Unusual consequences of status epilepticus in Dravet syndrome

AbstractAlthough status epilepticus (SE) affects the course of Dravet syndrome (DS), it rarely alters dramatically psychomotor outcome. We report an unusual pattern in 3 patients who following refractory SE lasting respectively 2, 7 and 12h experienced persistent and severe cognitive and motor deterioration. We compared these patients to published data and to personal experience in Necker hospital, to find links between severe outcome and clinical features such as treatment or duration of refractory SE. The key point was that anoxoischemic-like lesions appeared on MRI although cardiovascular function had remained stable. Therefore, neither hemodynamic failure, nor abnormalities of cardiac rhythm could explain the lesions and neurological worsening. For theoretical reasons the responsibility of therapy common for the 3 patients, e.g., barbiturates was suspected

Long term response to steroid therapy in Rasmussen encephalitis

SummaryRasmussen encephalitis (RE) is a severe and progressive focal epilepsy of unknown origin that leads to deterioration of motor and cognitive function. In a previous study, we described positive effect of high doses of steroids during the first year after the onset of RE. The objective of this study was to evaluate this therapy at long term.We reviewed 11 patients (7 girls and 4 boys) with RE of the right hemisphere (7) and the left (4) at a follow-up of 9±2 years. Age at onset of RE ranged from 2 to 14 years.Six patients had no benefit from steroid therapy and underwent hemispherotomy. Five had significant reduction of seizure frequency with disappearance of epilepsia partialis continua, and improved motor function. Of these, two died of unexpected sudden death 5 and 7 years after seizure control. Two others with initial response experienced progressive recurrence of seizures 1 to 4 years after the end of steroid therapy and required hemispherotomy. Finally, only one patient exhibited total cessation of seizures with steroids for 3 years, but seizures progressively recurred although the frequency was moderate.Our data confirm that although steroid treatment can be useful when given early in the course of RE, long term relapse can occur among the good responders requiring delayed hemispheric disconnection

Molecular Organization of Vomeronasal Chemoreception

The vomeronasal organ (VNO) has a key role in mediating the social and defensive responses of many terrestrial vertebrates to species- and sex-specific chemosignals. More than 250 putative pheromone receptors have been identified in the mouse VNO, but the nature of the signals detected by individual VNO receptors has not yet been elucidated. To gain insight into the molecular logic of VNO detection leading to mating, aggression or defensive responses, we sought to uncover the response profiles of individual vomeronasal receptors to a wide range of animal cues. Here we describe the repertoire of behaviourally and physiologically relevant stimuli detected by a large number of individual vomeronasal receptors in mice, and define a global map of vomeronasal signal detection. We demonstrate that the two classes (V1R and V2R) of vomeronasal receptors use fundamentally different strategies to encode chemosensory information, and that distinct receptor subfamilies have evolved towards the specific recognition of certain animal groups or chemical structures. The association of large subsets of vomeronasal receptors with cognate, ethologically and physiologically relevant stimuli establishes the molecular foundation of vomeronasal information coding, and opens new avenues for further investigating the neural mechanisms underlying behaviour specificity.Molecular and Cellular Biolog

Electricity savings and greenhouse gas emission reductions from global phase-down of hydrofluorocarbons

Hydrofluorocarbons (HFCs) are widely used as cooling agents in refrigeration and air conditioning, as solvents in industrial processes, as fire-extinguishing agents, for foam blowing, and as aerosol propellants. They have been used in large quantities as the primary substitutes for ozone-depleting substances regulated under the Montreal Protocol. However, many HFCs are potent greenhouse gases (GHGs) and as such subject to global phase-down under the Kigali Amendment (KA) to the Montreal Protocol. In this study, we develop a range of long-term scenarios for HFC emissions under varying degrees of stringency in climate policy and assess co-benefits in the form of electricity savings and associated reductions in GHG and air pollutant emissions. Due to technical opportunities to improve energy efficiency in cooling technologies, there exist potentials for significant electricity savings under a well-managed phase-down of HFCs. Our results reveal that the opportunity to simultaneously improve energy efficiency in stationary cooling technologies could bring additional climate benefits of about the same magnitude as that attributed to the HFCs phase-down. If technical energy efficiency improvements are fully implemented, the resulting electricity savings could exceed 20 % of future global electricity consumption, while the corresponding figure for economic energy efficiency improvements would be about 15 %. The combined effect of HFC phase-down, energy efficiency improvement of the stationary cooling technologies, and future changes in the electricity generation fuel mix would prevent between 411 and 631 Pg CO2 equivalent of GHG emissions between 2018 and 2100, thereby making a significant contribution towards keeping the global temperature rise below 2 ∘C. Reduced electricity consumption also means lower air pollution emissions in the power sector, estimated at about 5 %–10 % for sulfur dioxide (SO2), 8 %–16 % for nitrogen oxides (NOx), and 4 %–9 % for fine particulate matter (PM2.5) emissions compared with a pre-Kigali baseline

Specific Mesenchymal/Epithelial Induction of Olfactory Receptor, Vomeronasal, and Gonadotropin-Releasing Hormone (GnRH) Neurons

We asked whether specific mesenchymal/epithelial (M/E) induction generates olfactory receptor neurons (ORNs), vomeronasal neurons (VRNs), and gonadotropin-releasing hormone (GnRH) neurons, the major neuron classes associated with the olfactory epithelium (OE). To assess specificity of M/E-mediated neurogenesis, we compared the influence of frontonasal mesenchyme on frontonasal epithelium, which becomes the OE, with that of the forelimb bud. Despite differences in position, morphogenetic and cytogenic capacity, both mesenchymal tissues support neurogenesis, expression of several signaling molecules and neurogenic transcription factors in the frontonasal epithelium. Only frontonasal mesenchyme, however, supports OE-specific patterning and activity of a subset of signals and factors associated with OE differentiation. Moreover, only appropriate pairing of frontonasal epithelial and mesenchymal partners yields ORNs, VRNs, and GnRH neurons. Accordingly, the position and molecular identity of specialized frontonasal epithelia and mesenchyme early in gestation and subsequent inductive interactions specify the genesis and differentiation of peripheral chemosensory and neuroendocrine neurons.Molecular and Cellular Biolog

Three-dimensional coherent X-ray diffraction imaging of a ceramic nanofoam: determination of structural deformation mechanisms

Ultra-low density polymers, metals, and ceramic nanofoams are valued for their high strength-to-weight ratio, high surface area and insulating properties ascribed to their structural geometry. We obtain the labrynthine internal structure of a tantalum oxide nanofoam by X-ray diffractive imaging. Finite element analysis from the structure reveals mechanical properties consistent with bulk samples and with a diffusion limited cluster aggregation model, while excess mass on the nodes discounts the dangling fragments hypothesis of percolation theory.Comment: 8 pages, 5 figures, 30 reference

Probing deeper into the risks of slips, trips and falls for an ageing rail passenger population: applying a systems approach

In this study, the authors report the findings from a study of the contributory factors leading to slips, trips and falls (STFs) amongst elderly passengers at train stations and how these are likely to change in the future over the medium to long term (the period 2035–2050). Their data draws on: stakeholder interviews with rail personnel and elderly passengers; a set of station observations carried out across the UK; and, a survey of the views of station managers. The findings point to a set of 22 contributory factors covering aspects of organisational, station environment and passenger (individual) influence on STFs. Amongst the factors which most concern station managers at the present and over the next few decades are: rushing behaviour on train platforms; the consumption of alcohol by passengers; aspects of station design (e.g. flooring); and, training for station staff as regard the risks of STFs. The authors summarise their findings in the form of a systems model which highlights priorities with regard to STFs in terms of all of the stakeholders taking part in the study. A final section discusses a set of issues which might form the basis for a future agenda for research and practice in this area

MFN2 overexpression in skeletal muscles of young and old mice causes a mild hypertrophy without altering mitochondrial respiration and H2O2 emission

Abstract Aim Sarcopenia, the aging-related loss of muscle mass and function, is a debilitating process negatively impacting the quality of life of affected individuals. Although the mechanisms underlying sarcopenia are incompletely understood, impairments in mitochondrial dynamics, including mitochondrial fusion, have been proposed as a contributing factor. However, the potential of upregulating mitochondrial fusion proteins to alleviate the effects of aging on skeletal muscles remains unexplored. We therefore hypothesized that overexpressing Mitofusin 2 (MFN2) in skeletal muscle in vivo would mitigate the effects of aging on muscle mass and improve mitochondrial function. Methods MFN2 was overexpressed in young (7 mo) and old (24 mo) male mice for 4 months through intramuscular injections of an adeno-associated viruses. The impacts of MFN2 overexpression on muscle mass and fiber size (histology), mitochondrial respiration, and H2O2 emission (Oroboros fluororespirometry), and various signaling pathways (qPCR and western blotting) were investigated. Results MFN2 overexpression increased muscle mass and fiber size in both young and old mice. No sign of fibrosis, necrosis, or inflammation was found upon MFN2 overexpression, indicating that the hypertrophy triggered by MFN2 overexpression was not pathological. MFN2 overexpression even reduced the proportion of fibers with central nuclei in old muscles. Importantly, MFN2 overexpression had no impact on muscle mitochondrial respiration and H2O2 emission in both young and old mice. MFN2 overexpression attenuated the increase in markers of impaired autophagy in old muscles. Conclusion MFN2 overexpression may be a viable approach to mitigate aging-related muscle atrophy and may have applications for other muscle disorders