Epicardial fat volume is associated with coronary endothelium-dependent vasomotor response in healthy subjects

Poster presentationInternational audienc

Gender differences in response to cold pressor test assessed with velocity-encoded cardiovascular magnetic resonance of the coronary sinus

BACKGROUND: Gender-specific differences in cardiovascular risk are well known, and current evidence supports an existing role of endothelium in these differences. The purpose of this study was to assess non invasively coronary endothelial function in male and female young volunteers by myocardial blood flow (MBF) measurement using coronary sinus (CS) flow quantification by velocity encoded cine cardiovascular magnetic resonance (CMR) at rest and during cold pressor test (CPT). METHODS: Twenty-four healthy volunteers (12 men, 12 women) underwent CMR in a 3 Tesla MR imager. Coronary sinus flow was measured at rest and during CPT using non breath-hold velocity encoded phase contrast cine-CMR. Myocardial function and morphology were acquired using a cine steady-state free precession sequence. RESULTS: At baseline, mean MBF was 0.63 ± 0.23 mL·g⁻¹·min⁻¹ in men and 0.79 ± 0.21 mL·g⁻¹·min⁻¹ in women. During CPT, the rate pressure product in men significantly increased by 49 ± 36% (p \textless 0.0001) and in women by 52 ± 22% (p \textless 0.0001). MBF increased significantly in both men and women by 0.22 ± 0.19 mL·g⁻¹·min⁻¹ (p = 0.0022) and by 0.73 ± 0.43 mL·g⁻¹·min⁻¹ (p = 0.0001), respectively. The increase in MBF was significantly higher in women than in men (p = 0.0012). CONCLUSION: CMR coronary sinus flow quantification for measuring myocardial blood flow revealed a higher response of MBF to CPT in women than in men. This finding may reflect gender differences in endothelial-dependent vasodilatation in these young subjects. This non invasive rest/stress protocol may become helpful to study endothelial function in normal physiology and in physiopathology

Dual role of striatal astrocytes in behavioral flexibility and metabolism in the context of obesity

Brain circuits involved in metabolic control and reward-associated behaviors are potent drivers of feeding behavior and are both dramatically altered in obesity, a multifactorial disease resulting from genetic and environmental factors. In both mice and human, exposure to calorie-dense food has been associated with increased astrocyte reactivity and pro-inflammatory response in the brain. Although our understanding of how astrocytes regulate brain circuits has recently flourish, whether and how striatal astrocytes contribute in regulating food-related behaviors and whole-body metabolism is still unknown. In this study, we show that exposure to enriched food leads to profound changes in neuronal activity and synchrony. Chemogenetic manipulation of astrocytes activity in the dorsal striatum was sufficient to restore the cognitive defect in flexible behaviors induced by obesity, while manipulation of astrocyte in the nucleus accumbens led to acute change in whole-body substrate utilization and energy expenditure. Altogether, this work reveals a yet unappreciated role for striatal astrocyte as a direct operator of reward-driven behavior and metabolic control

Clinical Effect of Early vs Late Amyloid Positron Emission Tomography in Memory Clinic Patients: The AMYPAD-DPMS Randomized Clinical Trial

IMPORTANCE: Amyloid positron emission tomography (PET) allows the direct assessment of amyloid deposition, one of the main hallmarks of Alzheimer disease. However, this technique is currently not widely reimbursed because of the lack of appropriately designed studies demonstrating its clinical effect. OBJECTIVE: To assess the clinical effect of amyloid PET in memory clinic patients. DESIGN, SETTING, AND PARTICIPANTS: The AMYPAD-DPMS is a prospective randomized clinical trial in 8 European memory clinics. Participants were allocated (using a minimization method) to 3 study groups based on the performance of amyloid PET: arm 1, early in the diagnostic workup (within 1 month); arm 2, late in the diagnostic workup (after a mean [SD] 8 [2] months); or arm 3, if and when the managing physician chose. Participants were patients with subjective cognitive decline plus (SCD+; SCD plus clinical features increasing the likelihood of preclinical Alzheimer disease), mild cognitive impairment (MCI), or dementia; they were assessed at baseline and after 3 months. Recruitment took place between April 16, 2018, and October 30, 2020. Data analysis was performed from July 2022 to January 2023. INTERVENTION: Amyloid PET. MAIN OUTCOME AND MEASURE: The main outcome was the difference between arm 1 and arm 2 in the proportion of participants receiving an etiological diagnosis with a very high confidence (ie, ≥90% on a 50%-100% visual numeric scale) after 3 months. RESULTS: A total of 844 participants were screened, and 840 were enrolled (291 in arm 1, 271 in arm 2, 278 in arm 3). Baseline and 3-month visit data were available for 272 participants in arm 1 and 260 in arm 2 (median [IQR] age: 71 [65-77] and 71 [65-77] years; 150/272 male [55%] and 135/260 male [52%]; 122/272 female [45%] and 125/260 female [48%]; median [IQR] education: 12 [10-15] and 13 [10-16] years, respectively). After 3 months, 109 of 272 participants (40%) in arm 1 had a diagnosis with very high confidence vs 30 of 260 (11%) in arm 2 (P < .001). This was consistent across cognitive stages (SCD+: 25/84 [30%] vs 5/78 [6%]; P < .001; MCI: 45/108 [42%] vs 9/102 [9%]; P < .001; dementia: 39/80 [49%] vs 16/80 [20%]; P < .001). CONCLUSION AND RELEVANCE: In this study, early amyloid PET allowed memory clinic patients to receive an etiological diagnosis with very high confidence after only 3 months compared with patients who had not undergone amyloid PET. These findings support the implementation of amyloid PET early in the diagnostic workup of memory clinic patients. TRIAL REGISTRATION: EudraCT Number: 2017-002527-21

Description of a European memory clinic cohort undergoing amyloid-PET: The AMYPAD Diagnostic and Patient Management Study

INTRODUCTION: AMYPAD Diagnostic and Patient Management Study (DPMS) aims to investigate the clinical utility and cost-effectiveness of amyloid-PET in Europe. Here we present participants' baseline features and discuss the representativeness of the cohort. METHODS: Participants with subjective cognitive decline plus (SCD+), mild cognitive impairment (MCI), or dementia were recruited in eight European memory clinics from April 16, 2018, to October 30, 2020, and randomized into three arms: ARM1, early amyloid-PET; ARM2, late amyloid-PET; and ARM3, free-choice. RESULTS: A total of 840 participants (244 SCD+, 341 MCI, and 255 dementia) were enrolled. Sociodemographic/clinical features did not differ significantly among recruiting memory clinics or with previously reported cohorts. The randomization assigned 35% of participants to ARM1, 32% to ARM2, and 33% to ARM3; cognitive stages were distributed equally across the arms. DISCUSSION: The features of AMYPAD-DPMS participants are as expected for a memory clinic population. This ensures the generalizability of future study results

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Validation d'une méthode non invasive d'évaluation de la fonction de l'endothélium coronaire en imagerie par résonance magnétique 3 Tesla

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Liver GCN2 controls hepatic FGF21 secretion and modulates whole-body postprandial oxidation profile under a low-protein diet

Epub ahead of printOBJECTIVE: GCN2 is a kinase which detects amino acid deficiency and is involved in the control of protein synthesis and energy metabolism. However, the role of hepatic GCN2 in the metabolic adaptations in response to the modulation of dietary protein has been seldom studied. METHODS: Wild-type (WT) and liver GCN2-deficient (KO) mice were fed either a normo-protein diet, a low-protein diet or a high-protein diet for 3 weeks. During this period, body weight, food intake and metabolic parameters were followed. RESULTS: In mice fed normo- and high protein diets, GCN2 pathway in the liver is not activated in WT mice leading to a similar metabolic profile with the one of KO mice. On the contrary, a low protein diet activates GCN2 in WT mice inducing FGF21 secretion. In turn, FGF21 maintains a high level of lipid oxidation leading to a different postprandial oxidation profile compared with KO mice. CONCLUSIONS: Hepatic GCN2 controls FGF21 secretion under a low protein diet, and modulates a whole-body postprandial oxidation profile