Activities as diverse as migration, proliferation and patterning occur simultaneously and in a coordinated fashion during tissue morphogenesis. In the growing vasculature, the formation of motile, invasive and filopodia-carrying endothelial sprouts is balanced with the stabilisation of blood-transporting vessels. Here, we show that sprouting endothelial cells in the retina have high rates of VEGF uptake, VEGF receptor endocytosis and turnover. These internalisation processes are opposed by atypical protein kinase C activity in more stable and mature vessels. aPKC phosphorylates Dab2, a clathrin-associated sorting protein that, together with the transmembrane protein ephrin-B2 and the cell polarity regulator PAR-3, enables VEGF receptor endocytosis and downstream signal transduction. Accordingly, VEGF receptor internalisation and the angiogenic growth of vascular beds are defective in loss-of-function mice lacking key components of this regulatory pathway. Our work uncovers how vessel growth is dynamically controlled by local VEGFR endocytosis and the activity of cell polarity proteins.

Stroke-associated pneumonia is a frequent complication after stroke associated with poor outcome. Dysphagia is a known risk factor for stroke-associated pneumonia but accumulating evidence suggests that stroke induces an immunodepressive state increasing susceptibility for stroke-associated pneumonia. We aimed to confirm that stroke-induced immunodepression syndrome is associated with stroke-associated pneumonia independently from dysphagia by investigating the predictive properties of monocytic HLA-DR expression as a marker of immunodepression as well as biomarkers for inflammation (interleukin-6) and infection (lipopolysaccharide-binding protein). This was a prospective, multicenter study with 11 study sites in Germany and Spain, including 486 patients with acute ischemic stroke. Daily screening for stroke-associated pneumonia, dysphagia and biomarkers was performed. Frequency of stroke-associated pneumonia was 5.2%. Dysphagia and decreased monocytic HLA-DR were independent predictors for stroke-associated pneumonia in multivariable regression analysis. Proportion of pneumonia ranged between 0.9% in the higher monocytic HLA-DR quartile (≥21,876 mAb/cell) and 8.5% in the lower quartile (≤12,369 mAb/cell). In the presence of dysphagia, proportion of pneumonia increased to 5.9% and 18.8%, respectively. Patients without dysphagia and normal monocytic HLA-DR expression had no stroke-associated pneumonia risk. We demonstrate that dysphagia and stroke-induced immunodepression syndrome are independent risk factors for stroke-associated pneumonia. Screening for immunodepression and dysphagia might be useful for identifying patients at high risk for stroke-associated pneumonia.

; for the Berlin Stroke Register and the Stroke Register of Northwest Germany Background and Purpose-Poststroke pneumonia is a potentially preventable complication after stroke associated with poor outcome. We developed and externally validated a prognostic score for predicting risk of pneumonia after ischemic stroke. Methods-The prognostic score was developed based on clinical data routinely collected after admission from the Berlin Stroke Register, Germany. The association of demographics, comorbidities, and clinical characteristics with poststroke pneumonia was investigated using multivariable logistic regression analyses. Independent predictors of poststroke pneumonia were translated into a point scoring system based on the corresponding regression coefficients. The predictive properties of the developed prognostic score were externally validated using an independent data set from the Stroke Register Northwest-Germany. Results-Between 2007 and 2009, 15 335 patients with ischemic stroke were registered within the Berlin Stroke Register.The observed rate of pneumonia in hospital was 7.2%. A 10-point score was derived for prediction of poststroke pneumonia (Age Ն75 yearsϭ1, Atrial fibrillationϭ1, Dysphagiaϭ2, male Sexϭ1, stroke Severity, National Institutes of Health Stroke Scale 0 -4ϭ0, 5-15ϭ3, Ն16ϭ5; A 2 DS 2 ). The proportion of pneumonia varied between 0.3% in patients with a score of 0 point to 39.4% in patients with a score of 10 points. The score demonstrated excellent discrimination (C-statistic 0.84; 95% CI, 0.83-0.85) and calibration (McFadden R 2 ϭ0.21). Prediction, discrimination, and calibration properties were reproduced in the validation cohort consisting of 45 085 patients with ischemic stroke. Conclusions-The

ObjectivesEmerging evidence suggests that fatigue in myasthenia gravis (MG) is a relevant problem that negatively impacts activities of daily living (ADL). The relationship between fatigue and quality of life (QoL) has never been systematically explored in MG patients. The study aimed to assess the prevalence of fatigue and its relation to ADL and QoL as well as to identify factors associated with fatigue in MG.Material and MethodsThis was a cross‐sectional observational study in patients with confirmed diagnosis of MG independent of disease severity. Prevalence of fatigue was assessed using the Chalder Fatigue Scale (CFQ). Impact of fatigue on ADL and QoL was assessed by the MG activities of daily living profile (MG‐ADL) and the MG‐specific quality‐of‐life instrument (MG‐QoL), respectively. Association of fatigue with sociodemographics, clinical characteristics of MG, and comorbidities including mood and anxiety disorders as well as sleep disorders was investigated using multivariable logistic regression analyses.ResultsOverall, 200 MG patients were included. The observed rate of fatigue was 56.1%, of those 70.4% fulfilled the criteria of chronic fatigue (CF) with a duration of ≥6 months. Relevant fatigue was strongly associated to ADL and QoL. Factors associated with relevant fatigue were disease severity and depressive state. Furthermore, positive muscle‐specific tyrosine kinase (MuSK) antibody status showed a strong association with relevant fatigue.Conclusions MG patients have a high prevalence of fatigue which negatively impacts ADL and QoL. MG‐specific clinical characteristics are related to fatigue and might help to identify MG patients at risk for fatigue.