Ryvlin P.,University Claude Bernard Lyon 1
Epilepsia | Year: 2013
Sudden unexpected death in epilepsy (SUDEP) represents one of the most severe consequences of drug-resistant epilepsy, for which no evidence-based prevention is available. Development of effective prevention will depend on the following: (1) better understanding of the pathophysiology of SUDEP to define the most appropriate targets of intervention, and (2) identification of risk factors for SUDEP that would allow for the design of feasible clinical trials to test targeted interventions in high-risk populations. The most important known risk factor is the occurrence and frequency of generalized tonic-clonic seizure (GTCS), a seizure type that triggers the majority of witnessed SUDEP. Therefore, one likely way to prevent SUDEP is to minimize the risk of GTCS with optimal medical management and patient education. However, whether one might prevent SUDEP in patients with refractory epilepsy by using more frequent review of antiepileptic treatment and earlier referral for presurgical evaluation, remains to be seen. Another hypothetical strategy to prevent SUDEP is to reduce the risk of GTCS-induced postictal respiratory distress. This might be achieved by using lattice pillow, providing nocturnal supervision, reinforcing interictal serotoninergic tone, and lowering opiate- or adenosine-induced postictal brainstem depression. Promising interventions can be tested first on surrogate markers, such as postictal hypoxia in epilepsy monitoring units (EMUs), before SUDEP trials can be implemented. EMU safety should also be improved to avoid SUDEP occurrence in that setting. Finally, the development of ambulatory SUDEP prevention devices should be encouraged but raises a number of unsolved issues. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.
Haned H.,University Claude Bernard Lyon 1
Forensic Science International: Genetics | Year: 2011
Forensim is a new package for the R statistical software that is dedicated to forensic DNA evidence interpretation. As far as we know, forensim is the first open-source tool that allows for the simulation of data encountered in forensic genetics studies. The package also implements common statistical methods used for reporting the weight of DNA evidence. Forensim is written in the R language and is freely available from http://forensim.r-forge.r-project. org. This paper presents an overview of the software's functionalities. © 2010 Elsevier Ireland Ltd. All rights reserved.
Calvo F.,University Claude Bernard Lyon 1
Physical Review B - Condensed Matter and Materials Physics | Year: 2012
The structural and dynamical stabilities of C60+He N clusters are theoretically investigated using global optimization and path-integral simulation methods. Up to N=32, the fullerene ion traps the helium atoms onto sixfold and fivefold faces, strongly enough to negate vibrational delocalization. Above this size, geometric frustration takes over and the clusters grow as a thin but homogeneous liquid layer. However, as their size reaches 60 atoms, corrugation barriers are suppressed and the cluster is again rigidlike. Additional fluid layers are predicted to arise above 72 atoms. © 2012 American Physical Society.
Arrigo A.-P.,University Claude Bernard Lyon 1
FEBS Letters | Year: 2013
Small heat shock proteins (sHsps) regulate a large number of fundamental cellular processes and are involved in many pathological diseases. They share complex oligomerization and phosphorylation properties allowing them to interact and modulate the activity of many client proteins. Here, the up-to date protein interactome of the ten human sHsps is presented as an illustration of their multiple cellular functions. In addition of forming homo-oligomers, some of these proteins interact whith each other and form hetero-oligomeric complexes that could bear new protein targets recognition abilities. Here, novel informations are presented on how the formation of HspB1/HspB5 complex can stimulate the activity of the oxidoresistance promoting enzyme glucose 6-phosphate dehydrogenase through its interaction with newly formed highly phosphorylated HspB1 homo-oligomers. © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Cottin V.,University Claude Bernard Lyon 1
Respiratory Research | Year: 2013
Idiopathic pulmonary fibrosis (IPF) is a progressive disease, with a median survival time of 2-5 years. The search for effective treatment has involved numerous clinical trials of investigational agents without significant success. However, in 2011, pirfenidone was the first drug to be approved for the treatment of IPF in Europe. Four key clinical trials supported the efficacy and tolerability of pirfenidone.In the two recently published Phase III CAPACITY trials evaluating pirfenidone (studies 004 and 006), patients with mild-to-moderate IPF were treated with pirfenidone or placebo. Study 004 and pooled analysis of primary endpoint data from both studies showed that pirfenidone significantly reduced decline in percent-predicted forced vital capacity (FVC) compared with placebo (p<0.005). Evidence of beneficial effects of pirfenidone treatment was also observed with regard to several secondary endpoints. Pirfenidone was generally well tolerated, with the most common side effects being gastrointestinal and photosensitivity. Data from the RECAP extension phase of the CAPACITY studies, where patients were treated with pirfenidone for up to three years, further support the manageable tolerability profile of pirfenidone. The efficacy data, coupled with long-term safety data, provide further evidence of a clinically-meaningful treatment effect with pirfenidone in patients with IPF. © 2013 Cottin; licensee BioMed Central Ltd.