Adherence to secondary stroke prevention strategies - Results from the German stroke data bank

Only very limited data are available concerning patient adherence to antithrombotic medication intended to prevent a recurrent stroke. Reduced adherence and compliance could significantly influence the effects of any stroke prevention strategies. This study from a large stroke data bank provides representative data concerning the rate of stroke victims adhering to their recommended preventive medication. During a 2-year period beginning January 1, 1998, all patients with acute stroke or TIA in 23 neurological departments with an acute stroke unit were included in the German Stroke Data Bank. Data were collected prospectively, reviewed, validated and processed in a central data management unit. Only 12 centers with a follow-up rate of 80% or higher were included in this evaluation. 3,420 patients were followed up after 3 months, and 2,640 patients were followed up one year after their stroke. After one year, 96% of all patients reported still adhere to at least one medical stroke prevention strategy. Of the patients receiving aspirin at discharge, 92.6% reported to use that medication after 3 months and 84% after one year, while 81.6 and 61.6% were the respective figures for clopidogrel, and 85.2 and 77.4% for oral anticoagulation. Most patients who changed medication switched from aspirin to clopidogrel. Under the conditions of this observational study, adherence to stroke prevention strategies is excellent. The highest adherence rate is noticed for aspirin and oral anticoagulation. After one year, very few patients stopped taking stroke preventive medication. Copyright (C) 2003 S. Karger AG, Basel

Geostatistical interpretation of paleoceanographic data over large ocean basins - Reality and fiction

A promising approach to reconstruct oceanographic scenarios of past time slices is to drive numerical ocean circulation models with sea surface temperatures, salinities, and ice distributions derived from sediment core data. Set up properly, this combination of boundary conditions provided by the data and physical constraints represented by the model can yield physically consistent sets of three-dimensional water mass distribution and circulation patterns. This idea is not only promising but dangerous, too. Numerical models cannot be fed directly with data from single core locations distributed unevenly and, as it is the common case, scarcely in space. Conversely, most models require forcing data sets on a regular grid with no missing points, and some method of interpolation between punctual source data and model grid has to be employed. An ideal gridding scheme must retain as much of the information present in the sediment core data while generating as few artifacts in the interpolated field as possible. Based on a set of oxygen isotope ratios, we discuss several standard interpolation strategies, namely nearest neighbour schemes, bicubic splines, Delaunay triangulation, and ordinary and indicator kriging. We assess the gridded fields with regard to their physical consistence and their implications for the oceanic circulation

Utility of Lymphoblastoid Cell Lines for Induced Pluripotent Stem Cell Generation

A large number of EBV immortalized LCLs have been generated and maintained in genetic/epidemiological studies as a perpetual source of DNA and as a surrogate in vitro cell model. Recent successes in reprograming LCLs into iPSCs have paved the way for generating more relevant in vitro disease models using this existing bioresource. However, the overall reprogramming efficiency and success rate remain poor and very little is known about the mechanistic changes that take place at the transcriptome and cellular functional level during LCL-to-iPSC reprogramming. Here, we report a new optimized LCL-to-iPSC reprogramming protocol using episomal plasmids encoding pluripotency transcription factors and mouse p53DD (p53 carboxy-terminal dominant-negative fragment) and commercially available reprogramming media. We achieved a consistently high reprogramming efficiency and 100% success rate using this optimized protocol. Further, we investigated the transcriptional changes in mRNA and miRNA levels, using FC-abs ≥ 2.0 and FDR ≤ 0.05 cutoffs; 5,228 mRNAs and 77 miRNAs were differentially expressed during LCL-to-iPSC reprogramming. The functional enrichment analysis of the upregulated genes and activation of human pluripotency pathways in the reprogrammed iPSCs showed that the generated iPSCs possess transcriptional and functional profiles very similar to those of human ESCs

Highly efficient induced pluripotent stem cell reprogramming of cryopreserved lymphoblastoid cell lines

Tissue culture based in-vitro experimental modeling of human inherited disorders provides insight into the cellular and molecular mechanisms involved and the underlying genetic component influencing the disease phenotype. The breakthrough development of induced pluripotent stem cell (iPSC) technology represents a quantum leap in experimental modeling of human diseases, providing investigators with a self-renewing and thus unlimited source of pluripotent cells for targeted differentiation into functionally relevant disease specific tissue/cell types. The existing rich bio-resource of Epstein-Barr virus (EBV) immortalized lymphoblastoid cell line (LCL) repositories generated from a wide array of patients in genetic and epidemiological studies worldwide, many of them with extensive genotypic, genomic and phenotypic data already existing, provides a great opportunity to reprogram iPSCs from any of these LCL donors in the context of their own genetic identity for disease modeling and disease gene identification. However, due to the low reprogramming efficiency and poor success rate of LCL to iPSC reprogramming, these LCL resources remain severely underused for this purpose. Here, we detailed step-by-step instructions to perform our highly efficient LCL-to-iPSC reprogramming protocol using EBNA1/OriP episomal plasmids encoding pluripotency transcription factors (i.e., OCT3/4, SOX2, KLF4, L-MYC, and LIN28), mouse p53DD (p53 carboxy-terminal dominant-negative fragment) and commercially available reprogramming media. We achieved a consistently high reprogramming efficiency and 100% success rate (\u3e 200 reprogrammed iPSC lines) using this protocol