Dynamic control of proinflammatory cytokines Il-1β and Tnf-α by macrophages in zebrafish spinal cord regeneration

Spinal cord injury leads to a massive response of innate immune cells in non-regenerating mammals, but also in successfully regenerating zebrafish. However, the role of the immune response in successful regeneration is poorly defined. Here we show that inhibiting inflammation reduces and promoting it accelerates axonal regeneration in spinal-lesioned zebrafish larvae. Mutant analyses show that peripheral macrophages, but not neutrophils or microglia, are necessary for repair. Macrophage-less irf8 mutants show prolonged inflammation with elevated levels of Tnf-α and Il-1β. Inhibiting Tnf-α does not rescue axonal growth in irf8 mutants, but impairs it in wildtype animals, indicating a pro-regenerative role of Tnf-α. In contrast, decreasing Il-1β levels or number of Il-1β+ neutrophils rescue functional regeneration in irf8 mutants. However, during early regeneration, interference with Il-1β function impairs regeneration in irf8 and wildtype animals. Hence, inflammation is dynamically controlled by macrophages to promote functional spinal cord regeneration in zebrafish

La séméiotique de Charles S. Peirce

Savan David. La séméiotique de Charles S. Peirce. In: Langages, 14ᵉ année, n°58, 1980. La sémiotique de C.S Peirce, sous la direction de François Peraldi. pp. 9-23

Multivariate model for predicting postoperative blood loss in children undergoing cardiac surgery: A preliminary study

Background Postoperative bleeding and blood product transfusion increase morbidity, mortality, and costs after cardiac surgery. However, factors that could accurately predict bleeding have not been well studied in children undergoing cardiac surgery. This study aims at determining factors that could be used to predict postoperative bleeding in this paediatric population. Methods We included 182 children undergoing congenital heart surgery. Significant bleeding was defined as a blood loss that exceeds 10% of total blood volume within the first 6 postoperative hours. Univariate and multivariate logistic regression analyses were performed to determine variables independently associated with bleeding. These variables were used to calculate a probability for each individual child to develop postoperative bleeding. Results According to the definition of bleeding, 44 patients were included into the 'bleeder' group and 138 into the 'non-bleeder' group. Factors independently associated with postoperative bleeding were preoperative body weight, the presence of a cyanotic disease, and the time required for wound closure. Based on these three parameters, we calculated the probability of bleeding and found a significant relationship with postoperative bleeding. Finally, a calculated probability of 0.59 can predict significant postoperative blood loss with a sensitivity of 84% and a specificity of 64%. Conclusions This study shows that preoperative body weight, cyanotic disease, and wound closure duration are best predictors of bleeding in the paediatric population after cardiac surgery. The combination of these three factors could be used at the end of the surgery to estimate the probability of postoperative bleeding. The Author [2013].SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Plasma fibrinogen concentration is correlated with postoperative blood loss in children undergoing cardiac surgery: A retrospective review

BACKGROUND: Fibrinogen supplementation is increasingly recommended with the use of rotational thromboelastometry (ROTEM). However, data regarding the paediatric population are sparse. OBJECTIVE: We aimed to assess the relationship between plasma fibrinogen concentration and postoperative blood loss in children undergoing cardiac surgery. DESIGN: Retrospective analysis. SETTING: Data prospectively recorded in our departmental database between September 2010 and January 2012. PATIENTS: Data from 156 children scheduled for congenital heart surgery with ROTEM performed at the end of cardiopulmonary bypass (CPB) were analysed. INTERVENTION: None. MAIN OUTCOME MEASURES: Abnormal bleeding was defined as blood loss that exceeded 10% of total blood volume within the first 6 postoperative hours. Logistic regression analyses were used to determine variables associated with bleeding. Correlation analyses and receiver operating characteristic (ROC) curves were designed to evaluate the relationship between blood loss and plasma fibrinogen concentration or ROTEM variables, if relevant. RESULTS: Thirty-six children were considered as 'bleeders' and 120 as 'nonbleeders'. Univariate and multivariate logistic regression analysis revealed time for wound closure, clot formation time, maximal clot firmness (MCF) and plasma fibrinogen concentration as variables independently associated with postoperative bleeding. MCF was best correlated with plasma fibrinogen concentration. ROC curves for blood loss versus fibrinogen concentration and MCF showed that a plasma fibrinogen concentration of 1.5 g l-1 and a MCF value 3mm or less could be used to predict blood loss. CONCLUSION: Post-CPB plasma fibrinogen concentration significantly influences blood loss in children undergoing cardiac surgery. A fibrinogen concentration of at least 1.5 g l-1 or a MCF of at least 3mm should accurately predict excessive blood loss in cardiac surgery children. Further prospective trials are needed to assess the effect of fibrinogen supplementation on postoperative blood loss in this population. © 2014 Copyright European Society of Anaesthesiology.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

2-Furanylmethyl <i>N</i>-(2-propenyl)carbamate

The overexpression of protein phosphatase 5 (PP5) has been correlated to tumor cell reproduction, making it a candidate for small molecule drug therapy. Prior work has focused on functionalized and decorated scaffolds that maximize contacts within and around the active site. The assembly and testing of cantharidin derivatives decorated with functionalized attachments has been our focus in order to affect the optimal binding of PP5. Condensation of 2-hydroxymethylfuran with allyl isocyanate meets the metrics of the rapid installment of functionality, as part of the core scaffold. Once condensed, cycloaddition followed by hydrogenation produces the desired derivative of norcantharidin in three synthetic steps

Angle Stable Nails Provide Improved Healing for a Complex Fracture Model in the Femur

Background Conventional nails are being used for an expanding range of fractures from simple to more complex. Angle stable designs are a relatively new innovation; however, it is unknown if they will improve healing for complex fractures. Questions/purposes When comparing traditional and angle stable nails to treat complex open canine femur fractures, the current study addressed the following questions: do the two constructs differ in (1) radiographic evidence of bone union across the cortices; (2) stability as determined by toggle (torsional motion with little accompanying torque) and angular deformation; (3) biomechanical properties, including stiffness in bending, axial compression, and torsional loading, and construct failure properties in torsion; and (4) degree of bone tissue mineralization? Methods Ten hounds with a 1-cm femoral defect and periosteal stripping were treated with a reamed titanium angle stable or nonangle stable nail after the creation of a long soft tissue wound. Before the study, the animals were randomly assigned to receive one of the nails and to be evaluated with biomechanical testing or histology. After euthanasia at 16 weeks, all operative femora were assessed radiographically. Histological or biomechanical evaluation was conducted of the operative bones with nails left in situ compared with the nonoperative contralateral femora. Results Radiographic and gross inspection demonstrated hypertrophic nonunion in all 10 animals treated with the nonangle stable nail, whereas six of 10 animals treated with the angle stable nail bridged at least one cortex (p = 0.023). The angle stable nail construct demonstrated no toggle in nine of 10 animals, whereas all control femora exhibited toggle. The angle stable nail demonstrated less angular deformation and toggle (p ≤ 0.005) and increased compressive stiffness (p = 0.001) compared with the conventional nonangle stable nail. Histology demonstrated more nonmineralized tissue in the limbs treated with the conventional nail (p = 0.005). Conclusions Angle stable nails that eliminate toggle lead to enhanced yet incomplete fracture healing in a complex canine fracture model. Clinical Relevance Care should be taken in tailoring the nail design features to the characteristics of the fracture and the patient