Nutrition and the ageing brain: moving towards clinical applications

The global increases in life expectancy and population have resulted in a growing ageing population and with it a growing number of people living with age-related neurodegenerative conditions and dementia, shifting focus towards methods of prevention, with lifestyle approaches such as nutrition representing a promising avenue for further development. This overview summarises the main themes discussed during the 3 Symposium on "Nutrition for the Ageing Brain: Moving Towards Clinical Applications" held in Madrid in August 2018, enlarged with the current state of knowledge on how nutrition influences healthy ageing and gives recommendations regarding how the critical field of nutrition and neurodegeneration research should move forward into the future. Specific nutrients are discussed as well as the impact of multi-nutrient and whole diet approaches, showing particular promise to combatting the growing burden of age-related cognitive decline. The emergence of new avenues for exploring the role of diet in healthy ageing, such as the impact of the gut microbiome and development of new techniques (imaging measures of brain metabolism, metabolomics, biomarkers) are enabling researchers to approach finding answers to these questions. But the translation of these findings into clinical and public health contexts remains an obstacle due to significant shortcomings in nutrition research or pressure on the scientific community to communicate recommendations to the general public in a convincing and accessible way. Some promising programs exist but further investigation to improve our understanding of the mechanisms by which nutrition can improve brain health across the human lifespan is still required

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

DEBATS -Discussion sur les Effets du Bruit des Aéronefs Touchant la Santé- Bilan méthodologique. Décembre 2013

En 2012, l'Ifsttar a souhaité débuter la phase d'inclusion de l'étude individuelle longitudinale du programme de recherche DEBATS. Cette phase d'inclusion s'est déroulée en deux étapes sur une période d'un an. La première étape a consisté à recruter des volontaires, riverains des aéroports Paris-Charles de Gaulle, Lyon Saint-Exupéry et Toulouse-Blagnac. La seconde étape a consisté en la passation d'un questionnaire en face-à-face et la réalisation de mesures physiologiques et acoustiques. Fin 2012, l'Ifsttar a confié à GfK ISL la première étape du protocole d'inclusion, c'est-à-dire le recrutement par téléphone de 1 236 volontaires acceptant de participer à l'enquête individuelle longitudinale. Le présent rapport décrit la méthodologie utilisée et les résultats obtenus par GfK ISL concernant la phase de recrutement téléphonique des 1 236 volontaires qui a été menée entre novembre 2012 et octobre 2013

A connectome-based approach to assess motor outcome after neonatal arterial ischemic stroke

International audienceOBJECTIVE: Studies of motor outcome after Neonatal Arterial Ischemic Stroke (NAIS) often rely on lesion mapping using MRI. However, clinical measurements indicate that motor deficit can be different than what would solely be anticipated by the lesion extent and location. Because this may be explained by the cortical disconnections between motor areas due to necrosis following the stroke, the investigation of the motor network can help in the understanding of visual inspection and outcome discrepancy. In this study, we propose to examine the structural connectivity between motor areas in NAIS patients compared to healthy controls in order to define the cortical and subcortical connections that can reflect the motor outcome.METHODS: Thirty healthy controls and 32 NAIS patients with and without Cerebral Palsy (CP) underwent MRI acquisition and manual assessment. The connectome of all participants was obtained from T1-weighted and diffusion-weighted imaging.RESULTS: Significant disconnections in the lesioned and contra-lesioned hemispheres of patients were found. Furthermore, significant correlations were detected between the structural connectivity metric of specific motor areas and manuality assessed by the Box and Block Test (BBT) scores in patients.INTERPRETATION: Using the connectivity measures of these links, the BBT score can be estimated using a multiple linear regression model. In addition, the presence or not of CP can also be predicted using the KNN classification algorithm. According to our results, the structural connectome can be an asset in the estimation of gross manual dexterity and can help uncover structural changes between brain regions related to NAIS

Systematic Review of Antiphospholipid Antibodies in COVID-19 Patients: Culprits or Bystanders?

International audiencePurpose of review: COVID-19 patients have a procoagulant state with a high prevalence of thrombotic events. The hypothesis of an involvement of antiphospholipid antibodies (aPL) has been suggested by several reports. Here, we reviewed 48 studies investigating aPL in COVID-19 patients.Recent findings: Prevalence of Lupus Anticoagulant (LA) ranged from 35% to 92% in ICU patients. Anti-cardiolipin (aCL) IgG and IgM were found in up to 52% and up to 40% of patients respectively. Anti-β2-glycoprotein I (aβ2-GPI) IgG and IgM were found in up to 39% and up to 34% of patients respectively. Between 1% and 12% of patients had a triple positive aPL profile. There was a high prevalence of aβ2-GPI and aCL IgA isotype. Two cohort studies found few persistent LA but more persistent solid phase assay aPL over time. aPL determination and their potential role is a real challenge for the treatment of this disease

Le Grand écho du Nord de la France

09 mars 19031903/03/09 (A85,N68).Appartient à l’ensemble documentaire : NordPdeC

How to quantify enzyme activity and kinetics in "non-bulk" systems? An example through the enzymatic hydrolysis of hemicellulose thin films

In the carbohydrate-based bioindustry, enzymes are often used in conditions where they have to work on solid surfaces and/or penetrate within structures that are locally highly concentrated. The effect of such physical constraints on the enzyme activity and kinetics is however poorly understood; mostly because following and quantifying the hydrolysis in such conditions is still a challenge. With this work, our intention is to provide a detailed characterization of an enzyme's activity when its substrate is both concentrated and immobilized at a solid interface. This is essentially done by monitoring the in-situ degradation of a thin film of a model hemicellulose using a Quartz Crystal Microbalance with Dissipation (QCM-D). The thin film is composed of a unique arabinoxylan, extracted from wheat bran, and that is chemically modified for covalently binding onto gold.1 The film is partly swollen by water, and its water content (hence its local dry concentration) can be tuned by partially removing the Larabinofuranosyl units that decorate the xylan chain.2 The film is then put into contact with a solution containing an endo-1,4-β-xylanase (NpXyn11A3 ), into the QCM-D cell, and the loss of mass in the film is followed with time as degradation occurs. Using mathematical models that are under development in our laboratory, we aim at converting the raw QCM-D data into kinetics curves that give the reaction rate as a function of the polymer concentration in the film. Such a procedure would allow us to accurately compare the behavior of the enzyme in a film with its "bulk" behavior; the latter having been characterized classically with a dilute solution of the same substrate. Our results should reveal precious indications about the effect of substrate immobilization and conformation/concentration on the action of an enzyme

Personnalisation de l’apprentissage : comparaison des besoins et approches à travers l’étude de quelques dispositifs

National audienceLa personnalisation de l’apprentissage est au cœur des recherches actuelles en EIAH (Environnements Informatiques pour l’Apprentissage Humain). Les approches pour développer des EIAH permettant une personnalisation de l'apprentissage varient tant d’un point de vue didactique qu’informatique. Dans cet article, nous présentons les résultats d’une étude menée sur plusieurs dispositifs de formation. Cette étude avait pour buts d’une part d’identifier les besoins actuels en terme de personnalisation de l’apprentissage et d’autre part de comparer des approches permettant cette personnalisation. Elle nous a permis de déterminer des verrous informatiques à dépasser pour permettre une personnalisation de l’apprentissage, et de mettre en avant les avantages et les inconvénients des solutions étudiées

Personnalisation de l’apprentissage : comparaison des besoins et approches à travers l’étude de quelques dispositifs

National audienceLa personnalisation de l’apprentissage est au cœur des recherches actuelles en EIAH (Environnements Informatiques pour l’Apprentissage Humain). Les approches pour développer des EIAH permettant une personnalisation de l'apprentissage varient tant d’un point de vue didactique qu’informatique. Dans cet article, nous présentons les résultats d’une étude menée sur plusieurs dispositifs de formation. Cette étude avait pour buts d’une part d’identifier les besoins actuels en terme de personnalisation de l’apprentissage et d’autre part de comparer des approches permettant cette personnalisation. Elle nous a permis de déterminer des verrous informatiques à dépasser pour permettre une personnalisation de l’apprentissage, et de mettre en avant les avantages et les inconvénients des solutions étudiées

Characterization and functional interrogation of the SARS-CoV-2 RNA interactome

International audienceSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic, which has led to a devastating global health crisis. The emergence of variants that escape neutralizing responses emphasizes the urgent need to deepen our understanding of SARS-CoV-2 biology. Using a comprehensive identification of RNA-binding proteins (RBPs) by mass spectrometry (ChIRP-MS) approach, we identify 107 high-confidence cellular factors that interact with the SARS-CoV-2 genome during infection. By systematically knocking down their expression in human lung epithelial cells, we find that the majority of the identified RBPs are SARS-CoV-2 proviral factors. In particular, we show that HNRNPA2B1, ILF3, QKI, and SFPQ interact with the SARS-CoV-2 genome and promote viral RNA amplification. Our study provides valuable resources for future investigations into the mechanisms of SARS-CoV-2 replication and the identification of host-centered antiviral therapies