Tyrosine kinase inhibition is an important factor for gene expression of CRTH2 in human eosinophils and lymphocytes: A novel mechanism for explaining eosinophils recruitment by the neuro-immune axis in allergic rhinitis.

We recently shown a novel neuro-immune competition between vasoactive intestinal peptide (VIP) and PGD2 for CRTH2 receptor, and that genistein augmented VIP and PGD2-induced eosinophil chemotaxis. However, there are neither studies on the CRTH2 gene expression in allergic rhinitis (AR) nor in the effect of tyrosine kinase inhibitors in CRTH2 gene regulation. Our Objectives were to study the gene expression modulation of CRTH2 receptor in AR patients and the effect of tyrosine kinase inhibitors (TKIs) on CRTH2 gene modulation. Nasal provocation tests, ELISA, qRT-PCR, western blot, flow cytometry and chemotaxis assays in modified micro-Boyden chambers, were all used, to achieve our objectives. Herein we show that AR patients increased the amounts of VIP and PGD2 in their nasal secretions in the early phase reaction, however CRTH2 gene expression from leukocytes recovered in their nasal secretions was upregulated only during the late phase reaction. The TKIs; Genistein, Erbstatin and Herbimycin A, induced the gene expression of CRTH2 and increased the protein content of CRTH2 in both human lymphocytes and eosinophils. This was functional as PGD2/VIP-induced eosinophil chemotaxis was augmented by the TKIs and inhibited by pervanadate, the tyrosine phosphatase inhibitor. These results open channels for therapeutic modalities targeting CRTH2 molecules in AR

“I wanted to know what was hurting so much”: a qualitative study exploring patients’ expectations and experiences with primary care management

Abstract Background The management of shoulder pain is challenging for primary care clinicians considering that 40% of affected individuals remain symptomatic one year after initial consultation. Developing tailored knowledge mobilization interventions founded on evidence-based recommendations while also considering patients’ expectations could improve primary care for shoulder pain. The aim of this qualitative study is to explore patients’ expectations and experiences of their primary care consultation for shoulder pain. Methods In this qualitative study, participants with shoulder pain and having consulted a primary care clinician in the past year were interviewed. All the semi-structured interviews were transcribed verbatim, and inductive thematic analysis was performed to identify themes related to the participants’ expectations and experiences of primary care consultations for shoulder pain. Results Thirteen participants with shoulder pain were interviewed (8 women, 5 men; mean age 50 ± 12 years). Eleven of them initially consulted a family physician or an emergency physician, and two participants initially consulted a physiotherapist. Four overarching themes related to patients’ expectations and experiences were identified from our thematic analysis: 1) I can’t sleep because of my shoulder; 2) I need to know what is happening with my shoulder; 3) But… we need to really see what is going on to help me!; and 4) Please take some time with me so I can understand what to do!. Several participants waited until they experienced a high level of shoulder pain before making an appointment since they were not confident about what their family physician could do to manage their condition. Although some participants felt that their physician took the time to listen to their concerns, many were dissatisfied with the limited assessment and education provided by the clinician. Conclusions Implementing evidence-based recommendations while considering patients’ expectations is important as it may improve patients’ satisfaction with healthcare. Several participants reported that their expectations were not met, especially when it came to the explanations provided. One unexpected finding that emerged from this study was the waiting period between the onset of shoulder pain and when patients decided to consult their primary care clinician

Poses - Le Vivier - Le Clos-Saint-Quentin (Eure). L'occupation de la plaine inondable au Néolithique et au début de l'Age du Bronze

From 1989 to 1991, a rescue-dig took place at Poses, «Le Vivier- Le Clos-Saint-Quentin». The area studied is situated on the flood-plain, which explains in this place important alluvial deposits, and consequently exceptionnal conservation of neolithic and chalcolithic seulement levels. On four hectares, the excavation has induced the study of seven settlements and also secondary areas (particularly combustion structures of polynesian type and accumulation of blocks of sandstone). The two oldest settlements belong to the «post-rubané» cultures (Villeneuve-Saint-Germain, Cerny) and the five others to the chalcolithic cultures. The most important resuit concerns, on one hand, the first neolithisation of the country and, on the other hand, the development of a chrono-cultural framework for the Late Neolithic - Early Bronze Age transition. The excavations have shown the existence of original late neolithic features (assemblages 3 and 4), have confirmed the large impact of Bell Beakers espansion in a late time in the Lower Valley of the Seine River and their evolution (assemblages 5 and 6), and finally have allowed to discover an unknown chalcolithic feature (assemblage 7). This operation enables us also to approach the theme of the development of marginal lands in areas liable to flooding.De 1989 à 1991, s'est déroulé un sauvetage programmé sur la commune de Poses, aux lieux-dits «Le Vivier- Le Clos-St-Quentin» sur une surface de quatre hectares. La zone étudiée se trouve dans la plaine inondable, ce qui explique à cet endroit d'importants dépôts de limons de débordement et, par conséquence, l'exceptionnelle conservation de niveaux d'occupation néolithiques et chalcolithi- ques en place. Sur quatre hectares, un total de sept stations d'habitat ont pu être étudiées ainsi que plusieurs zones d'occupation secondaires (en particulier, des fours de type polynésien et des amas de blocs de grès taillés ou brûlés). Les deux stations les plus anciennes appartiennent aux cultures post-rubanées (V.S.G. tardifet Cerny) et les cinq autres au Chalcolithique. Les résultats principaux de cette opération concernent donc, d'une part, les modalités de la première neolithisation de la région et d'autre part, la mise en place d'un cadre chrono-culturel pour la transition Néolithique final - Bronze ancien : la fouille a ainsi mis en valeur l'existence de faciès Néolithique final très originaux (ensembles 3 et 4), a confirmé l'impact important de l'expansion des populations à gobelets campaniformes dans une phase tardive en Basse-Vallée de Seine et leur évolution sur place (ensembles 5 et 6) et enfin, a fait découvrir un faciès chalcolithique inconnu jusqu'à présent (ensemble 7). Enfin, cette opération permet d'aborder le thème de la mise en valeur de zones marginales au terroir villageois que sont les plaines inondables.Billard Cyrille, Aubry Bruno, Blancquaert Gertrud, Bourhis Jean-Roger, Habasque Gilles, Marinval Philippe, Pinel Carole, Ropars Anne, Lebret Patrick, Lefèbvre Dominique, Marguerie Dominique, Paulet-Locard Marie-Armelle. Poses - Le Vivier - Le Clos-Saint-Quentin (Eure). L'occupation de la plaine inondable au Néolithique et au début de l'Age du Bronze. In: Revue archéologique de l'ouest, tome 11, 1994. pp. 53-113

Additional file 1 of “I wanted to know what was hurting so much”: a qualitative study exploring patients’ expectations and experiences with primary care management

Additional file 1

Les cahiers de l'école qualité en recherche et en enseignement supérieur - Numéro 6

Ce cahier regroupe les actes relatifs à la quinzième école inter-organismes « Qualité en recherche et en enseignement supérieur » organisée par l’association QuaRES à Montpellier (France), du 6 au 8 septembre 2017

Les cahiers de l'école qualité en recherche et en enseignement supérieur - Numéro 6

Ce cahier regroupe les actes relatifs à la quinzième école inter-organismes « Qualité en recherche et en enseignement supérieur » organisée par l’association QuaRES à Montpellier (France), du 6 au 8 septembre 2017

Les cahiers de l'école qualité en recherche et en enseignement supérieur - Numéro 6

Ce cahier regroupe les actes relatifs à la quinzième école inter-organismes « Qualité en recherche et en enseignement supérieur » organisée par l’association QuaRES à Montpellier (France), du 6 au 8 septembre 2017

Les cahiers de l'école qualité en recherche et en enseignement supérieur - Numéro 6

Ce cahier regroupe les actes relatifs à la quinzième école inter-organismes « Qualité en recherche et en enseignement supérieur » organisée par l’association QuaRES à Montpellier (France), du 6 au 8 septembre 2017

Cerebral perfusion using ASL in patients with COVID-19 and neurological manifestations: A retrospective multicenter observational study

Background and purpose: Cerebral hypoperfusion has been reported in patients with COVID-19 and neurological manifestations in small cohorts. We aimed to systematically assess changes in cerebral perfusion in a cohort of 59 of these patients, with or without abnormalities on morphological MRI sequences.Methods: Patients with biologically-confirmed COVID-19 and neurological manifestations undergoing a brain MRI with technically adequate arterial spin labeling (ASL) perfusion were included in this retrospective multicenter study. ASL maps were jointly reviewed by two readers blinded to clinical data. They assessed abnormal perfusion in four regions of interest in each brain hemisphere: frontal lobe, parietal lobe, posterior temporal lobe, and temporal pole extended to the amygdalo-hippocampal complex.Results: Fifty-nine patients (44 men (75%), mean age 61.2 years) were included. Most patients had a severe COVID-19, 57 (97%) needed oxygen therapy and 43 (73%) were hospitalized in intensive care unit at the time of MRI. Morphological brain MRI was abnormal in 44 (75%) patients. ASL perfusion was abnormal in 53 (90%) patients, and particularly in all patients with normal morphological MRI. Hypoperfusion occurred in 48 (81%) patients, mostly in temporal poles (52 (44%)) and frontal lobes (40 (34%)). Hyperperfusion occurred in 9 (15%) patients and was closely associated with post-contrast FLAIR leptomeningeal enhancement (100% [66.4%-100%] of hyperperfusion with enhancement versus 28.6% [16.6%-43.2%] without, p=0.002). Studied clinical parameters (especially sedation) and other morphological MRI anomalies had no significant impact on perfusion anomalies.Conclusion: Brain ASL perfusion showed hypoperfusion in more than 80% of patients with severe COVID-19, with or without visible lesion on conventional MRI abnormalities

Cerebral perfusion using ASL in patients with COVID-19 and neurological manifestations: A retrospective multicenter observational study

Background and purpose: Cerebral hypoperfusion has been reported in patients with COVID-19 and neurological manifestations in small cohorts. We aimed to systematically assess changes in cerebral perfusion in a cohort of 59 of these patients, with or without abnormalities on morphological MRI sequences.Methods: Patients with biologically-confirmed COVID-19 and neurological manifestations undergoing a brain MRI with technically adequate arterial spin labeling (ASL) perfusion were included in this retrospective multicenter study. ASL maps were jointly reviewed by two readers blinded to clinical data. They assessed abnormal perfusion in four regions of interest in each brain hemisphere: frontal lobe, parietal lobe, posterior temporal lobe, and temporal pole extended to the amygdalo-hippocampal complex.Results: Fifty-nine patients (44 men (75%), mean age 61.2 years) were included. Most patients had a severe COVID-19, 57 (97%) needed oxygen therapy and 43 (73%) were hospitalized in intensive care unit at the time of MRI. Morphological brain MRI was abnormal in 44 (75%) patients. ASL perfusion was abnormal in 53 (90%) patients, and particularly in all patients with normal morphological MRI. Hypoperfusion occurred in 48 (81%) patients, mostly in temporal poles (52 (44%)) and frontal lobes (40 (34%)). Hyperperfusion occurred in 9 (15%) patients and was closely associated with post-contrast FLAIR leptomeningeal enhancement (100% [66.4%-100%] of hyperperfusion with enhancement versus 28.6% [16.6%-43.2%] without, p=0.002). Studied clinical parameters (especially sedation) and other morphological MRI anomalies had no significant impact on perfusion anomalies.Conclusion: Brain ASL perfusion showed hypoperfusion in more than 80% of patients with severe COVID-19, with or without visible lesion on conventional MRI abnormalities