Hypothermie thérapeutique en traumatologie crânienne grave [Therapeutic hypothermia for severe traumatic brain injury].

Therapeutic hypothermia (TH) is considered a standard of care in the post-resuscitation phase of cardiac arrest. In experimental models of traumatic brain injury (TBI), TH was found to have neuroprotective properties. However, TH failed to demonstrate beneficial effects on neurological outcome in patients with TBI. The absence of benefits of TH uniformly applied in TBI patients should not question the use of TH as a second-tier therapy to treat elevated intracranial pressure. The management of all the practical aspects of TH is a key factor to avoid side effects and to optimize the potential benefit of TH in the treatment of intracranial hypertension. Induction of TH can be achieved with external surface cooling or with intra-vascular devices. The therapeutic target should be set at a 35°C using brain temperature as reference, and should be maintained at least during 48 hours and ideally over the entire period of elevated intracranial pressure. The control of the rewarming phase is crucial to avoid temperature overshooting and should not exceed 1°C/day. Besides its use in the management of intracranial hypertension, therapeutic cooling is also essential to treat hyperthermia in brain-injured patients. In this review, we will discuss the benefit-risk balance and practical aspects of therapeutic temperature management in TBI patients.

Validation française d'un questionnaire de stress post-traumatique destiné aux parents d'enfants présentant un risque périnatal élevé = French validation of the "Perinatal PTSD Questionnaire" assessing parent's posttraumatic stress reactions following the birth of a high risk infant.

(from the journal abstract) Objectives: The birth of a high risk infant--such as a very or extremely premature infant--can represent an important traumatic experience for parents. R. DeMier, M. Hynan et al's "Perinatal PTSD Questionnaire" aims at exploring, retrospectively, parent's posttraumatic stress reactions following the birth of a high risk infant. This paper describes the French validation of this questionnaire. Methods: Fifty-two families with a very or extremely premature infant and 25 families with a full term infant responded to the "Perinatal PTSD Questionnaire" and the "Impact of Event Scale" when children were 18 months old. Results: Parents of high risk infants can present posttraumatic stress reactions such as intrusion, avoidance or arousal symptoms. The French version of the "Perinatal PTSD Questionnaire" has satisfactory psychometric properties. Conclusions: As posttraumatic reactions are not directly related to objective descriptions of the stressful event, it may be essential to the liaison child psychiatrist to consider individual posttraumatic reactions in order to optimise preventive intervention with the parents. A questionnaire should not replace a clinical interview, however it may represent a useful screening tool. Also, this questionnaire should be useful for research purposes. (PsycINFO Database Record (c) 2005 APA, all rights reserved)

CO2 production of the chick embryo during the first day of post-laying development.

The carbon dioxide production of the chick embryo cultured in vitro has been determined during the first 24 h of post-laying development using a non-invasive conductometric microtechnique. The mean CO2 production of the whole blastoderm (1) increased from 16 nmol/h at laying to 231 nmol/h at early neurulation, (2) became dependent on exogenous glucose and (3) was closely linked to mechanical tension generated in the blastoderm (loosening from vitelline membrane resulted in a decrease of 56%). In our experimental conditions, no significant influence of carbonic anhydrase on the CO2 production has been detected. The value of the respiratory exchange ratio varied from about 3 at pregastrular stages to 1 at neurula stage and CO2 was produced transiently in presence of antimycin A. Such results indicate that the source of CO2 is not exclusively mitochondrial and that the relative proportions of mitochondrial and non-mitochondrial CO2 productions might vary significantly throughout the early development. Our findings confirm that the metabolism of the chick embryo becomes more and more oxidative from laying onwards and suggest that the modifications of metabolism observed during the studied period of development could be associated with functional differentiation.

Post-axial polydactyly type A2, overgrowth and autistic traits associated with a chromosome 13q31.3 microduplication encompassing miR-17-92 and GPC5.

Genomic rearrangements at chromosome 13q31.3q32.1 have been associated with digital anomalies, dysmorphic features, and variable degree of mental disability. Microdeletions leading to haploinsufficiency of miR17∼92, a cluster of micro RNA genes closely linked to GPC5 in both mouse and human genomes, has recently been associated with digital anomalies in the Feingold like syndrome. Here, we report on a boy with familial dominant post-axial polydactyly (PAP) type A, overgrowth, significant facial dysmorphisms and autistic traits who carries the smallest germline microduplication known so far in that region. The microduplication encompasses the whole miR17∼92 cluster and the first 5 exons of GPC5. This report supports the newly recognized role of miR17∼92 gene dosage in digital developmental anomalies, and suggests a possible role of GPC5 in growth regulation and in cognitive development.

Geometry, petrology and growth of a shallow crustal laccolith : the Torres del Paine Mafic Complex (Patagonia)

1. ABSTRACTS - RÉSUMÉSSCIENTIFIC ABSTRACT - ENGLISH VERSIONGeometry, petrology and growth of a shallow crustal laccolith: the Torres del Paine Mafi c Complex (Patagonia)The Torres del Paine intrusive complex (TPIC) is a composite mafic-granitic intrusion, ~70km2, belonging to a chain of isolated Miocene plutons in southern Patagonia. Their position is intermediate between the Mesozoic-Cenozoic calc-alkaline subduction related Patagonian batholith in the West and the late Cenozoic alkaline basaltic back-arc related plateau lavas in the East. The Torres del Paine complex formed during an important reconfiguration of the Patagonian geodynamic setting, with a migration of magmatism from the arc to the back-arc, possibly related to the Chile ridge subductionThe complex intruded the flysch of the Cretaceous Cerro Toro and Punta Barrosa Formations during the Miocene, creating a well-defined narrow contact aureole of 200-400 m width.In its eastern part, the Torres del Paine intrusive complex is a laccolith, composed of a succession of hornblende-gabbro to diorite sills at its base, with a total thickness of ~250m, showing brittle contacts with the overlying granitic sills, that form spectacular cliffs of more than 1000m. This laccolith is connected, in the western part, to its feeding system, with vertical alternating sheets of layered gabbronorite and Hbl-gabbro, surrounded and percolated by diorites. ID-TIMS U-Pb on zircons on feeder zone (FZ) gab- bros yield 12.593±0.009Ma and 12.587±0.009Ma, which is identifcal within error to the oldest granite dated so far by Michel et al. (2008). In contrast, the laccolith mafic complex is younger than than the youngest granite (12.50±0.02Ma), and has been emplaced from 12.472±0.009Ma to 12.431 ±0.006Ma, by under-accretion beneath the youngest granite at the interface with previously emplaced mafic sills.The gabbronorite crystallization sequence in the feeder zone is dominated by olivine, plagioclase, clinopyroxene and orthopyroxene, while amphibole forms late interstitial crystals. The crystallization sequence is identical in Hornblende-gabbro from the feeder zone, with higher modal hornblende. Gabbronorite and Hornblende-gabbro both display distinct Eu and Sr positive anomalies. In the laccolith, a lower Hornblende-gabbro crystallized in sills and evolved to a high alkali shoshonitic series. The Al203, Ti02, Na20, K20, Ba and Sr composition of these gabbros is highly variable and increases up to ~50wt% Si02. The lower hornblende-gabbro is characterized by kaersutite anhedral cores with inclusions of olivine, clino- and orthopyroxene and rare apatite and An70 plagioclase. Trace element modelling indicates that hornblende and clinopyroxene are in equilibrium with a liquid whose composition is similar to late basaltic trachyandesitic dikes that cut the complex. The matrix in the lower hornblende gabbro is composed of normally zoned oligoclase, Magnesio-hornblende, biotite, ilmenite and rare quartz and potassium feldspar. This assemblage crystallized in-situ from a Ba and Sr-depleted melts. In contrast, the upper Hbl-gabbro is high-K calc-alkaline. Poikilitic pargasite cores have inclusions of euhedral An70 plagioclase inclusions, and contain occasionally clinopyroxene, olivine and orthopyroxene. The matrix composition is identical to the lower hornblende-gabbro and similar to the diorite. Diorite bulk rock compositions show the same mineralogy but different modal proportions relative to hornblende-gabbrosThe Torres del Paine Intrusive Complex isotopic composition is 87Sr/86Sr=0.704, 143Nd/144Nd=0.5127, 206Pb/204Pb=18.70 and 207Pb/204Pb=15.65. Differentiated dioritic and granitic units may be linked to the gabbroic cumulates series, with 20-50% trapped interstitial melt, through fractionation of olivine-bearing gabbronorite or hornblende-gabbro fractionation The relative homogeneity of the isotopic compositions indicate that only small amounts of assimilation occurred. Two-pyroxenes thermometry, clinopyroxene barometry and amphibole-plagioclase thermometry was used to estimate pressure and temperature conditions. The early fractionation of ultramafic cumulates occurs at mid to lower crustal conditions, at temperatures exceeding 900°C. In contrast, the TPIC emplacement conditions have been estimated to ~0.7±0.5kbar and 790±60°C.Based on field and microtextural observations and geochemical modelling, fractionation of basaltic-trachyandesitic liquids at intermediate to lower crustal levels, has led to the formation of the Torres del Paine granites. Repetitive replenishment of basaltic trachy- andesitic liquid in crustal reservoirs led to mixed magmas that will ascend via the feeder zone, and crystallize into a laccolith, in the form of successive dioritic and gabbroic sills. Dynamic fractionation during emplacement concentrated hornblende rich cumulates in the center of individual sills. Variable degrees.of post-emplacement compaction led to the expulsion of felsic liquids that preferentially concentrated at the top of the sills. Incremental sills amalgamation of the entire Torres del Paine Intrusive Complex has lasted for ~160ka.RESUME SCIENTIFIQUE - VERSION FRANÇAISEGéométrie, pétrologie et croissance d'un laccolite peu profond : Le complexe ma- fique du Torres del Paine (Patagonie)Le Complexe Intrusif du Torres del Paine (CITP) est une intrusion bimodale, d'environ 70km2, appartenant à une chaîne de plutons Miocènes isolés, dans le sud de la Patago-nie. Leur position est intermédiaire entre le batholite patagonien calco-alcalin, à l'Ouest, mis en place au Mesozoïque-Cenozoïque dans un contexte de subduction, et les basal-tes andésitiques et trachybasaltes alcalins de plateau, plus jeune, à l'Est, lié à l'ouverture d'un arrière-arc.A son extrémité Est, le CITP est une succession de sills de gabbro à Hbl et de diorite, sur une épaisseur de ~250m, avec des évidences de mélange. Les contacts avec les sills de granite au-dessus, formant des parois de plus de 1000m, sont cassants. Ce laccolite est connecté, dans sa partie Ouest, à une zone d'alimentation, avec des intrusions sub-ver- ticales de gabbronorite litée et de gabbro à Hbl, en alternance. Celles-ci sont traversées et entourées par des diorites. Les zircons des gabbros de la zone d'alimentation, datés par ID-TIMS, ont cristallisés à 12.593±0.009Ma et 12.587±0.009Ma, ce qui correspond au plus vieux granite daté à ce jour par Michel et al. (2008). A l'inverse, les roches manques du laccolite se sont mises en place entre 12.472±0.009Ma et 12.431 ±0.006Ma, par sous-plaquage successifs à l'interface avec le granite le plus jeune daté à ce jour (12.50±0.02Ma).La séquence de cristallisation des gabbronorites est dominée par Ol, Plg, Cpx et Opx, alors que la Hbl est un cristal interstitiel. Elle est identique dans les gabbros à Hbl de la zone d'alimentation, avec ~30%vol de Hbl. Les gabbros de la zone d'alimentation montrent des anomalies positives en Eu et Sr distinctes. Dans le laccolite, le gabbro à Hbl inférieur évolue le long d'une série shoshonitique, riche en éléments incompatibles. Sa concentration en Al203, Ti02, Na20, K20, Ba et Sr est très variable et augmente rapide-ment jusqu'à ~50wt% Si02. Il est caractérisé par la présence de coeurs résorbés de kaer- sutite, entourés de Bt, et contenant des inclusions d'OI, Cpx et Opx, ou alors d'Ap et de rares Plg (An70). Hbl et Cpx ont cristallisés à partir d'un liquide de composition similaire aux dykes trachy-andesite basaltique du CITP. La matrice, cristallisée in-situ à partir d'un liquide pauvre en Ba et Sr, est composée d'oligoclase zoné de façon simple, de Mg-Hbl, Bt, llm ainsi que de rares Qtz et KF. Le gabbro à Hbl supérieur, quant à lui, appartient à une suite chimique calco-alcaline riche en K. Des coeurs poecilitiques de pargasite con-tiennent de nombreuses inclusions de Plg (An70) automorphe, ainsi que des Ol, Cpx et Opx. La composition de la matrice est identique à celle des gabbros à Hbl inférieurs et toutes deux sont similaires à la minéralogie des diorites. Les analyses sur roches totales de diorites montrent la même variabilité que celles de gabbros à Hbl, mais avec une ten-eur en Si02 plus élevée.La composition isotopique des liquides primitifs du CITP a été mesurée à 87Sr/86Sr=0.704, 143Nd/144Nd=0.5127, 206Pb/204Pb=18.70 et 207Pb/204Pb=15.65. Les granites et diorites différenciés peuvent être reliés à des cumulais gabbronoritiques (F=0.74 pour les granites et F=1-0.5 pour les diorites) et gabbroïques à Hbl (fractionnement supplémentaire pour les granites, avec F=0.3). La cristallisation de 20 à 50%vol de liquide interstitiel piégé dans les gabbros du CITP explique leur signature géochimique. Seules de faibles quantités de croûte continentale ont été assimilées. La température et la pression de fractionnement ont été estimées, sur la base des thermobaromètres Opx-Cpx, Hbl-Plg et Cpx, à plus de 900°C et une profondeur correspondant à la croûte inférieure-moyenne. A l'inverse, les conditions de cristallisation de la matrice des gabbros et diorites du laccolite ont été estimées à 790±60°C et ~0.7±0.5kbar.Je propose que les liquides felsiques du CITP se soient formés par cristallisation frac-tionnée en profondeur des assemblages minéralogiques observés dans les gabbros du CITP, à partir d'un liquide trachy-andesite basaltique. La percolation de magma dans les cristaux accumulés permet la remontée du mélange à travers la zone d'alimentation, vers le laccolite, où des sills se mettent en place successivement. L'amalgamation de sills dans le CITP a duré ~160ka.Le CITP s'est formé durant une reconfiguration importante du contexte géodynamique en Patagonie, avec un changement du magmatisme d'arc vers un volcanisme d'arrière- arc. Ce changement est certainement lié à la subduction de la ride du Chili.RESUME GRAND PUBLIC - VERSION FRANÇAISEGéométrie, pétrologie et croissance d'une chambre magmatique peu profonde : Le complexe mafique du Torres del Paine (Patagonie)Le pourtour de l'Océan Pacifique est caractérisé par une zone de convergence de plaques tectoniques, appelée zone de subduction, avec le plongement de croûte océa-nique sous les Andes dans le cas de la Patagonie. De nombreux volcans y sont associés, formant la ceinture de feu. Mais seuls quelques pourcents de tout le magma traversant la croûte terrestre parviennent à la surface et la majeure partie cristallise en profondeur, dans des chambres magmatiques. Quelles est leur forme, croissance, cristallisation et durée de vie ? Le complexe magmatique du Torres del Paine représente l'un des meilleurs endroits au monde pour répondre à ces questions. Il se situe au sud de la Patagonie, formant un massif de 70km2. Des réponses peuvent être trouvées à différentes échelles, variant de la montagne à des minéraux de quelques 1000ème de millimètres.Il est possible de distinguer trois types de roches : des gabbros et des diorites sur une épaisseur de 250m, surmontées par des parois de granite de plus de 1000m. Les contacts entre ces roches sont tous horizontaux. Entre granites et gabbro-diorite, le contact est net, indiquant que le second magma s'est mis en place au contact avec un magma plus ancien, totalement solidifié. Entre gabbros et diorites, les contacts sont diffus, souvent non-linéaires, indiquant à l'inverse la mise en contact de magmas encore partiellement liquides. Dans la partie Ouest de cette chambre magmatique, les contacts entre roches sont verticaux. Il s'agit certainement du lieu de remplissage de la chambre magmatique.Lors du refroidissement d'un magma, différents cristaux vont se former. Leur stabilité et leur composition varient en fonction de la pression, de la température ou de la chimie du magma. La séquence de cristallisation peut être définie sur la base d'observations microscopiques et de la composition chimique des minéraux. Différents gabbros sont ainsi distingués : le gabbro à la base est riche en hornblende, d'une taille de ~5mm, sans inclusion de plagioclase mais avec des cristaux d'olivine, clinopyroxene et orthopyroxene inclus ; le gabbro supérieur est lui-aussi riche en hornblende (~5mm), avec les mêmes inclusions additionnées de plagioclase. Ces cristaux se sont formés à une température supérieure à 900°C et une profondeur correspondant à la croûte moyenne ou inférieure. Les minéraux plus fin, se trouvant hors des cristaux de hornblende des deux gabbros, sont similaires à ceux des diorites : plagioclase, biotite, hornblende, apatite, quartz et feldspath alcalin. Ces minéraux sont caractéristiques des granites. Ils ont cristallisé à ~790°C et ~2km de profondeur.La cristallisation des minéraux et leur extraction du magma par gravité provoque un changement progressif de la composition de ce dernier. Ainsi, après extraction d'olivine et d'orthopyroxene riches en Mg, de clinopyroxene riche en Ca, de plagioclase riche en Ca et Al et d'hornblende riche en Ca, Al et Mg, le liquide final sera appauvri en ces élé-ments. Un lien peut ainsi être proposé entre les diorites dont la composition est proche du liquide de départ, les granites dont la composition est similaire au liquide final, et les gabbros dont la minéralogie correspond aux minéraux extraits.L'utilisation de zircons, un minéral riche en U dont les atomes se transforment en Pb par décomposition radioactive au cours de millions d'années, permet de dater le refroidissement des roches qui les contiennent. Ainsi, il a été observé que les roches de la zone d'alimentation, à l'Ouest du complexe magmatique, ont cristallisés il y a 12.59±0.01 Ma, en même temps que les granites les plus vieux, se trouvant au sommet de la chambre magmatique, datés par Michel et al. (2008). Les deux roches pourraient donc avoir la même origine. A l'inverse, les gabbros et diorites de la chambre magmatique ont cristallisé entre 12.47±0.01Ma et 12.43±0.01Ma, les roches les plus vieilles étant à la base.En comparant la composition des roches du Torres del Paine avec celles d'autres en-tités géologiques de Patagonie, les causes du magmatisme peuvent être recherchées. A l'Ouest, on trouve en effet des intrusions granitiques, plus anciennes, caractéristiques de zones de convergence de plaque tectonique, alors qu'à l'Est, des laves basaltiques plus jeunes sont caractéristiques d'une dynamique d'extension. Sur la base des compositions chimiques des roches de ces différentes entités, l'évolution progressive de l'une à l'autre a pu être démontrée. Elle est certainement due à l'arrivée d'une dorsale océanique (zone d'extension crustale et de création de croûte océanique par la remontée de magma) dans la zone de subduction, le long des Andes.Je propose que, dans un premier temps, des magmas granitiques sont remontés dans la chambre magmatique, laissant d'importants volumes de cristaux dans la croûte pro-fonde. Dans un second épisode, les cristaux formés en profondeur ont été transportés à travers la croûte continentale, suite au mélange avec un nouveau magma injecté. Ces magmas chargés de cristaux ont traversé la zone d'alimentation avant de s'injecter dans la chambre magmatique. Différents puises ont été distingués, injectés dans la chambre magmatique du sommet à la base concernant les granites, puis à la base du granite le plus jeune pour les gabbros et diorites. Le complexe magmatique du Torres del Paine s'est construit sur une période totale de 160'000±20'000 ans.

Video-assisted right supradiaphragmatic thoracic duct ligation for non traumatic recurrent chylothorax

Introduction : Un chylothorax est une pathologie comprenant des manifestations respiratoires, nutritionnelles et immunologiques. La récidive du chylothorax ou l'échec du traitement conservateur imposent un traitement chirurgical. Ce travail rapporte notre expérience de ligature supra-diaphragmatique, vidéo-assistée du canal thoracique, pour chylothorax récurrent non traumatique. Patients et méthodes : Entre 1999 et 2004, nous avons recensé six observations (quatre du côté droit, un du côté gauche et un bilateral) Le chylothorax s'est développé chez trois patients traités par radio et chimiothérapie pour tumeur (deux lymphomes et une tumeur du sein) un dans le contexte d'une lymphangioléiomatose et un après greffe cardiaque. Résultats : Les patients ont bénéficié sous anesthésie générale, d'une ligature du canal thoracique supra-diaphragmatique, vidéo-assistée. Le temps opératoire moyen a été de 102 minutes. Le chylothorax a régressé chez cinq des six patients en sept jours. Un patient a été repris par thoracotomie droite au huitième jour pour chylothorax persistant. Dans la phase post-opératoire, un patient a développé une détresse respiratoire nécessitant une ventilation mécanique. Un autre patient a présenté un chylopéritoine important traité par un stent de Le Veen®. Le séjour moyen a été de quatorze jours sans mortalité péri-opératoire. Conclusion : Le traitement du chylothorax non traumatique récurrent est, en première intention, un traitement médical. En cas de récidive ou d'échec du traitement conservateur, le traitement chirurgical par ligature du canal thoracique supra- diaphragmatique, vidéo-assistée, permet de traiter avec succès le chylothorax récurrent non traumatique. -- Background: Chylothorax is an uncommon disorder with respiratory, nutritional and immunological manifestations. Surgical management is indicated in case of recurrence or failure after conservative treatment. We report our experience with video-assisted right-sided supradiaphrag¬matic thoracic duct ligation for non-traumatic, non-postoperative persistent or recurrent chylothorax. Patients and methods: The medical records of six patients operated at our institution between 1999 and 2004 were retrospectively reviewed. A right-sided chylothorax was found in four patients, a left-sided in one, and a bilateral in one. Three patients developed chylothorax after chemotherapy and chest irradiation for malignant diseases (lymphoma in two patients and breast cancer in one), one in the context of lymphangioleiomyomatosis, one due to a non-diagnosed lymphoma, and one after heart transplantation. Results: The mean operative time was 102 min, with an average length of hospital stay of 14 days. Persistent cessation of chylous effusion within 7 days after surgery was observed in 5/6 patients without recurrence during a mean follow-up time of 41 months. One patient with undiagnosed mediastinal lymphoma required re-operation and thoracic duct ligation on day 8 by right-sided thoracotomy due to persistent chylothorax. No 30-day mortality was recorded. Two patients presented postoperative complications including respiratory insufficiency requiring mechanical ventilation in one, and chylous ascites development requiring peritoneo-venous LeVeen shunting in one patient. Conclusions: Recurrent or persistent non-traumatic chylothorax may be successfully treated by video-assisted right supradiaphragmatic thoracic duct ligation.

Composition of weight gain during the neonatal period and longitudinal growth follow-up in premature babies.

Changes in the rate of growth and adiposity index (Quetelet index), calculated as weight/(length)2, kg/m2, were monitored from birth to 3 years in 19 premature babies (post-conceptional age 31.2 +/- 2 weeks) who were subjected during rapid growth (16 +/- 4 g/kg.day) to initial metabolic balance studies in the first weeks of life. These studies showed that the rate of fat accretion in these infants (3.3 +/- 0.9 g/kg.day) was substantially greater than that observed in fetuses of the same gestational age (2 g/kg.day) but the adiposity index was lower (9.6 +/- 1 kg/m2) than intrauterine values (11 kg/m2). Since at 6 months of age (corrected for gestational age at birth) the adiposity index was close to normality (103% of standard), the greater rate of fat accretion in early life contributed to progressively restore total body fat in premature babies. It is concluded that despite substantial fat deposition during the first weeks of life, the future evolution of these premature babies is favourable as judged from the normalization of adiposity index within the first 2 years of life.

Extreme prematurity and intra uterine growth restriction effects in brain network topology at school age

Higher risk for long-term behavioral and emotional sequelae, with attentional problems (with or without hyperactivity) is now becoming one of the hallmarks of extreme premature (EP) birth and birth after pregancy conditions leading to poor intra uterine growth restriction (IUGR) [1,2]. However, little is know so far about the neurostructural basis of these complexe brain functional abnormalities that seem to have their origins in early critical periods of brain development. The development of cortical axonal pathways happens in a series of sequential events. The preterm phase (24-36 post conecptional weeks PCW) is known for being crucial for growth of the thalamocortical fiber bundles as well as for the development of long projectional, commisural and projectional fibers [3]. Is it logical to expect, thus, that being exposed to altered intrauterine environment (altered nutrition) or to extrauterine environment earlier that expected, lead to alterations in the structural organization and, consequently, alter the underlying white matter (WM) structure. Understanding rate and variability of normal brain development, and detect differences from typical development may offer insight into the neurodevelopmental anomalies that can be imaged at later stages. Due to its unique ability to non-invasively visualize and quantify in vivo white matter tracts in the brain, in this study we used diffusion MRI (dMRI) tractography to derive brain graphs [4,5,6]. This relatively simple way of modeling the brain enable us to use graph theory to study topological properties of brain graphs in order to study the effects of EP and IUGR on childrens brain connectivity at age 6 years old.

Delayed priming promotes CNS regeneration post-rhizotomy in Neurocan and Brevican-deficient mice.

A wealth of literature has provided evidence that reactive tissue at the site of CNS injury is rich in chondroitin sulfate proteoglycans which may contribute to the non-permissive nature of the CNS. We have recently demonstrated using a murine model of human brachial plexus injury that the chondroitin sulfate proteoglycans Neurocan and Brevican are differentially expressed by two subsets of astrocytes in the spinal cord dorsal root entry zone (DREZ) following dorsal root lesion (Beggah et al., Neuroscience 133: 749-762, 2005). However, direct evidence for a growth-inhibitory role of these proteoglycans in vivo is still lacking. We therefore performed dorsal root lesion (rhizotomy) in mice deficient in both Neurocan and Brevican. Rhizotomy in these animals resulted in no significant increase in the number of sensory fibres regenerating through the DREZ compared to genetically matched controls. Likewise, a conditioning peripheral nerve lesion prior to rhizotomy, which increases the intrinsic growth capacity of sensory neurons, enhanced growth to the same extent in transgenic and control mice, indicating that absence of these proteoglycans alone is not sufficient to further promote entry into the spinal cord. In contrast, when priming of the median nerve was performed at a clinically relevant time, i.e. 7 weeks post-rhizotomy, the growth of a subpopulation of sensory axons across the DREZ was facilitated in Neurocan/Brevican-deficient, but not in control animals. This demonstrates for the first time that (i) Neurocan and/or Brevican contribute to the non-permissive environment of the DREZ several weeks after lesion and that (ii) delayed stimulation of the growth program of sensory neurons can facilitate regeneration across the DREZ provided its growth-inhibitory properties are attenuated. Post-injury enhancement of the intrinsic growth capacity of sensory neurons combined with removal of inhibitory chondroitin sulfate proteoglycans may therefore help to restore sensory function and thus attenuate the chronic pain resulting from human brachial plexus injury.

ATP citrate lyase activity is post-translationally regulated by sink strength and impacts the wax, cutin and rubber biosynthetic pathways.

Cytosolic acetyl-CoA is involved in the synthesis of a variety of compounds, including waxes, sterols and rubber, and is generated by the ATP citrate lyase (ACL). Plants over-expressing ACL were generated in an effort to understand the contribution of ACL activity to the carbon flux of acetyl-CoA to metabolic pathways occurring in the cytosol. Transgenic Arabidopsis plants synthesizing the polyester polyhydroxybutyrate (PHB) from cytosolic acetyl-CoA have reduced growth and wax content, consistent with a reduction in the availability of cytosolic acetyl-CoA to endogenous pathways. Increasing the ACL activity via the over-expression of the ACLA and ACLB subunits reversed the phenotypes associated with PHB synthesis while maintaining polymer synthesis. PHB production by itself was associated with an increase in ACL activity that occurred in the absence of changes in steady-state mRNA or protein level, indicating a post-translational regulation of ACL activity in response to sink strength. Over-expression of ACL in Arabidopsis was associated with a 30% increase in wax on stems, while over-expression of a chimeric homomeric ACL in the laticifer of roots of dandelion led to a four- and two-fold increase in rubber and triterpene content, respectively. Synthesis of PHB and over-expression of ACL also changed the amount of the cutin monomer octadecadien-1,18-dioic acid, revealing an unsuspected link between cytosolic acetyl-CoA and cutin biosynthesis. Together, these results reveal the complexity of ACL regulation and its central role in influencing the carbon flux to metabolic pathways using cytosolic acetyl-CoA, including wax and polyisoprenoids.

A simple score for estimating ischemic heart disease in patients with non-traumatic chest pain in primary care

Background: Modelling epidemiological knowledge in validated clinical scores is a practical mean of integrating EBM to usual care. Existing scores about cardiovascular disease have been largely developed in emergency settings, but few in primary care. Such a toll is needed for general practitioners (GP) to evaluate the probability of ischemic heart disease (IHD) in patients with non-traumatic chest pain. Objective: To develop a predictive model to use as a clinical score for detecting IHD in patients with non-traumatic chest-pain in primary care. Methods: A post-hoc secondary analysis on data from an observational study including 672 patients with chest pain of which 85 had IHD diagnosed by their GP during the year following their inclusion. Best subset method was used to select 8 predictive variables from univariate analysis and fitted in a multivariate logistic regression model to define the score. Reliability of the model was assessed using split-group method. Results: Significant predictors were: age (0-3 points), gender (1 point), having at least one cardiovascular risks factor (hypertension, dyslipidemia, diabetes, smoking, family history of CVD; 3 points), personal history of cardiovascular disease (1 point), duration of chest pain from 1 to 60 minutes (2 points), substernal chest pain (1 point), pain increasing with exertion (1 point) and absence of tenderness at palpation (1 point). Area under the ROC curve for the score was of 0.95 (IC95% 0.93; 0.97). Patients were categorised in three groups, low risk of IHD (score under 6; n = 360), moderate risk of IHD (score from 6 to 8; n = 187) and high risk of IHD (score from 9-13; n = 125). Prevalence of IHD in each group was respectively of 0%, 6.7%, 58.5%. Reliability of the model seems satisfactory as the model developed from the derivation set predicted perfectly (p = 0.948) the number of patients in each group in the validation set. Conclusion: This clinical score based only on history and physical exams can be an important tool in the practice of the general physician for the prediction of ischemic heart disease in patients complaining of chest pain. The score below 6 points (in more than half of our population) can avoid demanding complementary exams for selected patients (ECG, laboratory tests) because of the very low risk of IHD. Score above 6 points needs investigation to detect or rule out IHD. Further external validation is required in ambulatory settings.

Caveolin expression changes in the neurovascular unit after juvenile traumatic brain injury: signs of blood-brain barrier healing?

Traumatic brain injury (TBI) is one of the major causes of death and disability in pediatrics, and results in a complex cascade of events including the disruption of the blood-brain barrier (BBB). A controlled-cortical impact on post-natal 17 day-old rats induced BBB disruption by IgG extravasation from 1 to 3 days after injury and returned to normal at day 7. In parallel, we characterized the expression of three caveolin isoforms, cav-1, cav-2 and cav-3. While cav-1 and cav-2 are expressed on endothelial cells, both cav-1 and cav-3 were found to be present on reactive astrocytes, in vivo and in vitro. Following TBI, cav-1 expression was increased in blood vessels at 1 and 7 days in the perilesional cortex. An increase of vascular cav-2 expression was observed 7 days after TBI. In contrast, astrocytic cav-3 expression decreased 3 and 7 days after TBI. Activation of eNOS (via its phosphorylation) was detected 1 day after TBI and phospho-eNOS was detected both in association with blood vessels and with astrocytes. The molecular changes involving caveolins occurring in endothelial cells following juvenile-TBI might participate, independently of eNOS activation, to a mechanism of BBB repair while, they might subserve other undefined roles in astrocytes.

Evidence for a new post-translational modification in Staphylococcus aureus: Hydroxymethylation of asparagine and glutamine.

Staphylococcus aureus is an opportunistic pathogen whose infectious capacity depends on surface proteins, which enable bacteria to colonize and invade host tissues and cells. We analyzed "trypsin-shaved" surface proteins of S. aureus cultures by high resolution LC-MS/MS at different growth stages and culture conditions. Some modified peptides were identified, with a mass shift corresponding to the addition of a CH(2)O group (+30.0106u). We present evidence that this shift corresponds to a hyxdroxymethylation of asparagine and glutamine residues. This known but poorly documented post-translational modification was only found in a few proteins of S. aureus grown under specific conditions. This specificity seemed to exclude the hypothesis of an artifact due to sample preparation. Altogether hydroxymethylation was observed in 35 peptides from 15 proteins in our dataset, which corresponded to 41 modified sites, 35 of them being univocally localized. While no function can currently be assigned to this post-translational modification, we hypothesize that it could be linked to modulation of virulence factors, since it was mostly found on some surface proteins of S. aureus.

Post-mortem β-hydroxybutyrate determination in synovial fluid.

β-hydroxybutyrate concentrations were determined in blood and synovial fluid in a series of medico-legal cases including hypothermia fatalities, individuals found dead in a cold environment and non-hypothermia cases with various, non-traumatic causes of death. Hypothermia was considered to be the cause of death according to circumstantial elements indicating exposure to cold, autopsy findings, biochemical investigation results and exclusion of other causes of death. The intention of this study was to characterize β-hydroxybutyrate distribution in synovial fluid and assess its usefulness for the postmortem diagnosis of antemortem abnormalities in blood β-hydroxybutyrate levels. Unenhanced CT scans, autopsies, histology, neuropathology, toxicology, and biochemistry were systematically performed. Within the limited number of subjects included in the study, the results indicate that abnormalities in antemortem β-hydroxybutyrate blood levels, as may be observed in hypothermia fatalities, are reflected in postmortem synovial fluid values. These preliminary findings notwithstanding, synovial fluid analysis to determine β-hydroxybutyrate is unlikely to be generally applied due to the more invasive collection technique it requires and could be limited to special cases in which biological fluids systematically collected upon autopsy are unavailable.

Normobaric Hyperoxia is Associated with Increased Cerebral Excitotoxicity After Severe Traumatic Brain Injury.

BACKGROUND: Normobaric oxygen therapy is frequently applied in neurocritical care, however, whether supplemental FiO2 has beneficial cerebral effects is still controversial. We examined in patients with severe traumatic brain injury (TBI) the effect of incremental FiO2 on cerebral excitotoxicity, quantified by cerebral microdialysis (CMD) glutamate. METHODS: This was a retrospective analysis of a database of severe TBI patients monitored with CMD and brain tissue oxygen (PbtO2). The relationship of FiO2-categorized into four separate ranges (<40, 41-60, 61-80, and >80 %)-with CMD glutamate was examined using ANOVA with Tukey's post hoc test. RESULTS: A total of 1,130 CMD samples from 36 patients-monitored for a median of 4 days-were examined. After adjusting for brain (PbtO2, intracranial pressure, cerebral perfusion pressure, lactate/pyruvate ratio, Marshall CT score) and systemic (PaCO2, PaO2, hemoglobin, APACHE score) covariates, high FiO2 was associated with a progressive increase in CMD glutamate [8.8 (95 % confidence interval 7.4-10.2) µmol/L at FiO2 < 40 % vs. 12.8 (10.9-14.7) µmol/L at 41-60 % FiO2, 19.3 (15.6-23) µmol/L at 61-80 % FiO2, and 22.6 (16.7-28.5) µmol/L at FiO2 > 80 %; multivariate-adjusted p < 0.05]. The threshold of FiO2-related increase in CMD glutamate was lower for samples with normal versus low PbtO2 < 20 mmHg (FiO2 > 40 % vs. FiO2 > 60 %). Hyperoxia (PaO2 > 150 mmHg) was also associated with increased CMD glutamate (adjusted p < 0.001). CONCLUSIONS: Incremental normobaric FiO2 levels were associated with increased cerebral excitotoxicity in patients with severe TBI, independent from PbtO2 and other important cerebral and systemic determinants. These data suggest that supra-normal oxygen may aggravate secondary brain damage after severe TBI.