942 resultados para Rothschild, Hannah Luise vonRothschild, Hannah Luise vonHannah LuiseRothschildvon


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Vorbesitzer: Freiherrlich Carl von Rothschild'sche Bibliothek Frankfurt am Main; Akzessionsnummer: x18722; Bemerkung: Maße ohne Passepartout

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BACKGROUND The aim of this study was to analyze the influence of the location of middle cerebral artery (MCA) occlusion on recanalization, complications and outcome after endovascular therapy. METHODS Four-hundred sixty-four patients with acute MCA occlusions were treated with endovascular therapy. RESULTS Two-hundred ninety-three patients had M1 occlusions, 116 had M2, and 55 had M3/4 occlusions. Partial or complete recanalization was more frequently achieved in M1 (76.8%) than in M2 (59.1%) or M3/4 (47.3%, p < 0.001) occlusions, but favorable outcome (modified Rankin Scale 0-2) was less frequent in M1 (50.9%) than M2 (63.7%) or M3/4 (72.7%, p = 0.018) occlusions. Symptomatic intracerebral hemorrhage (ICH) did not differ between occlusion sites, but asymptomatic ICH was more common in M1 (22.6%) than in M2 occlusions (8.6%, p = 0.003). Recanalization was associated with favorable outcome in M1 (p < 0.001) and proximal M2 (p = 0.003) but not in distal M2 or M3/4 occlusions. CONCLUSIONS Recanalization with endovascular therapy was more frequently achieved in patients with proximal than distal MCA occlusions, but recanalization was associated with favorable outcome only in M1 and proximal M2 occlusions. Outcome was better with distal than proximal occlusions. This study shows that recanalization can be used as a surrogate marker for clinical outcome only in patients with proximal occlusions.

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A series of N6-bicyclic and N6-(2-hydroxy)cyclopentyl derivatives of adenosine were synthesized as novel A1R agonists and their A1R/A2R selectivity assessed using a simple yeast screening platform. We observed that the most selective, high potency ligands were achieved through N6-adamantyl substitution in combination with 5′-N-ethylcarboxamido or 5′-hydroxymethyl groups. In addition, we determined that 5′-(2-fluoro)thiophenyl derivatives all failed to generate a signaling response despite showing an interaction with the A1R. Some selected compounds were also tested on A1R and A3R in mammalian cells revealing that four of them are entirely A1R-selective agonists. By using in silico homology modeling and ligand docking, we provide insight into their mechanisms of recognition and activation of the A1R. We believe that given the broad tissue distribution, but contrasting signaling profiles, of adenosine receptor subtypes, these compounds might have therapeutic potential.

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Prospektive 1-Jahres-Follow-up-Untersuchung in der kombinierte multidimensionale Früherkennung und alters- und fachübergreifende integrierte Versorgung (Interventionsbedingung, n = 120) mit einer Standardbehandlung (historische Kontrollgruppe, n = 105) bei Jugendlichen und jungen Erwachsenen in der frühen Phase einer psychotischen Störung verglichen wird. Daten bei Aufnahme in die Studie weisen auf eine hohe Komplexität und Schwere der Erkrankung hin. Primäres Zielkriterium ist die Rate einer 6-monatigen kombiniert symptomatischen und funktionalen Remission zum Studienendpunkt.

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Skepticism toward climate change has a long tradition in the United States. We focus on mass media as the conveyors of the image of climate change and ask: Is climate change skepticism still a characteristic of US print media coverage? If so, to what degree and in what form? And which factors might pave the way for skeptics entering mass media debates? We conducted a quantitative content analysis of US print media during one year (1 June 2012 to 31 May 2013). Our results show that the debate has changed: fundamental forms of climate change skepticism (such as denial of anthropogenic causes) have been abandoned in the coverage, being replaced by more subtle forms (such as the goal to avoid binding regulations). We find no evidence for the norm of journalistic balance, nor do our data support the idea that it is the conservative press that boosts skepticism.

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RATIONALE Platelets are known to play a crucial role in hemostasis. Sphingosine kinases (Sphk) 1 and 2 catalyze the conversion of sphingosine to the bioactive metabolite sphingosine 1-phosphate (S1P). Although platelets are able to secrete S1P on activation, little is known about a potential intrinsic effect of S1P on platelet function. OBJECTIVE To investigate the role of Sphk1- and Sphk2-derived S1P in the regulation of platelet function. METHODS AND RESULTS We found a 100-fold reduction in intracellular S1P levels in platelets derived from Sphk2(-/-) mutants compared with Sphk1(-/-) or wild-type mice, as analyzed by mass spectrometry. Sphk2(-/-) platelets also failed to secrete S1P on stimulation. Blood from Sphk2-deficient mice showed decreased aggregation after protease-activated receptor 4-peptide and adenosine diphosphate stimulation in vitro, as assessed by whole blood impedance aggregometry. We revealed that S1P controls platelet aggregation via the sphingosine 1-phosphate receptor 1 through modulation of protease-activated receptor 4-peptide and adenosine diphosphate-induced platelet activation. Finally, we show by intravital microscopy that defective platelet aggregation in Sphk2-deficient mice translates into reduced arterial thrombus stability in vivo. CONCLUSIONS We demonstrate that Sphk2 is the major Sphk isoform responsible for the generation of S1P in platelets and plays a pivotal intrinsic role in the control of platelet activation. Correspondingly, Sphk2-deficient mice are protected from arterial thrombosis after vascular injury, but have normal bleeding times. Targeting this pathway could therefore present a new therapeutic strategy to prevent thrombosis.