Efficacy of Four-Channel Functional Electrical Stimulation on Moderate Arm Paresis in Subacute Stroke Patients-Results from a Randomized Controlled Trial.

This preliminary randomized clinical trial explores the efficacy of task-oriented electromyography (EMG)-triggered multichannel functional electrical stimulation (EMG-MES) compared to single-channel cyclic neuromuscular electrical stimulation (cNMES) on regaining control of voluntary movements (CVM) and the ability to execute arm-hand-activities in subacute stroke patients with moderate arm paresis. Twelve ischemic stroke patients (Fugl-Meyer Assessment Arm Section (FMA-AS) score: 19-47) with comparable demographics were block-randomized to receive 15 sessions of cNMES or EMG-MES over three weeks additionally to a conventional neurorehabilitation program including task-oriented arm training. FMA-AS, Box-and-Block Test (BBT), and Stroke-Impact-Scale (SIS) were recorded at baseline and follow-up. All participants demonstrated significant improvement in FMA-AS and BBT. Participants treated with EMG-MES had a higher mean gain in FMA-AS than those treated with cNMES. In the SIS daily activities domain, both groups improved non-significantly; participants in the EMG-MES group had higher improvement in arm-hand use and stroke recovery. EMG-MES treatment demonstrated a higher gain of CVM and self-reported daily activities, arm-hand use, and stroke recovery compared to cNMES treatment of the wrist only. The protocol of this proof-of-concept study seems robust enough to be used in a larger trial to confirm these preliminary findings.

Towards a Synthetic Mitochondrion.

Our group at the University of Bern uses biochemical and biophysical techniques to unravel details of the molecular mechanism of membrane proteins. Of special interest are the large multi-subunit complexes of the universally conserved respiratory chain and the ATP synthase that are found in mitochondria and aerobic bacteria. In a bottom-up approach using purified membrane proteins and synthetic lipids, we aim to mimic the basic processes of oxidative phosphorylation. We further develop methodologies to increase the complexity of such artificial systems, paving the way for a synthetic mitochondrion. In this minireview, we summarize recent efforts of our groups and others towards a synthetic respiratory chain.

Synergy effects of combined multichannel EMG-triggered electrical stimulation and mirror therapy in subacute stroke patients with severe or very severe arm/hand paresis.

BACKGROUND: Neurorehabilitation requires the development of severity-dependent and successful therapies for arm/hand rehabilitation in stroke patients. OBJECTIVE: To evaluate the effectiveness of adding mirror therapy to bilateral EMG-triggered multi-channel electrostimulation for the treatment of severe arm/hand paresis in stroke patients. METHODS: The subjects of this randomized, controlled, multicentre study were stroke patients who had suffered their first insult between 1 and 6 months before study start and had severe or very severe arm/hand paresis, as classified by Fugl-Meyer-Assessment. Subjects were randomly allocated to an intervention group (n = 16) or control group (n = 17). Both groups were treated for 3 weeks (5x week, 30 minutes) with bilateral EMG-triggered multi-channel electrostimulation. The intervention group additionally received mirror feedback of the unaffected limb. The primary outcome measure was motor recovery of the upper extremities, as measured by the Fugl-Meyer Assessment. RESULTS: The Intervention Group with very severe paresis had significantly better motor recovery in total Fugl-Meyer Assessment (p = 0.017) at a medium effect size (Cohen) of d = 0.7, due to a significant recovery of shoulder and elbow function (p = 0.003) in the Fugl-Meyer Assessment Part A subtest. For subjects with severe paresis, additional mirror therapy did not significantly influence outcome. CONCLUSION: Additional mirror therapy in combination with EMG-triggered multi-channel electrostimulation is therapeutically beneficial for post-acute stroke patients with very severe arm/hand paresis.

Discovery of a Selective Aurora A Kinase Inhibitor by Virtual Screening.

Here we report the discovery of a selective inhibitor of Aurora A, a key regulator of cell division and potential anticancer target. We used the atom category extended ligand overlap score (xLOS), a 3D ligand-based virtual screening method recently developed in our group, to select 437 shape and pharmacophore analogs of reference kinase inhibitors. Biochemical screening uncovered two inhibitor series with scaffolds unprecedented among kinase inhibitors. One of them was successfully optimized by structure-based design to a potent Aurora A inhibitor (IC50 = 2 nM) with very high kinome selectivity for Aurora kinases. This inhibitor locks Aurora A in an inactive conformation and disrupts binding to its activator protein TPX2, which impairs Aurora A localization at the mitotic spindle and induces cell division defects. This phenotype can be rescued by inhibitor-resistant Aurora A mutants. The inhibitor furthermore does not induce Aurora B specific effects in cells.

Delivery of membrane proteins into small and giant unilamellar vesicles by charge-mediated fusion.

One of the current challenges in synthetic biology is the production of stable membrane mimetic systems and the insertion of components in these systems. Here, we employ fusion of oppositely charged liposomes to deliver separately reconstituted membrane proteins into a common lipid bilayer. After a systematic evaluation of different lipid compositions by lipid mixing and size distribution analysis, suitable conditions were further investigated for proteoliposome fusion. With this technique, we functionally coreconstituted bo3 oxidase and ATP synthase from Escherichia coli into unilamellar liposomes ranging from 100 nm to 50 µm in size. The presented method is a simple and versatile tool for oriented membrane protein reconstitution to produce biomimetic systems with increased complexity.