Écrits de la "Petite école" porrétaine

Conférence Albert-le-Grand 196

Subthalamic Nucleus Stimulation Affects Theory of Mind Network: A PET Study in Parkinson's Disease

Background: There appears to be an overlap between the limbic system, which is modulated by subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson’s disease (PD), and the brain network that mediates theory of mind (ToM). Accordingly, the aim of the present study was to investigate the effects of STN DBS on ToM of PD patients and to correlate ToM modifications with changes in glucose metabolism. Methodology/Principal Findings: To this end, we conducted 18 FDG-PET scans in 13 PD patients in pre- and post-STN DBS conditions and correlated changes in their glucose metabolism with modified performances on the Eyes test, a visual ToM task requiring them to describe thoughts or feelings conveyed by photographs of the eye region. Postoperative PD performances on this emotion recognition task were significantly worse than either preoperative PD performances or those of healthy controls (HC), whereas there was no significant difference between preoperative PD and HC. Conversely, PD patients in the postoperative condition performed within the normal range on the gender attribution task included in the Eyes test. As far as the metabolic results are concerned, there were correlations between decreased cerebral glucos

Assessing the Predictive Validity of Simple Dementia Risk Models in Harmonized Stroke Cohorts

BACKGROUND AND PURPOSE: Stroke is associated with an increased risk of dementia. To assist in the early identification of individuals at high risk of future dementia, numerous prediction models have been developed for use in the general population. However, it is not known whether such models also provide accurate predictions among stroke patients. Therefore, the aim of this study was to determine whether existing dementia risk prediction models that were developed for use in the general population can also be applied to individuals with a history of stroke to predict poststroke dementia with equivalent predictive validity. METHODS: Data were harmonized from 4 stroke studies (follow-up range, ≈12–18 months poststroke) from Hong Kong, the United States, the Netherlands, and France. Regression analysis was used to test 3 risk prediction models: the Cardiovascular Risk Factors, Aging and Dementia score, the Australian National University Alzheimer Disease Risk Index, and the Brief Dementia Screening Indicator. Model performance or discrimination accuracy was assessed using the C statistic or area under the curve. Calibration was tested using the Grønnesby and Borgan and the goodness-of-fit tests. RESULTS: The predictive accuracy of the models varied but was generally low compared with the original development cohorts, with the Australian National University Alzheimer Disease Risk Index (C-statistic, 0.66) and the Brief Dementia Screening Indicator (C-statistic, 0.61) both performing better than the Cardiovascular Risk Factors, Aging and Dementia score (area under the curve, 0.53). CONCLUSIONS: Dementia risk prediction models developed for the general population do not perform well in individuals with stroke. Their poor performance could have been due to the need for additional or different predictors related to stroke and vascular risk factors or methodological differences across studies (eg, length of follow-up, age distribution)

Network impact score is an independent predictor of post-stroke cognitive impairment: A multicenter cohort study in 2341 patients with acute ischemic stroke

BACKGROUND: Post-stroke cognitive impairment (PSCI) is a common consequence of stroke. Accurate prediction of PSCI risk is challenging. The recently developed network impact score, which integrates information on infarct location and size with brain network topology, may improve PSCI risk prediction. AIMS: To determine if the network impact score is an independent predictor of PSCI, and of cognitive recovery or decline. METHODS: We pooled data from patients with acute ischemic stroke from 12 cohorts through the Meta VCI Map consortium. PSCI was defined as impairment in ≥ 1 cognitive domain on neuropsychological examination, or abnormal Montreal Cognitive Assessment. Cognitive recovery was defined as conversion from PSCI 24 months) and cognitive recovery or decline using logistic regression. Models were adjusted for age, sex, education, prior stroke, infarct volume, and study site. RESULTS: We included 2341 patients with 4657 cognitive assessments. PSCI was present in 398/844 patients (47%) 24 months. Cognitive recovery occurred in 64/181 (35%) patients and cognitive decline in 26/287 (9%). The network impact score predicted PSCI in the univariable (OR 1.50, 95%CI 1.34-1.68) and multivariable (OR 1.27, 95%CI 1.10-1.46) GEE model, with similar ORs in the logistic regression models for specified post-stroke intervals. The network impact score was not associated with cognitive recovery or decline. CONCLUSIONS: The network impact score is an independent predictor of PSCI. As such, the network impact score may contribute to a more precise and individualized cognitive prognostication in patients with ischemic stroke. Future studies should address if multimodal prediction models, combining the network impact score with demographics, clinical characteristics and other advanced brain imaging biomarkers, will provide accurate individualized prediction of PSCI. A tool for calculating the network impact score is freely available at https://metavcimap.org/features/software-tools/lsm-viewer/

Dihydropyridine receptor (DHPR, CACNA1S) congenital myopathy

Muscle contraction upon nerve stimulation relies on excitation–contraction coupling (ECC) to promote the rapid and generalized release of calcium within myofibers. In skeletal muscle, ECC is performed by the direct coupling of a voltage-gated L-type Ca2+ channel (dihydropyridine receptor; DHPR) located on the T-tubule with a Ca2+ release channel (ryanodine receptor; RYR1) on the sarcoplasmic reticulum (SR) component of the triad. Here, we characterize a novel class of congenital myopathy at the morphological, molecular, and functional levels. We describe a cohort of 11 patients from 7 families presenting with perinatal hypotonia, severe axial and generalized weakness. Ophthalmoplegia is present in four patients. The analysis of muscle biopsies demonstrated a characteristic intermyofibrillar network due to SR dilatation, internal nuclei, and areas of myofibrillar disorganization in some samples. Exome sequencing revealed ten recessive or dominant mutations in CACNA1S (Cav1.1), the pore-forming subunit of DHPR in skeletal muscle. Both recessive and dominant mutations correlated with a consistent phenotype, a decrease in protein level, and with a major impairment of Ca2+ release induced by depolarization in cultured myotubes. While dominant CACNA1S mutations were previously linked to malignant hyperthermia susceptibility or hypokalemic periodic paralysis, our findings strengthen the importance of DHPR for perinatal muscle function in human. These data also highlight CACNA1S and ECC as therapeutic targets for the development of treatments that may be facilitated by the previous knowledge accumulated on DHPR

« Post-scriptum »

Dondaine Antoine. « Post-scriptum ». In: Scriptorium, Tome 32 n°1, 1978. pp. 54-55

Le registre d'Inquisition de Jacques Fournier. A propos d'une édition récente

Examen critique de l'édition donnée par M. Jean Duvernoy.Dondaine Antoine. Le registre d'Inquisition de Jacques Fournier. A propos d'une édition récente. In: Revue de l'histoire des religions, tome 178, n°1, 1970. pp. 49-56

Etude du rôle d'un donneur de monoxyde d'azote (Glycéryl Trinitrate) dans la mort cellulaire immunogène induite par des chimiothérapies (FOX) et/ou radiothérapie dans le cancer colique

Le cancer colorectal se situe au 3ème rang mondial des cancers les plus fréquents derrière les cancers du sein et du poumon. Dans le cas de cancer colorectal métastatique, la première ligne thérapeutique repose sur l’utilisation d’une association de chimiothérapies : le FOLFOX (acide FOLinique, 5-Fluorouracile et OXaliplatine). Malgré une forte efficacité anti-tumorale de cette combinaison, de nombreuses rechutent apparaissent nécessitant l’utilisation de nouvelles stratégies basées sur l’association du FOLFOX à d’autres agents anti-cancéreux ou stimulant le système immunitaire. Cette étude a eu comme objectif d’étudier l’effet anti-tumoral del’association du FOX (5-Fluorouracile et OXaliplatine) à un donneur de monoxyde d’azote (NO) tel que le Glycéryl Trinitrate (GTN) combiné ou non à de la radiothérapie dans le cancer colique. En clinique, l’utilisation du GTN, un agent couramment utilisé dans le traitement des angines de poitrine, a montré un bénéfice réel chez des patients porteurs de cancer du poumon non à petites cellules et traités par chimiothérapies associées ou non à de la radiothérapie. Dans nos modèles précliniques de cancer du côlon, nous avons montré que l’association du GTN au FOX potentialisait l’effet anti-tumoral de ces chimiothérapies. L’utilisation de modèles murinsimmunodéficients nous a permis de montrer l’importance du système immunitaire dans l’activité anti-tumorale de cette combinaison. Nous avons alors recherché par quel mécanisme le GTN pouvait induire l’activation du système immunitaire et avons alors montré que le GTN induisait l’externalisation de la calréticuline, un des éléments nécessaire à l’induction de la mort cellulaire immunogène (ICD). Cette mort immunogène est caractérisée par la libération de facteurs immunogènes (HMGB1 et ATP) et par l’externalisation de la calréticuline. Cette ICD représente un des mécanismes par lequel la radiothérapie mais également certaines chimiothérapies peuvent activer le système immunitaire et ainsi potentialiser l’efficacité de ces thérapies. Ainsi et pour la première fois, nous avons montré le rôle primordial du NO dans le mécanisme d’externalisation de la calréticuline induit par l’ajout d’un donneur de NO, ou par ajout de chimiothérapies pouvant induire la production de NO. Tous ces travaux montrent l’importance du NO dans l’efficacité des thérapies conventionnelles (chimiothérapies, radiothérapie) et mettent en exergue l’utilisation de GTN en association à des thérapies non immunogènes afin de potentialiser leur efficacité anti-tumorale

Notules critiques à propos du cahier 5 du manuscrit Vatic., Lat. 781

Dondaine Antoine. Notules critiques à propos du cahier 5 du manuscrit Vatic., Lat. 781. In: Scriptorium, Tome 19 n°2, 1965. pp. 214-227