Overexpression of Wild-Type Human Alpha-Synuclein Causes Metabolism Abnormalities in Thy1-aSYN Transgenic Mice

Parkinson’s disease is a progressive neurodegenerative disorder characterized by loss of dopaminergic neurons, pathological accumulation of alpha-synuclein and motor symptoms, but also by non-motor symptoms. Metabolic abnormalities including body weight loss have been reported in patients and could precede by several years the emergence of classical motor manifestations. However, our understanding of the pathophysiological mechanisms underlying body weight loss in PD is limited. The present study investigated the links between alpha-synuclein accumulation and energy metabolism in transgenic mice overexpressing Human wild-type (WT) alpha-synuclein under the Thy1 promoter (Thy1-aSYN mice). Results showed that Thy1-aSYN mice gained less body weight throughout life than WT mice, with significant difference observed from 3 months of age. Body composition analysis of 6-month-old transgenic animals showed that body mass loss was due to lower adiposity. Thy1-aSYN mice displayed lower food consumption, increased spontaneous activity, as well as a reduced energy expenditure compared to control mice. While no significant change in glucose or insulin responses were observed, Thy1-aSYN mice had significantly lower plasmatic levels of insulin and leptin than control animals. Moreover, the pathological accumulation of alpha-synuclein in the hypothalamus of 6-month-old Thy1-aSYN mice was associated with a down-regulation of the phosphorylated active form of the signal transducer and activator of transcription 3 (STAT3) and of Rictor (the mTORC2 signaling pathway), known to couple hormonal signals with the maintenance of metabolic and energy homeostasis. Collectively, our results suggest that (i) metabolic alterations are an important phenotype of alpha-synuclein overexpression in mice and that (ii) impaired STAT3 activation and mTORC2 levels in the hypothalamus may underlie the disruption of feeding regulation and energy metabolism in Thy1-aSYN mice

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 < 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

Prevalence and Determinants of Vaccine Hesitancy and Vaccines Recommendation Discrepancies among General Practitioners in French-Speaking Parts of Belgium

International audienceGeneral practitioners (GPs) play a critical role in patient acceptance of vaccination. Vaccine hesitancy (VH) is a growing phenomenon in the general population but also affects GPs. Few data exist on VH among GPs. The objectives of this analysis of a population of GPs in the Belgian Wallonia-Brussels Federation (WBF) were to: (1) determine the prevalence and the features of VH, (2) identify the correlates, and (3) estimate the discrepancy in vaccination’s behaviors between the GPs’ children and the recommendations made to their patients. An online survey was carried out among the population of general practitioners practicing in the WBF between 7 January and 18 March 2020. A hierarchical cluster analysis was carried out based on various dimensions of vaccine hesitancy: perception of the risks and the usefulness of vaccines as well as vaccine recommendations for their patients. A total of 251 GPs answered the survey. The average percentage of moderate to high vaccine hesitancy was 50.6%. Three factors were independently associated with increased risk of vaccine hesitancy: an age <50 years old, having no children, and having no contact with selected vaccine-preventable disease (measles, complicated influenza, chronic hepatitis B (HBV), bacterial meningitis, or cervical cancer) in the past 5 years. VH was associated with controversies on vaccines’ safety. GPs who had vaccinated their children against six diseases (MMR, meningococcus C (MenC), HBV, and HPV) tended not to recommend the same vaccines to their patients. Among GPs with all children vaccinated against HBV, only 37.5% recommended catch-up HBV immunization to their patients. In this small cohort of GP, moderate to high VH was associated with controversies on vaccines’ safety and with specific personal characteristics (age <50, no children, and no recent experience with a serious VPD). As previously reported, GPs have different vaccine prescription attitude toward their patients and children. These findings should be confirmed in larger cohorts

Marketing social. De la compréhension des publics au changement de comportement

2e édition / Ouvrage labellisé FNEGE 2020 dans la catégorie Manuel (1ère édition)International audienceLe marketing social a pour but de faire évoluer les comportements des individus dans différents domaines: promotion de la santé (tabagisme, obésité, …), protection de l’environnement, sécurité routière, violence familiale, droits de la personne, racisme, etc. Cette discipline est aujourd’hui utilisée par des organismes internationaux prestigieux tels que l’ONU ou encore Santé publique France.Pour répondre aux besoins des acteurs de terrain, cet ouvrage pratique et pédagogique, illustré par des exemples concrets de campagnes et de projets menés par Santé publique France, propose de présenter le marketing social et d’en faire découvrir les techniques, permettant ainsi d’améliorer l’impact des programmes de prévention sur la population.➜ Ce livre s’adresse à tous ceux qui veulent en savoir plus sur le marketing social: acteurs de terrain, chargé·e·s de prévention et de communication, mais aussi décideurs·ses et partenaires, enseignant·e·s, chercheurs·ses et étudiant·e·s en santé, marketing et communication

Understanding providers' offering and patients' acceptance of HIV screening in emergency departments: a multilevel analysis. ANRS 95008, Paris, France.

OBJECTIVE: We assessed the EDs' characteristics associated with the offer and acceptance rates of a nontargeted HIV rapid-test screening in 29 Emergency Departments (EDs) in the metropolitan Paris region (11.7 million inhabitants), where half of France's new HIV cases are diagnosed annually. METHODS: EDs nurses offered testing to all patients 18-64-year-old, able to provide consent, either with or without supplemental staff (hybrid staff model or indigenous staff model). The EDS' characteristics collected included structural characteristics (location, type, size), daily workload (patients' number and severity, length of stay in hours), staff's participation (training, support to the intervention, leadership), type of week day (weekends vs weekdays) and time (in days). Associations between these variables and the staff model, the offer and acceptance rates were studied using multilevel modeling. RESULTS: Indigenous staff model was more frequent in EDs with a lower daily patient flow and a higher staff support score to the intervention. In indigenous-model EDs, the offer rate was associated with the patient flow (OR = 0.838, 95% CI = 0.773-0.908), was lower during weekends (OR = 0.623, 95% CI = 0.581-0.667) and decreased over time (OR = 0.978, 95% CI = 0.975-0.981). Similar results were found in hybrid-model EDs. Acceptance was poorly associated with EDs characteristics in indigenous-model EDs while in hybrid-model EDs it was lower during weekends (OR = 0.713, 95% CI = 0.623-0.816) and increased after the first positive test (OR = 1.526, 95% CI = 1.142-2.038). The EDs' characteristics explained respectively 38.5% and 15% of the total variance in the offer rate across indigenous model-EDs and hybrid model-EDs vs 12% and 1% for the acceptance rate. CONCLUSION: Our findings suggest the need for taking into account EDs' characteristics while considering the implementation of an ED-based HIV screening program. Strategies allowing the optimization of human resources' utilization such as HIV targeted screening in the EDs might be privileged

EDs’ characteristics associated with the offering and acceptance of HIV-RT in the EDs (multivariate analysis^a).

<p>^aTeam support, proportion of seriously ill patients, length of stay, time and number of beds in the hospital are continuous variables. All the others are categorical variables *P<.05.</p

Patient flow diagram.

<p>*Exclusion criteria were the following: age <18 years or age >65 years (51%), serious/unstable illness (15%), inability to provide consent (31%), known HIV seropositivity (2%).</p

Components of the offering/acceptance variance and impact of entering EDs’ characteristics in the regression analysis.

*<p>The variance partition coefficient (VPC) indicates the proportion of the total variance (the sum of 1st level (days) and 2nd level (EDs) variances) that it is accounted for by the 2nd level variance. The VPC was calculated using the equation VPC_h = σ²_h/(σ²_h +3.29), where σ²_h represents the ED level variance (Snijders, T. and Bosker, R. [1999]. Multilevel Analysis. Sage).</p