Oral and Gastrointestinal Sensing of Dietary Fat and Appetite Regulation in Humans: Modification by Diet and Obesity

Dietary fat interacts with receptors in both the oral cavity and the gastrointestinal (GI) tract to regulate fat and energy intake. This review discusses recent developments in our understanding of the mechanisms underlying the effects of fat, through its digestive products, fatty acids (FAs), on GI function and energy intake, the role of oral and intestinal FA receptors, and the implications that changes in oral and small intestinal sensitivity in response to ingested fat may have for the development of obesity

European marine biodiversity monitoring networks: Strengths, weaknesses, opportunities and threats

© 2016 Patrício, Little, Mazik, Papadopoulou, Smith, Teixeira, Hoffmann, Uyarra, Solaun, Zenetos, Kaboglu, Kryvenko, Churilova, Moncheva, Bucas, Borja, Hoepffner and Elliott. By 2020, European Union Member States should achieve Good Environmental Status (GES) for 11 environmental quality descriptors for their marine waters to fulfill the Marine Strategy Framework Directive (MSFD). By the end of 2015, in coordination with the Regional Seas Conventions, each EU Member State was required to develop a marine strategy for their waters, together with other countries within the same marine region or sub-region. Coherent monitoring programs, submitted in 2014, form a key component of this strategy, which then aimed to lead to a Program of Measures (submitted in 2015). The European DEVOTES FP7 project has produced and interrogated a catalog of EU marine monitoring related to MSFD descriptors 1 (biological diversity), 2 [non-indigenous species (NIS)], 4 (food webs), and 6 (seafloor integrity). Here we detail the monitoring activity at the regional and sub-regional level for these descriptors, as well as for 11 biodiversity components, 22 habitats and the 37 anthropogenic pressures addressed. The metadata collated for existing European monitoring networks were subject to a SWOT (strengths, weaknesses, opportunities, and threats) analysis. This interrogation has indicated case studies to address the following questions: (a) what are the types of monitoring currently in place? (b) who does what and how? (c) is the monitoring fit-for-purpose for addressing the MSFD requirements? and (d) what are the impediments to better monitoring (e.g., costs, shared responsibilities between countries, overlaps, co-ordination, etc.)? We recommend the future means to overcome the identified impediments and develop more robust monitoring strategies. As such the results are especially relevant to implementing comprehensive and coordinated monitoring networks throughout Europe, for marine policy makers, government agencies and regulatory bodies. It is emphasized that while many of the recommendations given here require better, more extensive and perhaps more costly monitoring, this is required to avoid any legal challenges to the assessments or to bodies and industries accused of causing a deterioration in marine quality. More importantly the monitoring is required to demonstrate the efficacy of management measures employed. Furthermore, given the similarity in marine management approaches in other developed systems, we consider that the recommendations are also of relevance to other regimes worldwide

A Protein Preload Enhances the Glucose-Lowering Efficacy of Vildagliptin in Type 2 Diabetes

Ranking and judging political misbehaviours: the benefits of focus group approach and of quantitative method for analysing qualitative dataQualitative researches based on focus group offer valuable insights in analyzing moral conflicts. This article suggests they also prove very useful to explore citizens’ perceptions of political misbehaviours. Moral expectations regarding politicians’ behaviours are ambiguous judgements because of the various criteria that underpin their perceptions of politics. This article is based on the analysis of eight different, socio-culturally homogeneous focus groups. Collected arguments are analysed through a quantitative method examining discursive contents. The existence of a common grid for ranking political misbehaviours is emphasized. The moderating effects of collective discussion on judgements are also outlined. The article emphasizes variations in judgments, differentiating groups according to their social and occupational experiences. At last, different “repertoires of arguments” are identified relying on different principles.Les enjeux de probité publique se prêtent bien aux recherches qualitatives menées par focus group, habituellement utilisées dans l’exploration des conflits moraux et normatifs. La démarche est ici mobilisée pour explorer l’ambiguïté des jugements portés par les citoyens sur les pratiques et transgressions des élus. Elle repose sur huit groupes socio-culturellement différenciés et sur une exploitation originale à partir d’une méthode de quantification du contenu des discours recueillis. L’article montre l’existence d’une échelle homogène de qualification et de classification des pratiques politiques qui graduent les jugements de réprobation. La discussion collective favorise l’expression de formes de modération dans les jugements. L’exploitation pointe des différences liées aux caractéristiques sociales des groupes. Elle identifie des « répertoires argumentatifs », mobilisant des principes de jugement divergents

Platelet factor XIII-A regulates platelet function and promotes clot retraction and stability.

Factor XIII (FXIII) is an important proenzyme in the hemostatic system. The plasma-derived enzyme activated FXIII cross-links fibrin fibers within thrombi to increase their mechanical strength and cross-links fibrin to fibrinolytic inhibitors, specifically α2-antiplasmin, to increase resistance to fibrinolysis. We have previously shown that cellular FXIII (factor XIII-A [FXIII-A]), which is abundant in the platelet cytoplasm, is externalized onto the activated membrane and cross-links extracellular substrates. The contribution of cellular FXIII-A to platelet activation and platelet function has not been extensively studied. This study aims to identify the role of platelet FXIII-A in platelet function. We used normal healthy platelets with a cell permeable FXIII inhibitor and platelets from FXIII-deficient patients as a FXIII-free platelet model in a range of platelet function and clotting tests. Our data demonstrate that platelet FXIII-A enhances fibrinogen binding to the platelet surface upon agonist stimulation and improves the binding of platelets to fibrinogen and aggregation under flow in a whole-blood thrombus formation assay. In the absence of FXIII-A, platelets show reduced sensitivity to agonist stimulation, including decreased P-selectin exposure and fibrinogen binding. We show that FXIII-A is involved in platelet spreading where a lack of FXIII-A reduces the ability of platelets to fully spread on fibrinogen and collagen. Our data demonstrate that platelet FXIII-A is important for clot retraction where clots formed in its absence retracted to a lesser extent. Overall, this study shows that platelet FXIII-A functions during thrombus formation by aiding platelet activation and thrombus retraction in addition to its antifibrinolytic roles

Fully automated platelet differential interference contrast image analysis via deep learning

Platelets mediate arterial thrombosis, a leading cause of myocardial infarction and stroke. During injury, platelets adhere and spread over exposed subendothelial matrix substrates of the damaged blood vessel wall. The mechanisms which govern platelet activation and their interaction with a range of substrates are therefore regularly investigated using platelet spreading assays. These assays often use differential interference contrast (DIC) microscopy to assess platelet morphology and analysis performed using manual annotation. Here, a convolutional neural network (CNN) allowed fully automated analysis of platelet spreading assays captured by DIC microscopy. The CNN was trained using 120 generalised training images. Increasing the number of training images increases the mean average precision of the CNN. The CNN performance was compared to six manual annotators. Significant variation was observed between annotators, highlighting bias when manual analysis is performed. The CNN effectively analysed platelet morphology when platelets spread over a range of substrates (CRP-XL, vWF and fibrinogen), in the presence and absence of inhibitors (dasatinib, ibrutinib and PRT-060318) and agonist (thrombin), with results consistent in quantifying spread platelet area which is comparable to published literature. The application of a CNN enables, for the first time, automated analysis of platelet spreading assays captured by DIC microscopy

Pooled-data analysis identifies pyloric pressures and plasma cholecystokinin concentrations as major determinants of acute energy intake in healthy, lean men

Background: The interaction of nutrients with the small intestine modulates gastropyloroduodenal motility, stimulates the release of gut hormones, and suppresses appetite and energy intake. Objective: We evaluated which, if any, of these variables are independent determinants of acute energy intake in healthy, lean men. Design: We pooled data from 8 published studies that involved a total of 67 healthy, lean men in whom antropyloroduodenal pressures, gastrointestinal hormones, and perceptions were measured during intraduodenal nutrient or intravenous hormone infusions. In all of the studies, the energy intake at a buffet lunch was quantified immediately after the infusions. To select specific motor, hormone, or perception variables for inclusion in a multivariable mixed-effects model for determination of independent predictors of energy intake, we assessed all variables for collinearity and determined within-subject correlations between energy intake and these variables by using bivariate analyses adjusted for repeated measures. Results: Although correlations were shown between energy intake and antropyloroduodenal pressures, plasma hormone concentrations, and gastrointestinal perceptions, only the peak number of isolated pyloric-pressure waves, peak plasma cholecystokinin concentration, and area under the curve of nausea were identified as independent predictors of energy intake (all P < 0.05), so that increases of 1 pressure wave, 1 pmol/L, and 1 mm · min were associated with reductions in energy intake of 36, 88, and 0.4, respectively. Conclusion: We identified specific changes in gastrointestinal motor and hormone functions (ie, stimulation of pyloric pressures and plasma cholecystokinin) and nausea that are associated with the suppression of acute energy intake.Radhika V Seimon, Kylie Lange, Tanya J Little, Ixchel M Brennan, Amelia N Pilichiewicz, Kate L Feltrin, Astrid J Smeets, Michael Horowitz and Christine Feinle-Bisse

Technology in Parkinson's disease:challenges and opportunities

The miniaturization, sophistication, proliferation, and accessibility of technologies are enabling the capture of more and previously inaccessible phenomena in Parkinson's disease (PD). However, more information has not translated into a greater understanding of disease complexity to satisfy diagnostic and therapeutic needs. Challenges include noncompatible technology platforms, the need for wide-scale and long-term deployment of sensor technology (among vulnerable elderly patients in particular), and the gap between the "big data" acquired with sensitive measurement technologies and their limited clinical application. Major opportunities could be realized if new technologies are developed as part of open-source and/or open-hardware platforms that enable multichannel data capture sensitive to the broad range of motor and nonmotor problems that characterize PD and are adaptable into self-adjusting, individualized treatment delivery systems. The International Parkinson and Movement Disorders Society Task Force on Technology is entrusted to convene engineers, clinicians, researchers, and patients to promote the development of integrated measurement and closed-loop therapeutic systems with high patient adherence that also serve to (1) encourage the adoption of clinico-pathophysiologic phenotyping and early detection of critical disease milestones, (2) enhance the tailoring of symptomatic therapy, (3) improve subgroup targeting of patients for future testing of disease-modifying treatments, and (4) identify objective biomarkers to improve the longitudinal tracking of impairments in clinical care and research. This article summarizes the work carried out by the task force toward identifying challenges and opportunities in the development of technologies with potential for improving the clinical management and the quality of life of individuals with PD. © 2016 International Parkinson and Movement Disorder Society

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy