Etude et conservation-restauration d’un Qilin en émail cloisonné chinois provenant du musée des Arts décoratifs de Paris

The documentary background on Chinese cloisonné enamels is incomplete, therefore its conservation enables the better understanding of their origin, technical nature and history. The last year of conservation studies at the Institut national du patrimoine was focused on the study of an 18th-century Chinese cloisonné enamel from the Arts décoratifs Museum (Paris). A research was carried out on the use of paper rubbers for the cleaning of copper cloisons gilded with mercury amalgam. Cleaning operations were completed by the use of peelable gel on large gilded areas, the dismantling and cleaning, as well as the conservation of the enamel.La documentation sur les émaux cloisonnés chinois est lacunaire. Ainsi leur conservation-restauration aide à la compréhension de leur origine, leur technicité et leur histoire. Le mémoire de fin d’étude à l’Institut national du patrimoine a permis d’étudier un émail cloisonné chinois du xviiie siècle du musée des Arts décoratifs (Paris). Une recherche a alors été développée sur l’usage de gommes de papeterie pour le nettoyage de fines cloisons de cuivre dorées au mercure. Ce nettoyage a été complété par l’utilisation d’un gel pelable sur les larges plages dorées de l’objet, par un démontage complexe, mais également par un travail de nettoyage et de restauration de l’émail

Implementation of optimized supportive care and hospital needs along the management of patients with advanced lung cancer

Background: Supportive care in cancer (SCC) have been recommended to be integrated in the management of patients with lung cancer all along the course of the disease. We took advantage of a pilot program of early implementation of optimized SCC, to report the feasibility such program in patients with advanced lung cancer, and correlate patient characteristics and outcomes with the actual use of optimized SCC.Methods: This study is a retrospective analysis of all consecutive patients with lung cancer treated at our center between 2012 and 2016. Optimized SCC included the intervention of a nurse for the home-hospital network coordination, as well as socio-aesthetics, psychomotricity, art-therapy, adapted physical activity, and also establishment of at-home hospitalization.Results: 309 patients were included. Median overall survival was 11.2 months. Unplanned hospitalizations occurred for 276 (89%) patients. The median duration of hospital stay was 19 days. Unplanned hospitalizations more frequently occurred within the first 3 months after the diagnosis of advanced cancer, and in the last 3 months before death. A short - less than 3 months - delay between diagnosis and unplanned hospitalization was associated with poor outcome. 272 (88%) patients received optimized SCC, within a median delay of 8 weeks after diagnosis. Intervention of the nurse for in- and out-patient network coordination was done for 143 (46%) patients, and at-home hospitalization was organized for 78 (25%) patients. The outcome of patients who received optimized SCC was numerically, but not significantly better (median overall survival of 11.8 vs. 6.9 months, p = 0.270).Conclusion: Our study provides landmark data to support an early integration of optimized SCC for patients with advanced lung cancer, that includes multimodal supportive care interventions along the course of the disease. This highlights the role of multidisciplinary teams to optimize the management of patients with advanced lung cancer

Identification and characterization of super-responders after cardiac resynchronization therapy.

International audienceCardiac resynchronization therapy (CRT) has been shown to induce a spectacular effect on left ventricular (LV) function in certain patients. Our aim was to analyze and characterize the super-responders (SRs) to CRT using echocardiography in 186 patients with a conventional indication according to the European Society Cardiology guidelines. The investigation took place before and 6 months after implantation. CRT-SRs were defined by an improvement of the New York Heart Association functional class and LV ejection fraction to > or = 50% in absolute values associated with a relative LV end-systolic volume reduction of > or = 15%. Of the 186 patients, 18 (9.7%) were identified as CRT-SRs and had a significantly lower prevalence of ischemic etiology (11%), lower LV dimensions, lower left atrial volume, and greater global longitudinal strain at baseline. Receiver operating characteristics curves identified global longitudinal strain as the strongest parameter for predicting CRT-SRs, with a cutoff value of -12% (area under the curve 0.87, sensitivity 71%, and specificity 85%, p <0.01). In conclusion, in the present retrospective study, only a left atrial volume <55 ml and global longitudinal strain < or = -12% were independent predictors of CRT-SRs

Interaction between the SifA Virulence Factor and Its Host Target SKIP Is Essential for Salmonella Pathogenesis*

SifA is a Salmonella effector that is translocated into infected cells by the pathogenicity island 2-encoded type 3 secretion system. SifA is a critical virulence factor. Previous studies demonstrated that, upon translocation, SifA binds the pleckstrin homology motif of the eukaryotic host protein SKIP. In turn, the SifA-SKIP complex regulates the mobilization of the molecular motor kinesin-1 on the bacterial vacuole. SifA exhibits multiple domains containing functional motifs. Here we performed a molecular dissection and a mutational study of SifA to evaluate the relative contribution of the different domains to SifA functions. Biochemical and crystallographic analysis confirmed that the N-terminal domain of SifA is sufficient to interact with the pleckstrin homology domain of SKIP, forming a 1:1 complex with a micromolar dissociation constant. Mutation of the tryptophan residue in the WXXXE motif, which has been proposed to mimic active form of GTPase, deeply affected the stability and the translocation of SifA while mutations of the glutamic residue had no functional impact. A SifA L130D mutant that does not bind SKIP showed a ΔsifA-like phenotype both in infected cells and in the mouse model of infection. We concluded that the WXXXE motif is essential for maintaining the tertiary structure of SifA, the functions of which require the interaction with the eukaryotic protein SKIP

Global longitudinal strain as a major predictor of cardiac events in patients with depressed left ventricular function: a multicenter study.

International audienceBACKGROUND: The risk stratification of patients with left ventricular (LV) dysfunction can be performed using echocardiographic parameters such as the ejection fraction (EF). Recently, new technologies based on deformation measurements have been shown to identify early myocardial dysfunction before EF decrease. Consequently, tools such as two-dimensional strain have been incorporated into echocardiographic systems, allowing for fast, reliable, and reproducible calculation of longitudinal components of LV systolic deformation. The hypothesis in this study was that as a more sensitive marker of LV dysfunction, longitudinal strain would allow for the risk stratification of patients with heart failure. METHODS: This multicenter study included 147 patients with heart failure with LV EFs ≤ 45% (mean age, 64 ± 14 years; 74% men; mean LV EF, 29.9 ± 8.9%). Conventional echocardiographic parameters as well as global and segmental longitudinal strain were measured and compared with these values in a control population. Patients were monitored for cardiac events, defined as a composite criterion, over 12 months. RESULTS: Clinical events were observed in 20% of patients during the 12-month follow-up period. On receiver operating characteristic curve analysis, global longitudinal strain had the highest prognostic value (area under the curve, 0.83) and the highest combination of sensitivity (73%) and specificity (83%), using a cutoff value of -7%. CONCLUSION: Strain assessment is highly feasible and reliable in patients with LV dysfunction and allows for cardiovascular risk stratification in patients with heart failure with greater accuracy than LV EF

Validation of an echocardiographic multiparametric strategy to increase responders patients after cardiac resynchronization: a multicentre study.

International audienceAIMS: We sought to develop and validate a multiparametric algorithm by applying previously validated criteria to predict cardiac resynchronization therapy (CRT) response in a multicentre study. Thirty per cent of patients treated by CRT fail to respond to the treatment. Although dyssynchrony by echocardiography has been used to improve the selection of patients, the complexity of myocardial contraction has generated a moderate improvement using any of several individual parameters. METHODS AND RESULTS: Two hundred end-stage heart failure patients [NYHA 3-4 and left ventricular ejection fraction (LVEF)120 ms were included. Echocardiography analysis focused on the following parameters: atrioventricular dyssynchrony, interventricular dyssynchrony, and intraventricular dyssynchrony that integrated radial (PSAX M-mode) and longitudinal [tissue Doppler imaging (TDI)] evaluations for spatial (wall to wall) and temporal (wall end-systole to mitral valve opening) dyssynchrony diagnosis. Following CRT implantation, patients were monitored for 6 months with functional and echo evaluations defining responders by a 15% reduction in end-systolic volume. Mean QRS duration and LVEF were 152 +/- 17 ms and 25 +/- 8%. There was a CRT response in 57% of patients, independent of QRS width. Mean prevalence of positive criteria was 34 +/- 8%. Feasibility and variability averages were 81 +/- 20% and 9 +/- 4%. In a single parametric approach, ranges of sensitivities and specificities were 18-65% and 45-84% with a mean of 41% and 66%. A multiparametric approach by focusing on criteria combination decreased the mean rate of false-positive results to 14 +/- 12%, 5 +/- 4%, 2 +/- 2%, and 1 +/- 2% from one to four parameters, respectively. More than three parameters were associated with a specificity above 90% and a positive predictive value above 65%. Reproducibility of this global strategy was 91%. CONCLUSION: A multiparametric echocardiographic strategy based on the association of conventional criteria is a better indicator of CRT response than the existing single parametric approaches

Combining Homologous Recombination and Phosphopeptide-binding Data to Predict the Impact of BRCA1 BRCT Variants on Cancer Risk

International audienceBRCA1 mutations have been identified that increase the risk of developing hereditary breast and ovarian cancers. Genetic screening is now offered to patients with a family history of cancer, to adapt their treatment and the management of their relatives. However, a large number of BRCA1 variants of uncertain significance (VUS) are detected. To better understand the significance of these variants, a high-throughput structural and functional analysis was performed on a large set of BRCA1 VUS. Information on both cellular localization and homology-directed DNA repair (HR) capacity was obtained for 78 BRCT missense variants in the UMD-BRCA1 database and measurement of the structural stability and phosphopeptide-binding capacities was performed for 42 mutated BRCT domains. This extensive and systematic analysis revealed that most characterized causal variants affect BRCT-domain solubility in bacteria and all impair BRCA1 HR activity in cells. Furthermore, binding to a set of 5 different phosphopeptides was tested: all causal variants showed phosphopeptide-binding defects and no neutral variant showed such defects. A classification is presented on the basis of mutated BRCT domain solubility, phosphopeptide-binding properties, and VUS HR capacity. These data suggest that HR-defective variants, which present, in addition, BRCT domains either insoluble in bacteria or defective for phosphopeptide binding, lead to an increased cancer risk. Furthermore, the data suggest that variants with a WT HR activity and whose BRCT domains bind with a WT affinity to the 5 phosphopeptides are neutral. The case of variants with WT HR activity and defective phosphopeptide binding should be further characterized, as this last functional defect might be sufficient per se to lead to tumorigenesis. IMPLICATIONS: The analysis of the current study on BRCA1 structural and functional defects on cancer risk and classification presented may improve clinical interpretation and therapeutic selection