Regional cerebral blood flow during wakeful rest in older subjects with mild to severe obstructive sleep apnea

Objectives: To evaluate changes in regional cerebral blood flow (rCBF) during wakeful rest in older subjects with mild to severe obstructive sleep apnea (OSA) and healthy controls, and to identify markers of OSA severity that predict altered rCBF. Design: High-resolution 99mTc-HMPAO SPECT images during wakeful rest. Setting: Research sleep laboratory affiliated with a University hospital. Participants: Fifty untreated OSA patients aged between 55 and 85 years divided into mild, moderate and severe OSA and 20 age-matched healthy controls. Interventions: N/A Measurements: Using statistical parametrical mapping, rCBF was compared between groups and correlated with clinical, respiratory and sleep variables. Results: Whereas no rCBF change was observed in mild and moderate groups, participants with severe OSA had reduced rCBF compared to controls in the left parietal lobules, precentral gyrus, bilateral postcentral gyri, and right precuneus. Reduced rCBF in these regions and in areas of the bilateral frontal and left temporal cortex was associated with more hypopneas, snoring, hypoxemia, and sleepiness. Higher apnea, micro-arousal, and body mass indexes were correlated to increased rCBF in the basal ganglia, insula, and limbic system. Conclusions: While older individuals with severe OSA had hypoperfusions in the sensorimotor and parietal areas, respiratory variables and subjective sleepiness were correlated with extended regions of hypoperfusion in the lateral cortex. Interestingly, OSA severity, sleep fragmentation and obesity correlated with increased perfusion in subcortical and medial cortical regions. Anomalies with such a distribution could result in cognitive deficits and reflect impaired vascular regulation, altered neuronal integrity, and/or undergoing neurodegenerative processes

Gray matter hypertrophy and thickening with obstructive sleep apnea in middle-aged and older adults

Rationale: Obstructive sleep apnea causes intermittent hypoxemia, hemodynamic fluctuations, and sleep fragmentation, all of which could damage cerebral gray matter that can be indirectly assessed with neuroimaging. Objectives: To investigate whether markers of obstructive sleep apnea severity are associated with gray matter changes among middle-aged and older individuals. Methods: Seventy-one subjects (ages: 55 to 76; apnea–hypopnea index: 0.2 to 96.6 events/h) were evaluated with magnetic resonance imaging. Two techniques were used: 1) voxel-based morphometry, which measures gray matter volume and concentration; 2) FreeSurfer automated segmentation, which estimates the volume of predefined cortical/subcortical regions and cortical thickness. Regression analyses were performed between gray matter characteristics and markers of obstructive sleep apnea severity (hypoxemia, respiratory disturbances, sleep fragmentation). Measurements and Main Results: Subjects had few symptoms, i.e. sleepiness, depression, anxiety and cognitive deficits. While no association was found with voxel-based morphometry, FreeSurfer revealed increased gray matter with obstructive sleep apnea. Higher levels of hypoxemia correlated with increased volume and thickness of the left lateral prefrontal cortex as well as increased thickness of the right frontal pole, the right lateral parietal lobules, and the left posterior cingulate cortex. Respiratory disturbances positively correlated with right amygdala volume while more severe sleep fragmentation was associated with increased thickness of the inferior frontal gyrus. Conclusions: Gray matter hypertrophy and thickening were associated with hypoxemia, respiratory disturbances, and sleep fragmentation. These structural changes in a group of middle-aged and older individuals may represent adaptive/reactive brain mechanisms attributed to a presymptomatic stage of obstructive sleep apnea

BDNF Val66Met polymorphism interacts with sleep consolidation to predict ability to create new declarative memories

It is hypothesized that a fundamental function of sleep is to restore an individual's day-to-day ability to learn and to constantly adapt to a changing environment through brain plasticity. Brain-derived neurotrophic factor (BDNF) is among the key regulators that shape brain plasticity. However, advancing age and carrying the BDNF Met allele were both identified as factors that potentially reduce BDNF secretion, brain plasticity, and memory. Here, we investigated the moderating role of BDNF polymorphism on sleep and next-morning learning ability in 107 nondemented individuals who were between 55 and 84 years of age. All subjects were tested with 1 night of in-laboratory polysomnography followed by a cognitive evaluation the next morning. We found that in subjects carrying the BDNF Val66Val polymorphism, consolidated sleep was associated with significantly better performance on hippocampus-dependent episodic memory tasks the next morning (β-values from 0.290 to 0.434, p ≤ 0.01). In subjects carrying at least one copy of the BDNF Met allele, a more consolidated sleep was not associated with better memory performance in most memory tests (β-values from -0.309 to -0.392, p values from 0.06 to 0.15). Strikingly, increased sleep consolidation was associated with poorer performance in learning a short story presented verbally in Met allele carriers (β = -0.585, p = 0.005). This study provides new evidence regarding the interacting roles of consolidated sleep and BDNF polymorphism in the ability to learn and stresses the importance of considering BDNF polymorphism when studying how sleep affects cognition

Assessing the safety, impact and effectiveness of RTS,S/AS01E malaria vaccine following its introduction in three sub-Saharan African countries: methodological approaches and study set-up

Background Following a 30-year development process, RTS,S/AS01E (GSK, Belgium) is the first malaria vaccine to reach Phase IV assessments. The World Health Organization-commissioned Malaria Vaccine Implementation Programme (MVIP) is coordinating the delivery of RTS,S/AS01E through routine national immunization programmes in areas of 3 countries in sub-Saharan Africa. The first doses were given in the participating MVIP areas in Malawi on 23 April, Ghana on 30 April, and Kenya on 13 September 2019. The countries participating in the MVIP have little or no baseline incidence data on rare diseases, some of which may be associated with immunization, a deficit that could compromise the interpretation of possible adverse events reported following the introduction of a new vaccine in the paediatric population. Further, effects of vaccination on malaria transmission, existing malaria control strategies, and possible vaccine-mediated selective pressure on Plasmodium falciparum variants, could also impact long-term malaria control. To address this data gap and as part of its post-approval commitments, GSK has developed a post-approval plan comprising of 4 complementary Phase IV studies that will evaluate safety, effectiveness and impact of RTS,S/AS01E through active participant follow-up in the context of its real-life implementation. Methods EPI-MAL-002 (NCT02374450) is a pre-implementation safety surveillance study that is establishing the background incidence rates of protocol-defined adverse events of special interest. EPI-MAL-003 (NCT03855995) is an identically designed post-implementation safety and vaccine impact study. EPI-MAL-005 (NCT02251704) is a cross-sectional pre- and post-implementation study to measure malaria transmission intensity and monitor the use of other malaria control interventions in the study areas, and EPI-MAL-010 (EUPAS42948) will evaluate the P. falciparum genetic diversity in the periods before and after vaccine implementation. Conclusion GSK’s post-approval plan has been designed to address important knowledge gaps in RTS,S/AS01E vaccine safety, effectiveness and impact. The studies are currently being conducted in the MVIP areas. Their implementation has provided opportunities and posed challenges linked to conducting large studies in regions where healthcare infrastructure is limited. The results from these studies will support ongoing evaluation of RTS,S/AS01E’s benefit-risk and inform decision-making for its potential wider implementation across sub-Saharan Africa

Évaluation de la compréhension du test de dépistage de la trisomie 21 dans une maternité de niveau 1

Contexte : La compréhension du test de dépistage de la trisomie 21 est un sujet très - controversé. Méthode : Nous avons réalisé une étude rétrospective via un questionnaire auprès de 100 patientes en suites de couche dans une maternité de niveau 1. Le critère principal de jugement était d'évaluer la compréhension de l'information délivrée aux femmes enceintes concernant le test combiné de la trisomie 21. Résultats : 97 femmes (97%) ont réalisé le test. Il nous est apparu qu'elles possédaient de bonnes connaissances concernant le test de dépistage et leurs motifs de recours. Aucune patiente n'a fait partie d'un groupe à risque élevé. Le gynécologue obstétricien hospitalier a prescrit le test' i 55. femmes (55%). Le médecin généraliste a été désigné par 11 femmes (11%) et la sage femme par 29 femmes (29%). La qualification du professionnel de santé n'a pas influencé de manière significative la compréhension des explications (p = 0,642). Le colloque entre le prescripteur et la patiente joue un rôle majeur dans la prise de décision. La durée des explications a un lien direct avec la compréhension des explications mais non significatif (p = 0,884). Le niveau d'étude n'a pas influencé significativement le sentiment des patientes d'être ou non convenablement informées (p = 0,884). 87 femmes (87%) ne se sont pas renseignées auprès d'autres professionnels de santé et 76 femmes (76%) n'ont pas effectué de recherches complémentaires sur Internet. Conclusions : L'information délivrée doit être simple, complète, équilibrée et adaptée pour permettre une bonne compréhension. Les prescripteurs du test possèdent les mêmes qualités. La place du médecin généraliste est à valoriser.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

Métallurgie : ferblanterie-tôlerie : programme d'études : WZU-008, 5021 /

"Le programme de Ferblanterie-Tôlerie conduisant au diplôme d'études professionnelles, prépare à l'exercice du métier de ferblantier-tôlier et de ferblantière-tôlière"La couv. porte en outre: La formation professionnelle au secondaireGlossaire: p.

Blocking a novel 55 kDa melanoma-associated cell surface antigen inhibits the development of spontaneous metastases and interactions with frozen lung section

International audienceWe recently identified a novel 55-kDa cell-cell adhesion protein (p55) whose expression is upregulated in primary melanomas in the transition from radial growth phase to vertical growth phase. However, the functional role of p55 in various steps of the metastatic process had not been investigated. We provide evidence that subcutaneous injection of metastatic melanoma variant T1P26 in immunosuppressed newborn rats rapidly caused spontaneous metastatic lung lesions that could be readily detected by histochemical analysis with the anti-p55 monoclonal antibody (MAb) LY1. Subsequently, we were able to demonstrate that multiple subcutaneous injections of the LY1 MAb starting on the same day after tumor cell inoculation of T1P26 cells specifically blocked the formation of spontaneous lung metastases, yet had no effects on primary tumor growth, suggesting a critical role of p55 in the earlier steps of the intravasation process. To study later stages in spontaneous metastasis, we investigated the role of p55 in organ-specific cell adhesion of tumor cells in vitro. We showed that the T1P26 variant attached preferentially to lung frozen sections compared with other organs, reflecting the pattern of organ involvement of metastasis in vivo and that LY1 significantly blocked this interaction. However, no significant differences in attachment to lung sections were observed between the parental melanoma cell line M(4)Beu and its derived variant, although cellular topography analysis indicated a preferential attachment of a T1P26 variant on specific compartments of the lungs such as the perialveolar components, the endothelium and the vessel lumen of pulmonary venules. Attachment of the T1P26 variant to lung sections is not due to alterations of tumor cell adherence to basement membrane matrix by the LY1 MAb, suggesting that p55 is involved in cellular adhesion with cellular elements of the lung. p55 could represent a new functional constituent that contributes to the metastatic spread of melanoma cells by promoting the intravasation process and subsequent specific interactions between tumor cells and the target lung organ

Aide aux étudiants dans leur cheminement scolaire : problématique et résultats de recherche /

Également disponible en version électroniqueBibliogr. : f. 93-9