Off-axis electron holography of bacterial cells and magnetic nanoparticles in liquid

The mapping of electrostatic potentials and magnetic fields in liquids usingelectron holography has been considered to be unrealistic. Here, we showthat hydrated cells ofMagnetospirillum magneticumstrain AMB-1 and assem-blies of magnetic nanoparticles can be studied using off-axis electronholography in a fluid cell specimen holder within the transmission electronmicroscope. Considering that the holographic object and reference waveboth pass through liquid, the recorded electron holograms show sufficientinterference fringe contrast to permit reconstruction of the phase shift ofthe electron wave and mapping of the magnetic induction from bacterialmagnetite nanocrystals. We assess the challenges of performingin situmagne-tization reversal experiments using a fluid cell specimen holder, discussapproaches for improving spatial resolution and specimen stability, and outlinefuture perspectives for studying scientific phenomena, ranging from interpar-ticle interactions in liquids and electrical double layers at solid–liquidinterfaces to biomineralization and the mapping of electrostatic potentialsassociated with protein aggregation and folding

Chances and Challenges of Registry-Based Pharmacovigilance in Multiple Sclerosis: Lessons Learnt from the Implementation of the Multicenter REGIMS Registry

The long-term and potential rare side effects of new immunomodulating drugs for the treatment of multiple sclerosis (MS) are often not well known. Spontaneous case report systems of adverse drug effects are a valuable source in pharmacovigilance, but have several limitations. Primary data collections within registries allow a comprehensive analysis of potential side effects, but face several challenges. This article will outline the chances and challenges of registry-based adverse event reporting, using the example of the German immunotherapeutic registry REGIMS. REGIMS is an observational, clinical multicenter registry that aims to assess the incidence, type, and consequences of side effects of MS immunotherapies. Patients treated with an approved MS medication are recruited by their physicians during routine visits in hospitals, outpatient clinics, and MS-specialized practices. REGIMS incorporates an electronic physician-based documentation in each center and a paper-based patient documentation, both at baseline and regular follow-up visits. By the end of 2019, 43 REGIMS centers were actively recruiting patients and performing follow-up documentations. The majority of the first 1000 REGIMS patients were female (69.3%), had relapse-remitting MS (89.8%), and were treated with a second-line therapy. During the implementation of REGIMS, several logistic and procedural challenges had to be overcome, which are outlined in this paper. Pharmacovigilance registries such as REGIMS provide high-quality primary data from a specific patient population in a real-world care setting and enable pharmacovigilance research that cannot be carried out using secondary data. Despite the logistic and procedural challenges in establishing a multicenter pharmacovigilance registry in Germany, the advantages outweigh the drawbacks