40 research outputs found
Digitales Bildkuratieren als Bereicherung des Museumsbesuchs
Das von der Deutschen Forschungsgemeinschaft (DFG) geförderte Forschungsprojekt Curating Digital Images: Ethnographic Perspectives on the Affordances of Digital Images in Museum and Heritage Contexts hat sich im Rahmen des Schwerpunktprogramms Das Digitale Bild mit diesen und anderen Fragen beschäftigt. Die Forscher:innen der Universität Tübingen und der Humboldt-Universität zu Berlin möchten mit dieser Handreichung einen Beitrag zur Debatte rund um digitale Bildtechnologien im Museums- und Kunstsektor leisten. Das Projekt umfasst zwei Arbeitsbereiche, die sich diesem Thema aus unterschiedlichen Richtungen annähern
Inflammatory bowel disease addressed by Caco-2 and monocyte-derived macrophages : an opportunity for an in vitro drug screening assay
Infammatory bowel disease (IBD) is a widespread disease, afecting a growing demographic. The treatment of chronic
infammation located in the GI-tract is dependent on the severity; therefore, the IBD treatment pyramid is commonly applied.
Animal experimentation plays a key role for novel IBD drug development; nevertheless, it is ethically questionable and
limited in its throughput. Reliable and valid in vitro assays ofer the opportunity to overcome these limitations.
We combined Caco-2 with monocyte-derived macrophages and exposed them to known drugs, targeting an in vitro-in vivo correlation (IVIVC) with a focus on the severity level and its related drug candidate. This co-culture assay addresses namely the
intestinal barrier and the immune response in IBD. The drug efcacy was analyzed by an LPS-infammation of the co-culture
and drug exposure according to the IBD treatment pyramid. Efcacy was defned as the range between LPS control (0%) and
untreated co-culture (100%) independent of the investigated read-out (TEER, Papp, cytokine release: IL-6, IL-8, IL-10, TNF-α).
The release of IL-6, IL-8, and TNF-α was identifed as an appropriate readout for a fast drug screening (“yes–no response”).
TEER showed a remarkable IVIVC correlation to the human treatment pyramid (5-ASA, Prednisolone, 6-mercaptopurine,
and infiximab) with an R2
of 0.68. Similar to the description of an adverse outcome pathway (AOP) framework, we advocate
establishing an “Efcacy Outcome Pathways (EOPs)” framework for drug efcacy assays. The in vitro assay ofers an easy
and scalable method for IBD drug screening with a focus on human data, which requires further validation
Oligodendroglia in cortical multiple sclerosis lesions decrease with disease progression, but regenerate after repeated experimental demyelination
Cerebral cortex shows a high endogenous propensity for remyelination. Yet, widespread subpial cortical demyelination (SCD) is a common feature in progressive multiple sclerosis (MS) and can already be found in early MS. In the present study, we compared oligodendroglial loss in SCD in early and chronic MS. Furthermore, we addressed in an experimental model whether repeated episodes of inflammatory SCD could alter oligodendroglial repopulation and subsequently lead to persistently demyelinated cortical lesions. NogoA+ mature oligodendrocytes and Olig2+ oligodendrocyte precursor cells were examined in SCD in patients with early and chronic MS, normal-appearing MS cortex, and control cortex as well as in the rat model of repeated targeted cortical experimental autoimmune encephalomyelitis (EAE). NogoA+ and Olig2+ cells were significantly reduced in SCD in patients with chronic, but not early MS. Repeated induction of SCD in rats resulted only in a transient loss of NogoA+, but not Olig2+ cells during the demyelination phase. This phase was followed by complete oligodendroglial repopulation and remyelination, even after four episodes of demyelination. Our data indicate efficient oligodendroglial repopulation in subpial cortical lesions in rats after repeated SCD that was similar to early, but not chronic MS cases. Accordingly, four cycles of experimental de- and remyelination were not sufficient to induce sustained remyelination failure as found in chronic cortical MS lesions. This suggests that alternative mechanisms contribute to oligodendrocyte depletion in chronic cortical demyelination in MS
Quality of Reporting and Study Design of CKD Cohort Studies Assessing Mortality in the Elderly Before and After STROBE:A Systematic Review
BACKGROUND:The STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement was published in October 2007 to improve quality of reporting of observational studies. The aim of this review was to assess the impact of the STROBE statement on observational study reporting and study design quality in the nephrology literature. STUDY DESIGN:Systematic literature review. SETTING & POPULATION:European and North American, Pre-dialysis Chronic Kidney Disease (CKD) cohort studies. SELECTION CRITERIA FOR STUDIES:Studies assessing the association between CKD and mortality in the elderly (>65 years) published from 1st January 2002 to 31st December 2013 were included, following systematic searching of MEDLINE & EMBASE. PREDICTOR:Time period before and after the publication of the STROBE statement. OUTCOME:Quality of study reporting using the STROBE statement and quality of study design using the Newcastle Ottawa Scale (NOS), Scottish Intercollegiate Guidelines Network (SIGN) and Critical Appraisal Skills Programme (CASP) tools. RESULTS:37 papers (11 Pre & 26 Post STROBE) were identified from 3621 potential articles. Only four of the 22 STROBE items and their sub-criteria (objectives reporting, choice of quantitative groups and description of and carrying out sensitivity analysis) showed improvements, with the majority of items showing little change between the period before and after publication of the STROBE statement. Pre- and post-period analysis revealed a Manuscript STROBE score increase (median score 77.8% (Inter-quartile range [IQR], 64.7-82.0) vs 83% (IQR, 78.4-84.9, p = 0.05). There was no change in quality of study design with identical median scores in the two periods for NOS (Manuscript NOS score 88.9), SIGN (Manuscript SIGN score 83.3) and CASP (Manuscript CASP score 91.7) tools. LIMITATIONS:Only 37 Studies from Europe and North America were included from one medical specialty. Assessment of study design largely reliant on good reporting. CONCLUSIONS:This study highlights continuing deficiencies in the reporting of STROBE items and their sub-criteria in cohort studies in nephrology. There was weak evidence of improvement in the overall reporting quality, with no improvement in methodological quality of CKD cohort studies between the period before and after publication of the STROBE statement
Methodology used in studies reporting chronic kidney disease prevalence: a systematic literature review
Background Many publications report the prevalence of chronic kidney disease (CKD) in the general population. Comparisons across studies are hampered as CKD prevalence estimations are influenced by study population characteristics and laboratory methods. Methods For this systematic review, two researchers independently searched PubMed, MEDLINE and EMBASE to identify all original research articles that were published between 1 January 2003 and 1 November 2014 reporting the prevalence of CKD in the European adult general population. Data on study methodology and reporting of CKD prevalence results were independently extracted by two researchers. Results We identified 82 eligible publications and included 48 publications of individual studies for the data extraction. There was considerable variation in population sample selection. The majority of studies did not report the sampling frame used, and the response ranged from 10 to 87%. With regard to the assessment of kidney function, 67% used a Jaffe assay, whereas 13% used the enzymatic assay for creatinine determination. Isotope dilution mass spectrometry calibration was used in 29%. The CKD-EPI (52%) and MDRD (75%) equations were most often used to estimate glomerular filtration rate (GFR). CKD was defined as estimated GFR (eGFR) <60 mL/min/1.73 m2 in 92% of studies. Urinary markers of CKD were assessed in 60% of the studies. CKD prevalence was reported by sex and age strata in 54 and 50% of the studies, respectively. In publications with a primary objective of reporting CKD prevalence, 39% reported a 95% confidence interval. Conclusions The findings from this systematic review showed considerable variation in methods for sampling the general population and assessment of kidney function across studies reporting CKD prevalence. These results are utilized to provide recommendations to help optimize both the design and the reporting of future CKD prevalence studies, which will enhance comparability of study result
Oligodendroglia in cortical multiple sclerosis lesions decrease with disease progression, but regenerate after repeated experimental demyelination
International differences in chronic kidney disease prevalence: a key public health and epidemiologic research issue
In this narrative review, we studied the association of risk factors for chronic kidney disease (CKD) and CKD prevalence at an ecological level and describe potential reasons for international differences in estimated CKD prevalence across European countries. We found substantial variation in risk factors for CKD such as in the prevalence of diabetes mellitus, obesity, raised blood pressure, physical inactivity, current smoking and salt intake per day. In general, the countries with a higher CKD prevalence also had a higher average score on CKD risk factors, and vice versa. There was no association between cardiovascular mortality rates and CKD prevalence. In countries with a high CKD prevalence, the prevention of noncommunicable diseases may be considered important, and, therefore, all five national response systems (e.g. an operational national policy, strategy or action plan to reduce physical inactivity and/or promote physical activity) have been implemented. Furthermore, both the heterogeneity in study methods to assess CKD prevalence as well as the international differences in the implementation of lifestyle measures will contribute to the observed variation in CKD prevalence. A robust public health approach to reduce risk factors in order to prevent CKD and reduce CKD progression risk is needed and will have co-benefits for other noncommunicable disease