Spatial Organization of Functional Groups on Bioactive Supramolecular Glycopeptide Nanofibers for Differentiation of Mesenchymal Stem Cells (MSCs) to Brown Adipogenesis

Spatial organization of bioactive moieties in biological materials has significant impact on the function and efficiency of these systems. Here, we demonstrate the effect of spatial organization of functional groups including carboxylate, amine, and glucose functionalities by using self-assembled peptide amphiphile (PA) nanofibers as a bioactive scaffold. We show that presentation of bioactive groups on glycopeptide nanofibers affects mesenchymal stem cells (MSCs) in a distinct manner by means of adhesion, proliferation, and differentiation. Strikingly, when the glutamic acid is present in the glycopeptide backbone, the PA nanofibers specifically induced differentiation of MSCs into brown adipocytes in the absence of any differentiation medium as shown by lipid droplet accumulation and adipogenic gene marker expression analyses. This effect was not evident in the other glycopeptide nanofibers, which displayed the same functional groups but with different spatial organization. Brown adipocytes are attractive targets for obesity treatment and are found in trace amounts in adults, which also makes this specific glycopeptide nanofiber system an attractive tool to study molecular pathways of brown adipocyte formation. © 2016 American Chemical Society

Practice patterns and outcomes after stroke across countries at different economic levels (INTERSTROKE):an international observational study

Background: Stroke disproportionately affects people in low-income and middle-income countries. Although improvements in stroke care and outcomes have been reported in high-income countries, little is known about practice and outcomes in low and middle-income countries. We aimed to compare patterns of care available and their association with patient outcomes across countries at different economic levels. Methods: We studied the patterns and effect of practice variations (ie, treatments used and access to services) among participants in the INTERSTROKE study, an international observational study that enrolled 13 447 stroke patients from 142 clinical sites in 32 countries between Jan 11, 2007, and Aug 8, 2015. We supplemented patient data with a questionnaire about health-care and stroke service facilities at all participating hospitals. Using univariate and multivariate regression analyses to account for patient casemix and service clustering, we estimated the association between services available, treatments given, and patient outcomes (death or dependency) at 1 month. Findings: We obtained full information for 12 342 (92%) of 13 447 INTERSTROKE patients, from 108 hospitals in 28 countries; 2576 from 38 hospitals in ten high-income countries and 9766 from 70 hospitals in 18 low and middle-income countries. Patients in low-income and middle-income countries more often had severe strokes, intracerebral haemorrhage, poorer access to services, and used fewer investigations and treatments (p<0·0001) than those in high-income countries, although only differences in patient characteristics explained the poorer clinical outcomes in low and middle-income countries. However across all countries, irrespective of economic level, access to a stroke unit was associated with improved use of investigations and treatments, access to other rehabilitation services, and improved survival without severe dependency (odds ratio [OR] 1·29; 95% CI 1·14–1·44; all p<0·0001), which was independent of patient casemix characteristics and other measures of care. Use of acute antiplatelet treatment was associated with improved survival (1·39; 1·12–1·72) irrespective of other patient and service characteristics. Interpretation: Evidence-based treatments, diagnostics, and stroke units were less commonly available or used in low and middle-income countries. Access to stroke units and appropriate use of antiplatelet treatment were associated with improved recovery. Improved care and facilities in low-income and middle-income countries are essential to improve outcomes