Early disruption of parvalbumin expression and perineuronal nets in the hippocampus of the Tg2576 mouse model of Alzheimer's disease can be rescued by enriched environment

International audienc

Generational changes in multiple sclerosis phenotype in North African immigrants in France: A population-based observational study

International audienc

L'homme et le climat : comprendre et agir. : Discussion entre Didier Paillard (CEA), Amy Dahan-Dalmedico (MNHM), Olivier Godard (Ecole Polytechnique) animée par Marie-Odile Monchicourt.

Le changement climatique provoqué par les activités humaines est un problème d'une telle complexité qu'il nécessite une approche globale - relevant des domaines de la climatologie, de l'environnement, de la gestion des sources d'énergie, de l'économie - où la modélisation joue un rôle crucial, tant pour comprendre que pour agir.Trois scientifiques, Didier PAILLARD (climatologue,Commissariat à l'Energie Atomique), Amy DAHAN-DALMEDICO (mathématicienne, historienne des sciences, Muséum National d'Histoire Naturelle), Olivier GODARD (économiste, Ecole Polytechnique) répondront aux questions du public à l'occasion d'un "café des sciences" animé par la journaliste Marie-Odile MONCHICOURT et co-organisé par les associations "Entre-Sciences" et " Bar des Sciences"

Neuronal hyperexcitability in the Tg2576 mouse model of Alzheimer's disease – the influence of sleep and noradrenergic transmission

International audienceThe link between Alzheimer's disease (AD) and network hypersynchrony-manifesting as epileptic activities-received considerable attention in the past decade. However, several questions remain unanswered as to its mechanistic underpinnings. Therefore, our objectives were (1) to better characterise epileptic events in the Tg2576 mouse model throughout the sleep-wake cycle and disease progression via electrophysiological recordings and (2) to explore the involvement of noradrenergic transmission in this pathological hypersynchrony. Over and above confirming the previously described early presence and predominance of epileptic events during rapid-eye-movement (REM) sleep, we also show that these events do not worsen with age and are highly phase-locked to the section of the theta cycle during REM sleep where hippocampal pyramidal cells reach their highest firing probability. Finally, we reveal an antiepileptic mechanism of noradrenergic transmission via α1-adrenoreceptors that could explain the intriguing distribution of epileptic events over the sleep-wake cycle in this model, with potential therapeutic implications in the treatment of the epileptic events occurring in many AD patients

Clinical outcome after biliary drainage for metastatic colorectal cancer: Survival analysis and prognostic factors

International audienceBiliary obstruction secondary to colorectal cancer liver metastases is associated with a poor prognosis especially when chemotherapy cannot be re-started. The aim of this study was to determine the survival after biliary drainage and the associated prognostic factors.METHODS:Patients from two French centers were included retrospectively after first biliary endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography drainage for biliary obstruction secondary to liver metastases of colorectal cancer, occurring during chemotherapy.RESULTS:The final analysis included 69 patients. Overall median survival was 115 days. In univariate analysis, a previous liver surgery, technical and functional success of drainage and restarted chemotherapy were significantly associated with an improved survival. Chemotherapy was restarted after a median of 27 days. When drainage was efficient, survival improved from 33 to 262days (p<0.001). In multivariate analysis, significant protective factors for survival included previous a hepatectomy (HR 0.41) and functional success of the drainage (HR 0.29). Predictive factors for death included increased lines of chemotherapy (HR 1.68) and fever before drainage (HR 2.97).CONCLUSIONS:This is the first study concerning the benefits of biliary drainage for malignant biliary obstruction during the course of chemotherapy for colorectal cancer. A successful biliary drainage leads to improved survival and allows achievement of chemotherapy for 70% of patients

Association between “origin/generation” and assignment to expanded disability status scale (EDSS) scores 3 and 6.

<p>Association between “origin/generation” and assignment to expanded disability status scale (EDSS) scores 3 and 6.</p

Survival curves for expanded disability status scale (EDSS) scores 3 (A) and 6 (B) of patients.

<p>First generation North Africans (NA1G), second generation North Africans (NA2G) and Europeans (E).</p

Intravenous immunoglobulin for patients with unexplained recurrent implantation failure: a 6-year single center retrospective review of clinical outcomes

Abstract The effectiveness of intravenous immunoglobulin (IVIg) for patients with unexplained recurrent implantation failure (uRIF) remains debated. We retrospectively analysed outcomes of uRIF patients treated with IVIg compared to a separate control uRIF cohort within our center (01/2014–12/2021). Primary outcomes included live birth, miscarriage, or transfer failure. We documented IVIg side effects and maternal/fetal outcomes. Logistic regression analysis was used to assess for association of IVIg exposure with outcomes and adjust for confounders. The study included 143 patients, with a 2:1 ratio of controls to patients receiving IVIg treatment. Patient characteristics were similar between groups. There was higher live birth rate (LBR) in patients receiving IVIg (32/49; 65.3%) compared to controls (32/94; 34%); p < 0.001). When stratifying patients into moderate and severe uRIF (respectively 3–4 and $$\ge$$ ≥ 5 previous good quality blastocyst transfer failures), only patients with severe uRIF benefited from IVIg (LBR (20/29 (69%) versus 5/25 (20%) for controls, p = 0.0004). In the logistic regression analysis, IVIg was associated with higher odds of live birth (OR 3.64; 95% CI 1.78–7.67; p = 0.0004). There were no serious adverse events with IVIg. IVIg can be considered in well selected patients with $$\ge$$ ≥ 5 previous unexplained, high quality blastocyst transfer failures. A randomized controlled trial is needed to confirm these findings

Predictive value of vascular endothelial growth factor polymorphisms for maintenance bevacizumab efficacy in metastatic colorectal cancer: an ancillary study of the PRODIGE 9 phase III trial

Background: Several studies have reported the impact of single nucleotide polymorphisms (SNPs) in vascular endothelial growth factor ( VEGF ) pathway genes on the efficacy of bevacizumab in metastatic colorectal cancer (mCRC), but results are still inconsistent. The PRODIGE 9 phase III study compared bevacizumab maintenance versus observation alone after induction chemotherapy with FOLFIRI plus bevacizumab. Objective: We evaluated the impact of SNPs of VEGF-A , VEGF receptors ( VEGFR-1, VEGFR-2 ), and hypoxia inducible factor-1α ( HIF-1α ) on tumor control duration (TCD), overall survival (OS), progression-free survival (PFS), and duration of first chemotherapy free-intervals (CFI). Patients and methods: We included 314/491 patients from PRODIGE 9 with a DNA blood sample available. Nine SNPs were genotyped on germline DNA using real-time Polymerase Chain Reaction TaqMan TM (Thermo Fisher Scientific, Waltham, MA , USA 02451). Results: In the bevacizumab arm, patients with the VEGFR-1 rs9582036 CC genotype ( n  = 14) had significantly longer TCD [22.4 months (95% confidence interval (CI): 14.75-not reached)] than patients with the AA or CA genotype [14.4 months (95% CI: 11.7–17.1)] ( p  = 0.036), whereas there was no significant difference in the observation arm. In the bevacizumab arm, no significant difference was found between the CC, and AA or CA genotype for OS [28.2 (95% CI: 18.1–42.8) versus 22.5 (95% CI: 18.6–24.6) months, p  = 0.5], PFS [9.4 (95% CI: 7.2–11.3) versus 9.2 (95% CI: 8.71–10.1)], and duration of the first CFI [4.6 (95% CI: 1.6–13.3) versus 4.14 (95% CI: 0.5–29.0) months, p  = 0.3]. Conclusion: Among mCRC patients treated with bevacizumab maintenance, those with the VEGFR-1 rs9582036 CC genotype experienced longer TCD. The presence of this genotype may thus predict a benefit of bevacizumab maintenance in mCRC