Extended interval dosing with ocrelizumab in multiple sclerosis.

Background: This study investigates clinical and biomarker differences between standard interval dosing (SID) and extended interval dosing (EID) of ocrelizumab therapy in multiple sclerosis (MS).

Methods: This is a prospective, double-arm, open-label, multi-center study in Denmark. Participants diagnosed with MS on ocrelizumab therapy >12 months were included ( = 184).

Discontinuation of dimethyl fumarate in multiple sclerosis - a nationwide study.

Background: Adherence is a prerequisite for the efficacy of any drug, and previous studies have shown that non-adherence is associated with disease activity and increased health care cost in multiple sclerosis (MS). The aim of this study was to investigate rates and reasons for discontinuation of dimethyl fumarate (DMF) among people with MS on a national level and differences between clinics in Denmark.

Methods: This was a nationwide, registry and population study of patients treated with DMF.

Rapid Sterility Test Systems in the Pharmaceutical Industry: Applying a Structured Approach to Their Evaluation, Validation and Global Implementation.

The current compendial sterility test has a 14-day incubation time and is often the time-limiting step in the Assess and Release Process of pharmaceutical products. There is an ever-increasing number of technologies available on the market that have benefits in addition to faster Time to Result, such as standardization and automation of readout (eliminating analyst subjectivity) and improved data integrity (including eliminating the need for contemporaneous verification of the result by another analyst). Regulators have been encouraging the pharmaceutical industry to adopt these innovative systems; however, it has taken a considerable time before receiving the first approvals from various health authorities (including both the European Medicines Agency and Food and Drug Administration) for the use of an alternative and rapid sterility test for the release of sterile drug product lots.

Temperature-Dependent Re-alignment of the Short Multifunctional Peptide BP100 in Membranes Revealed by Solid-State NMR Spectroscopy and Molecular Dynamics Simulations.

BP100 is a cationic undecamer peptide with antimicrobial and cell-penetrating activities. The orientation of this amphiphilic α-helix in lipid bilayers was examined under numerous conditions using solid-state F, N and H NMR. At high temperatures in saturated phosphatidylcholine lipids, BP100 lies flat on the membrane surface, as expected.

Ocrelizumab treatment in multiple sclerosis: A Danish population-based cohort study.

Background And Purpose: Real-world evidence regarding the effectiveness and safety of ocrelizumab for the treatment of multiple sclerosis (MS) is limited. The aim was to evaluate the effectiveness and safety of ocrelizumab treatment for MS in a real-world setting.

Methods: A nationwide population-based cohort study was conducted where clinical and magnetic resonance imaging data of MS patients enrolled prospectively in the Danish Multiple Sclerosis Registry who initiated ocrelizumab treatment between January 2018 and November 2020 were analyzed.

Existing fluid responsiveness studies using the mini-fluid challenge may be misleading: Methodological considerations and simulations.

Background: The mini-fluid challenge (MFC) is a clinical concept of predicting fluid responsiveness by rapidly infusing a small amount of intravenous fluids, typically 100 ml, and systematically assessing its haemodynamic effect. The MFC method is meant to predict if a patient will respond to a subsequent, larger fluid challenge, typically another 400 ml, with a significant increase in stroke volume.

Methods: We critically evaluated the general methodology of MFC studies, with statistical considerations, secondary analysis of an existing study and simulations.

Changes in arterial blood pressure characteristics following an extrasystolic beat or a fast 50 ml fluid challenge do not predict fluid responsiveness during cardiac surgery.

Prediction of fluid responsiveness is essential in perioperative goal directed therapy, but dynamic tests of fluid responsiveness are not applicable during open-chest surgery. We hypothesised that two methods could predict fluid responsiveness during cardiac surgery based on their ability to alter preload and thereby induce changes in arterial blood pressure characteristics: (1) the change caused by extrasystolic beats and (2) the change caused by a fast infusion of 50 ml crystalloid (micro-fluid challenge). Arterial blood pressure and electrocardiogram waveforms were collected during surgical preparation of the left internal mammary artery in patients undergoing coronary artery bypass surgery.

Using extra systoles and the micro-fluid challenge to predict fluid responsiveness during cardiac surgery.

Fluid responsiveness prediction is difficult during cardiac surgery. The micro-fluid challenge (micro-FC; rapid central infusion of 50 ml) and the extrasystolic method utilising post-extrasystolic preload increases may predict fluid responsiveness. Two study windows during coronary artery bypass graft surgery were defined, 1: After anaesthesia induction until surgical incision, 2: Left internal mammarian artery surgical preparation period.

Influence of Fluorescent Protein Maturation on FRET Measurements in Living Cells.

Förster resonance energy transfer (FRET)-based sensors are a valuable tool to quantify cell biology, yet it remains necessary to identify and prevent potential artifacts in order to exploit their full potential. We show here that artifacts arising from slow donor mCerulean3 maturation can be substantially diminished by constitutive expression in both prokaryotic and eukaryotic cells, which can also be achieved by incorporation of faster-maturing FRET donors. We developed an improved version of the donor mTurquoise2 that matures faster than the parent protein.

Effectiveness of Mindfulness- and Relaxation-Based eHealth Interventions for Patients with Medical Conditions: a Systematic Review and Synthesis.

Purpose: This systematic review aims to summarize eHealth studies with mindfulness- and relaxation-based interventions for medical conditions and to determine whether eHealth interventions have positive effects on health.

Method: A comprehensive search of five databases was conducted for all available studies from 1990 to 2015. Studies were included if the intervention was mainly technology delivered and included a mindfulness- or relaxation-based intervention strategy and if patients with a medical condition were treated.

Microorganisms maintain crowding homeostasis.

Macromolecular crowding affects the mobility of biomolecules, protein folding and stability, and the association of macromolecules with each other. Local differences in crowding that arise as a result of subcellular components and supramolecular assemblies contribute to the structural organization of the cytoplasm. In this Opinion article we discuss how macromolecular crowding affects the physicochemistry of the cytoplasm and how this, in turn, affects microbial physiology.

On the mobility, membrane location and functionality of mechanosensitive channels in Escherichia coli.

Bacterial mechanosensitive channels protect cells from structural damage during hypoosmotic shock. MscS, MscL and MscK are the most abundant channels in E. coli and arguably the most important ones in osmoprotection.

Action of the multifunctional peptide BP100 on native biomembranes examined by solid-state NMR.

Membrane composition is a key factor that regulates the destructive activity of antimicrobial peptides and the non-leaky permeation of cell penetrating peptides in vivo. Hence, the choice of model membrane is a crucial aspect in NMR studies and should reflect the biological situation as closely as possible. Here, we explore the structure and dynamics of the short multifunctional peptide BP100 using a multinuclear solid-state NMR approach.

Dynamical structure of the short multifunctional peptide BP100 in membranes.

BP100 is a multifunctional membrane-active peptide of only 11 amino acids, with a high antimicrobial activity, an efficient cell-penetrating ability, and low hemolytic side-effects. It forms an amphiphilic α-helix, similar to other antimicrobial peptides like magainin. However, BP100 is very short and thus unlikely to form membrane-spanning pores as proposed for longer peptides as a mechanism of action.

Compatibility assessment of CVD growth of carbon nanofibers on bulk CMOS devices.

We compare the level of deterioration in the basic functionality of individual transistors on ASIC chips fabricated in standard 130 nm bulk CMOS technology when subjected to three disparate CVD techniques with relatively low processing temperature to grow carbon nanostructures. We report that the growth technique with the lowest temperature has the least impact on the transistor behavior.

Electrical properties of Si-SiO(2)-Si nanogaps.

The chances of attaching organic molecules to silicon surfaces can be considerably enhanced if a robust nanogap structure with silicon electrodes can be used to connect the molecules. We describe the electrical properties of such an electrode structure, with a separation of the silicon surfaces in the 3-7 nm range. These silicon nanogaps are manufactured by partly removing the silicon dioxide insulator from a silicon-oxide-silicon material stack, by using a selective oxide etchant.