Evolution of the central West Greenland margin and the Nuussuaq Basin : Localised basin uplift along a stable continental margin proposed from thermochronological data

ACKNOWLEDGEMENTS Tim Redfield and a second anonymous reviewer are thanked for their constructive comments. The work con-tained in this publication contains work conducted during a PhD study undertaken as part of the Natural Environment Research Council (NERC) Centre for Doctoral Training(CDT) in Oil & Gas [grant number NEM00578X/1] and is sponsored by the University of Aberdeen.Peer reviewedPublisher PD

Activité et mécanismes d’action d’analogues de la quercétine sur la fonctionnalité des cellules β pancréatiques

The pancreatic β-cell regulates glucose homeostasis. Various factors such as oxidative stress and inflammation can lead to its dysfunction which is a core feature of the pathophysiology of type 2 diabetes (T2D). Preserving β-cell functionality could delay the onset or the evolution of the pathology and in this regards flavonoids are promising molecules. Flavonoids are natural compounds that occur in plant kingdom. They were initially described for their health effects due to their antioxidant action. Later on, they were reported to interact with pharmacological targets and to regulate cellular signaling pathways. Based on published data describing the ability of flavonoids to modulate voltage-dependent calcium channels at the vascular level, the effects of around ten molecules have been studied with regards to β-cell function. This fundamental pharmacology approach allows us to show that resokaempferol and galangin, despite very similar chemical structures, exert opposite effects on insulin secretion through the modulation of distinct pharmacological targets. Resokaempferol, which enhances insulin secretion, is thought to activate CaV at the plasma membrane. Galangin, which inhibits insulin secretion, would act as an uncoupler of mitochondrial oxidative phosphorylation. It would be interesting to complete this work by comparing the effects of these molecules in vivo on glycemic regulation. In a complementary structure-activity study, we aimed at investigating the structural determinants involved in the modulation of insulin secretion. Our data suggest that a double substitution by hydroxyl groups at the 3 and 4' position on the flavone ring seems to be a minimum requirement to confer the flavonoid a maximal stimulatory activity towards insulin secretion. On the other hand, hydroxylation of the flavonoid at the 2' position appears to be deleterious for its pharmacological activity regardless it is an agonist or an antagonist towards insulin secretion. This study could be continued and extended by analyzing the concentration effect curves and the mechanism of action of the most effective molecules to modulate and protect the β-cell function.La cellule β pancréatique régule l’homéostasie glucidique. Sa dysfonction, favorisée par divers facteurs tels que le stress oxydant et l’inflammation, joue un rôle clé dans la physiopathologie du diabète de type 2 (DT2). Le maintien de sa fonctionnalité, notamment par l’utilisation de flavonoïdes, pourrait retarder l’apparition ou l’évolution de la pathologie. En effet, les flavonoïdes, composés naturels du règne végétal, initialement décrits pour leurs effets santé du fait de leur action antioxydante, apparaissent désormais comme des molécules capables d’interagir avec des cibles pharmacologiques et de réguler des voies de signalisation cellulaires. Sur la base de résultats décrivant la capacité des flavonoïdes à moduler les canaux calciques voltage dépendants (CaV) au niveau vasculaire, les effets d’une dizaine de molécules ont été étudiés vis-à-vis de la fonction cellulaire β. Cette approche de pharmacologie fondamentale nous permet de montrer que le résokaempférol et la galangine, bien que possédant des structures chimiques très proches, exercent des effets opposés sur la sécrétion d’insuline via des cibles pharmacologiques distinctes. Le résokaempférol, qui amplifie la sécrétion d’insuline, activerait les CaV au niveau de la membrane plasmique. La galangine, qui au contraire inhibe la sécrétion d’insuline, se comporterait comme un agent découplant de la phosphorylation oxydative mitochondriale. Il serait intéressant de compléter ce travail en comparant les effets de ces molécules in vivo sur la régulation glycémique. Notre étude complémentaire de relation structure-activité visant à étudier les déterminants structuraux impliqués dans la modulation de la sécrétion d’insuline suggère qu’une double substitution par des groupements hydroxyles en position 3 et 4’ sur le noyau flavone semble être un minimum requis pour conférer au flavonoïde une activité stimulante maximale vis-à-vis de la sécrétion d’insuline. A l’opposé, une hydroxylation en position 2’ apparait délétère sur toute activité pharmacologique du flavonoïde, que celui-ci se révèle un agoniste ou un antagoniste vis-à-vis de la sécrétion d’insuline. Cette étude pourrait être poursuivie en analysant les courbes effet concentration et le mécanisme d’action des molécules les plus efficaces à moduler et protéger la fonction cellulaire β

Effects and mechanisms of action of quercetin-like compounds on pancreatic β-cells functions

La cellule β pancréatique régule l’homéostasie glucidique. Sa dysfonction, favorisée par divers facteurs tels que le stress oxydant et l’inflammation, joue un rôle clé dans la physiopathologie du diabète de type 2 (DT2). Le maintien de sa fonctionnalité, notamment par l’utilisation de flavonoïdes, pourrait retarder l’apparition ou l’évolution de la pathologie. En effet, les flavonoïdes, composés naturels du règne végétal, initialement décrits pour leurs effets santé du fait de leur action antioxydante, apparaissent désormais comme des molécules capables d’interagir avec des cibles pharmacologiques et de réguler des voies de signalisation cellulaires. Sur la base de résultats décrivant la capacité des flavonoïdes à moduler les canaux calciques voltage dépendants (CaV) au niveau vasculaire, les effets d’une dizaine de molécules ont été étudiés vis-à-vis de la fonction cellulaire β. Cette approche de pharmacologie fondamentale nous permet de montrer que le résokaempférol et la galangine, bien que possédant des structures chimiques très proches, exercent des effets opposés sur la sécrétion d’insuline via des cibles pharmacologiques distinctes. Le résokaempférol, qui amplifie la sécrétion d’insuline, activerait les CaV au niveau de la membrane plasmique. La galangine, qui au contraire inhibe la sécrétion d’insuline, se comporterait comme un agent découplant de la phosphorylation oxydative mitochondriale. Il serait intéressant de compléter ce travail en comparant les effets de ces molécules in vivo sur la régulation glycémique. Notre étude complémentaire de relation structure-activité visant à étudier les déterminants structuraux impliqués dans la modulation de la sécrétion d’insuline suggère qu’une double substitution par des groupements hydroxyles en position 3 et 4’ sur le noyau flavone semble être un minimum requis pour conférer au flavonoïde une activité stimulante maximale vis-à-vis de la sécrétion d’insuline. A l’opposé, une hydroxylation en position 2’ apparait délétère sur toute activité pharmacologique du flavonoïde, que celui-ci se révèle un agoniste ou un antagoniste vis-à-vis de la sécrétion d’insuline. Cette étude pourrait être poursuivie en analysant les courbes effet concentration et le mécanisme d’action des molécules les plus efficaces à moduler et protéger la fonction cellulaire β.The pancreatic β-cell regulates glucose homeostasis. Various factors such as oxidative stress and inflammation can lead to its dysfunction which is a core feature of the pathophysiology of type 2 diabetes (T2D). Preserving β-cell functionality could delay the onset or the evolution of the pathology and in this regards flavonoids are promising molecules. Flavonoids are natural compounds that occur in plant kingdom. They were initially described for their health effects due to their antioxidant action. Later on, they were reported to interact with pharmacological targets and to regulate cellular signaling pathways. Based on published data describing the ability of flavonoids to modulate voltage-dependent calcium channels at the vascular level, the effects of around ten molecules have been studied with regards to β-cell function. This fundamental pharmacology approach allows us to show that resokaempferol and galangin, despite very similar chemical structures, exert opposite effects on insulin secretion through the modulation of distinct pharmacological targets. Resokaempferol, which enhances insulin secretion, is thought to activate CaV at the plasma membrane. Galangin, which inhibits insulin secretion, would act as an uncoupler of mitochondrial oxidative phosphorylation. It would be interesting to complete this work by comparing the effects of these molecules in vivo on glycemic regulation. In a complementary structure-activity study, we aimed at investigating the structural determinants involved in the modulation of insulin secretion. Our data suggest that a double substitution by hydroxyl groups at the 3 and 4' position on the flavone ring seems to be a minimum requirement to confer the flavonoid a maximal stimulatory activity towards insulin secretion. On the other hand, hydroxylation of the flavonoid at the 2' position appears to be deleterious for its pharmacological activity regardless it is an agonist or an antagonist towards insulin secretion. This study could be continued and extended by analyzing the concentration effect curves and the mechanism of action of the most effective molecules to modulate and protect the β-cell function

Tracheotomy/Tracheostomy Management at Home and in Care Centers

Aim and objectives: Formalize a consensus about patient’s care management (nursing techniques, management of complications) with tracheotomy or tracheostomy at home and in care center. Background: Tracheotomy and tracheostomy are medical devices used for many years thus inspiring fear mainly by their symbolic impacts and the lack of training of health professionals.&nbsp;Design: This study is a mixed research with a qualitative methodology including iterative focus groups.&nbsp;Methods: A national call for project was performed on Internet to recruit multi-professional volunteers early 2015, anyone was accepted. Seven phone call with focus groups, each 2 hours, were set during 2015. Finally the project was presented and validated in “Guidelines and French Oncology Networks” J2R congress in Nantes, France in December 2015 and published on the web.&nbsp;Results: Definitions, anatomic and physiologic notions, then the different types of cannulas are presented in the document. The management of tracheotomy/tracheostomy daily cares with protocols and videos, of the complications (infections, bleeding …), of functional sequelae (phonation, swallowing) at home and in care centers is then explained and demonstrated.Conclusions: Finally, this work has led to a national consensus on the management, at home and in care centers, of tracheotomy and tracheostomy management and their potential complications.&nbsp;Relevance to clinical practice: Such a work has never been done before. It aims to be comprehensive and didactic by means of figures and decision trees. This study will be useful and could be implemented despite local habits.</p

Management of olfactory, gustatory and swallowing impairments in patients with head and neck cancer

International audienc

Management of olfactory, gustatory and swallowing impairments in patients with head and neck cancer

International audienc

Management of olfactory, gustatory and swallowing impairments in patients with head and neck cancer

International audienc

Intelligence test solving through eye-movements and mouse-movements

International audienceAmong intelligence tests, Raven’s Advanced Progressive Matrices (RAPM) are used to assess reasoning and problem-solving capabilities in adult humans through series of items of increasing difficulty. Each item is defined by a 3x3 matrix of pictograms whose spatial structure follows logical rules. One pictogram is always missing, and the participant must find the correct pictogram among 8 proposed answers. Classically, performance is based on the number of correct responses given by the participant. Yet, research has shown that performance is correlated to the strategies used to solve the items (Carpenter et al., 1990; Vigneau et al., 2006). Two extreme strategies can be defined and measured through eye-tracking: constructivism (inferring the rules from the matrix) vs. elimination (screening the answers for the most probable one).In the present work, we investigated whether the observed impact of visual active sampling on performance was specific to the test design or could be altered by constraining the interactions with the test items. For this purpose, we developed a computerized dynamic version of the RAPM test, with additional mouse interactivity options to select the visible pictograms: 1) full matrix and answers visible at all times (original design), 2) answers hidden and matrix made visible by clicking on it (and reciprocally), 3) a single line of the matrix or all answers visible at once, 4) three user-selected pictograms of the matrix or the answers visible at once. We previously replicated results from the literature by statistically predicting performance from mouse-movements. Nevertheless, the four experimental conditions allow to go further by studying how much of the eye-movement patterns are transferred to mouse-movements (e.g. due to differences in timing and motor cost), and how both types of movements are coordinated and integrated into the overall participant behavioral strategy

Proposition d’un référentiel national de prise en charge des modifications des capacités olfactive, gustative et/ou de la déglutition dans les cancers des voies aérodigestives supérieures

International audienceMalnutrition is particularly related with olfactory, gustatory and swallowing disorders in patients with head and neck cancer. Nutrition is often considered with a therapeutic and quantitative point of view (sum of calories, of proteins, oral supplements, enteral feeding…). However, especially in France, eating is central in the social and familial dynamic and the cancer and its treatments can lead to a dramatic quality of life impairment.Proposition d'un référentiel national de prise en charge des modifications des capacités olfactives, gustative et/ou de la déglutition dans les cancers des voies aérodigestives supérieures. Nutr clin métab (2017)