The AMPA receptor antagonist perampanel suppresses epileptic activity in human focal cortical dysplasia

Focal cortical dysplasia (FCD) is one of the most common malformations causing refractory epilepsy. Dysregulation of glutamatergic systems plays a critical role in the hyperexcitability of dysplastic neurons in FCD lesions. The pharmacoresistant nature of epilepsy associated with FCD may be due to a lack of well tolerated and precise antiepileptic drugs that can target glutamate receptors. Here, for the first time in human FCD brain slices, we show that the established, non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, perampanel has potent antiepileptic action. Moreover, we demonstrate that this effect is due to a reduction in burst firing behavior in human FCD microcircuits. These data support a potential role for the treatment of refractory epilepsy associated with FCD in human patients

Site preference of Fe atoms in FeMgSiO<SUB>4</SUB> and FeMg(SiO<SUB>3</SUB>)<SUB>2</SUB> studied by density functional calculations

Using first-principles density functional calculation we investigate site preference of Fe in FeMgSiO4 olivine and FeMg(SiO3)2 pyroxene, which are the major constituents of the earth's upper mantle. A combination of state-of-the-art methods has been used for this purpose. The strong correlation effect at Fe site has been taken care of by means of local-density approximation+U calculations, and the crystal structures have been optimized by means of total-energy calculations. Our T=0 K study in the total-energy-minimized structures indicate a strong preference for Fe to occupy M2 site in case of pyroxene and a preference for Fe to occupy M1 site in case of olivine. We provide the microscopic understanding of our finding in terms of density of states and charge densities

Data_Sheet_1_Effects of non-invasive vagus nerve stimulation on clinical symptoms and molecular biomarkers in Parkinson’s disease.doc

Non-invasive vagus nerve stimulation (nVNS) is an established neurostimulation therapy used in the treatment of epilepsy, migraine and cluster headache. In this randomized, double-blind, sham-controlled trial we explored the role of nVNS in the treatment of gait and other motor symptoms in Parkinson’s disease (PD) patients. In a subgroup of patients, we measured selected neurotrophins, inflammatory markers and markers of oxidative stress in serum. Thirty-three PD patients with freezing of gait (FOG) were randomized to either active nVNS or sham nVNS. After baseline assessments, patients were instructed to deliver six 2  min stimulations (12  min/day) of the active nVNS/sham nVNS device for 1  month at home. Patients were then re-assessed. After a one-month washout period, they were allocated to the alternate treatment arm and the same process was followed. Significant improvements in key gait parameters (speed, stance time and step length) were observed with active nVNS. While serum tumor necrosis factor- α decreased, glutathione and brain-derived neurotrophic factor levels increased significantly (p Clinical trial registration: identifier ISRCTN14797144.</p

Search for intermediate-mass black hole binaries in the third observing run of Advanced LIGO and Advanced Virgo

International audienceIntermediate-mass black holes (IMBHs) span the approximate mass range 100−105 M⊙, between black holes (BHs) that formed by stellar collapse and the supermassive BHs at the centers of galaxies. Mergers of IMBH binaries are the most energetic gravitational-wave sources accessible by the terrestrial detector network. Searches of the first two observing runs of Advanced LIGO and Advanced Virgo did not yield any significant IMBH binary signals. In the third observing run (O3), the increased network sensitivity enabled the detection of GW190521, a signal consistent with a binary merger of mass ∼150 M⊙ providing direct evidence of IMBH formation. Here, we report on a dedicated search of O3 data for further IMBH binary mergers, combining both modeled (matched filter) and model-independent search methods. We find some marginal candidates, but none are sufficiently significant to indicate detection of further IMBH mergers. We quantify the sensitivity of the individual search methods and of the combined search using a suite of IMBH binary signals obtained via numerical relativity, including the effects of spins misaligned with the binary orbital axis, and present the resulting upper limits on astrophysical merger rates. Our most stringent limit is for equal mass and aligned spin BH binary of total mass 200 M⊙ and effective aligned spin 0.8 at 0.056 Gpc−3 yr−1 (90% confidence), a factor of 3.5 more constraining than previous LIGO-Virgo limits. We also update the estimated rate of mergers similar to GW190521 to 0.08 Gpc−3 yr−1.Key words: gravitational waves / stars: black holes / black hole physicsCorresponding author: W. Del Pozzo, e-mail: [email protected]† Deceased, August 2020