UK Efficacy and Mechanism Evaluation Programme and National Institutes of Health.

No abstract

Ultrasound for diagnostic and procedural purposes is becoming a standard in daily clinical practice including anaesthesiology and peri-operative medicine. The project of European Society of Anaesthesiology (ESA) Task Force for the development of clinical guidelines on the PERioperative uSE of Ultra-Sound (PERSEUS) project has focused on the use of ultrasound in two areas that account for the majority of procedures performed routinely in the operating room: vascular access and regional anaesthesia. Given the extensive literature available in these two areas, this paper will focus on the use of ultrasound-guidance for vascular access. A second part will be dedicated to peripheral nerve/neuraxial blocks. The Taskforce identified three main domains of application in ultrasound-guided vascular cannulation: adults, children and training. The literature search were performed by a professional librarian from the Cochrane Anaesthesia and Critical and Emergency Care Group in collaboration with the ESA Taskforce. The Grading of Recommendation Assessment (GRADE) system for assessing levels of evidence and grade of recommendations were used. For the use of ultrasound-guided cannulation of the internal jugular vein, femoral vein and arterial access, the level evidence was classified 1B. For other accesses, the evidence remains limited. For training in ultrasound guidance, there were no studies. The importance of proper training for achieving competency and full proficiency before performing any ultrasound-guided vascular procedure must be emphasised.

No abstract

Toll-like receptors (TLRs) constitute an archetypal pattern recognition system. Their sophisticated biology underpins the ability of innate immunity to discriminate between highly diverse microbial pathogens and self. However, the remarkable progress made in describing this biology has also revealed new immunological systems and processes previously hidden to investigators. In particular, TLRs appear to have a fundamental role in the generation of clonal adaptive immune responses, non-infectious disease pathogenesis and even in the maintenance of normal mammalian homeostasis. Although an understanding of TLRs has answered some fundamental questions at the host-pathogen interface, further issues, particularly regarding therapeutic modulation of these receptors, have yet to be resolved.

During an infection, the coordinated orchestration of many factors by the invading organism is required for disease to be initiated and to progress. The elucidation of the processes involved is critical to the development of a clear understanding of host-pathogen interactions. For Candida species, the inactivation of many fungal attributes has been shown to result in attenuation. Here we demonstrate that the Candida glabrata homolog of the Saccharomyces cerevisiae transcription factor gene ACE2 encodes a function that mediates virulence in a novel way. Inactivation of C. glabrata ACE2 does not result in attenuation but, conversely, in a strain that is hypervirulent in a murine model of invasive candidiasis. C. glabrata ace2 null mutants cause systemic infections characterized by fungal escape from the vasculature, tissue penetration, proliferation in vivo, and considerable overstimulation of the proinflammatory arm of the innate immune response. Compared to the case with wild-type fungi, mortality occurs much earlier in mice infected with C. glabrata ace2 cells, and furthermore, 200-fold lower doses are required to induce uniformly fatal infections. These data demonstrate that C. glabrata ACE2 encodes a function that plays a critical role in mediating the host-Candida interaction. It is the first virulence-moderating gene to be described for a Candida species.

No abstract

Microcirculatory hypoperfusion immediately following traumatic hemorrhagic shock and resuscitation is associated with increased multiple organ dysfunction syndrome. Microcirculatory variables are better prognostic indicators for the development of multiple organ dysfunction syndrome than more traditional indices. Microcirculatory perfusion is a potential endpoint of resuscitation following traumatic hemorrhagic shock.