Inhibition of Schistosoma mansoni ether-a-go-go related gene-encoded potassium channels leads to hypermotility and impaired egg production.

The purpose of this work was to investigate the effect of ether-a-go-go related gene (ERG) potassium channel inhibition on Schistosoma mansoni. Use of dofetilide to block the schistosome ERGs resulted in a striking 'corkscrew' effect. The worms were unable to control their motility; they were hypermotile. The treated worms produced abnormal eggs, some of which consisted of little more than a spine. One of the S. mansoni ERGs (SmERGs), Smp_161140, was chosen for further study by RNAi. The transcript was knocked down to 50% compared to the controls. These RNAi-treated worms demonstrated seizure-like movements. In S. mansoni, as in other organisms, ERG channels seem to play a role in regulating muscle excitability. This work shows that egg production can be greatly reduced by effectively targeting muscle coordination in these important parasites.

Deconvolution of 40 Hz steady-state fields reveals two overlapping source activities of the human auditory cortex.

Steady-state auditory evoked fields were recorded from 15 subjects using a whole head MEG system. Stimuli were 800 ms trains of binaural clicks with constant stimulus onset asynchrony (SOA). Seven different SOA settings (19, 21, 23, 25, 27, 29 and 31 ms) were used to give click rates near 40 Hz. Transient responses to each click were reconstructed using a new algorithm that deconvoluted the averaged responses to the different trains. Spatio-temporal multiple dipole modelling in relation to 3D MRI scans revealed two overlapping source components in both the left and right auditory cortex. The primary sources in the medial part of Heschl's gyrus exhibited a N19-P30-N40 m pattern. The secondary, weaker sources at more lateral sites on Heschl's gyrus showed a N24-P36-N46 m pattern. When applied to transient middle latency auditory evoked fields (MAEFs) recorded at SOAs of 95-135 ms, the primary sources imaged activities similar to the deconvoluted steady-state responses, but the secondary source activities were inconsistent. Linear summation of the deconvoluted source waveforms accounted for more than 96% of the steady-state variance. This indicates that the primary activity of the auditory cortex remains constant up to high stimulation rates and is not specifically enhanced around 40 Hz.

Magnetic resonance imaging with implanted neurostimulators: an in vitro and in vivo study.

OBJECTIVE: The goal was to assess the safety of magnetic resonance imaging (MRI) with implanted neurostimulators, in an in vitro and in vivo study. METHODS: Two different implantable pulse generators (IPGs) (ITREL II and 3; Medtronic, Minneapolis, MN) and different leads (separately and connected to an IPG) were tested in three different MRI scanners (0.2, 0.25, and 1.5 T). Measurements of the induced voltages (using an external oscilloscope) and the induced heat (using an infrared camera) were performed in an in vitro study. Finally, 38 patients with implanted neurostimulator systems (leads and IPGs) underwent MRI in 50 examinations, with continuous monitoring by a physician with uninterrupted visual and vocal contact with the patient. Twenty-five patients were studied prospectively, with documented printouts of the parameter settings before and after MRI. RESULTS: An induced voltage of 2.4 to 5.5 V was measured in the experimental configuration with a lead connected to an IPG. The voltage was higher with the leads alone, compared with the leads connected to the IPG, and was dependent on the MRI scanner, the sequences, and the type of lead. No heat induction was observed in any part of the hardware. No change of pulse shape or change of IPG parameters was observed during MRI. No adverse effects occurred in patients with chronically implanted deep brain leads connected to an IPG. CONCLUSION: MRI can be safely performed in patients with implanted neurostimulation systems with the tested deep brain leads connected to an IPG (ITREL II and 3), with running parameters. No heat induction was detected, and the experimentally measured induced voltage did not seem to harm the patients. Only the reed switch of the IPGs was activated; the other parameters remained unchanged. Further investigations must be performed to study the local electrical effects in larger plate electrodes; these effects might cause slight discomfort. There is no danger with any type of electrode during MRI examinations if the electrodes lie outside the region of interest. These observations are restricted to the tested devices. A conscientious estimation of the risks and benefits of MRI for patients with implanted devices is recommended. If the type of device is not known to the examiner, MRI should still be considered to be contraindicated.