Analysis of a Clostridium difficile PCR ribotype 078 100 kilobase island reveals the presence of a novel transposon, Tn6164.

Clostridium difficile is the main cause of antibiotic associated diarrhea. In the past decade, the number of C. difficile patients has increased dramatically, coinciding with the emergence of two PCR ribotypes 027 and 078. PCR ribotype 078 is also frequently found during C. difficile outbreaks in pigfarms. Previously, the genome of the PCR ribotype 078 strain M120, a human isolate, was described to contain a unique insert of 100 kilobases

Optimal neighborhood indexing for protein similarity search

Background: Similarity inference, one of the main bioinformatics tasks, has to face an exponential growth of the biological data. A classical approach used to cope with this data flow involves heuristics with large seed indexes. In order to speed up this technique, the index can be enhanced by storing additional information to limit the number of random memory accesses. However, this improvement leads to a larger index that may become a bottleneck. In the case of protein similarity search, we propose to decrease the index size by reducing the amino acid alphabet.\ud \ud Results: The paper presents two main contributions. First, we show that an optimal neighborhood indexing combining an alphabet reduction and a longer neighborhood leads to a reduction of 35% of memory involved into the process, without sacrificing the quality of results nor the computational time. Second, our approach led us to develop a new kind of substitution score matrices and their associated e-value parameters. In contrast to usual matrices, these matrices are rectangular since they compare amino acid groups from different alphabets. We describe the method used for computing those matrices and we provide some typical examples that can be used in such comparisons. Supplementary data can be found on the website http://bioinfo.lifl.fr/reblosum.\ud \ud Conclusions: We propose a practical index size reduction of the neighborhood data, that does not negatively affect the performance of large-scale search in protein sequences. Such an index can be used in any study involving large protein data. Moreover, rectangular substitution score matrices and their associated statistical parameters can have applications in any study involving an alphabet reduction

Prolonged high-dose intravenous magnesium therapy for severe tetanus in the intensive care unit: a case series

<p>Abstract</p> <p>Introduction</p> <p>Tetanus rarely occurs in developed countries, but it can result in fatal complications including respiratory failure due to generalized muscle spasms. Magnesium infusion has been used to treat spasticity in tetanus, and its effectiveness is supported by several case reports and a recent randomized controlled trial.</p> <p>Case presentations</p> <p>Three Caucasian Greek men aged 30, 50 and 77 years old were diagnosed with tetanus and admitted to a general 12-bed intensive care unit in 2006 and 2007 for respiratory failure due to generalized spasticity. Intensive care unit treatment included antibiotics, hydration, enteral nutrition, early tracheostomy and mechanical ventilation. Intravenous magnesium therapy controlled spasticity without the need for additional muscle relaxants. Their medications were continued for up to 26 days, and adjusted as needed to control spasticity. Plasma magnesium levels, which were measured twice a day, remained in the 3 to 4.5 mmol/L range. We did not observe hemodynamic instability, arrhythmias or other complications related to magnesium therapy in these patients. All patients improved, came off mechanical ventilation, and were discharged from the intensive care unit in a stable condition.</p> <p>Conclusion</p> <p>In comparison with previous reports, our case series contributes the following meaningful additional information: intravenous magnesium therapy was used on patients already requiring mechanical ventilation and remained effective for up to 26 days (significantly longer than in previous reports) without significant toxicity in two patients. The overall outcome was good in all our patients. However, the optimal dose, optimal duration and maximum safe duration of intravenous magnesium therapy are unknown. Therefore, until more data on the safety and efficacy of magnesium therapy are available, its use should be limited to carefully selected tetanus cases.</p

Azotobacter genomes: the genome of Azotobacter chroococcum NCIMB 8003 (ATCC 4412)

The genome of the soil-dwelling heterotrophic N2-fixing Gram-negative bacterium Azotobacter chroococcum NCIMB 8003 (ATCC 4412) (Ac-8003) has been determined. It consists of 7 circular replicons totalling 5,192,291 bp comprising a circular chromosome of 4,591,803 bp and six plasmids pAcX50a, b, c, d, e, f of 10,435 bp, 13,852, 62,783, 69,713, 132,724, and 311,724 bp respectively. The chromosome has a G+C content of 66.27% and the six plasmids have G+C contents of 58.1, 55.3, 56.7, 59.2, 61.9, and 62.6% respectively. The methylome has also been determined and 5 methylation motifs have been identified. The genome also contains a very high number of transposase/inactivated transposase genes from at least 12 of the 17 recognised insertion sequence families. The Ac-8003 genome has been compared with that of Azotobacter vinelandii ATCC BAA-1303 (Av-DJ), a derivative of strain O, the only other member of the Azotobacteraceae determined so far which has a single chromosome of 5,365,318 bp and no plasmids. The chromosomes show significant stretches of synteny throughout but also reveal a history of many deletion/insertion events. The Ac-8003 genome encodes 4628 predicted protein-encoding genes of which 568 (12.2%) are plasmid borne. 3048 (65%) of these show > 85% identity to the 5050 protein-encoding genes identified in Av-DJ, and of these 99 are plasmid-borne. The core biosynthetic and metabolic pathways and macromolecular architectures and machineries of these organisms appear largely conserved including genes for CO-dehydrogenase, formate dehydrogenase and a soluble NiFe-hydrogenase. The genetic bases for many of the detailed phenotypic differences reported for these organisms have also been identified. Also many other potential phenotypic differences have been uncovered. Properties endowed by the plasmids are described including the presence of an entire aerobic corrin synthesis pathway in pAcX50f and the presence of genes for retro-conjugation in pAcX50c. All these findings are related to the potentially different environmental niches from which these organisms were isolated and to emerging theories about how microbes contribute to their communities

How do we improve men’s mental health via primary care? An evaluation of the Atlas Men’s Well-being Pilot Programme for stressed/distressed men

Background Over three-quarters of all suicides are men (England and Wales), this is despite higher levels of anxiety and depression being reported by women. This disparity may in part be explained by atypical presentations of distress in men, and gendered issues around help-seeking. Consequently, the Atlas Men’s Well-being Programme was designed to engage stressed/distressed men who were patients at a London-based GP surgery. Atlas encouraged GPs to identify and refer men for counselling and/or acupuncture by raising their awareness of men’s distress. The aim of this pilot study was to evaluate Atlas in terms of patients’ characteristics, service utilisation, patient outcomes and cost implications. Methods All patients using the Programme were asked to complete a questionnaire before and after their Atlas sessions. Outcome measures included the Hospital Anxiety and Depression scale, Perceived Stress Scale, Warwick-Edinburgh Mental Well-being Scale, a 11-point scale measuring physical health, and the Psychological Outcome Profiles (PSYCHLOPS), a patient-generated outcome measure. Additionally, for cost calculations, participants were asked about their employment, number of days off work due to illness, and their health and social care service use. Results 102 participants were recruited, 82 completed pre- and post-treatment questionnaires. Comparisons pre- and post-treatment revealed a statistically significant improvement in anxious mood (p <0.001), perceived stress (p < 0.001), positive well-being (p = <0.001), PSYCHLOPS (p = <0.001) and physical health (p = 0.001), though not depressed mood (p = 0.660). Additionally, reductions in costs related to lost employment and health and social care use, exceeded the cost of Atlas counselling and acupuncture sessions, with an average saving of nearly £700 per patient. Conclusions Atlas attendance was associated with improvements in patients’ mental and physical health, and demonstrated likely cost savings. It is now important to understand patient and stakeholder perspectives. Further research could compare usual care with the Atlas approach, and investigate full cost-effectiveness

Protein structure and evolution: are they constrained globally by a principle derived from information theory?

That the physicochemical properties of amino acids constrain the structure, function and evolution of proteins is not in doubt. However, principles derived from information theory may also set bounds on the structure (and thus also the evolution) of proteins. Here we analyze the global properties of the full set of proteins in release 13-11 of the SwissProt database, showing by experimental test of predictions from information theory that their collective structure exhibits properties that are consistent with their being guided by a conservation principle. This principle (Conservation of Information) defines the global properties of systems composed of discrete components each of which is in turn assembled from discrete smaller pieces. In the system of proteins, each protein is a component, and each protein is assembled from amino acids. Central to this principle is the inter-relationship of the unique amino acid count and total length of a protein and its implications for both average protein length and occurrence of proteins with specific unique amino acid counts. The unique amino acid count is simply the number of distinct amino acids (including those that are post-translationally modified) that occur in a protein, and is independent of the number of times that the particular amino acid occurs in the sequence. Conservation of Information does not operate at the local level (it is independent of the physicochemical properties of the amino acids) where the influences of natural selection are manifest in the variety of protein structure and function that is well understood. Rather, this analysis implies that Conservation of Information would define the global bounds within which the whole system of proteins is constrained; thus it appears to be acting to constrain evolution at a level different from natural selection, a conclusion that appears counter-intuitive but is supported by the studies described herein

Towards coordinated regional multi-satellite InSAR volcano observations:results from the Latin America pilot project

Within Latin America, about 319 volcanoes have been active in the Holocene, but 202 of these volcanoes have no seismic, deformation or gas monitoring. Following the 2012 Santorini Report on satellite Earth Observation and Geohazards, the Committee on Earth Observation Satellites (CEOS) developed a 4-year pilot project (2013-2017) to demonstrate how satellite observations can be used to monitor large numbers of volcanoes cost-effectively, particularly in areas with scarce instrumentation and/or difficult access. The pilot aims to improve disaster risk management (DRM) by working directly with the volcano observatories that are governmentally responsible for volcano monitoring as well as with the international space agencies (ESA, CSA, ASI, DLR, JAXA, NASA, CNES). The goal is to make sure that the most useful data are collected at each volcano following the guidelines of the Santorini report that observation frequency is related to volcano activity, and to communicate the results to the local institutions in a timely fashion. Here we highlight how coordinated multi-satellite observations have been used by volcano observatories to monitor volcanoes and respond to crises. Our primary tool is measurements of ground deformation made by Interferometric Synthetic Aperture Radar (InSAR), which have been used in conjunction with other observations to determine the alert level at these volcanoes, served as an independent check on ground sensors, guided the deployment of ground instruments, and aided situational awareness. During this time period, we find 26 volcanoes deforming, including 18 of the 28 volcanoes that erupted – those eruptions without deformation were less than 2 on the VEI scale. Another 7 volcanoes were restless and the volcano observatories requested satellite observations, but no deformation was detected. We describe the lessons learned about the data products and information that are most needed by the volcano observatories in the different countries using information collected by questionnaires. We propose a practical strategy for regional to global satellite volcano monitoring for use by volcano observatories in Latin America and elsewhere to realize the vision of the Santorini report