Identification of in vitro phosphorylation sites in the growth cone protein SCG10. Effect Of phosphorylation site mutants on microtubule-destabilizing activity.

SCG10 is a neuron-specific, membrane-associated protein that is highly concentrated in growth cones of developing neurons. Previous studies have suggested that it is a regulator of microtubule dynamics and that it may influence microtubule polymerization in growth cones. Here, we demonstrate that in vivo, SCG10 exists in both phosphorylated and unphosphorylated forms. By two-dimensional gel electrophoresis, two phosphoisoforms were detected in neonatal rat brain. Using in vitro phosphorylated recombinant protein, four phosphorylation sites were identified in the SCG10 sequence. Ser-50 and Ser-97 were the target sites for protein kinase A, Ser-62 and Ser-73 for mitogen-activated protein kinase and Ser-73 for cyclin-dependent kinase. We also show that overexpression of SCG10 induces a disruption of the microtubule network in COS-7 cells. By expressing different phosphorylation site mutants, we have dissected the roles of the individual phosphorylation sites in regulating its microtubule-destabilizing activity. We show that nonphosphorylatable mutants have increased activity, whereas mutants in which phosphorylation is mimicked by serine-to-aspartate substitutions have decreased activity. These data suggest that the microtubule-destabilizing activity of SCG10 is regulated by phosphorylation, and that SCG10 may link signal transduction of growth or guidance cues involving serine/threonine protein kinases to alterations of microtubule dynamics in the growth cone.

Evaluating spine micro-architectural texture (via TBS) discriminates major osteoporotic fractures from controls both as well as and independent of site matched BMD: the Eastern European TBS study.

The aim of the study was to assess the clinical performance of the model combining areal bone mineral density (aBMD) at spine and microarchitecural texture (TBS) for the detection of the osteoporotic fracture. The Eastern European Study is a multicenter study (Serbia, Bulgaria, Romania and Ukraine) evaluating the role of TBS in routine clinical practice as a complement to aBMD. All scans were acquired on Hologic Discovery and GE Prodigy densitometers in a routine clinical manner. The additional clinical values of aBMD and TBS were analyzed using a two steps classification tree approach (aBMD followed by TBS tertiles) for all type of osteoporotic fracture (All-OP Fx). Sensitivity, specificity and accuracy of fracture detection as well as the Net Reclassification Index (NRI) were calculated. This study involves 1031 women subjects aged 45 and older recruited in east European countries. Clinical centers were cross-calibrated in terms of BMD and TBS. As expected, areal BMD (aBMD) at spine and TBS were only moderately correlated (r (2) = 0.19). Prevalence rate for All-OP Fx was 26 %. Subjects with fracture have significant lower TBS and aBMD than subjects without fracture (p < 0.01). TBS remains associated with the fracture even after adjustment for age and aBMD with an OR of 1.27 [1.07-1.51]. When using aBMD T-score of -2.5 and the lowest TBS tertile thresholds, both BMD and TBS were similar in terms of sensitivity (35 vs. 39 %), specificity (78 vs. 80 %) and accuracy (64 vs. 66 %). aBMD and TBS combination, induced a significant improvement in sensitivity (+28 %) and accuracy (+17 %) compared to aBMD alone whereas a moderate improvement was observed in terms of specificity (+9 %). The overall combination gain was 36 % as expressed using the NRI. aBMD and TBS combination decrease significantly the number of subjects needed to diagnose from 7 for aBMD alone to 2. In a multi-centre Eastern European cohort, we have shown that the use of TBS in addition to the aBMD permit to reclassified correctly more than one-third of the overall subjects. Furthermore, the number of subjects needed to diagnose fell to 2 subjects. Economical studies have to be performed to evaluate the gain induced by the use of TBS for the healthcare system.

Measures to prevent surgical site infections: what surgeons (should) do.

BACKGROUND: The present study was designed to evaluate surgeons' strategies and adherence to preventive measures against surgical site infections (SSIs). MATERIALS AND METHODS: All surgeons participating in a prospective Swiss multicentric surveillance program for SSIs received a questionnaire developed from the 2008 National (United Kingdom) Institute for Health and Clinical Excellence (NICE) clinical guidelines on prevention and treatment of SSIs. We focused on perioperative management and surgical technique in hernia surgery, cholecystectomy, appendectomy, and colon surgery (COL). RESULTS: Forty-five of 50 surgeons contacted (90%) responded. Smoking cessation and nutritional screening are regularly propagated by 1/3 and 1/2 of surgeons, respectively. Thirty-eight percent practice bowel preparation before COL. Preoperative hair removal is routinely (90%) performed in the operating room with electric clippers. About 50% administer antibiotic prophylaxis within 30 min before incision. Intra-abdominal drains are common after COL (43%). Two thirds of respondents apply nonocclusive wound dressings that are manipulated after hand disinfection (87%). Dressings are usually changed on postoperative day (POD) 2 (75%), and wounds remain undressed on POD 2-3 or 4-5 (36% each). CONCLUSIONS: Surgeons' strategies to prevent SSIs still differ widely. The adherence to the current NICE guidelines is low for many procedures regardless of the available level of evidence. Further research should provide convincing data in order to justify standardization of perioperative management.

Homing phenotypes of tumor-specific CD8 T cells are predetermined at the tumor site by crosspresenting APCs.

Expression of tissue-specific homing molecules directs antigen-experienced T cells to particular peripheral tissues. In studies using soluble antigens that focused on skin and gut, antigen-presenting cells (APCs) within regional lymphoid tissues were proposed to be responsible for imprinting homing phenotypes. Whether this occurs in other sites and after physiologic antigen processing and presentation is unknown. We define in vivo imprinting of distinct homing phenotypes on monospecific T cells responding to antigens expressed by tumors in intracerebral, subcutaneous, and intraperitoneal sites with efficient brain-tropism of CD8 T cells crossprimed in the cervical lymph nodes (LNs). Multiple imprinting programs could occur simultaneously in the same LN when tumors were present in more than one site. Thus, the identity of the LN is not paramount in determining the homing phenotype; this critical functional parameter is dictated upstream at the site of antigen capture by crosspresenting APCs.

Ground-state order and spin-lattice coupling in tetrahedral spin systems Cu2Te2O5X2 (X = Br or Cl)

High-resolution ac susceptibility and thermal conductivity measurement on Cu2Te2O5X2 (X=Br,Cl) single crystals are reported. For Br-sample, sample dependence prevents one from distinguishing between possibilities of magnetically ordered and spin-singlet ground states. In Cl-sample a three-dimensional transition at 18.5 K is accompanied by almost isotropic behavior of susceptibility and almost switching behavior of thermal conductivity. Thermal conductivity studies suggest the presence of a tremendous spin-lattice coupling characterizing Cl- but not Br-sample. Below the transition Cl-sample is in a complex magnetic state involving AF order but also the elements consistent with the presence of a gap in the excitation spectrum.

Risk Factors for Incisional and Organ Space Surgical Site Infections After Liver Resection are Different.

BACKGROUND: Surgical site infection (SSI) is a common cause of major morbidity after liver resection. This study aimed to identify the risk factors for incisional and organ/space SSIs after liver resection. METHODS: Our liver surgery database was retrospectively analyzed for patients treated between January 2009 and November 2012 in a tertiary care Swiss hospital. Univariate and multivariate analyses were conducted on preoperative, intraoperative, and postoperative variables to identify risk factors for incisional and organ/space SSIs. RESULTS: In a total of 226 patients, SSI incidences were 12.8 % (incisional), 4.0 % (organ/space), and 1.8 % (both). Univariate analysis showed that incisional SSIs were associated with high American Society of Anesthesiologists (ASA) scores, preoperative anemia, hypoalbuminemia, low prothrombin time, viral or alcoholic chronic hepatitis, liver cirrhosis, and prolonged operation times. Organ/space SSIs were associated with high rates of red blood cell transfusions, concomitant bowel surgery, and prolonged operation times. Multivariate analysis revealed that risk factors for incisional SSIs were anemia [odds ratio (OR) 2.82], high ASA scores (OR 2.88), presence of hepatitis or cirrhosis (OR 5.07), and prolonged operation times (OR 9.61). The only risk factor for organ/space SSIs was concomitant bowel surgery (OR 5.53). Hospital stays were similar in organ/space and incisional SSI groups, but significantly longer for those with both organ/space and incisional SSIs. CONCLUSIONS: High ASA scores, anemia, chronic hepatitis or liver cirrhosis, and prolonged operations increased the risk of incisional SSIs; concomitant bowel surgery increased the risk of organ/space SSI. Specific precautions to prevent organ/space and incisional SSIs may shorten hospital stays.

T cells at the site of autoimmune inflammation show increased potential for trogocytosis

Les lymphocytes T CD4+ sont connus pour leur potentiel d'acquisition de fragments membraneux de cellules présentatrices d'antigène (CPA) dans un processus nommé trogocytose. Ce phénomène est observé lors de l'interaction entre le lymphocyte T CD4+ antigène-spécifique et la CPA lors de la présentation de l'antigène en question, et dépend donc de la spécificité du lymphocyte T CD4+. L'identification des lymphocytes T CD4+ sujets à la trogocytose en co-culture avec des CPA chargées d'un antigène connu permet d'enrichir des lymphocytes T antigène-spécifiques sans connaître leur spécificité exacte ou leur profil de production de cytokines. Dans cette étude, nous avons donc cherché à évaluer l'utilité de cette méthode dans l'identification de la spécificité des lymphocytes T effecteurs et régulateurs lors de l'inflammation auto-immune avec des spécificités souvent inconnues. La trogocytose a démontré son efficacité dans la détection de lymphocytes T réactifs à la protéine basique de myéline in vitro ainsi qu'ex vivo après immunisation. Cependant, le potentiel de la trogocytose à identifier des lymphocytes T régulateurs antigène-spécifiques est limité par le fait que les lymphocytes T régulateurs Foxp3+ montrent un taux élevé de manière constitutive de trogocytose comparé aux lymphocytes T Foxp3-, Un taux localement élevé de trogocytose lors d'un état inflammatoire (observé au niveau des lymphocytes T effecteurs et régulateurs isolés du système nerveux central enflammé) empêche l'utilisation de la trogocytose dans l'évaluation de la réactivité antigénique de cellules extraites d'un site inflammatoire. Nos résultats montrent la possibilité d'enrichir des lymphocytes T conventionnels antigène- réactifs en périphérie par détection au moyen de la trogocytose. Nous avons aussi montré les limitations de cette méthode dans sa capacité d'identifier des lymphocytes T effecteurs et régulateurs antigène- réactifs extraits de sites inflammatoires. Le potentiel de trogocytose élevé dans les sites d'inflammation soulève la question de la signification biologique de ce phénomène dans l'inflammation, dans la suppression médiée par les lymphocytes T régulateurs et dans le maintien de la tolérance immunologique dans des états de santé variables.

Evaluation 2015 du site www.ciao.ch

En 2015, l'Association CIAO a démarré un processus de réflexion en profondeur sur son offre et son identité de manière générale, avec l'objectif de pouvoir être reconnue comme un service d'utilité publique. L'évaluation vise ainsi à situer le rôle du site ciao.ch au sein du dispositif de santé publique, et plus particulièrement des outils de prévention-santé destinés aux adolescents. La notoriété et l'effet du site sur son public-cible et pour les professionnels travaillant au contact des adolescents sont également évalués. Les résultats de cette évaluation permettront à l'équipe de CIAO de compléter les indices qu'elle possède déjà dans les aspects évalués. Les recommandations finales conduiront à une éventuelle redéfinition de certains aspects du site, de son public et de ses vecteurs de promotion, dans le but de correspondre au mieux aux besoins et aux modes de vie de ses bénéficiaires, et de garantir son efficacité.