10 research outputs found

    MyD88 Signaling Regulates Steady-State Migration of Intestinal CD103<sup>+ </sup>Dendritic Cells Independently of TNF-α and the Gut Microbiota

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    Intestinal homeostasis and induction of systemic tolerance to fed Ags (i.e., oral tolerance) rely on the steady-state migration of small intestinal lamina propria dendritic cells (DCs) into draining mesenteric lymph nodes (MLN). The majority of these migratory DCs express the α integrin chain CD103, and in this study we demonstrate that the steady-state mobilization of CD103(+) DCs into the MLN is in part governed by the IL-1R family/TLR signaling adaptor molecule MyD88. Similar to mice with complete MyD88 deficiency, specific deletion of MyD88 in DCs resulted in a 50-60% reduction in short-term accumulation of both CD103(+)CD11b(+) and CD103(+)CD11b(-) DCs in the MLN. DC migration was independent of caspase-1, which is responsible for the inflammasome-dependent proteolytic activation of IL-1 cytokine family members, and was not affected by treatment with broad-spectrum antibiotics. Consistent with the latter finding, the proportion and phenotypic composition of DCs were similar in mesenteric lymph from germ-free and conventionally housed mice. Although TNF-α was required for CD103(+) DC migration to the MLN after oral administration of the TLR7 agonist R848, it was not required for the steady-state migration of these cells. Similarly, TLR signaling through the adaptor molecule Toll/IL-1R domain-containing adapter inducing IFN-β and downstream production of type I IFN were not required for steady-state CD103(+) DC migration. Taken together, our results demonstrate that MyD88 signaling in DCs, independently of the microbiota and TNF-α, is required for optimal steady-state migration of small intestinal lamina propria CD103(+) DCs into the MLN

    Experiences of Patients With Atrial Fibrillation With Combination Antithrombotic Therapy Post–Percutaneous Coronary Intervention

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    Background: Up to 30% of patients with atrial fibrillation (AF) have coronary artery disease, and many undergo percutaneous coronary intervention (PCI). In the setting of acute coronary syndrome with PCI, or high-risk elective PCI, Canadian AF guidelines recommend 1-30 days of acetylsalicylic acid, 1-12 months of clopidogrel, and oral anticoagulation (OAC) with doses that may change throughout the 12 months post-PCI. The complexity of these regimens may contribute to unplanned modifications (UPMs), increasing the risk of thrombosis and/or bleeding. We describe what happens to these patients and their antithrombotic therapy (ATT) after discharge. Methods: Prospective follow-up was conducted of patients with AF requiring OAC who underwent PCI and were discharged on combination ATT. Patients were contacted at 1, 3, 6, and 12 months post-PCI. Results: Sixty-five patients were enrolled, with data at any time point available for 61 of them (94%). Of these, 44 (68%) experienced at least one UPM to ATT. In total, 105 UPMs occurred. The most common UPM was an extended duration of P2Y12 inhibitor (23 instances; 22%). The most common UPM with acetylsalicylic acid was extended (11 instances; 11%) or shortened (11 instances; 11%) duration. Thirty-nine UPMs (37%) were related to OACs; 9 (23%) were related to warfarin, and 30 (77%) were related to direct OACs. Of all patients with at least one UPM, 33 (75%) experienced bleeding. Conclusions: More than 2 in 3 patients with AF undergoing PCI experienced a UPM to their ATT. This study underscores the challenges of combination ATT for patients and clinicians alike, emphasizing the need for patient support after discharge. Résumé: Contexte: Jusqu’à 30 % des patients atteints de fibrillation auriculaire (FA) ont une coronaropathie, et nombre d’entre eux doivent subir une intervention coronarienne percutanée (ICP). En présence d’un syndrome coronarien aigu nécessitant une ICP ou dans le cas d’une ICP non urgente associée à un risque élevé, on recommande, dans les lignes directrices canadiennes sur la FA, un traitement de 1 à 30 jours par l’acide acétylsalicylique, de 1 à 12 mois par le clopidogrel, et une anticoagulothérapie orale (ACO) à des doses pouvant varier durant les 12 mois suivant l’ICP. La complexité de ces schémas posologiques peut contribuer à des modifications non planifiées (MNP) du traitement, ce qui accroît le risque de thrombose et/ou de saignement. Nous décrivons ce qui advient de ces patients et de leur traitement antithrombotique (TAT) après le congé de l’hôpital. Méthodologie: Un suivi prospectif a été réalisé chez des patients atteints de FA nécessitant une ACO, ayant subi une ICP et recevant un TAT lors de leur congé de l’hôpital. Les patients ont été contactés 1, 3, 6 et 12 mois après leur ICP. Résultats: Parmi les soixante-cinq patients inscrits, des données ont été obtenues pour 61 d’entre eux (94 %) à un moment ou à un autre. Au moins une MNP du TAT a eu lieu chez 44 (68 %) de ces 61 patients, pour un total de 105 MNP. La MNP la plus fréquente était la prolongation de la durée du traitement par un inhibiteur du P2Y12 (23 cas, soit 22 %). La MNP la plus fréquente du traitement par l’acide acétylsalicylique était la prolongation (11 cas, soit 11 %) ou le raccourcissement (11 cas, soit 11 %) de la durée du traitement. Au total, 39 MNP (37 %) étaient liées à des anticoagulants oraux, 9 (23 %) à la warfarine et 30 (77 %) à des anticoagulants oraux directs. Sur l’ensemble des patients ayant fait l’objet d’au moins une MNP, 33 (75 %) ont subi un saignement. Conclusions: Une MNP du TAT a eu lieu chez plus des deux tiers des patients atteints de FA ayant subi une ICP. Cette étude souligne les difficultés que pose un TAT d’association, tant pour les patients que pour les médecins, ce qui met en évidence la nécessité d’accompagner les patients après leur congé de l’hôpital

    The role of MPAs in reconciling fisheries management with conservation of biological diversity

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    A workshop of over 100 participants, balanced between fisheries management and biodiversity conservation backgrounds, reviewed and synthesised experiences regarding policy and institutional frameworks for use of MPAs in the contexts of fisheries management and conservation of biological diversity. The workshop concluded that although fisheries managers and biodiversity conservation agencies may give differing and sometimes opposing weights to the many objectives that could be set for MPAs, only 25% of fisheries objectives and 30% of biodiversity objectives were considered to be potential sources of conflict. MPAs that segregate activities in space could contribute to resolving all but one of the potential conflicts over objectives associated with desired ecological outcomes. Conflicts over social or economic objectives could be improved, made worse, or not be affected by MPAs, depending on how the MPAs were developed and managed. Seven features of planning processes and six features of the governance processes for MPAs were identified that could help find broadly supported solutions to the conflicts that did occur. Once established, the management of the MPA should be inclusive and participatory, as well as continuously learning and adaptive. Approaches to ensure management had those properties were identified, including twelve specific mechanisms that should be available to the MPA managers. On the basis of these conclusions about objectives, planning, and management, a general framework for the governance of MPAs for both fisheries and biodiversity conservation was developed. Its ten general characteristics and twelve steps necessary for progress were identified. We discuss the special challenges of establishing and managing MPAs for fisheries and biodiversity conservation on the high seas that deserve further attention include information-sharing, coordination and defining jurisdictions and stake-holding

    A framework for understanding climate change impacts on coral reef social–ecological systems

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