NT-proBNP and Circulating Inflammation Markers in Prediction of a Normal Myocardial Scintigraphy in Patients with Symptoms of Coronary Artery Disease

Myocardial perfusion imaging (MPI) can detect myocardial perfusion abnormalities but many examinations are without pathological findings. This study examines whether circulating biomarkers can be used as screening modality prior to MPI.243 patients with an intermediate risk of CAD or with known CAD with renewed suspicion of ischemia were referred to MPI. Blood samples were analyzed for N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP), YKL-40, IL-6, matrix metalloproteinase 9 (MMP-9) and high sensitive C-reactive protein (hsCRP). Patients with myocardial perfusion defects had elevated levels of NT-proBNP (p<0.0001), YKL-40 (p = 0.03) and IL-6 (p = 0.03) but not of hsCRP (p = 0.58) nor of MMP-9 (p = 0.14). The NT-proBNP increase was observed in both genders (p<0.0001), whereas YKL-40 (p = 0.005) and IL-6 (p = 0.02) were elevated only in men. A NT-proBNP cut off-concentration at 25 ng/l predicted a normal MPI with a negative predictive value >95% regardless of existing CAD.20-25% of patients suspected of CAD could have been spared a MPI by using a NT-proBNP cut-off concentration at 25 ng/l with a negative predictive value >95%. NT-proBNP has the potential use of being a screening marker of CAD before referral of the patient to MPI

Microscopy and its focal switch.

Until not very long ago, it was widely accepted that lens-based (far-field) optical microscopes cannot visualize details much finer than about half the wavelength of light. The advent of viable physical concepts for overcoming the limiting role of diffraction in the early 1990s set off a quest that has led to readily applicable and widely accessible fluorescence microscopes with nanoscale spatial resolution. Here I discuss the principles of these methods together with their differences in implementation and operation. Finally, I outline potential developments

Anterior Medial Prefrontal Cortex Exhibits Activation during Task Preparation but Deactivation during Task Execution

BACKGROUND: The anterior prefrontal cortex (PFC) exhibits activation during some cognitive tasks, including episodic memory, reasoning, attention, multitasking, task sets, decision making, mentalizing, and processing of self-referenced information. However, the medial part of anterior PFC is part of the default mode network (DMN), which shows deactivation during various goal-directed cognitive tasks compared to a resting baseline. One possible factor for this pattern is that activity in the anterior medial PFC (MPFC) is affected by dynamic allocation of attentional resources depending on task demands. We investigated this possibility using an event related fMRI with a face working memory task. METHODOLOGY/PRINCIPAL FINDINGS: Sixteen students participated in a single fMRI session. They were asked to form a task set to remember the faces (Face memory condition) or to ignore them (No face memory condition), then they were given 6 seconds of preparation period before the onset of the face stimuli. During this 6-second period, four single digits were presented one at a time at the center of the display, and participants were asked to add them and to remember the final answer. When participants formed a task set to remember faces, the anterior MPFC exhibited activation during a task preparation period but deactivation during a task execution period within a single trial. CONCLUSIONS/SIGNIFICANCE: The results suggest that the anterior MPFC plays a role in task set formation but is not involved in execution of the face working memory task. Therefore, when attentional resources are allocated to other brain regions during task execution, the anterior MPFC shows deactivation. The results suggest that activation and deactivation in the anterior MPFC are affected by dynamic allocation of processing resources across different phases of processing

Guidelines for management of ischaemic stroke and transient ischaemic attack 2008

This article represents the update of the European Stroke Initiative Recommendations for Stroke Management. These guidelines cover both ischaemic stroke and transient ischaemic attacks, which are now considered to be a single entity. The article covers referral and emergency management, Stroke Unit service, diagnostics, primary and secondary prevention, general stroke treatment, specific treatment including acute management, management of complications, and rehabilitation

Tyr702 is an important determinant of agonist binding and domain closure of the ligand-binding core of GluR2.

Ionotropic glutamate receptors mediate most rapid excitatory synaptic transmission in the mammalian central nervous system, and their involvement in neurological diseases has stimulated widespread interest in their structure and function. Despite a large number of agonists developed so far, few display selectivity among (S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionic acid (AMPA)-receptor subtypes. The present study provides X-ray structures of the glutamate receptor 2 (GluR2)-selective partial agonist (S)-2-amino-3-(1,3,5,6,7- pentahydro-2,4-dioxocyclopenta[e] pyrimidin-1-yl) propanoic acid [(S)-CPW399] in complex with the ligand-binding core of GluR2 (GluR2-S1S2J) and with a (Y702F)GluR2-S1S2J mutant. In addition, the structure of the nonselective partial agonist kainate in complex with (Y702F)GluR2-S1S2J was determined. The results show that the selectivity of (S)-CPW399 toward full-length GluR2 relative to GluR3 is reflected in the binding data on the two soluble constructs, allowing the use of (Y702F)GluR2-S1S2J as a model system for studying GluR2/GluR3 selectivity. Structural comparisons suggest that selectivity arises from disruption of a watermediated network between ligand and receptor. A D1-D2 domain closure occurs upon agonist binding. (S)-CPW399 and kainate induce greater domain closure in the Y702F mutant, indicating that these partial agonists here act in a manner more reminiscent of full agonists. Both kainate and (S)-CPW399 exhibited higher efficacy at (Y702F)GluR2(Q)i than at wild-type GluR2(Q)i. Whereas an excellent correlation exists between domain closure and efficacy of a range of agonists at full-length GluR2 determined by electrophysiology in Xenopus laevis oocytes, a direct correlation between agonist induced domain closure of (Y702F)GluR2-S1S2J and efficacy at the GluR3 receptor is not observed. Although it clearly controls selectivity, mutation of this residue alone is insufficient to explain agonist-induced conformational rearrangements occurring in this varian