Inhibition of platelet activation prevents the P-selectin and integrin-dependent accumulation of cancer cell microparticles and reduces tumor growth and metastasis in vivo

International audienceVenous thromboembolism constitutes one of the main causes of death during the progression of a cancer. We previously demonstrated that tissue factor (TF)-bearing cancer cell-derived microparticles accumulate at the site of injury in mice developing a pancreatic cancer. The presence of these microparticles at the site of thrombosis correlates with the size of the platelet-rich thrombus. The objective of this study was to determine the involvement of TF expressed by cancer cell-derived microparticles on thrombosis associated with cancer. We observed that pancreatic cancer cell derived microparticles expressed TF, its inhibi-tor tissue factor pathway inhibitor (TFPI) as well as the integrins avb1 and avb3. In mice bearing a tumor under-expressing TF, a significant decrease in circulating TF activity associated with an increase bleeding time and a 100-fold diminished fibrin generation and platelet accumulation at the site of injury were observed. This was mainly due to the interaction of circulating cancer cell-derived microparticles expressing TFPI with activated platelets and fibrinogen. In an ectopic model of cancer, treatment of mice with Clopidogrel, an anti-platelet drug, decreased the size of the tumors and restored hemostasis by preventing the accumulation of cancer cell-derived microparticles at the site of thrombosis. In a syngeneic orthotopic model of pancreatic cancer Clopidogrel also significantly inhibited the development of metastases. Together, these results indicate that an anti-platelet strategy may efficiently treat thrombosis associated with cancer and reduce the progression of pancreatic cancer in mice

Promising New Treatments for Psoriasis

Psoriasis is a chronic, proliferative, and inflammatory skin disease affecting 2-3% of the population and is characterized by red plaques with white scales. Psoriasis is a disease that can affect many aspects of professional and social life. Currently, several treatments are available to help control psoriasis such as methotrexate, ciclosporin, and oral retinoids. However, the available treatments are only able to relieve the symptoms and lives of individuals. The discovery of new immunological factors and a better understanding of psoriasis have turned to the use of immunological pathways and could develop new biological drugs against specific immunological elements that cause psoriasis. Biological drugs are less toxic to the body and more effective than traditional therapies. Thus, they should improve the quality of life of patients with psoriasis. This review describes new psoriasis treatments, which are on the market or currently in clinical trials that are being used to treat moderate-to-severe plaque psoriasis. In addition, this paper describes the characteristics and mechanisms in detail. In general, biological drugs are well tolerated and appear to be an effective alternative to conventional therapies. However, their effectiveness and long-term side effects need to be further researched

In-Person and Remote Workshops for People With Neurocognitive Disorders: Recommendations From a Delphi Panel

Workshops using arts and board games are forms of non-pharmacological intervention widely employed in seniors with neurocognitive disorders. However, clear guidelines on how to conduct these workshops are missing. The objective of the Art and Game project (AGAP) was to draft recommendations on the structure and content of workshops for elderly people with neurocognitive disorders and healthy seniors, with a particular focus on remote/hybrid workshops, in which at least a part of the participants is connected remotely. Recommendations were gathered using a Delphi methodology. The expert panel (N = 18) included experts in the health, art and/or board games domains. They answered questions via two rounds of web-surveys, and then discussed the results in a plenary meeting. Some of the questions were also shared with the general public (N = 101). Both the experts and the general public suggested that organizing workshops in a hybrid format (some face-to-face sessions, some virtual session) is feasible and interesting for people with neurocognitive disorders. We reported guidelines on the overall structure of workshops, practical tips on how to organize remote workshops, and a SWOT analysis of the use of remote/hybrid workshops. The guidelines may be employed by clinicians to decide, based on their needs and constraints, what interventions and what kind of workshop format to employ, as well as by researcher to standardize procedures to assess the effectiveness of non-pharmacological treatments for people with neurocognitive disorders

Safety and Outcome of High-Flow Nasal Oxygen Therapy Outside ICU Setting in Hypoxemic Patients With COVID-19∗

OBJECTIVE: High-flow nasal oxygen (HFNO) therapy is frequently applied outside ICU setting in hypoxemic patients with COVID-19. However, safety concerns limit more widespread use. We aimed to assess the safety and clinical outcomes of initiation of HFNO therapy in COVID-19 on non-ICU wards. DESIGN: Prospective observational multicenter pragmatic study. SETTING: Respiratory wards and ICUs of 10 hospitals in The Netherlands. PATIENTS: Adult patients treated with HFNO for COVID-19-associated hypoxemia between December 2020 and July 2021 were included. Patients with treatment limitations were excluded from this analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Outcomes included intubation and mortality rate, duration of hospital and ICU stay, severity of respiratory failure, and complications. Using propensity-matched analysis, we compared patients who initiated HFNO on the wards versus those in ICU. Six hundred eight patients were included, of whom 379 started HFNO on the ward and 229 in the ICU. The intubation rate in the matched cohort (n = 214 patients) was 53% and 60% in ward and ICU starters, respectively (p = 0.41). Mortality rates were comparable between groups (28-d [8% vs 13%], p = 0.28). ICU-free days were significantly higher in ward starters (21 vs 17 d, p &lt; 0.001). No patient died before endotracheal intubation, and the severity of respiratory failure surrounding invasive ventilation and clinical outcomes did not differ between intubated ward and ICU starters (respiratory rate-oxygenation index 3.20 vs 3.38; Pao2:Fio2ratio 65 vs 64 mm Hg; prone positioning after intubation 81 vs 78%; mortality rate 17 vs 25% and ventilator-free days at 28 d 15 vs 13 d, all p values &gt; 0.05). CONCLUSIONS: In this large cohort of hypoxemic patients with COVID-19, initiation of HFNO outside the ICU was safe, and clinical outcomes were similar to initiation in the ICU. Furthermore, the initiation of HFNO on wards saved time in ICU without excess mortality or complicated course. Our results indicate that HFNO initiation outside ICU should be further explored in other hypoxemic diseases and clinical settings aiming to preserve ICU capacity and healthcare costs.</p

Le Quartier Mu (Malia, Crète) : étude fonctionnelle d’un important complexe archéologique du Minoen Moyen IIB

Le Quartier Mu est un important complexe archéologique, composé de dix bâtiments, faisant partie du site de Malia, au nord-est de la Crète. Il est un témoin exceptionnel de la vie quotidienne et de la production artisanale, dans des contextes qui sont présents côte à côte, à la fin de la période des premiers palais. Détruit par incendie, il offre un « arrêt sur image » d’un moment de vie, avec un matériel nombreux et riche en contexte, qui a été amplement publié par l’Ecole française d’Athènes, par types de matériaux (vases en céramique, armes, vases en pierre, sceaux, etc.). Toutefois, on connait encore assez peu les fonctions des différents bâtiments et ateliers, mais surtout les relations qu’ils entretenaient entre eux. Nous avons donc réalisé une étude fonctionnelle intégrée, basée sur l’ensemble du matériel archéologique. Chaque objet a été répertorié dans une base de données totalisant plus de 2800 références, selon un classement par catégorie fonctionnelles qui ont par ailleurs chacune fait l’objet d’une description. Chaque contexte a ensuite été étudié individuellement (ensemble du matériel, architecture, stratigraphie). Nous avons procédé de la sorte systématiquement pour toutes les pièces et tous les bâtiments. Cela nous a permis, outre de les identifier, de mieux comprendre les différentes fonctions, et les différentes manifestations de celles-ci, prenant place dans chaque pièce et au sein de chaque bâtiment. Nous avons également pu mieux caractériser la production artisanale et le lien qu’entretiennent ces lieux de production avec les autres bâtiments du Quartier Mu. Enfin, nous avons abordé l’organisation sociale en nous penchant sur le statut des occupants de ces bâtiments. Cette étude nous a permis, in fine, de nuancer les hypothèses fonctionnelles déjà émises au sujet de ce Quartier, principalement la question de savoir si cet ensemble de bâtiments fonctionnait de manière unitaire ou si les bâtiments étaient plutôt autonomes.Master [120] en histoire de l'art et archéologie, orientation générale, Université catholique de Louvain, 201

On some late Prepalatial pricket lamps in White-on-Dark Ware from beneath the North Wing of the Malia Palace

In 2021, eight pricket lamps or lampes à piton were identified during the study of ceramic materials from the sounding undertaken by Olivier Pelon in 1978 and 1985 in Room IX b, located in the North Wing of the Malia Palace. These lamps, contained in an EM III-MM IA assemblage from the northern part of the room, are local productions in semi-fine red fabric that imitate the elaborate patterns of the Whiteon- Dark Ware, the hallmark of the late Prepalatial productions of East Crete. These elaborate, white-on-dark pricket lamps from the late Prepalatial levels of the Malia Palace seem to represent the prototype of the later monochrome lampes à piton, well-attested across the Malia site from MM I to MM II. This paper aims to present the eight lamps and their context, to provide parallels both from Malia and Minoan Crete, and to trace the development of this specific shape from late Prepalatial through the Protopalatial period in the whole island

From fragmented evidence to the identification of cooking practices. A diachronic approach from Minoan Crete

This paper discussed the identification of cooking practices in the archaeological context of Minoan Crete

Targeting endosomal pH for cancer chemotherapy

Altered pH homeostasis in cancer cells has been linked with essentially all classical hallmarks of cancer, including chemoresistance. We recently identified a conceptually novel mechanism for how dysregulated pH in hypoxic cells causes chemoresistance which is based on the aberrant cellular distribution of the endosomal pH regulator, the sodium/hydrogen exchanger 6 (NHE6)

Les péripéties du prédicat en Suisse romande : hier, aujourd’hui et demain…

L’article propose un état des lieux de l’enseignement grammatical en Suisse romande avec une focale sur l’usage du terme de prédicat. Nous regardons d’abord les reformulations successives du terme au cours de l’histoire. Puis, grâce à une analyse des prescriptions institutionnelles, aux résultats d’une enquête menée par nos étudiants auprès des responsables de stage, à des témoignages de formateurs des divers cantons romands, nous mettons en évidence un écart entre les savoirs de la formation et les pratiques déclarées. Cet état des lieux nous conduit à formuler un argumentaire en faveur de l’usage du terme de prédicat dans la grammaire scolaire et à envisager quelques pistes pour l’effectivité de son usage dans les classes.This contribution gives an overview of grammar teaching in French Switzerland and highlights the use of a specific notion: the predicate. After a brief historical perspective and the presentation of the official documents (curriculum and others official teaching resources), we discuss the results of an inquiry on the use of the notion of predicate in French Swiss teaching practices. Based on all these elements, we develop arguments that state our position on the necessary use of the notion in order to give a systematic view of the functioning of French language. We also suggest some avenues to explore in teacher training programmes