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Relevance. The relevance of the study is due to the risk of developing large-scale radiation accidents with a large number of victims, who will need primary medical triage and early prediction of the severity of injury for correct routing from the source of sanitary losses.Intention. Validation of the method of estimating dose by time-to-emesis under various exposure conditions for pre-hospital triage of victims.Methodology. The object of the study is the data from State Research Center – Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (Moscow) database of acute radiation injuries.Results and Discussion: We have analyzed individual data for the victims of the 1986 Chernobyl disaster (114 persons) with a separate analysis of the irradiation conditions (short-term exposure for less than 20 minutes and prolonged exposure in selected groups), as well as the data from victims of other radiation accidents in the former USSR (26 persons) and 8 patients with total body radiotherapy without the use of antiemetics. It was shown that for the equal time-to-emesis intervals, predicted radiation injury is more severe in case of prolonged exposure vs short-term exposure. This may be due to varying rate of dose accumulation and so-called “unnecessary dose” effect – when the biological mechanism of vomiting has already been triggered against ongoing exposure. Results are presented as interval estimates of radiation injury severity by time-to-emesis for both short-term and prolonged exposures. We also have formulated two criteria for primary triage purposes in case of moderate or large numbers of victims due to large-scale radiation accidents.Conclusion. Recommendations for pre-hospital triage of victims are proposed.

Levetiracetam (LEV) is one of the most commonly prescribed antiepileptic drugs (AED). However, there were no studies on its efficacy and safety in terms of the correlation with epileptiform activity index (EAI) performed among the Russian population.Aim. To evaluate the efficacy and tolerability of LEV monotherapy in patients with newly-diagnosed epilepsy using epileptiform activity index (EAI) assessment.Materials and methods. The study included 107 patients (46 (43.0%) male and 61 (57.0%) female) with focal epilepsy (FE) (39.3%; n=42) or idiopathic generalized epilepsy (IGE) (60.7%; n=65). At each visit, video-electroencephalographic (video-EEG) monitoring was performed (baseline and in 1, 3, 6, and 12 months of the therapy). Therapeutic drug monitoring was performed at dose titration in 1 month of the therapy or in case of therapy correction. Treatment efficacy was assessed using the criteria of seizure absence (medically induced remission), seizure rate decrease by >50% (responders), seizure rate decrease by Results. Total EAI at baseline was 5.2-fold higher in patients with IGE compared to FE patients (23.4±3.0 and 4.5±0.97, respectively). After 1 month of LEV therapy, EAI decreased to 3.4±1.1 and 1.9±0.4 in patients with IGE and FE, respectively (pConclusions. LEV is an effective drug of choice for the initial treatment of newly-diagnosed FE and IGE in monotherapy along with a significant decrease in EAI. EAI is an objective measure of LEV treatment efficacy.

Policy management of institutes and business organizations’ activity, dealing with radiation sources, has more of a bulky and confusing complex of requirements at the present day. The requirements being very substantial, slow down economic growth of entire branches in the field of the beneficial use of radiation technologies, and, at the same time, do not provide the condition of radiation safety. Prime Minister Dmitriy Medvedev, without any coincidence, pointed out the problem during a plenary meeting as an overpressure of regulatory and supervisory bodies on the Russian private sector. According to him, the task can be solved with ‘a regulatory guillotine’. The upcoming article resembles the first attempt to analyze and sort reasons and factors, providing a glimpse of the current situation, search key elements that cause negative influence in the field taken. On the ground of analysis of regulatory documents, vast survey experience and estimation of radiation objects and technologies, authors suggest a new complex of requirements to provide radiation security, their breakdown of classes depending on danger level of radiation objects and operating with sources of ionizing radiation. The article presents the analysis of current regulatory documents on radiation hygiene field and radiation security, retrospective view on valid documents, the expertise of activity of regulatory and supervisory bodies as part of licensing of the activity with man-made sources of ionizing radiation.

The effect of different polyoxyethylene–polyoxypropylene triblock copolymers, their concentration, and mode of action on the loading of poly-(lactic-co-glycolic acid) copolymer-based microparticles containing such medicinal agents as radachlorin (chlorin e6) or ethidium bromide in mesenchymal stem cells was studied. It has been shown that medicinal agents encapsulated inside microparticles affect the loading of these particles in the cytoplasm of mesenchymal stem cells. The number of cells that absorbed the particles with chlorin e6 is approximately two times lower than that in the experiments with ethidium bromide. It has been shown that pretreatment of microparticles with triblock copolymers is more efficient for loading them in cells compared with simultaneous introduction of triblock copolymers and particles into the culture medium. Treatment of ethidium bromide-containing microparticles with triblock copolymers is not efficient for their loading in mesenchymal stem cells compared to the control. The exception is Pluronic 123; when particles are treated with it at concentrations of 1 and 2%, the loading of particles in cells increases compared to the control by factors of approximately 11 and 5, respectively. For particles with chlorin e6, their pretreatment with triblock copolymers at a concentration of 4% is most efficient; the loading of the pretreated particles in cells is increased by factors of approximately 3 to 11.

We present the cases of three patients with severe, life-threatening coronavirus disease 2019 (COVID-19) who had failed to achieve substantial improvement on intial treatment. They subsequently received pulse therapy with methylprednisolone [1,000 mg/day intravenously (IV) for three consecutive days] and IV immunoglobulin (20 g/day). This treatment regimen was associated with a prompt resolution of respiratory failure, elimination of clinical manifestations of the cytokine release syndrome (CRS), and reversal of pulmonary CT changes. The treatment was generally safe and well-tolerated. There was no evidence of protracted persistence of the virus in the patients. Further randomized controlled trials are required to better understand the efficacy and safety of high-dose methylprednisolone and IV immunoglobulin, separately or in combination with each other, in the treatment of severe, life-threatening COVID-19.

Planned surgical interven ons account for more than half of all opera ons in the Russian Federa on, of which more than 20–30% are performed for oncological diseases. Characteris c is an increase in the number of operated pa ents in older age groups with severe concomitant pathology and a high percentage of postopera ve complica ons, including due to psychoemo onal pathology, which can be excluded or adjusted at the preopera ve stage.Purpose.Evalua on of the infl uence of the psychoemo onal state of the oncochirical soma cally burdened patient on the lethality and revealing the possibility of correc on of the psychoemo onal state at the preopera ve stage.Paents and methods. In the period from 2006 to 2016 in the departments of therapy and oncology of the Regional Clinical Hospital of the City Clinical Hospital No. 40 of the Moscow City Health Department, AI.Burnazyan The FMBA of Russia analyzed the treatment of 958 soma cally burdened pa ents with various oncopathology who underwent opera ve interven on in a planned manner. An analysis of the psychoemo onal state of pa ents before and aft er surgery was performed using Hamilton diagnos c scales.Results.After a retrospec ve evalua on, it was determined that prac cally all patients of the oncosurgical profi le undergo various psychoemo onal strains of varying strength and dura on, both before and after surgery. This can disrupt the blood fl ow in the organs andssues, and lead to various complica ons, which manifests itself in the form of hypoxia and ischemia, which, in turn, jus fy the development of postopera ve delirium and myocardial infarc on.Conclusions.Clear distinctions between the anxiety severity in groups on outcomes of hospitaliza on of the oncosurgical patient were determined, and the tendency of the rela onship between the level of the anxiety state and the postopera ve complica ons that had been ridden in the early postopera ve period in soma cally burdened pa ents was determined. Patients of the oncosurgical profi le without fail are shown psychopharmacotherapy in the pre- and postopera ve periods, depending on the revealed pathology.

Aim.To develop a safe protocol for cryopreservation of segments of iliac arteries straight after their retrieval from post-mortem donor with the use of polydimethylsiloxane as a coolant and cryoprotectant.Materials and methods.Eleven segments of iliac arteries were retrieved from post-mortem donor and divided into four groups including control. Based on preliminary heat and cold transfer mathematical modeling and tests with tissueequivalent phantom arterial segments were placed on plastic mounts and cryopreserved by following protocol: groups 1 and 2 were immersed in polydimethylsiloxane and cooled rapidly at 180 °С/min to –75 °С. Group 3 segments were cryopreserved at 1,6 °С/min in PDMS – fi lled cryo-container placed in the freezer at –80 °С. All segments were defrosted by immersion in PDMS at +24 °С and then examined for morphology changes by histological methods and SEM. EDS analysis with the use of AzTech software also was performed for Si – content evaluation. Restricted biomechanical tests were conducted for group 2 segments.Results.There were no signifi cant morphological differences between segments of the control and cryopreserved groups except for the segment with slow cooling.Conclusion.Mobile cryopreservation may allow increasing the effi ciency of retrieval of a large number of donor tissues for possible later use in the processing of bioprostheses of blood vessels; or, after decellularization, as well as tissue-specifi c matrices for tissue-engineering blood vessels.

Background Nosocomial CNS infection (NI-CNS) is a common and serious complication in neurocritical care patients. Timely, accurate diagnosis of NI-CNS is crucial, yet current infection markers lack specificity and/or sensitivity. Presepsin (PSP) is a novel biomarker of macrophage activation. Its utility in NI-CNS has not been explored. We first determined the normal range of cerebrospinal fluid (CSF) PSP in a control group without brain injury before collecting data on CSF PSP levels in neurocritical care patients. Samples were analyzed in four groups defined by systemic and neurological infection status. Results CSF PSP levels in 15 control patients without neurological injury were 50–100 pg/ml. Ninety-seven CSF samples were collected from 21 neurocritical care patients. In patients without NI-CNS or systemic infection, CSF PSP was 340.4 ± 201.1 pg/ml. Isolated NI-CNS was associated with CSF PSP levels of 640.8 ± 235.5 pg/ml, while levels in systemic infection without NI-CNS were 580.1 ± 329.7 pg/ml. Patients with both NI-CNS and systemic infection had CSF PSP levels of 1,047.7 ± 166.2 pg/ml. In neurocritical care patients without systemic infection, a cut-off value of 321 pg/ml gives sensitivity and specificity for NI-CNS of 100 and 58.3%, respectively. Conclusion CSF PSP may prove useful in diagnosing NI-CNS, but its current utility is as an additional marker only.

Active physical exercises and growth are associated with mineral imbalances in young athletes. The purpose of this study was to examine the impact of sport-related factors on tissue mineral status in adolescent female athletes. Saliva and hair samples were used for the analysis of immediate and more permanent tissue mineral status, respectively. Samples taken from a control non-athletic female group and two groups of female athletes (field hockey and fencing) were analyzed for seven essential minerals: calcium, chromium, iron, potassium, magnesium, selenium and zinc. Inductively-coupled plasma mass spectrometry was used for the quantification of elements having very low concentration range in samples (Se, Cr and Zn) whereas inductively coupled plasma optical emission spectrometry was used for quantification of more ubiquitous elements (Mg, К, Са, Fe). The obtained results for athletic groups were compared with control. Female athletes had increased levels of selenium in both saliva and hair as well as chromium in saliva. Field hockey players had the higher level of zinc in hair whereas fencers had the lower levels of salivary calcium. Strong negative correlation between potassium levels in saliva and hair was identified. Iron and magnesium did not differ between the studied groups. In conclusion, novel sport-specific features of chromium tissue levels in female athletes were found. The studied sport disciplines have different impact on the distribution of osteoporosis-related minerals (calcium and zinc). Our finding can help in the development of osteoporosis preventive trainings and in the proper nutrient supplementation to correct mineral imbalances in female athletes.

Background In most sequenced organisms the number of known regulatory genes (e.g., transcription factors (TFs)) vastly exceeds the number of experimentally-verified regulons that could be associated with them. At present, identification of TF regulons is mostly done through comparative genomics approaches. Such methods could miss organism-specific regulatory interactions and often require expensive and time-consuming experimental techniques to generate the underlying data. Results In this work, we present an efficient algorithm that aims to identify a given transcription factor’s regulon through inference of its unknown binding sites, based on the discovery of its binding motif. The proposed approach relies on computational methods that utilize gene expression data sets and knockout fitness data sets which are available or may be straightforwardly obtained for many organisms. We computationally constructed the profiles of putative regulons for the TFs LexA, PurR and Fur in E. coli K12 and identified their binding motifs. Comparisons with an experimentally-verified database showed high recovery rates of the known regulon members, and indicated good predictions for the newly found genes with high biological significance. The proposed approach is also applicable to novel organisms for predicting unknown regulons of the transcriptional regulators. Results for the hypothetical protein D d e0289 in D. alaskensis include the discovery of a Fis-type TF binding motif. Conclusions The proposed motif-based regulon inference approach can discover the organism-specific regulatory interactions on a single genome, which may be missed by current comparative genomics techniques due to their limitations. Electronic supplementary material The online version of this article (doi:10.1186/s12859-015-0685-y) contains supplementary material, which is available to authorized users.

Motivation: Genome-wide fitness is an emerging type of high-throughput biological data generated for individual organisms by creating libraries of knockouts, subjecting them to broad ranges of environmental conditions, and measuring the resulting clone-specific fitnesses. Since fitness is an organism-scale measure of gene regulatory network behaviour, it may offer certain advantages when insights into such phenotypical and functional features are of primary interest over individual gene expression. Previous works have shown that genome-wide fitness data can be used to uncover novel gene regulatory interactions, when compared with results of more conventional gene expression analysis. Yet, to date, few algorithms have been proposed for systematically using genome-wide mutant fitness data for gene regulatory network inference. Results: In this article, we describe a model and propose an inference algorithm for using fitness data from knockout libraries to identify underlying gene regulatory networks. Unlike most prior methods, the presented approach captures not only structural, but also dynamical and non-linear nature of biomolecular systems involved. A state–space model with non-linear basis is used for dynamically describing gene regulatory networks. Network structure is then elucidated by estimating unknown model parameters. Unscented Kalman filter is used to cope with the non-linearities introduced in the model, which also enables the algorithm to run in on-line mode for practical use. Here, we demonstrate that the algorithm provides satisfying results for both synthetic data as well as empirical measurements of GAL network in yeast Saccharomyces cerevisiae and TyrR–LiuR network in bacteria Shewanella oneidensis. Availability: MATLAB code and datasets are available to download at http://www.duke.edu/∼lw174/Fitness.zip and http://genomics.lbl.gov/supplemental/fitness-bioinf/ Contact: wangx@ee.columbia.edu or mssamoilov@lbl.gov Supplementary information: Supplementary data are available at Bioinformatics online

Finding conserved motifs in genomic sequences represents one of essential bioinformatic problems. However, achieving high discovery performance without imposing substantial auxiliary constraints on possible motif features remains a key algorithmic challenge. This work describes BAMBI-a sequential Monte Carlo motif-identification algorithm, which is based on a position weight matrix model that does not require additional constraints and is able to estimate such motif properties as length, logo, number of instances and their locations solely on the basis of primary nucleotide sequence data. Furthermore, should biologically meaningful information about motif attributes be available, BAMBI takes advantage of this knowledge to further refine the discovery results. In practical applications, we show that the proposed approach can be used to find sites of such diverse DNA-binding molecules as the cAMP receptor protein (CRP) and Din-family site-specific serine recombinases. Results obtained by BAMBI in these and other settings demonstrate better statistical performance than any of the four widely-used profile-based motif discovery methods: MEME, BioProspector with BioOptimizer, SeSiMCMC and Motif Sampler as measured by the nucleotide-level correlation coefficient. Additionally, in the case of Din-family recombinase target site discovery, the BAMBI-inferred motif is found to be the only one functionally accurate from the underlying biochemical mechanism standpoint. C++ and Matlab code is available at http://www.ee.columbia.edu/~guido/BAMBI or http://genomics.lbl.gov/BAMBI/.

Uropathogenic Escherichia coli (UPEC) represent the predominant cause of urinary tract infections (UTIs). A key UPEC molecular virulence mechanism is type 1 fimbriae, whose expression is controlled by the orientation of an invertible chromosomal DNA element—the fim switch. Temperature has been shown to act as a major regulator of fim switching behavior and is overall an important indicator as well as functional feature of many urologic diseases, including UPEC host-pathogen interaction dynamics. Given this panoptic physiological role of temperature during UTI progression and notable empirical challenges to its direct in vivo studies, in silico modeling of corresponding biochemical and biophysical mechanisms essential to UPEC pathogenicity may significantly aid our understanding of the underlying disease processes. However, rigorous computational analysis of biological systems, such as fim switch temperature control circuit, has hereto presented a notoriously demanding problem due to both the substantial complexity of the gene regulatory networks involved as well as their often characteristically discrete and stochastic dynamics. To address these issues, we have developed an approach that enables automated multiscale abstraction of biological system descriptions based on reaction kinetics. Implemented as a computational tool, this method has allowed us to efficiently analyze the modular organization and behavior of the E. coli fimbriation switch circuit at different temperature settings, thus facilitating new insights into this mode of UPEC molecular virulence regulation. In particular, our results suggest that, with respect to its role in shutting down fimbriae expression, the primary function of FimB recombinase may be to effect a controlled down-regulation (rather than increase) of the ON-to-OFF fim switching rate via temperature-dependent suppression of competing dynamics mediated by recombinase FimE. Our computational analysis further implies that this down-regulation mechanism could be particularly significant inside the host environment, thus potentially contributing further understanding toward the development of novel therapeutic approaches to UPEC-caused UTIs., Author Summary Urinary tract infections (UTIs) represent a major growing threat to global public health. With over 15 million cases a year in the United States alone, UTIs are characterized by very high recurrence/reinfection rates, particularly among women and minority groups [1]. The predominant cause of UTIs is uropathogenic Escherichia coli (UPEC) bacteria, whose wide-spread and increasing antibiotic-resistance has made the development of alternative anti-UPEC treatments progressively more important and urgent. UPEC's foremost virulence factor is hair-like surface structures called type 1 fimbriae. Thus, one such potentially promising therapeutic approach may be to manipulate bacteria's own cellular circuitry toward inducing UPEC to turn off their fimbriae expression—rendering individual microbes benign. This task requires detailed understanding of molecular mechanisms involved, which may be significantly aided by in silico modeling. However, for UPEC fimbriation control circuit and many other systems, low-level all-inclusive quantitative models inevitably become too computationally demanding to remain practical, while high-level qualitative representations frequently prove inadequate owing to the substantial organizational and behavioral complexity of biological processes involved. We have developed an automated multiscale model abstraction methodology that helps address these problems by systematically generating intermediate-level representations that rigorously balance computational efficiency and modeling accuracy. Here, we use such an approach to examine how different temperature settings quantitatively affect UPEC transitions between fimbriate and afimbriate phases, to gain new understanding of the underlying modular circuit switch control logic, and to suggest further insights into ways this knowledge could potentially be used in therapeutic applications.