On a stochastic partial differential equation with non-local diffusion

In this paper, we prove existence, uniqueness and regularity for a class of stochastic partial differential equations with a fractional Laplacian driven by a space-time white noise in dimension one. The equation we consider may also include a reaction term

Predictors and indicators of disability and quality of life 4 years after a severe traumatic brain injury. A Structural Equation Modelling analysis from the PariS-TBI study

ObjectiveTo assess the predictors and indicators of disability and quality of life four years after a severe traumatic brain injury (TBI), using a Structural Equation Modelling (SEM). SEM is a multivariate approach permitting to take into account the complex inter-relationships between individual predictors, in order to disentangle factors which have a direct or indirect relationship with the dependant variable.MethodsThe Paris-TBI study is a longitudinal inception cohort study of 504 patients with severe TBI in the Parisian area [1]. Among 245 survivors, 147 patients were assessed four years post-injury. Two outcome measures were analysed separately using SEM: the Glasgow Outcome Scale-extended (GOS-E) [2], which is a global measure of disability after TBI, and the QOLIBRI, a disease-specific measure of quality of life after TBI [3]. Four groups of variable were entered in the model: demographics; injury severity; psychological and cognitive impairments; somatic impairments.ResultsThe GOS-E was directly significantly related to all four groups of variables (age, gender, severity of injury, psycho-cognitive and somatic impairments). Education duration had an indirect effect, mediated by psycho-cognitive impairments. In contrast, the QOLIBRI was only directly predicted by psycho-cognitive impairments. Age and somatic impairments had an indirect influence on the QOLIBRI, via psycho-cognitive impairments.Discussion/ConclusionDisability and quality of life were directly influenced by different factors. While disability appeared to result from an interaction of a wide range of factors, including demographics, injury severity, psycho-cognitive and somatic deficiencies, quality of life was solely directly related to psycho-cognitive factors. Other factors, such as age and somatic impairments only had an indirect effect

Metformin:historical overview

Metformin (dimethylbiguanide) has become the preferred first-line oral blood glucose-lowering agent to manage type 2 diabetes. Its history is linked to Galega officinalis (also known as goat's rue), a traditional herbal medicine in Europe, found to be rich in guanidine, which, in 1918, was shown to lower blood glucose. Guanidine derivatives, including metformin, were synthesised and some (not metformin) were used to treat diabetes in the 1920s and 1930s but were discontinued due to toxicity and the increased availability of insulin. Metformin was rediscovered in the search for antimalarial agents in the 1940s and, during clinical tests, proved useful to treat influenza when it sometimes lowered blood glucose. This property was pursued by the French physician Jean Sterne, who first reported the use of metformin to treat diabetes in 1957. However, metformin received limited attention as it was less potent than other glucose-lowering biguanides (phenformin and buformin), which were generally discontinued in the late 1970s due to high risk of lactic acidosis. Metformin's future was precarious, its reputation tarnished by association with other biguanides despite evident differences. The ability of metformin to counter insulin resistance and address adult-onset hyperglycaemia without weight gain or increased risk of hypoglycaemia gradually gathered credence in Europe, and after intensive scrutiny metformin was introduced into the USA in 1995. Long-term cardiovascular benefits of metformin were identified by the UK Prospective Diabetes Study (UKPDS) in 1998, providing a new rationale to adopt metformin as initial therapy to manage hyperglycaemia in type 2 diabetes. Sixty years after its introduction in diabetes treatment, metformin has become the most prescribed glucose-lowering medicine worldwide with the potential for further therapeutic applications

Glycine Inhibitory Dysfunction Turns Touch into Pain through PKCgamma Interneurons

Dynamic mechanical allodynia is a widespread and intractable symptom of neuropathic pain for which there is a lack of effective therapy. During tactile allodynia, activation of the sensory fibers which normally detect touch elicits pain. Here we provide a new behavioral investigation into the dynamic component of tactile allodynia that developed in rats after segmental removal of glycine inhibition. Using in vivo electrophysiological recordings, we show that in this condition innocuous mechanical stimuli could activate superficial dorsal horn nociceptive specific neurons. These neurons do not normally respond to touch. We anatomically show that the activation was mediated through a local circuit involving neurons expressing the gamma isoform of protein kinase C (PKCγ). Selective inhibition of PKCγ as well as selective blockade of glutamate NMDA receptors in the superficial dorsal horn prevented both activation of the circuit and allodynia. Thus, our data demonstrates that a normally inactive circuit in the dorsal horn can be recruited to convert touch into pain. It also provides evidence that glycine inhibitory dysfunction gates tactile input to nociceptive specific neurons through PKCγ-dependent activation of a local, excitatory, NMDA receptor-dependent, circuit. As a consequence of these findings, we suggest that pharmacological inhibition of PKCγ might provide a new tool for alleviating allodynia in the clinical setting

Activation radicalaire d’un modèle de vitamine K par les radicaux OH

L’oxydation de la forme hydroquinonique d’un modèle de vitamine K hydrosoluble, notée KH2p, a été étudiée par radiolyse γ grâce aux radicaux libres OH• ou N3•, en utilisant des doses allant de 0 à 300 Gy (I = 6,7 × 10-2 Gy.s-1). L’analyse des produits finals par spectrophotométrie d’absorption ou par HPLC a permis de mettre en évidence la formation de la quinone K et d’évaluer quantitativement les rendements de disparition de KH2p et de formation de K. Les radicaux N3• conduisent sélectivement à la formation de la quinone K avec un rendement égal à (3,0 ± 0,3) × 10-7 mol / J, impliquant un mécanisme simple d’oxydation monoélectronique de KH2P. En revanche, lors de l’oxydation de KH2p par les radicaux OH•, outre la quinone K, d’autres produits non identifiés apparaissent simultanément au cours de la radiolyse traduisant un mécanisme d’oxydation plus complexe

Microbial hydroxylation/functionalization of terpenoid synthons derived from communic acids

International audienceIncubation of a communic acid-derived synthon with Cunninghamella elegans quantitatively affords 1ß, 3ß- and 7ß-monohydroxylated derivatives. (C) 2000 Elsevier Science Ltd