Circulating Secretory Phospholipase A2 Activity Predicts Recurrent Events in Patients With Severe Acute Coronary Syndromes

ObjectivesThe purpose of this study was to determine the prognostic value of circulating secretory phospholipase A2 (sPLA2) activity in patients with acute coronary syndromes (ACS).BackgroundThe plasma level of type IIA sPLA2 is a risk factor for coronary artery disease (CAD) and is associated with adverse outcomes in patients with stable CAD. The prognostic impact of sPLA2 in patients with ACS is unknown.MethodsSecretory phospholipase A2 antigen levels and activity were measured in plasma samples of 446 patients with ACS, obtained at the time of enrollment.ResultsBaseline sPLA2 activity was associated with the risk of death and myocardial infarction (MI). The unadjusted rate of death and MI increased in a stepwise fashion with increasing tertiles of sPLA2 activity (p < 0.0001). The association remained significant in the subgroup of patients who had MI with ST-segment elevation (p = 0.014) and the subgroup of patients who had unstable angina or non–ST-segment elevation MI (p < 0.002). After adjustment for clinical and biological variables, the hazard ratios for the combined end point of death or MI in the third tertile of sPLA2 compared with the first and second tertiles was 3.08 (95% confidence interval, 1.37 to 6.91, p = 0.006).ConclusionsA single measurement of plasma sPLA2 activity at the time of enrollment provides strong independent information to predict recurrent events in patients with ACS

Characteristics and impact of infiltration of B-cells from systemic sclerosis patients in a 3D healthy skin model

IntroductionIn systemic sclerosis (SSc), B-cells are activated and present in the skin and lung of patients where they can interact with fibroblasts. The precise impact and mechanisms of the interaction of B-cells and fibroblasts at the tissular level are poorly studied.ObjectiveWe investigated the impact and mechanisms of B-cell/fibroblast interactions in cocultures between B-cells from patients with SSc and 3-dimensional reconstituted healthy skin model including fibroblasts, keratinocytes and extracellular matrix.MethodsThe quantification and description of the B-cell infiltration in 3D cocultures were performed using cells imagery strategy and cytometry. The effect of coculture on the transcriptome of B-cells and fibroblasts was studied with bulk and single-cell RNA sequencing approaches. The mechanisms of this interaction were studied by blocking key cytokines like IL-6 and TNF.ResultsWe showed a significant infiltration of B-cells in the 3D healthy skin model. The amount but not the depth of infiltration was higher with B-cells from SSc patients and with activated B-cells. B-cell infiltrates were mainly composed of naïve and memory cells, whose frequencies differed depending on B-cells origin and activation state: infiltrated B-cells from patients with SSc showed an activated profile and an overexpression of immunoglobulin genes compared to circulating B-cells before infiltration. Our study has shown for the first time that activated B-cells modified the transcriptomic profile of both healthy and SSc fibroblasts, toward a pro-inflammatory (TNF and IL-17 signaling) and interferon profile, with a key role of the TNF pathway.ConclusionB-cells and 3D skin cocultures allowed the modelization of B-cells infiltration in tissues observed in SSc, uncovering an influence of the underlying disease and the activation state of B-cells. We showed a pro-inflammatory effect on skin fibroblasts and pro-activation effect on infiltrating B-cells during coculture. This reinforces the role of B-cells in SSc and provide potential targets for future therapeutic approach in this disease

Développement d'une alternative à l'utilisation des AlphaHydroxyAcides dans les produits cosmétiques

NANCY1-SCD Pharmacie-Odontologie (543952101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

CONSULTATION NEPHROLOGIQUE DU POST-PARTUM (EN CAS DE COMPLICATIONS GRAVIDIQUES)

RENNES1-BU Santé (352382103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Implicit Processing of Pitch in Postlingually Deafened Cochlear Implant Users

International audienceCochlear implant (CI) users can only access limited pitch information through their device, which hinders music appreciation. Poor music perception may not only be due to CI technical limitations; lack of training or negative attitudes toward the electric sound might also contribute to it. Our study investigated with an implicit (indirect) investigation method whether poorly transmitted pitch information, presented as musical chords, can activate listeners' knowledge about musical structures acquired prior to deafness. Seven postlingually deafened adult CI users participated in a musical priming paradigm investigating pitch processing without explicit judgments. Sequences made of eight sung-chords that ended on either a musically related (expected) target chord or a less-related (less-expected) target chord were presented. The use of a priming task based on linguistic features allowed CI patients to perform fast judgments on target chords in the sung music. If listeners' musical knowledge is activated and allows for tonal expectations (as in normal-hearing listeners), faster response times were expected for related targets than less-related targets. However, if the pitch percept is too different and does not activate musical knowledge acquired prior to deafness, storing pitch information in a short-term memory buffer predicts the opposite pattern. If transmitted pitch information is too poor, no difference in response times should be observed. Results showed that CI patients were able to perform the linguistic task on the sung chords, but correct response times indicated sensory priming, with faster response times observed for the less-related targets: CI patients processed at least some of the pitch information of the musical sequences, which was stored in an auditory short-term memory and influenced chord processing. This finding suggests that the signal transmitted via electric hearing led to a pitch percept that was too different from that based on acoustic hearing, so that it did not automatically activate listeners' previously acquired musical structure knowledge. However, the transmitted signal seems sufficiently informative to lead to sensory priming. These findings are encouraging for the development of pitch-related training programs for CI patients, despite the current technological limitations of the CI coding