Abstract Background The prevalence of measles antibodies was investigated by an enzyme immunoassay (EIA) in students aged 14 every year since 1996 in a Swiss municipality. This region has wide ...measles vaccine coverage (first dose ≥95%, second dose ≥65%) without any reported measles outbreaks since 20 years. In 2003 and 2004, in contrast to previous years, surprisingly many negative results (33% and 54%, respectively) were observed. Objectives To corroborate the measles antibody values by different methods. Study design Serum samples from 101 students with known vaccination status were available. Sera with equivocal and negative results obtained by two different EIAs were retested by indirect immunofluorescence test (IFT) and plaque neutralisation test (PNT). Results Retesting by IFT showed a positive result in 17/21 sera (81%) and retesting by PNT indicated that 46/49 sera (94%) were positive; the three sera with negative PNT result were from unvaccinated individuals. Only 3/96 vaccinated students showed measles antibodies below the putative protective level of 0.2 IU/ml after retesting by PNT. Conclusions Negative EIA results should be interpreted with caution in a widely vaccinated population without booster by circulation of wild viruses. Retesting by IFT or PNT is recommended.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Competent nursing and effective leadership are essential attributes for the provision of high-quality care which is patient-centred, evidence-based and outcome-oriented. The Department of Clinical ...Nursing science (DCN) of the University Hospital Basel (USB) initiated and implemented programmes of targeted practice development to promote competence in nursing and leadership. With the aim of generating data on nursing and leadership competencies, as well as on the quality of nursing care and the nursing work environment, an evaluation study with a mixed-method design was implemented in 2007. Within the quantitative portion of the study 679 nurses and 27 nurse managers participated. The descriptive results showed that nurses rated their overall level of competence on the Nurse Competence Scale high with a mean score of 75.1 (VAS 0 - 100). The rating of leadership competencies of nurse managers on the Leadership Practice Inventory was in the upper third of the 10-point Likert scale with mean scores of 40 to 50 (6 - 60). In order to permit ongoing monitoring of practice development, follow-up evaluations at regularly scheduled intervals are planned. With the introduction of a reimbursement system on the basis of Diagnosis Related Groups into Swiss health care, effective monitoring of nursing service contextual factors is crucial, now and in the future.
Currently most liver fibrosis research is performed in vivo, since suitable alternative in vitro systems which are able to recapitulate the cellular events leading to liver fibrosis are lacking. Here ...we aimed at generating a system containing cells representing the three key players of liver fibrosis (hepatocyte, Kupffer cells and stellate cells) and assess their response to pro-fibrotic compounds such as TGF-β1, methotrexate (MTX) and thioacetamide (TAA).
Human cell lines representing hepatocytes (HepaRG), Kupffer cell (THP-1 macrophages) and stellate cells (hTERT-HSC) were co-cultured using the InSphero hanging drop technology to generate scaffold-free 3D microtissues, that were treated with pro-fibrotic compounds (TGF-β1, MTX, TAA) for up to 14 days. The response of the microtissues was evaluated by determining the expression of cytokines (TNF-α, TGF-β1 and IL6), the deposition and secretion of ECM proteins and induction of gene expression of fibrosis biomarkers (e.g. αSMA). Induction of Nrf2 and Keap1, as key player of defence mechanism, was also evaluated.
We could demonstrate that the multicellular 3D microtissue cultures could be maintained in a non-activated status, based on the low expression levels of activation markers. Macrophages were activated by stimulation with LPS and hTERT-HSC showed activation by TGF-β1. In addition, MTX and TAA elicited a fibrotic phenotype, as assessed by gene-expression and protein-deposition of ECM proteins such as collagens and fibronectin. An involvement of the antioxidant pathway upon stimulation with pro-fibrotic compounds was also observed.
Here, for the first time, we demonstrate the in vitro recapitulation of key molecular and cellular events leading to liver fibrosis: hepatocellular injury, antioxidant defence response, activation of Kupffer cells and activation of HSC leading to deposition of ECM.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Drug-induced liver injury (DILI) is the major cause for liver failure and post-marketing drug withdrawals. Due to species-specific differences in hepatocellular function, animal experiments to assess ...potential liabilities of drug candidates can predict hepatotoxicity in humans only to a certain extent. In addition to animal experimentation, primary hepatocytes from rat or human are widely used for pre-clinical safety assessment. However, as many toxic responses in vivo are mediated by a complex interplay among different cell types and often require chronic drug exposures, the predictive performance of hepatocytes is very limited. Here, we established and characterized human and rat in vitro three-dimensional (3D) liver co-culture systems containing primary parenchymal and non-parenchymal hepatic cells. Our data demonstrate that cells cultured on a 3D scaffold have a preserved composition of hepatocytes, stellate, Kupffer and endothelial cells and maintain liver function for up to 3months, as measured by the production of albumin, fibrinogen, transferrin and urea. Additionally, 3D liver co-cultures maintain cytochrome P450 inducibility, form bile canaliculi-like structures and respond to inflammatory stimuli. Upon incubation with selected hepatotoxicants including drugs which have been shown to induce idiosyncratic toxicity, we demonstrated that this model better detected in vivo drug-induced toxicity, including species-specific drug effects, when compared to monolayer hepatocyte cultures.
In conclusion, our results underline the importance of more complex and long lasting in vitro cell culture models that contain all liver cell types and allow repeated drug-treatments for detection of in vivo-relevant adverse drug effects.
► 3D liver co-cultures maintain liver specific functions for up to three months. ► Activities of Cytochrome P450s remain drug- inducible accross three months. ► 3D liver co-cultures recapitulate drug-induced liver toxicity observed in vivo. ► 3D liver co-cultures can detect species-specific drug toxicity observed in vivo. ► This in vitro model may improve assessment of human relevance of preclinical findings.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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