Procalcitonin-guided therapy in intensive care unit patients with severe sepsis and septic shock – a systematic review and meta-analysis

INTRODUCTION: Procalcitonin (PCT) algorithms for antibiotic treatment decisions have been studied in adult patients from primary care, emergency department, and intensive care unit (ICU) settings, suggesting that procalcitonin-guided therapy may reduce antibiotic exposure without increasing the mortality rate. However, information on the efficacy and safety of this approach in the most vulnerable population of critically ill patients with severe sepsis and septic shock is missing. METHOD: Two reviewers independently performed a systematic search in PubMed, Embase, ISI Web of Knowledge, BioMed Central, ScienceDirect, Cochrane Central Register of Controlled Trials, http://www.ClinicalTrials.gov and http://www.ISRCTN.org. Eligible studies had to be randomized controlled clinical trials or cohort studies which compare procalcitonin-guided therapy with standard care in severe sepsis patients and report at least one of the following outcomes: hospital mortality, 28-day mortality, duration of antimicrobial therapy, length of stay in the intensive care unit or length of hospital stay. Disagreements about inclusion of studies and judgment of bias were solved by consensus. RESULTS: Finally seven studies comprising a total of 1,075 patients with severe sepsis or septic shock were included in the meta-analysis. Both hospital mortality (RR [relative risk]: 0.91, 95%CI [confidence interval]: 0.61; 1.36) and 28-day mortality (RR: 1.02, 95%CI: 0.85; 1.23) were not different between procalcitonin-guided therapy and standard treatment groups. Duration of antimicrobial therapy was significantly reduced in favor of procalcitonin-guided therapy (HR [hazard ratio]: 1.27, 95%CI: 1.01; 1.53). Combined estimates of the length of stay in the ICU and in hospital did not differ between groups. CONCLUSION: Procalcitonin-guided therapy is a helpful approach to guide antibiotic therapy and surgical interventions without a beneficial effect on mortality. The major benefit of PCT-guided therapy consists of a shorter duration of antibiotic treatment compared to standard care. Trials are needed to investigate the effect of PCT-guided therapy on mortality, length of ICU and in-hospital stay in severe sepsis patients

Die Hamburger HafenCity - Leben (in) der Zukunft?

Der Hamburger Hafen prägt die Wirtschaft und Optik der Stadt. Der stattfindende Strukturwandel von Gewerbebetrieben zu einer Mischung aus Wohnen und modernen Dienstleistungen soll Image prägend nicht nur für das Gebiet um den Hafen, sondern ganz Hamburg werden. Das städtebauliche Großprojekt HafenCity und insbesondere die Elbphilharmonie werden hier einer Analyse aus kulturanthropologischer Perspektive unterzogen

Die Hamburger HafenCity – Leben (in) der Zukunft?

Der Hamburger Hafen prägt die Wirtschaft und Optik der Stadt. Der stattfindende Strukturwandel von Gewerbebetrieben zu einer Mischung aus Wohnen und modernen Dienstleistungen soll Image prägend nicht nur für das Gebiet um den Hafen, sondern ganz Hamburg werden. Das städtebauliche Großprojekt HafenCity und insbesondere die Elbphilharmonie werden hier einer Analyse aus kulturanthropologischer Perspektive unterzogen

SUSY Simplified Models at 14, 33, and 100 TeV Proton Colliders

Results are presented for a variety of SUSY Simplified Models at the 14 TeV LHC as well as a 33 and 100 TeV proton collider. Our focus is on models whose signals are driven by colored production. We present projections of the upper limit and discovery reach in the gluino-neutralino (for both light and heavy flavor decays), squark-neutralino, and gluino-squark Simplified Model planes. Depending on the model a jets + MET, mono-jet, or same-sign di-lepton search is applied. The impact of pileup is explored. This study utilizes the Snowmass backgrounds and combined detector. Assuming 3000 fb^{-1} of integrated luminosity, a gluino that decays to light flavor quarks can be discovered below 2.3 TeV at the 14 TeV LHC and below 11 TeV at a 100 TeV machine.Comment: 81 pages, 55 figures; v2 journal versio

No Abuse Potential of Silexan in Healthy Recreational Drug Users: A Randomized Controlled Trial

BACKGROUND Silexan is a lavender essential oil with established anxiolytic and calming efficacy. Here we asked whether there is a potential for abuse in human patients. METHODS We carried out a phase I abuse liability single-center, double-blind, 5-way crossover study in healthy users of recreational central nervous system depressants. They received single oral doses of 80 mg (therapeutic dose) and 640 mg Silexan, 2 mg and 4 mg lorazepam (active control) and placebo in randomized order, with 4- to 14-day washout periods between treatments. Pharmacodynamic measures included validated visual analogue scales assessing positive, negative, and sedative drug effects and balance of effects; a short form of the Addiction Research Center Inventory; and a drug similarity assessment. The primary outcome measure was the individual maximum value on the drug liking visual analogue scale during 24 hours post-dose. RESULTS Forty participants were randomized and 34 were evaluable for pharmacodynamic outcomes. In intraindividual head-to-head comparisons of the drug liking visual analogue scale maximum value, both doses of Silexan were rated similar to placebo whereas differences were observed between Silexan and lorazepam and between placebo and lorazepam (P < .001). These data were supported by all secondary measures of positive drug effects and of balance of effects. Differences between placebo and both doses of Silexan were always negligible in magnitude. Moreover, Silexan showed no sedative effects and was not perceived to be similar to commonly used drugs that participants had used in the past. CONCLUSIONS Silexan did not exhibit any abuse potential in a standard abuse potential detection screen study and is unlikely to be recreationally abused

Influence of ground-state structure and Mg2+ binding on folding kinetics of the guanine-sensing riboswitch aptamer domain

Riboswitch RNAs fold into complex tertiary structures upon binding to their cognate ligand. Ligand recognition is accomplished by key residues in the binding pocket. In addition, it often crucially depends on the stability of peripheral structural elements. The ligand-bound complex of the guanine-sensing riboswitch from Bacillus subtilis, for example, is stabilized by extensive interactions between apical loop regions of the aptamer domain. Previously, we have shown that destabilization of this tertiary loop–loop interaction abrogates ligand binding of the G37A/C61U-mutant aptamer domain (Gswloop) in the absence of Mg2+. However, if Mg2+ is available, ligand-binding capability is restored by a population shift of the ground-state RNA ensemble toward RNA conformations with pre-formed loop–loop interactions. Here, we characterize the striking influence of long-range tertiary structure on RNA folding kinetics and on ligand-bound complex structure, both by X-ray crystallography and time-resolved NMR. The X-ray structure of the ligand-bound complex reveals that the global architecture is almost identical to the wild-type aptamer domain. The population of ligand-binding competent conformations in the ground-state ensemble of Gswloop is tunable through variation of the Mg2+ concentration. We quantitatively describe the influence of distinct Mg2+ concentrations on ligand-induced folding trajectories both by equilibrium and time-resolved NMR spectroscopy at single-residue resolution

Structure and dynamics of the deoxyguanosine-sensing riboswitch studied by NMR-spectroscopy

The mfl-riboswitch regulates expression of ribonucleotide reductase subunit in Mesoplasma florum by binding to 2′-deoxyguanosine and thereby promoting transcription termination. We characterized the structure of the ligand-bound aptamer domain by NMR spectroscopy and compared the mfl-aptamer to the aptamer domain of the closely related purine-sensing riboswitches. We show that the mfl-aptamer accommodates the extra 2′-deoxyribose unit of the ligand by forming a more relaxed binding pocket than these found in the purine-sensing riboswitches. Tertiary structures of the xpt-aptamer bound to guanine and of the mfl-aptamer bound to 2′-deoxyguanosine exhibit very similar features, although the sequence of the mfl-aptamer contains several alterations compared to the purine-aptamer consensus sequence. These alterations include the truncation of a hairpin loop which is crucial for complex formation in all purine-sensing riboswitches characterized to date. We further defined structural features and ligand binding requirements of the free mfl-aptamer and found that the presence of Mg2+ is not essential for complex formation, but facilitates ligand binding by promoting pre-organization of key structural motifs in the free aptamer

Use of KikGR a photoconvertible green-to-red fluorescent protein for cell labeling and lineage analysis in ES cells and mouse embryos

<p>Abstract</p> <p>Background</p> <p>The use of genetically-encoded fluorescent proteins has revolutionized the fields of cell and developmental biology and in doing so redefined our understanding of the dynamic morphogenetic processes that shape the embryo. With the advent of more accessible and sophisticated imaging technologies as well as an abundance of fluorescent proteins with different spectral characteristics, the dynamic processes taking place <it>in situ </it>in living cells and tissues can now be probed. Photomodulatable fluorescent proteins are one of the emerging classes of genetically-encoded fluorescent proteins.</p> <p>Results</p> <p>We have compared PA-GFP, PS-CFP2, Kaede and KikGR four readily available and commonly used photomodulatable fluorescent proteins for use in ES cells and mice. Our results suggest that the green-to-red photoconvertible fluorescent protein, Kikume Green-Red (KikGR), is most suitable for cell labeling and lineage studies in ES cells and mice because it is developmentally neutral, bright and undergoes rapid and complete photoconversion. We have generated transgenic ES cell lines and strains of mice exhibiting robust widespread expression of KikGR. By efficient photoconversion of KikGR we labeled subpopulations of ES cells in culture, and groups of cells within <it>ex utero </it>cultured mouse embryos. Red fluorescent photoconverted cells and their progeny could be followed for extended periods of time.</p> <p>Conclusion</p> <p>Transgenic ES cells and mice exhibiting widespread readily detectable expression of KikGR are indistinguishable from their wild type counterparts and are amenable to efficient photoconversion. They represent novel tools for non-invasive selective labeling specific cell populations and live imaging cell dynamics and cell fate. Genetically-encoded photomodulatable proteins such as KikGR represent emergent attractive alternatives to commonly used vital dyes, tissue grafts and genetic methods for investigating dynamic behaviors of individual cells, collective cell dynamics and fate mapping applications.</p

Is the beck anxiety inventory a good tool to assess the severity of anxiety? A primary care study in The Netherlands study of depression and anxiety (NESDA)

<p>Abstract</p> <p>Background</p> <p>Appropriate management of anxiety disorders in primary care requires clinical assessment and monitoring of the severity of the anxiety. This study focuses on the Beck Anxiety Inventory (BAI) as a severity indicator for anxiety in primary care patients with different anxiety disorders (social phobia, panic disorder with or without agoraphobia, agoraphobia or generalized anxiety disorder), depressive disorders or no disorder (controls).</p> <p>Methods</p> <p>Participants were 1601 primary care patients participating in the Netherlands Study of Depression and Anxiety (NESDA). Regression analyses were used to compare the mean BAI scores of the different diagnostic groups and to correct for age and gender.</p> <p>Results</p> <p>Patients with any anxiety disorder had a significantly higher mean score than the controls. A significantly higher score was found for patients with panic disorder and agoraphobia compared to patients with agoraphobia only or social phobia only. BAI scores in patients with an anxiety disorder with a co-morbid anxiety disorder and in patients with an anxiety disorder with a co-morbid depressive disorder were significantly higher than BAI scores in patients with an anxiety disorder alone or patients with a depressive disorder alone. Depressed and anxious patients did not differ significantly in their mean scores.</p> <p>Conclusions</p> <p>The results suggest that the BAI may be used as a severity indicator of anxiety in primary care patients with different anxiety disorders. However, because the instrument seems to reflect the severity of depression as well, it is not a suitable instrument to discriminate between anxiety and depression in a primary care population.</p