Automated entire thrombus density measurements for robust and comprehensive thrombus characterization in patients with acute ischemic stroke

Background and Purpose: In acute ischemic stroke (AIS) management, CT-based thrombus density has been associated with treatment success. However, currently used thrombus measurements are prone to inter-observer variability and oversimplify the heterogeneous thrombus composition. Our aim was first to introduce an automated method to assess the entire thrombus density and then to compare the measured entire thrombus density with respect to current standard manual measurements. Materials and Method: In 135 AIS patients, the density distribution of the entire thrombus was determined. Density distributions were described usingmedians, interquartile ranges (IQR), kurtosis, and skewedness. Differences between themedian of entire thrombusmeasurements and commonly applied manualmeasurements using 3 regions of interest were determined using linear regression. Results: Density distributions varied considerably with medians ranging from 20.0 to 62.8 HU and IQRs ranging from 9.3 to 55.8 HU. The average median of the thrombus density distributions (43.5 ± 10.2 HU) was lower than the manual assessment (49.6 ± 8.0 HU) (p<0.05). The difference between manual measurements and median density of entire thrombus decreased with increasing density (r = 0.64; p<0.05), revealing relatively higher manual measurements for low density thrombi such that manual density measurement tend overestimates the real thrombus density. Conclusions: Automatic measurements of the full thrombus expose a wide variety of thrombi density distribution, which is not grasped with currently used manual measurement. Furthermore, d

Two-year clinical follow-up of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN): Design and statistical analysis plan of the extended follow-up study

Background: MR CLEAN was the first randomized trial to demonstrate the short-term clinical effectiveness of endovascular treatment in patients with acute ischemic stroke caused by large vessel occlusion in the anterior circulation. Several other trials confirmed that endovascular treatment improves clinical outcome at three months. However, limited data are available on long-term clinical outcome. We aimed to estimate the effect of endovascular treatment on functional outcome at two-year follow-up in patients with acute ischemic stroke. Secondly, we aimed to assess the effect of endovascular treatment on major vascular events and mortality during two years of follow-up. Methods: MR CLEAN is a multicenter clinical trial with randomized treatment allocation, open-label treatment, and blinded endpoint evaluation. Patients included were 18 years or older with acute ischemic stroke caused by a proven anterior proximal artery occlusion who could be treated within six hours after stroke onset. The intervention contrast was endovascular treatment and usual care versus no endovascular treatment and usual care. The current study extended the follow-up duration from three months to two years. The primary outcome is the score on the modified Rankin scale at two years. Secondary outcomes include all-cause mortality and the occurrence of major vascular events within two years of follow-up. Discussion: The results of our study provide information on the long-term clinical effectiveness of endovascular treatment, which may have implications for individual treatment decisions and estimates of cost-effectiveness. Trial registration:NTR1804. Registered on 7 May 2009; ISRCTN10888758. Registered on 24 July 2012 (main MR CLEAN trial); NTR5073. Registered on 26 February 2015 (extended follow-up study)

Phosphorylation target site specificity for AGC kinases DMPK E and Lats2.

Contains fulltext : 109053.pdf (publisher's version ) (Closed access)Serine/threonine kinases of the AGC group are important regulators of cell growth and motility. To examine the candidate substrate profile for two members of this group, DMPK E and Lats2, we performed in vitro kinase assays on peptide arrays. Substrate peptides for both kinases exhibited a predominance of basic residues surrounding the phosphorylation target site. 3D homology modeling of the kinase domains of DMPK E and Lats2 indicated that presence of two negative pockets in the peptide binding groove provides an explanation for the substrate preference. These findings will aid future research toward signaling functions of Lats2 and DMPK E within cells.1 juni 201

Gene duplication and conversion events shaped three homologous, differentially expressed myosin regulatory light chain (MLC2) genes.

Myosin II is a hexameric protein complex consisting of two myosin heavy chains, two myosin essential light chains and two myosin regulatory light chains. Multiple subunit isoforms exist, allowing great diversity in myosin II composition which likely impacts on its contractile properties. Little is known about the evolutionary origin, expression pattern and function of myosin regulatory light chain (MLC2) isoforms. We analysed the evolutionary relationship between smooth muscle (sm), nonmuscle (nm) and nonmuscle-like (nml) MLC2 genes, which encode three homologous proteins expressed in nonmuscle cells. The three genes arose by successive gene duplication events. The high sequence similarity between the tandemly arranged nm- and nml-MLC2 genes is best explained by gene conversion. Urea/glycerol-polyacrylamide gel electrophoresis and RNA analysis were employed to monitor expression of sm-, nm- and nml-MLC2 in human and mouse cell lines. Conspicuous differences between transformed and non-transformed cells were observed, with sm-MLC2 being suppressed in Ras-transformed cells. Our findings shed light on the evolutionary history of three homologous MLC2 proteins and point to isoform-specific cell growth-related roles in nonmuscle cell myosin II contractility

Superior Two-year Results of Externally Unsupported Polyester Compared to Supported Grafts in Above-knee Bypass Grafting:A Multicenter Randomised Trial

<p>Objectives: The aim of this study was to compare externally supported thin wall knitted polyester (P-EXS) and externally unsupported thin wall knitted polyester (P-non-EXS) for above-knee (AK) femoro-popliteal bypass grafting.</p><p>Design: A prospective multicenter randomised clinical trial.</p><p>Material and methods: Between 1999 and 2008, 265 AK femoro-popliteal bypass grafts (6 mm in diameter) were performed, including 136 P-EXS and 129 P-non-EXS. The selection of patients was based on the presence of disabling claudication or critical ischaemia. Follow-up took place at 3, 6, 12, 18, and 24 months and included clinical examination and duplex ultrasonography. The main end points of this study were primary patency rates at one and two years. Secondary end points were mortality, and primary assisted and secondary patency rates. Cumulative patency rates were calculated with life-table analysis and log-rank testing.</p><p>Results: The 1-year primary, primary assisted and secondary patency rates were 65%, 70% and 84%, respectively, for P-EXS and 76% (p = 0.05), 82% (p = 0.03) and 88% (p = 0.35), respectively, for P-non-EXS. Two-year primary, primary assisted and secondary patency rates were 45%, 57% and 70%, respectively, for P-EXS and 62% (p = 0.003), 75% (p = 0.005) and 84% (p = 0.02), respectively, for P-non-EXS. The overall mortality rate after two years was 11.3%.</p><p>Conclusion: In above-knee femoro-popliteal bypass grafting patency rates of externally supported knitted polyester grafts were inferior to their unsupported counterpart. ISRCTN: At the time this study started this number was not the standard. (C) 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.</p>

Endoderme com atividade meristem\ue1tica em raiz de Canna edulis Kerr-Gawler (Cannaceae)

Canna edulis é uma planta ornamental utilizada em muitos países como fonte alimentar alternativa. O objetivo deste trabalho foi descrever a formação do córtex radicular a partir da análise anatômica da região apical. Na região situada a 220µm do pró-meristema, os tecidos meristemáticos apicais já se apresentam organizados em protoderme, meristema fundamental e procâmbio. Em fase subseqüente na diferenciação celular, a 450µm do pró-meristema, as camadas de células do córtex estão dispostas em fileiras radiais iniciando-se na endoderme. Depois que as iniciais endodérmicas cessam as divisões, adquirem estrias de Caspary. Na raiz, a 1.700µm do pró-meristema, os tecidos primários já se encontram diferenciados, sendo o padrão de distribuição celular observado no córtex de C. edulis característico ao apresentado por outras espécies de Zingiberales. A análise anatômica da região apical levou à constatação que 2/3 do córtex é resultante da atividade meristemática da endoderme e o restante das células corticais são originadas diretamente do meristema fundamental