Critical role for the lactate transporter, monocarboxylate transporter 1 (mct1), in the regeneration of peripheral nerves

Axons, and particularly regenerating axons, have high metabolic needs in order to maintain critical functions such as axon transport and membrane depolarization. Though some of the required energy likely comes form extracellular glucose and ATP generated in the soma, we and others hypothesize that some of the energy may be supplied by lactate. Unlike glucose that requires glycolytic enzymes to produce pyruvate, lactate can be converted directly to pyruvate by lactate dehydrogenase and transported into mitochondria for oxidative metabolism. In order to be transported into or out of cells, lactate requires specific monocarboxylate transporters (MCTs), the most abundant of which is MCT1. If MCT1 and lactate are critical for nerve function and regeneration, we hypothesize that MCT1 heterozygote null mice, which appear phenotypically normal despite having approximately 40% MCT1 as compared to wildtype littermate mice, would have reduced capacity for repair following nerve injury. To investigate this, adult MCT1 heterozygote null mice or wild-type mice underwent unilateral sciatic nerve crush in the proximal thigh. We found that regeneration of the sciatic nerve, as measured by recovery of compound muscle action potentials (CMAP) in the lateral plantar muscles following proximal sciatic nerve stimulation, was delayed from a median of 21 days in wildtype mice to 38.5 days in MCT1 heterozygote mice. In fact, half of the MCT1 heterozygote null mice had no recovery of CMAP by the endpoint of the study at 42 days, while all of the wild-type mice had recovered. In addition, the maximal amplitude of CMAP recovery in MCT1 heterozygote mull mice was reduced from a mean of 3 mV to 0.5 mV. As would be expected, the denervated gastrocnemius muscle of MCT1 heterozygote null mice remained atrophic at 42 days compared to wild-type mice. Our experiments show that lactate supplied through MCT1 is necessary for nerve regeneration. Experiments are underway to determine whether loss of MCT1 prevents nerve regrowth directly due to reduced energy supply to axons or indirectly by dysfunctional Schwann cells normally dependent on lactate supply through MCT1.

Espace public, médiations, reconnaissance : Eléments de reconstruction d'une théorie critique de la communication

Résumé en français Après un examen critique de la théorie des médias et de la culture développée par l'Ecole de Francfort, abordée ici principalement au travers des oeuvres de T.W. Adorno et de Jürgen Habeimas, ce travail en propose une reconstruction en s'inspirant de la théorie de la reconnaissance d'Axel Honneth. Envisagée sous un angle narratif, la communication publique est vue comme un processus engageant à la fois des relations de reconnaissance et leur négation sous la double forme de la réification et du mépris. La recherche développe une approche des médias sensible à ces tensions et conflits ainsi qu'aux luttes pour la reconnaissance qui travaillent la scène publique, y compris dans sa dimension esthétique. Title and abstract in english « Public sphere, mediations, recognition. Reconstruction elements of a critical theory of communication ». After a critical discussion of media and culture theory developped by the Frankfurt School presented here mainly through the works of T.W. Adorno and Jürgen Habermas, this research proposes to reconstruct it on the basis of the theory of recognition developed by Axel Honneth. Considered through the perspective of narrative, public communication in is seen as a process implying at the same time recognition relations and their negation through the double process of reification and disrespect. The research develops an approach of media which is attentive to those tensions and conflicts and to the struggles for recognition that forms public sphere, also in his aesthetic dimension.

Screening for elevated blood pressure in children and adolescents: a critical appraisal.

Although screening for elevated blood pressure (BP) in adults is beneficial, evidence of its beneficial effects in children is not clear. Elevated BP in children is associated with atherosclerosis early in life and tracks across the life course. However, because of the high variability in BP, tracking is weak, and having an elevated BP in childhood has a low predictive value for having elevated BP later in life. The absolute risk of cardiovascular diseases associated with a given level of BP in childhood and the long-term effect of treatment beginning in childhood are not known. No study has experimentally evaluated the benefits and harm of BP screening in children. One modeling study indicates that BP screen-and-treat strategies in adolescents are moderately cost-effective but less cost-effective than population-wide interventions to decrease BP for the reduction of coronary heart diseases. The US National Heart, Lung, and Blood Institute and the European Society of Hypertension recommend that children 3 years of age and older have their BP measured during every health care visit. According to the US Preventive Services Task Force, there is no sufficient evidence to recommend for or against screening, but their recommendations have to be updated. Whether the benefits of universal BP screening in children outweigh the harm has to be determined. Studies are needed to assess the absolute risk of cardiovascular diseases associated with elevated BP in childhood, to evaluate how to simplify the identification of elevated BP, to evaluate the long-term benefits and harm of treatment beginning in childhood, and to compare universal and targeted screening strategies.

How life history and demography promote or inhibit the evolution of helping behaviours.

In natural populations, dispersal tends to be limited so that individuals are in local competition with their neighbours. As a consequence, most behaviours tend to have a social component, e.g. they can be selfish, spiteful, cooperative or altruistic as usually considered in social evolutionary theory. How social behaviours translate into fitness costs and benefits depends considerably on life-history features, as well as on local demographic and ecological conditions. Over the last four decades, evolutionists have been able to explore many of the consequences of these factors for the evolution of social behaviours. In this paper, we first recall the main theoretical concepts required to understand social evolution. We then discuss how life history, demography and ecology promote or inhibit the evolution of helping behaviours, but the arguments developed for helping can be extended to essentially any social trait. The analysis suggests that, on a theoretical level, it is possible to contrast three critical benefit-to-cost ratios beyond which costly helping is selected for (three quantitative rules for the evolution of altruism). But comparison between theoretical results and empirical data has always been difficult in the literature, partly because of the perennial question of the scale at which relatedness should be measured under localized dispersal. We then provide three answers to this question.

Consensus summary statement of the International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care : A statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine.

Neurocritical care depends, in part, on careful patient monitoring but as yet there are little data on what processes are the most important to monitor, how these should be monitored, and whether monitoring these processes is cost-effective and impacts outcome. At the same time, bioinformatics is a rapidly emerging field in critical care but as yet there is little agreement or standardization on what information is important and how it should be displayed and analyzed. The Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine, and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to begin to address these needs. International experts from neurosurgery, neurocritical care, neurology, critical care, neuroanesthesiology, nursing, pharmacy, and informatics were recruited on the basis of their research, publication record, and expertise. They undertook a systematic literature review to develop recommendations about specific topics on physiologic processes important to the care of patients with disorders that require neurocritical care. This review does not make recommendations about treatment, imaging, and intraoperative monitoring. A multidisciplinary jury, selected for their expertise in clinical investigation and development of practice guidelines, guided this process. The GRADE system was used to develop recommendations based on literature review, discussion, integrating the literature with the participants' collective experience, and critical review by an impartial jury. Emphasis was placed on the principle that recommendations should be based on both data quality and on trade-offs and translation into clinical practice. Strong consideration was given to providing pragmatic guidance and recommendations for bedside neuromonitoring, even in the absence of high quality data.

Critical evaluation of outcome scales assessment of lateral ankle ligament reconstruction

Introduction: Les résultats d'une chirurgie du pied et de la cheville peuvent être évalués par des scores spécifiques à la région anatomique ainsi que par des scores spécifiques à la pathologie. Beaucoup de scores existent rendant la comparaison entre les études difficile. La présente étude se focalise sur une pathologie fréquente du pied et de la cheville et compare les résultats obtenu par deux scores spécifiques à la région et deux scores spécifiques à la pathologie. Méthode: Nous avons revu 41 patients ayant bénéficié d'une plastie ligamentaire externe de la cheville. Quatre scores ont été administrés simultanément: the Cumberland Ankle Instability Tool (CAIT) et the Chronic Ankle Instability Scale (CAIS), spécifiques à la pathologie, the American Orthopedic Foot & Ankle Society (AOFAS) hindfoot scale et the Foot and Ankle Ability Measure comprenant deux parties (FAAM1 et FAAM2), spécifiques à la région anatomique. Le degré de corrélation entre les scores a été évalué par le coefficient de corrélation de Pearson. L'analyse graphique des variances a été utilisée pour le choix de tests paramétriques versus non paramétriques. Des tests non paramétriques, le Kruskal-Wallis pour éliminer l'hypothèse nulle et le Mann-Whitney pour la comparaison entre les scores deux à deux, ont été utilisés. Résultats: Une différence significative (p<.005) a été démontrée entre le CAIS et l'AOFAS (p=.0002), entre le CAIS et le FAAM1 (p=.0001) et entre le CAIT et l'AOFAS (p=.0003) Conclusions: Cette étude compare les performances de quatre scores dont deux spécifiques à la région anatomique et deux spécifiques à la pathologie. Nous avons démontré une bonne corrélation entre les scores ainsi que des différences significatives entre les résultats obtenus par chacun d'eux. Les résultats obtenus par les scores spécifiques à la pathologie semblent être plus précis que ceux obtenus par les scores spécifiques à la région anatomique. De plus, nous avons mis en évidence une forte corrélation entre l'AOFAS et les autres scores. Le FAAM semble être un bon compromis car il offre la possibilité, du fait de ses deux parties, d'évaluer le résultat en fonction de la demande fonctionnelle du patient. Perspectives: Un algorithme est proposé qui permet d'évaluer la littérature spécifique de manière plus critique et peut s'adapter également à la recherche et à la clinique relative à d'autres pathologies du pied et de la cheville

War Signals: A Theory of Trade, Trust and Conflict

We construct a dynamic theory of civil conflict hinging on inter-ethnic trust and trade. The model economy is inhabitated by two ethnic groups. Inter-ethnic trade requires imperfectly observed bilateral investments and one group has to form beliefs on the average propensity to trade of the other group. Since conflict disrupts trade, the onset of a conflict signals that the aggressor has a low propensity to trade. Agents observe the history of conflicts and update their beliefs over time, transmitting them to the next generation. The theory bears a set of testable predictions. First, war is a stochastic process whose frequency depends on the state of endogenous beliefs. Second, the probability of future conflicts increases after each conflict episode. Third, "accidental" conflicts that do not reflect economic fundamentals can lead to a permanent breakdown of trust, plunging a society into a vicious cycle of recurrent conflicts (a war trap). The incidence of conflict can be reduced by policies abating cultural barriers, fostering inter-ethnic trade and human capital, and shifting beliefs. Coercive peace policies such as peacekeeping forces or externally imposed regime changes have instead no persistent effects.