Major cardiac rupture following surgical treatment for deep sternal wound infection.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.We report a case of an 80-year old male patient who sustained a major rupture of the right ventricle after surgical revision of an infected sternotomy wound following coronary artery bypass surgery. The rupture of the right ventricle occurred despite an early wound debridement and the use of negative pressure wound therapy on the sternum that did not provide sufficient stability to the sternum after the sternal wires were removed. The rupture resulted in a major bleeding but by establishing emergent cardiopulmonary bypass, the patient was saved

Surveillance of Ruminant Diseases in the Nordic Countries

<p/> <p>All the Nordic countries have a basis for their surveillance and disease control in ruminants in national legislation and regulations listing notifiable diseases of concern to the countries. The Nordic countries are a disease-free zone comparing to other parts of the world and the aim of the surveillance is to keep that status and be able to document it. Following is a short summary from each country.</p

The use of recombinant activated factor VIIa for major bleedings in open heart surgery

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenINTRODUCTION: We evaluated the efficacy of activated recombinant factor VIIa (rFVIIa) administration for critical bleeding during cardiothoracic surgery in Iceland. MATERIALS AND METHODS: Over a 33 month period, 10 consecutive patients with major life-threatening bleeding during or right after open cardiac surgery that received rFVIIa in 11 operations. Clinical information was retrospectively collected from hospital charts. RESULTS: The 10 patients were on average 66 year old, ranging 36-82 yrs. All patients were NYHA-class III or IV, there of three underwent emergency surgery. Complicated AVR+/-CABG was the most common type of operation (n=5), with average operation time 673 min. (range 475-932) and perfusion time 287 min. (range 198-615). After the administration of rFVIIa, haemostasis was acquired in 8 of 11 operations, with a significant improvement in coagulation parameters. Three patiens needed reoperation for bleeding. Transfusion of packed red cell (p=0.002) and plasma (p<0.02) decreased significantly after administration of rFVIIa and prothrombin time was shortened (p<0.004). Five patients succumbed, one of them with a cerebral infarction and pulmonary embolus, the latter confirmed at autopsy. Other causes of death were intractable bleeding, myocardial infarction, multiorgan failure and disseminated intravascular coagulopathy. CONCLUSIONS: rFVIIa can be used effectively to stop intractable bleedings in open heart surgery, with 8 out of 11 patients in this small series achieving hemostasis after its administration. Mortality in this group of patients was high (50%), however, in all cases rFVIIa was used as an end-of-the-line treatment where other therapy had failed. One patient died from pulmonary embolism and cerebral infarct, raising the question of hypercoagulation. Further studies on the side effects and indications of rFVIIa treatment are necessary.Inngangur: Rannsakaður var með aftursæjum hætti árangur meðhöndlunar lífshættulegra blæðinga í opnum hjartaaðgerðum á Landspítala með líftæknigerðum espuðum storkuþætti VII (recombinant factor VIIa, rFVIIa). Efniviður og aðferðir: Frá júní 2003 til mars 2006 fengu 10 sjúklingar rFVIIa vegna meiriháttar blæðinga sem ekki tókst að stöðva með hefðbundinni meðferð í 11 hjartaskurðaðgerðum. Upplýsingar voru fengnar úr sjúkraskrám. Niðurstöður: Meðalaldur var 66 ár (bil 36-82). Allir sjúklingarnir voru í NYHA-flokki III eða IV, þar af gengust þrír undir bráðaaðgerð. Algengustu aðgerðirnar voru ósæðarlokuskipti (n=5), með eða án kransæðahjáveitu. Tímalengd aðgerðanna var að meðaltali 673 mínútur (bil 475-932) og tími í hjarta- og lungnavél 287 mínútur (bil 198-615). Í 8 af 11 aðgerðum stöðvaðist blæðing skömmu eftir gjöf rFVIIa. Þrír sjúklingar þurftu þó enduraðgerð vegna blæðinga. Gjöf rauðkornaþykknis (p=0,002) og blóðvatns (p<0,02) minnkaði marktækt eftir gjöf rFVIIa og próþrombín-tími styttist (p<0,004). Fimm sjúklingar lifðu aðgerðina af en dánarorsakir hinna fimm voru óstöðvandi blæðing í aðgerð, segarek til lungna, hjartadrep, fjölkerfabilun og blóðstorkusótt. Ályktun: rFVIIa er virkt lyf til að stöðva meiriháttar blæðingar í opnum hjartaaðgerðum, en blæðing stöðvaðist í 8 af 11 aðgerðum við gjöf lyfsins. Fimm sjúklingar af tíu lifðu aðgerðirnar af og útskrifuðust heim en hafa verður í huga að lyfið var einungis gefið þegar öll önnur meðferð hafði verið reynd til hlítar og sjúklingarnir hefðu annars dáið úr blæðingu. Í einu tilviki lést sjúklingur úr óstöðvandi blæðingu þrátt fyrir gjöf rFVIIa. Einn sjúklingur lést úr segareki til lungna og annar vegna bráðs hjartadreps, hvort tveggja dauðsföll sem gætu hafa tengst gjöf lyfsins

Shared Metadata for Data-Centric Materials Science

The expansive production of data in materials science, their widespread sharing and repurposing requires educated support and stewardship. In order to ensure that this need helps rather than hinders scientific work, the implementation of the FAIR-data principles (Findable, Accessible, Interoperable, and Reusable) must not be too narrow. Besides, the wider materials-science community ought to agree on the strategies to tackle the challenges that are specific to its data, both from computations and experiments. In this paper, we present the result of the discussions held at the workshop on "Shared Metadata and Data Formats for Big-Data Driven Materials Science". We start from an operative definition of metadata, and what features a FAIR-compliant metadata schema should have. We will mainly focus on computational materials-science data and propose a constructive approach for the FAIRification of the (meta)data related to ground-state and excited-states calculations, potential-energy sampling, and generalized workflows. Finally, challenges with the FAIRification of experimental (meta)data and materials-science ontologies are presented together with an outlook of how to meet them

Analyzing and Biasing Simulations with PLUMED

This chapter discusses how the PLUMED plugin for molecular dynamics can be used to analyze and bias molecular dynamics trajectories. The chapter begins by introducing the notion of a collective variable and by then explaining how the free energy can be computed as a function of one or more collective variables. A number of practical issues mostly around periodic boundary conditions that arise when these types of calculations are performed using PLUMED are then discussed. Later parts of the chapter discuss how PLUMED can be used to perform enhanced sampling simulations that introduce simulation biases or multiple replicas of the system and Monte Carlo exchanges between these replicas. This section is then followed by a discussion on how free-energy surfaces and associated error bars can be extracted from such simulations by using weighted histogram and block averaging techniques

RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview

With both catalytic and genetic functions, ribonucleic acid (RNA) is perhaps the most pluripotent chemical species in molecular biology, and its functions are intimately linked to its structure and dynamics. Computer simulations, and in particular atomistic molecular dynamics (MD), allow structural dynamics of biomolecular systems to be investigated with unprecedented temporal and spatial resolution. We here provide a comprehensive overview of the fast-developing field of MD simulations of RNA molecules. We begin with an in-depth, evaluatory coverage of the most fundamental methodological challenges that set the basis for the future development of the field, in particular, the current developments and inherent physical limitations of the atomistic force fields and the recent advances in a broad spectrum of enhanced sampling methods. We also survey the closely related field of coarse-grained modeling of RNA systems. After dealing with the methodological aspects, we provide an exhaustive overview of the available RNA simulation literature, ranging from studies of the smallest RNA oligonucleotides to investigations of the entire ribosome. Our review encompasses tetranucleotides, tetraloops, a number of small RNA motifs, A-helix RNA, kissing-loop complexes, the TAR RNA element, the decoding center and other important regions of the ribosome, as well as assorted others systems. Extended sections are devoted to RNA-ion interactions, ribozymes, riboswitches, and protein/RNA complexes. Our overview is written for as broad of an audience as possible, aiming to provide a much-needed interdisciplinary bridge between computation and experiment, together with a perspective on the future of the field

Enhanced Conformational Sampling using Replica Exchange with Collective-Variable Tempering

The computational study of conformational transitions in RNA and proteins with atomistic molecular dynamics often requires suitable enhanced sampling techniques. We here introduce a novel method where concurrent metadynamics are integrated in a Hamiltonian replica-exchange scheme. The ladder of replicas is built with different strength of the bias potential exploiting the tunability of well-tempered metadynamics. Using this method, free-energy barriers of individual collective variables are significantly reduced compared with simple force-field scaling. The introduced methodology is flexible and allows adaptive bias potentials to be self-consistently constructed for a large number of simple collective variables, such as distances and dihedral angles. The method is tested on alanine dipeptide and applied to the difficult problem of conformational sampling in a tetranucleotide

Two distinct catalytic pathways for GH43 xylanolytic enzymes unveiled by X-ray and QM/MM simulations

Xylanolytic enzymes from glycoside hydrolase family 43 (GH43) are involved in the breakdown of hemicellulose, the second most abundant carbohydrate in plants. Here, we kinetically and mechanistically describe the non-reducing-end xylose-releasing exo-oligoxylanase activity and report the crystal structure of a native GH43 Michaelis complex with its substrate prior to hydrolysis. Two distinct calcium-stabilized conformations of the active site xylosyl unit are found, suggesting two alternative catalytic routes. These results are confirmed by QM/MM simulations that unveil the complete hydrolysis mechanism and identify two possible reaction pathways, involving different transition state conformations for the cleavage of xylooligosaccharides. Such catalytic conformational promiscuity in glycosidases is related to the open architecture of the active site and thus might be extended to other exo-acting enzymes. These findings expand the current general model of catalytic mechanism of glycosidases, a main reaction in nature, and impact on our understanding about their interaction with substrates and inhibitors

Using metadynamics to explore complex free-energy landscapes

Metadynamics is an atomistic simulation technique that allows, within the same framework, acceleration of rare events and estimation of the free energy of complex molecular systems. It is based on iteratively \u2018filling\u2019 the potential energy of the system by a sum of Gaussians centred along the trajectory followed by a suitably chosen set of collective variables (CVs), thereby forcing the system to migrate from one minimum to the next. The power of metadynamics is demonstrated by the large number of extensions and variants that have been developed. The first scope of this Technical Review is to present a critical comparison of these variants, discussing their advantages and disadvantages. The effectiveness of metadynamics, and that of the numerous alternative methods, is strongly influenced by the choice of the CVs. If an important variable is neglected, the resulting estimate of the free energy is unreliable, and predicted transition mechanisms may be qualitatively wrong. The second scope of this Technical Review is to discuss how the CVs should be selected, how to verify whether the chosen CVs are sufficient or redundant, and how to iteratively improve the CVs using machine learning approaches