No abstract

There is growing concern that nanoparticles (NPs) may accelerate amyloid protein aggregation and thus cause amyloid-related diseases. Here, the potential of silver and gold NPs is explored (diameter 20 nm) on the aggregation of the amyloid peptide sequences NNFGAIL from human islet amyloid polypeptide and the yeast prion protein sequence GNNQQNY, which are both the sequences of the full systems, which are able to aggregate into characteristic amyloid cross-beta sheet fi brillar structures. Here, it is shown that silver and gold NPs in physiological aqueous solution at ambient temperatures accelerate the aggregation kinetics of both peptides signifi cantly (in vitro). Scanning electron microscopy and X-ray diffraction provide solid evidence for a "structure-making" effect of the NPs. In particular, we are able to image the initial peptide corona and measure its structural reorganization in timeresolved kinetic experiments. After a conversion time Δ t , the coated NPs appear to act as templates or seeds for rapid fi brillation. Interestingly, crossfi brillation experiments with different peptide-coated NPs (pcNPs) reveal that they can effi ciently induce aggregation of similar peptides once the pcNPs are structurally converted. It is discussed that these structurally converted pcNPs may display similar kinetic features as toxic and aggregation inducing oligomers/protofi brils in normal amyloid aggregation, without being transient and very low-concentration species. Finally, we suggest and discuss a simple mechanistic picture with the biomolecule corona of NPs being central to the function of the coated NPs in amyloid fi brillation.

AimsThe rapidly increasing number of patients with implantable cardioverter-defibrillators (ICD) places a large burden on follow-up providers. This study investigated the possibility of longer in-office follow-up intervals in primary prevention ICD patients under remote monitoring with automatic daily data transmissions from the implant memory.Methods and resultsConducted in 155 ICD recipients with MADIT II indications, the study compared the burden of scheduled and unscheduled ICD follow-up visits, quality of life (SF-36), and clinical outcomes in patients randomized to either 3- or 12-month follow-up intervals in the period between 3 and 27 months after implantation. Remote monitoring (Biotronik Home Monitoring) was used equally in all patients. In contrast to previous clinical studies, no calendar-based remote data checks were performed between scheduled in-office visits. Compared with the 3-month follow-up interval, the 12-month interval resulted in a minor increase in the number of unscheduled follow-ups (0.64 vs. 0.27 per patient-year; P = 0.03) and in a major reduction in the total number of in-office ICD follow-ups (1.60 vs. 3.85 per patient-year; P < 0.001). No significant difference was found in mortality, hospitalization rate, or hospitalization length during the 2-year observation period, but more patients were lost to follow-up in the 12-month group (10 vs. 3; P = 0.04). The SF-36 scores favoured the 12-month intervals in the domains ‘social functioning’ and ‘mental health’.ConclusionIn prophylactic ICD recipients under automatic daily remote monitoring, the extension of the 3-month in-office follow-up interval to 12 months appeared to safely reduce the ICD follow-up burden during 27 months after implantation.ClinicalTrials.gov IdentifierNCT00401466 ().

Our data strengthen the value of CB ablation for the treatment of AF as an effective and safe procedure in elderly patients, with similar success and complication rates when compared with a younger population.