Inherited cavernous malformations of the central nervous system: clinical and genetic features in 19 Swiss families

Cavernous malformations (CCMs) are benign, well-circumscribed, and mulberry-like vascular malformations that may be found in the central nervous system in up to 0.5% of the population. Cavernous malformations can be sporadic or inherited. The common symptoms are epilepsy, hemorrhages, focal neurological deficits, and headaches. However, CCMs are often asymptomatic. The familiar form is associated with three gene loci, namely 7q21-q22 (CCM1), 7p13-p15 (CCM2), and 3q25.2-q27 (CCM3) and is inherited as an autosomal dominant trait with incomplete penetrance. The CCM genes are identified as Krit 1 (CCM1), MGC4607 (CCM2), and PDCD10 (CCM3). Here, we present the clinical and genetic features of CCMs in 19 Swiss families. Furthermore, surgical aspects in such families are also discusse

Diffusion-weighted MRI in acute spinal cord ischaemia

Abstract : Acute spinal cord ischaemia is often undetectable with conventional MRI. Diffusion-weighted MRI (DWI) has been difficult to use in the spine because of susceptibility artefacts. We assessed the diagnostic value of echoplanar DWI for early confirmation of spinal cord ischaemia. We performed conventional MRI and DWI in two men and three women, aged 54-75years with clinically suspected acute spinal cord ischaemia. Imaging was performed 9-46h after the onset of symptoms, and 2-9days later to assess the extent of ischaemic signal change. Spatial resolution of DWI within the spine using standard equipment was poor, but in all patients, early DWI revealed areas of high signal indicating decreased diffusion, confirmed by measurement of apparent diffusion coefficients. Follow-up MRI showed high signal on T2-weighted images and contrast enhancement at the expected levels. Neurological deficits corresponded with radiological findings in four patients: various syndromes, including isolated bilateral weakness or sensory change and combined deficits, were found. Echoplanar DWI may be helpful for confirmation of spinal cord ischaemia in the acute stage, but follow-up T2-weighted images have superior spatial resolution and correlation with clinical findings and lesion exten

Structural dissection of a complex Bacteroides ovatus gene locus conferring xyloglucan metabolism in the human gut

The human gastrointestinal tract harbours myriad bacterial species, collectively termed the microbiota, that strongly influence human health. Symbiotic members of our microbiota play a pivotal role in the digestion of complex carbohydrates that are otherwise recalcitrant to assimilation. Indeed, the intrinsic human polysaccharide-degrading enzyme repertoire is limited to various starch-based substrates; more complex polysaccharides demand microbial degradation. Select Bacteroidetes are responsible for the degradation of the ubiquitous vegetable xyloglucans (XyGs), through the concerted action of cohorts of enzymes and glycan-binding proteins encoded by specific xyloglucan utilization loci (XyGULs). Extending recent (meta) genomic, transcriptomic and biochemical analyses, significant questions remain regarding the structural biology of the molecular machinery required for XyG saccharification. Here, we reveal the three-dimensional structures of an α-xylosidase, a β-glucosidase, and two α-L-arabinofuranosidases from the Bacteroides ovatus XyGUL. Aided by bespoke ligand synthesis, our analyses highlight key adaptations in these enzymes that confer individual specificity for xyloglucan side chains and dictate concerted, stepwise disassembly of xyloglucan oligosaccharides. In harness with our recent structural characterization of the vanguard endo-xyloglucanse and cell-surface glycan-binding proteins, the present analysis provides a near-complete structural view of xyloglucan recognition and catalysis by XyGUL proteins

Electron transport in nanostructures: a key to high temperature superconductivity

Nanostructured GaAs Schottky barrier diodes are used as low noise THz heterodyne detectors. Different diodes show that the electron transport is ballistic and given by an optimized depletion thickness Depl which is shorter than the mean free path length. The best THz mixer noise temperature is achieved when the depletion thickness is twice the doping distance in GaAs with Depl=2x. There also is a linear relation between the depletion thickness and the carrier mobility μ by (2x)**2≈h/(2e)μ. Since the mobility is proportional to 1/energy and because of many similarities when comparing with properties of high temperature superconductors (HTSC) it has been investigated if the doping distance x in HTSCs is connected with 1/(kTc). It turns out that there is also a strong correlation between x and the critical transition temperature Tc given by (2x)**2 similar1/Tc. A detailed analysis and comparison suggest that the correlation equation for HTSCs is linked to the transition temperature Tc, the density of states in a 1D quantum wire, the lowest energy E1 in a 1D quantum well, and to the Fermi energy

Clinical and radiological predictors of recanalisation and outcome of 40 patients with acute basilar artery occlusion treated with intra-arterial thrombolysis

Objective: To define predictors of recanalisation and clinical outcome of patients with acute basilar artery occlusions treated with local intra-arterial thrombolysis (IAT). Methods: Vascular risk factors, severity of the neurological deficit graded by the National Institutes of Health stroke scale (NIHSS), and radiological findings were recorded at presentation. Outcome was measured using the modified Rankin scale (mRS) three months later and categorised as favourable (mRS 0–2), poor (mRS 3–5), or death (mRS 6). Results: 40 patients were studied. Median NIHSS on admission was 18. Mean time from symptom onset to treatment was 5.5 hours (range 2.3 to 11). Outcome was favourable in 14 patients (35%) and poor in nine (23%); 17 (42%) died. There were two symptomatic cerebral haemorrhages (5%). Recanalisation of the basilar artery was achieved in 32 patients (80%); it was complete (TIMI grade 3) in 20% and partial (TIMI grade 2) in 60%. In multivariate logistic regression analysis, low NIHSS score on admission (p = 0.002) and vessel recanalisation (p = 0.005) were independent predictors of favourable outcome. Recanalisation occurred more often with treatment within six hours of symptom onset (p = 0.003) and when admission computed tomography showed a hyperdense basilar artery sign (p = 0.007). In a univariate model, quadriplegia (p = 0.002) and coma (p = 0.004) were associated with a poor outcome or death. Conclusions: Low baseline NIHSS on admission and recanalisation of basilar artery occlusions predict a favourable outcome after intra-arterial thrombolysis. Early initiation of IAT and the presence of a hyperdense basilar artery sign on CT were associated with a higher likelihood of recanalisation

Inherited cavernous malformations of the central nervous system: clinical and genetic features in 19 Swiss families

Cavernous malformations (CCMs) are benign, well-circumscribed, and mulberry-like vascular malformations that may be found in the central nervous system in up to 0.5% of the population. Cavernous malformations can be sporadic or inherited. The common symptoms are epilepsy, hemorrhages, focal neurological deficits, and headaches. However, CCMs are often asymptomatic. The familiar form is associated with three gene loci, namely 7q21-q22 (CCM1), 7p13-p15 (CCM2), and 3q25.2-q27 (CCM3) and is inherited as an autosomal dominant trait with incomplete penetrance. The CCM genes are identified as Krit 1 (CCM1), MGC4607 (CCM2), and PDCD10 (CCM3). Here, we present the clinical and genetic features of CCMs in 19 Swiss families. Furthermore, surgical aspects in such families are also discussed