiography technique for image-guided stereotactic particle radiosurgery. Results of a first test for imaging biological and tissue-equivalent targets with high-energy (800 MeV) proton microscopy are presented here. Although we used a proton microscope setup at ITEP (Moscow, Russia) optimized for fast dynamic experiments in material research, we could reach a spatial resolution of 150 µm with approximately 10(10) protons per image. The potential of obtaining high-resolution online imaging of the target using a therapeutic proton beam in the GeV energy region suggests that high-energy proton microscopy may be used for image-guided proton radiosurgery.

[Current approaches to treating acute gastroduodenal ulcer bleedings].

The aim of the work was analysis of treatment of 560 patients with a gastrointestinal bleeding from acute ulcers. For estimation of patients was used universal integrated scale APACHE III. Tactics of treatment depend on secretory functions of a stomach and group of polyorganical difunction. At 428 (76,5%) patients with acute ulcers on the background increase secretion of stomach was treatment antysecretion therapy. At 132 (23,5%) patients with acute ulcers on the background of normal ore decrease secretion of stomach was treatment Cytoflavin - the metabolic preparation possessing antyoxidation, cytoprotection and immunomodulaytion activity. For studying antyoxidation and antihypoxation actions of Cytoflavin estimated of microcirculation mucous of a stomach with the laser Doppler floymetrya before course of treatment, observed increase of index efficiency of microcirculation and increase a blood-groove in a stomach at patients with acute peptic ulcers on a background of treatment of Cytoflavin. After course of treatment of Cytoflavin decrease in points on system APACHE III on 5,5-25% at all patients that has led to decrease mortality on 20% in this group of patients.

[Repeats in bacterial genomes: evolutionary considerations].

Contemporary data on repeated nucleotide sequences (repeats) in bacterial genomes are discussed. Different classifications and distribution of the repeats in the genomes of bacteria belonging to different species are reviewed. Comparative data on the density of repeats in the genomes of pathogenic and non-pathogenic bacteria, as well as in the genes encoding different functions of microbial cell (genes of stress response, genes controlling DNA metabolism and repair, etc.), are discussed. The role of the repeats in the uptake and loss of genetic material by bacterial genomes is discussed. It is suggested that repeats are responsible not only for the functioning of bacterial genome at the given moment of time, but also for the structures of the implicit genomes, which may appear in the future due to evolutionary significant genomic rearrangements.

The Dynamic Albedo of Neutrons (DAN) experiment for NASA's 2009 Mars Science Laboratory.

We present a summary of the physical principles and design of the Dynamic Albedo of Neutrons (DAN) instrument onboard NASA's 2009 Mars Science Laboratory (MSL) mission. The DAN instrument will use the method of neutron-neutron activation analysis in a space application to study the abundance and depth distribution of water in the martian subsurface along the path of the MSL rover.

[A comparative study of the role of the yadA, invA, and psaA genes in the pathogenicity of Yersinia pseudotuberculosis].

The roles of yadA, invA, and psaA genes introduced into the genetic background of the Y. pseudotuberculosis strain possessing the large p VM82 plasmid in virulence and invasion capacity were studied. Isogenic single mutants as well as double and multiple mutants of these genes were constructed and used. LD50 was used as a measure of virulence and the estimation of the ability to invade mammalian cells and the effect of infection on the weight changes of infected mice were used as additional indicators of pathogenicity. It was shown that the YadA had a major effect on the bacterial virulence when compared with the effects of PsaA and InvA. InvA appears to mediate the main pathway of the cellular invasion. YadA is responsible for the weight loss after infection of mice with sublethal doses of Y. pseudotuberculosis. The effects of YadA on virulence and of InvA on bacterial invasion were independent of the expression of the other genes studied. To our knowledge, this study showed for the first time the direct involvement of YadA in the virulence of Y. pseudotuberculosis in mice. Further pathomorphological studies are required to reveal the differences in the pathogenesis of pseudotuberculosis caused by yadA mutants or yadA+ bacteria of Y. pseudotuberculosis.

[Molecular genetic methods of typing of the Bartonellae].

The primer systems for the PCR detection of four house-keeping genes of bartonellae in clinical material were developed and tested. The tactics of the species RFLP typing was also developed and tested. The scheme of the species RFLP typing of bartonellae was tested using as an example two strains for the first time isolated in Russia from patients with endocarditis and fever of uncertain origin. The results of the typing were supported by sequencing of the amplicons obtained. According to the sequencing the isolates were attributed to the sub species Bartonella vinsonii, subsp. arupensis. The necessity of molecular epidemiological analysis of bartonelloses in Russia was substantiated.

[Wild small mammals are the reservoir hosts of the Bartonella genus bacteria in the south of Moscow region].

A total of 103 blood samples collected from wild small mammals captured in the Prioksko-Terrasny Reserve on the south of Moscow region were studied to determine the bartonellae prevalence. The examined species were the yellow-necked mice Apodemus flavicollis (35 samples), the European wood mouse Apodemus uralensis (10 samples), the bank vole Clethrionomys glareolus (51 samples), the house mouse Mus musculus (3 samples), the common vole Microtus arvalis (2 samples), and the shrew Sorex araneus (2 samples). Initially, we obtained 76 bacterial Bartonella-like isolates after plating onto the surface of the solid nutrient media. 66 of them were PCR-positive at least for three of four targets, gltA, ftsZ, ribC and 16S RNA. Thus, the percentage of the infection in the studied community was 64%. Subsequent RFLP assay showed that obtained isolates belonged to the Bartonella grahamii and/or B. taylorii species. In 7 cases we found both bartonellae species in one animal. These data were confirmed by direct sequencing of four ftsZ, four ribC and two gltA amplicons. According to our data, there is no any marked host specificity for these bartonellae species. Now we have laid the bartonellae strain collection consisting of 31 isolates. To our knowledge, this is the first investigation of the bartonellae prevalence in wild small mammals performed in Russia. The comparison of our data with those obtained by European researchers and issues of coinfection by different bartonellae species and host specificity are discussed.

Postoperative pain, morphine consumption, and genetic polymorphism of IL-1beta and IL-1 receptor antagonist.

Interleukin-1 beta (IL-1beta) and its endogenous IL-1 receptor antagonist (IL-1Ra) play an important role in inflammatory response and in pain modulation. It has recently been shown that polymorphism of the IL-1beta and IL-1Ra genes may account for variation in the production of these cytokines. The present study examined the hypothesis that polymorphism of IL-1beta and IL-1Ra genes is involved in pain sensitivity and morphine consumption in the immediate postoperative period. Genetic polymorphism was determined in 76 women undergoing transabdominal hysterectomy. The genotype of IL-1Ra was determined using PCR amplification of the variable number of tandem repeats (VNTR) of 86 base pair (bp) in intron 2, while for IL-1beta the cytosine to thymine transition at codon -511 of the promoter was determined by PCR. Morphine consumption and pain scores were evaluated in the first postoperative 24 h. The study group was divided based on morphine consumption to three sub-groups: low morphine consumers (LMC) (<28 mg/24 h), medium morphine consumers (MMC) (28-38 mg/24 h), and high morphine consumers (HMC) (>38 mg/24 h). Patients consuming the least amount of morphine postoperatively showed significant lower pain scores. IL-1Ra genetic polymorphism of the MMC group was significantly different compared to the other two groups. No difference in IL-1beta gene polymorphism was found among the three sub-groups. Since IL-1Ra polymorphism is known to affect the levels of both IL-1Ra and IL-1, cytokines associated with modulation of pain sensitivity and morphine analgesia, it is suggested that IL-1Ra genetic polymorphism may contribute to the variation in postoperative morphine consumption.

The FLUKA code: new developments and application to 1 GeV/n iron beams.

The modeling of ion transport and interactions in matter is a subject of growing interest, driven by the continuous increase of possible application fields. These include hadron therapy, dosimetry, and space missions, but there are also several issues involving fundamental research, accelerator physics, and cosmic ray physics, where a reliable description of heavy ion induced cascades is important. In the present work, the capabilities of the FLUKA code for ion beams will be briefly recalled and some recent developments presented. Applications of the code to the simulation of therapeutic carbon, nitrogen and oxygen ion beams, and of iron beams, which are of direct interest for space mission related experiments, will be also presented together with interesting consideration relative to the evaluation of dosimetric quantities. Both applications involve ion beams in the AGeV range.