Driving pressure during general anesthesia for open abdominal surgery (DESIGNATION) : study protocol of a randomized clinical trial

Background Intraoperative driving pressure (Delta P) is associated with development of postoperative pulmonary complications (PPC). When tidal volume (V-T) is kept constant, Delta P may change according to positive end-expiratory pressure (PEEP)-induced changes in lung aeration. Delta P may decrease if PEEP leads to a recruitment of collapsed lung tissue but will increase if PEEP mainly causes pulmonary overdistension. This study tests the hypothesis that individualized high PEEP, when compared to fixed low PEEP, protects against PPC in patients undergoing open abdominal surgery. Methods The "Driving prESsure durIng GeNeral AnesThesIa for Open abdomiNal surgery trial" (DESIGNATION) is an international, multicenter, two-group, double-blind randomized clinical superiority trial. A total of 1468 patients will be randomly assigned to one of the two intraoperative ventilation strategies. Investigators screen patients aged >= 18 years and with a body mass index <= 40 kg/m(2), scheduled for open abdominal surgery and at risk for PPC. Patients either receive an intraoperative ventilation strategy with individualized high PEEP with recruitment maneuvers (RM) ("individualized high PEEP") or one in which PEEP of 5 cm H2O without RM is used ("low PEEP"). In the "individualized high PEEP" group, PEEP is set at the level at which Delta P is lowest. In both groups of the trial, V-T is kept at 8 mL/kg predicted body weight. The primary endpoint is the occurrence of PPC, recorded as a collapsed composite of adverse pulmonary events. Discussion DESIGNATION will be the first randomized clinical trial that is adequately powered to compare the effects of individualized high PEEP with RM versus fixed low PEEP without RM on the occurrence of PPC after open abdominal surgery. The results of DESIGNATION will support anesthesiologists in their decisions regarding PEEP settings during open abdominal surgery

New archaeomagnetic data recovered from the study of Roman and Visigothic remains from central Spain (3rd–7th centuries)

New archaeomagnetic results from four heated/combustion structures recovered from two archaeological sites in central Spain are reported. They have been dated by archaeological evidence and in two cases by radiocarbon dating. Rock magnetic experiments indicate low coercivity magnetic phases, such as magnetite and thermally stable maghaemite, as the main carriers of the remanent magnetization. Haematite has been observed in poorly heated baked clays. Archaeomagnetic directions have been obtained from either alternating field or thermal demagnetization experiments performed on 57 specimens coming from 46 independently oriented samples. The four well-defined archaeomagnetic directions obtained are in good agreement with previous archaeomagnetic data and with recent regional and global field models. They define the beginning of easterly declination drift that was initiated around 350–400 AD and culminated around 800–850 AD, and delineate the maximum in inclination that took place around 600–650 AD. In addition, classical Thellier–Thellier experiments including thermal remanent magnetization anisotropy and cooling rate corrections were conducted on 23 specimens. Only 13 specimens, corresponding to well-defined single component behaviour, gave reliable results. New mean archaeointensities have been obtained for two of the four studied structures (VBK1, 64.2 ± 5.0 μT and VBT1, 62.4 ± 2.6 μT). The new data suggest that two relative intensity maxima occurred in Western Europe around 320 and 630 AD, being of lower magnitude that observed in Eastern Europe.Peer reviewe

Occurrence of genes of putative fibrinogen binding proteins and hemolysins, as well as of their phenotypic correlates in isolates of S. lugdunensis of different origins

<p>Abstract</p> <p>Background</p> <p><it>Staphylococcus lugdunensis </it>is an important human pathogen that causes potentially fatal endocarditis, osteomyelitis and skin and soft tissue infections similar to diseases caused by <it>Staphylococcus aureus</it>. Nevertheless, in contrast to <it>S. aureus</it>, data on pathogenicity factors of <it>S. lugdunensis </it>is scarce. Two adhesins, a fibrinogen and a von Willebrand factor binding protein, and a <it>S. lugdunensis </it>synergistic hemolysin (SLUSH) have been previously described. Moreover, the newly sequenced genome of <it>S. lugdunensis </it>revealed genes of other putative fibrinogen binding adhesins and hemolysins. The aim of this study was to gain more insight into the occurrence of genes likely coding for fibrinogen binding adhesins and hemolysins using clinical strains of <it>S. lugdunensis</it>.</p> <p>Findings</p> <p>Most of the putative adhesin genes and hemolysin genes investigated in this study were highly prevalent, except for the SLUSH gene cluster. In contrast to previous reports, binding to fibrinogen was detected in 29.3% of the <it>S. lugdunensis </it>strains. In most strains, hemolysis on blood agar plates was weak after 24 h and distinct after 48 h of incubation. The fibrinogen binding and hemolysis phenotypes were also independent of the type of clinical specimen, from which the isolates were obtained.</p> <p>Conclusion</p> <p>In this study we described a pyrrolidonyl arylamidase negative <it>S. lugdunensis </it>isolate. Our data indicate that a matrix-assisted laser desorption ionisation time-of-flight MS-based identification of <it>S. lugdunensis </it>or species-specific PCR's should be performed in favour of pyrrolidonyl arylamidase testing. In contrast to the high occurrence of putative fibrinogen binding protein genes, 29.3% of the <it>S. lugdunensis </it>strains bound to fibrinogen. Putative hemolysin genes were also prevalent in most of the <it>S. lugdunensis </it>strains, irrespective of their hemolysis activity on Columbia blood agar plates. Similar to a previous report, hemolysis after 48 h of incubation is also indicative for <it>S. lugdunensis</it>. The SLUSH gene cluster was detected in an estimated 50% of the strains, indicating that this locus is different or non-prevalent in many strains.</p

Archaeomagnetic and rock magnetic study of six kilns from North Africa (Tunisia and Morocco)

International audienceNew full-vector archaeomagnetic data for North Africa recovered from the study of six kilns, five from Tunisia and one from Morocco, are presented. Archaeological and historical considerations, along with three radiocarbon dates, indicate that the age of the kilns ranges between the 9th and 15th centuries AD. Rock magnetic analyses showed that the principal magnetic carriers are magnetite and low Ti titanomagnetite, along with variable contributions of thermally stable maghemite and a high coercivity phase with low unblocking temperatures. The magnetic mineralogy of the studied material is thermally stable and behaves ideally during archaeointensity experiments. Stepwise alternating field demagnetization isolated a single, stable, characteristic remanence component with very well defined directions at both specimen and structure levels. Mean archaeointensities have been obtained from successful classical Thellier experiments conducted on between five and eight independent samples per kiln. Thermoremanent magnetization (TRM) anisotropy and cooling rate effects upon TRM intensity have been investigated. The results showed that these effects are low for four of the six studied kilns, with differences between the uncorrected and corrected means of less than 3 per cent. For the other two structures differences between the uncorrected and corrected mean site intensities are 4.4 per cent and 5.8 per cent. These results highlight the necessity for TRM anisotropy and cooling rate corrections in archaeomagnetic studies if accurate archaeointensities are to be obtained. The new results suggest that high intensities occurred in Northwest Africa during the 9th century. Although more data are clearly needed to define this period of high intensity, the results are in agreement with the available European archaeointensity data. Acomparison between the newdata, other available archaeomagnetic determinations in nearby locations, and palaeosecular variation (PSV) curves derived from the regional SCHA.DIF.3k and global ARCH3K.1 geomagnetic field models shows good agreement between the new data and directional results derived from the models. However, some differences are observed between geomagnetic field models intensity results and available archaeointensity data for the studied regions. This highlights the need for new data for unexplored regions such as North Africa. The new data presented here better constrains the evolution of the geomagnetic field during historical times in this region. They represent a new step towards the construction of a reference PSV curve for Northwest Africa. Once established, this curve will represent a new dating method for this region

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

D-Serin-Deaminase von Staphylococcus saprophyticus\textit {Staphylococcus saprophyticus}

$\textit {Staphylococcus saprophyticus}$ ist die einzige typisch uropathogene Staphylokokkenspezies und besitzt eine D-Serin-Deaminase, die D-Serin zu Pyruvat und Ammoniak umsetzen kann. D-Serin kommt in relativ hohen Konzentrationen im Urin vor und ist bakteriostatisch bis toxisch für nicht-uropathogene Bakterienspezies. In dieser Arbeit konnte nach der Entwicklung eines chemisch definierten Mediums gezeigt werden, dass $\textit {S. saprophyticus}$ mit D-Serin als einziger Kohlenstoffquelle leben kann. Zur Verstoffwechselung des D-Serins findet eine Umstellung des Metabolismus von $\textit {S. saprophyticus}$ statt, welche hauptsächlich durch eine Hochregulation des Citratzyklus erfolgt. Die Adaptation an die Verwertung von D-Serin führt ebenfalls zu einer Hochregulation des bekannten Virulenzfaktors Ssp. Darüber hinaus konnte gezeigt werden, dass D-Serin auch eine inhibitorische Wirkung auf das Wachstum von $\textit {S. saprophyticus}$ haben kann. Des Weiteren wurde die D-Serin-Deaminase biochemisch charakterisiert