D-Dimers Predict Stroke Subtype when Assessed Early

Early classification of ischemic stroke subtype is important for secondary stroke prevention and may guide further investigations.

Coagulation factor XIII activation peptide and subunit levels in patients with acute ischaemic stroke: a pilot study

We have recently shown that FXIII activation peptide (AP-FXIII) can be measured in plasma. The objective of this pilot study was to investigate for the first time if AP-FXIII can be detected in plasma from patients with acute ischaemic stroke.

Posterior versus anterior circulation strokes: comparison of clinical, radiological and outcome characteristics

Physicians treating patients with posterior circulation strokes (PCS) tended to debate more on whether or not to introduce anticoagulation rather than performing investigations to identify stroke aetiology, as in patients with anterior circulation strokes (ACS). Recent findings suggest that stroke aetiologies of PCS and ACS are more alike than dissimilar, suggesting that PCS deserve the same investigations as ACS. The characteristics and current diagnostic evaluation between patients with PCS and ACS were compared.

Sensitive and selective detection of free FXIII activation peptide: a potential marker of acute thrombotic events

Coagulation factor XIII (FXIII) stabilizes fibrin fibers and is therefore a major player in the maintenance of hemostasis. FXIII is activated by thrombin resulting in cleavage and release of the FXIII activation peptide (AP-FXIII). The objective of this study was to characterize the released AP-FXIII and determine specific features that may be used for its specific detection. We analyzed the structure of bound AP-FXIII within the FXIII A-subunit and interactions of AP-FXIII by hydrogen bonds with both FXIII A-subunit monomers. We optimized our previously developed AP-FXIII ELISA by using 2 monoclonal antibodies. We determined high binding affinities between the antibodies and free AP-FXIII and demonstrated specific binding by epitope mapping analyses with surface plasmon resonance and enzyme-linked immunosorbent assay. Because the structure of free AP-FXIII had been characterized so far by molecular modeling only, we performed structural analysis by nuclear magnetic resonance. Recombinant AP-FXIII was largely flexible both in plasma and water, differing significantly from the rigid structure in the bound state. We suggest that the recognized epitope is either occluded in the noncleaved form or possesses a structure that does not allow binding to the antibodies. On the basis of our findings, we propose AP-FXIII as a possible new marker for acute thrombotic events.

Mutations affecting disulphide bonds contribute to a fairly common prevalence of F13B gene defects: results of a genetic study in 14 families with factor XIII B deficiency

Severe factor XIII (FXIII) deficiency is a rare autosomal recessive coagulation disorder affecting one in two million individuals. The aim of the present study was to screen for and analyse F13B gene defects in the German population. A total of 150 patients presenting with suspected FXIII deficiency and one patient with severe (homozygous) FXIII deficiency were screened for mutations in F13A and F13B genes. Twenty-five individuals presented with detectable heterozygous mutations, 12 of them in the F13A gene and 13 of them in the F13B gene. We report on the genotype-phenotype correlations of the individuals showing defects in the F13B gene. Direct sequencing revealed 12 unique mutations including seven missense mutations (Cys5Arg, Ile81Asn, Leu116Phe, Val217Ile, Cys316Phe, Val401Glu, Pro428Ser), two splice site mutations (IVS2-1G>C, IVS3-1G>C), two insertions (c.1155_1158dupACTT, c.1959insT) and one in-frame deletion (c.471-473delATT). Two of the missense mutations (Cys5Arg, Cys316Phe) eliminated disulphide bonds (Cys5-Cys56, Cys316-Cys358). Another three missense mutations, (Leu116Phe, Val401Glu, Pro428Ser) were located proximal to other cysteine disulphide bonds, therefore indicating that the region in and around these disulphide bonds is prone to functionally relevant mutations in the FXIII-B subunit. The present study reports on a fairly common prevalence of F13B gene defects in the German population. The regions in and around the cysteine disulphide bonds in the FXIII-B protein may be regions prone to frequent mutations.

Identification of eight novel coagulation factor XIII subunit A mutations: implied consequences for structure and function

Severe hereditary coagulation factor XIII deficiency is a rare homozygous bleeding disorder affecting one person in every two million individuals. In contrast, heterozygous factor XIII deficiency is more common, but usually not associated with severe hemorrhage such as intracranial bleeding or hemarthrosis. In most cases, the disease is caused by F13A gene mutations. Causative mutations associated with the F13B gene are rarer.

Stimulus predictability reduces responses in primary visual cortex

In this functional magnetic resonance imaging study we tested whether the predictability of stimuli affects responses in primary visual cortex (V1). The results of this study indicate that visual stimuli evoke smaller responses in V1 when their onset or motion direction can be predicted from the dynamics of surrounding illusory motion. We conclude from this finding that the human brain anticipates forthcoming sensory input that allows predictable visual stimuli to be processed with less neural activation at early stages of cortical processing.

Neuroelectromagnetic correlates of perceptual closure processes

Perceptual closure refers to the coherent perception of an object under circumstances when the visual information is incomplete. Although the perceptual closure index observed in electroencephalography reflects that an object has been recognized, the full spatiotemporal dynamics of cortical source activity underlying perceptual closure processing remain unknown so far. To address this question, we recorded magnetoencephalographic activity in 15 subjects (11 females) during a visual closure task and performed beamforming over a sequence of successive short time windows to localize high-frequency gamma-band activity (60–100 Hz). Two-tone images of human faces (Mooney faces) were used to examine perceptual closure. Event-related fields exhibited a magnetic closure index between 250 and 325 ms. Time-frequency analyses revealed sustained high-frequency gamma-band activity associated with the processing of Mooney stimuli; closure-related gamma-band activity was observed between 200 and 300 ms over occipitotemporal channels. Time-resolved source reconstruction revealed an early (0–200 ms) coactivation of caudal inferior temporal gyrus (cITG) and regions in posterior parietal cortex (PPC). At the time of perceptual closure (200–400 ms), the activation in cITG extended to the fusiform gyrus, if a face was perceived. Our data provide the first electrophysiological evidence that perceptual closure for Mooney faces starts with an interaction between areas related to processing of three-dimensional structure from shading cues (cITG) and areas associated with the activation of long-term memory templates (PPC). Later, at the moment of perceptual closure, inferior temporal cortex areas specialized for the perceived object are activated, i.e., the fusiform gyrus related to face processing for Mooney stimuli.

Imagery of a moving object: the role of occipital cortex and human MT/V5+

Visual imagery – similar to visual perception – activates feature-specific and category-specific visual areas. This is frequently observed in experiments where the instruction is to imagine stimuli that have been shown immediately before the imagery task. Hence, feature-specific activation could be related to the short-term memory retrieval of previously presented sensory information. Here, we investigated mental imagery of stimuli that subjects had not seen before, eliminating the effects of short-term memory. We recorded brain activation using fMRI while subjects performed a behaviourally controlled guided imagery task in predefined retinotopic coordinates to optimize sensitivity in early visual areas. Whole brain analyses revealed activation in a parieto-frontal network and lateral–occipital cortex. Region of interest (ROI) based analyses showed activation in left hMT/V5+. Granger causality mapping taking left hMT/V5+ as source revealed an imagery-specific directed influence from the left inferior parietal lobule (IPL). Interestingly, we observed a negative BOLD response in V1–3 during imagery, modulated by the retinotopic location of the imagined motion trace. Our results indicate that rule-based motion imagery can activate higher-order visual areas involved in motion perception, with a role for top-down directed influences originating in IPL. Lower-order visual areas (V1, V2 and V3) were down-regulated during this type of imagery, possibly reflecting inhibition to avoid visual input from interfering with the imagery construction. This suggests that the activation in early visual areas observed in previous studies might be related to short- or long-term memory retrieval of specific sensory experiences.

Low-dose recombinant factor VIIa for massive bleeding: A single centre observational cohort study with 73 patients

recombinant activated factor VII (rFVIIa) is used off-label for massive bleeding. There is no convincing evidence of the benefits of this practice and the minimal effective dose is unknown. The aim of the study was to evaluate our in-house guideline recommending a low dose of 60 μg/kg for off-label use of rFVIIa.

Intra-Arterial Thrombolysis for Acute Ischemic Stroke in Octogenarians

It is unclear whether octogenarians benefit from intra-arterial thrombolysis (IAT) for the treatment of acute ischemic stroke (AIS). The aim of the present study was to compare baseline characteristics, clinical outcome and complications of patients aged ≥80 with those of patients aged <80 years.

Mountains and Climate Change: A Global Concern

Editor's note: The text of this article originally appeared as the final chapter of a brochure entitled Mountains and Climate Change—From Understanding to Action, prepared at the Centre for Development and Environment, University of Bern, Switzerland, for presentation by the Swiss Agency for Development and Cooperation (SDC) at a side event at the United Nations Climate Change Conference in Copenhagen on 12 December 2009. Chapters of the brochure deal with various aspects of climate change and its impact in mountain regions. In light of the significance of the Copenhagen COP 15 conference, the editors of this publication believe MRD's readers will be interested in reading this summary written from the perspective of Swiss researchers and development experts. The full brochure may be viewed and downloaded at www.cde.unibe.ch/Research/MA_Re.asp