Affronter des enjeux clés liés à l’évaluation du rôle de promoteur de la santé

Introduction: Although the CanMEDS framework sets the standard for Canadian training, health advocacy competence does not appear to factor heavily into high stakes assessment decisions. Without forces motivating uptake, there is little movement by educational programs to integrate robust advocacy teaching and assessment practices. However, by adopting CanMEDS, the Canadian medical education community endorses that advocacy is required for competent medical practice. It’s time to back up that endorsement with meaningful action. Our purpose was to aid this work by answering the key questions that continue to challenge training for this intrinsic physician role. Methods: We used a critical review methodology to both examine literature relevant to the complexities impeding robust advocacy assessment, and develop recommendations. Our review moved iteratively through five phases: focusing the question, searching the literature, appraising and selecting sources, and analyzing results. Results: Improving advocacy training relies, in part, on the medical education community developing a shared vision of the Health Advocate (HA) role, designing, implementing, and integrating developmentally appropriate curricula, and considering ethical implications of assessing a role that may be risky to enact. Conclusion: Changes to assessment could be a key driver of curricular change for the HA role, provided implementation timelines and resources are sufficient to make necessary changes meaningful. To truly be meaningful, however, advocacy first needs to be perceived as valuable. Our recommendations are intended as a roadmap for transforming advocacy from a theoretical and aspirational value into one viewed as having both practical relevance and consequential implications. Introduction : Bien que le référentiel CanMEDS établisse les normes en matière de formation et de pratique médicale au Canada, la compétence de promotion de la santé (PS) ne semble pas peser lourd aux étapes décisives du continuum de la formation médicale. En l’absence de facteurs incitatifs, les programmes de formation sont peu enclins à intégrer des pratiques solides d’enseignement et d’évaluation en matière de PS. Un système de soins de santé marqué par l’iniquité appelle pourtant des efforts de sensibilisation. En adoptant le référentiel CanMEDS, le milieu canadien de l’éducation médicale a reconnu que la PS est nécessaire à la pratique compétente de la médecine. Il est temps que cet engagement soit traduit en actions concrètes. Méthodes : Employant une méthode d’analyse critique, nous avons examiné les écrits qui peuvent éclairer les obstacles à l’évaluation sérieuse de la PS et avons formulé des recommandations. L’examen a été effectué de manière itérative en cinq étapes : définition de la question de recherche, recherche documentaire, évaluation et sélection des sources, et analyse des résultats. Résultats : L’amélioration de la formation en matière de PS suppose, entre autres, que le milieu de l’éducation médicale s’attèle aux enjeux clés suivants : 1) l’élaborer une vision commune de la PS, 2) concevoir, mettre en œuvre et intégrer des programmes d’études évolutifs et 3) considérer les répercussions éthiques de l’évaluation d’un rôle qui comporte une part de risque. Conclusion : Le manque de visibilité et d’attention accordées à la PS dans la formation amène de nombreux apprenants à se demander si leur compétence en la matière compte vraiment. Nous estimons que la promotion de la santé est au cœur des soins centrés sur le patient. Nous lançons donc un appel à redoubler nos efforts collectifs pour faire passer la PS du statut de simple aspiration et de valeur théorique à celui d’une valeur ayant une pertinence et des incidences concrètes

Heat Shock Proteins Can Be Surrogate Autoantigens for Induction of Antigen Specific Therapeutic Tolerance in Rheumatoid Arthritis

Technologies that enable induction of therapeutic tolerance may revolutionize the treatment of autoimmune diseases by their supposed potential to induce drug-free and lasting disease remission. In combination with diagnostic tests that screen for individuals at risk, these approaches may offer chances to halt disease before serious damage in the tissues can occur. In fact, for healthy individuals at risk, this could lead to a preventive form of vaccination. For therapeutic tolerance to re-instate natural self-tolerance it seems essential to induce tolerance for the critical autoantigens involved in disease. However, for most autoimmune diseases such antigens are poorly defined. This is the case for both disease inciting autoantigens and antigens that become involved through epitope spreading. A possible source of surrogate auto-antigens expressed in tissues during inflammation are heat shock proteins (HSP) or stress proteins. In this mini-review we discuss unique characteristics of HSP which provide them with the capacity to inhibit inflammatory processes. Various studies have shown that epitopes of HSP60 and HSP70 molecules can function as vaccines to downregulate a variety of autoimmune inflammatory diseases. Currently, several research groups are developing cell therapies with the intention to reach therapeutic tolerance. In this review, in which we are proposing to ex vivo load tolerant dendritic cells with a Treg inducing HSP70 derived peptide called B29, we are discussing the chances to develop this as an autologous tolDC therapeutic tolerance therapy for rheumatoid arthritis

Combined field inoculations of pseudomonas bacteria, arbuscular mycorrhizal fungi, and entomopathogenic nematodes and their effects on wheat performance

In agricultural ecosystems, pest insects, pathogens, and reduced soil fertility pose major challenges to crop productivity and are responsible for significant yield losses worldwide. Management of belowground pests and diseases remains particularly challenging due to the complex nature of the soil and the limited reach of conventional agrochemicals. Boosting the presence of beneficial rhizosphere organisms is a potentially sustainable alternative and may help to optimize crop health and productivity. Field application of single beneficial soil organisms has shown satisfactory results under optimal conditions. This might be further enhanced by combining multiple beneficial soil organisms, but this remains poorly investigated. Here, we inoculated wheat plots with combinations of three beneficial soil organisms that have different rhizosphere functions and studied their effects on crop performance. Plant beneficial Pseudomonas bacteria, arbuscular mycorrhizal fungi (AMF), and entomopathogenic nematodes (EPN), were inoculated individually or in combinations at seeding, and their effects on plant performance were evaluated throughout the season. We used traditional and molecular identification tools to monitor their persistence over the cropping season in augmented and control treatments, and to estimate the possible displacement of native populations. In three separate trials, beneficial soil organisms were successfully introduced into the native populations and readily survived the field conditions. Various Pseudornonas, mycorrhiza, and nematode treatments improved plant health and productivity, while their combinations provided no significant additive or synergistic benefits compared to when applied alone. EPN application temporarily displaced some of the native EPN, but had no significant long-term effect on the associated food web. The strongest positive effect on wheat survival was observed for Pseudomonas and AMF during a season with heavy natural infestation by the frit fly, Oscinella frit, a major pest of cereals. Hence, beneficial impacts differed between the beneficial soil organisms and were most evident for plants under biotic stress. Overall, our findings indicate that in wheat production under the test conditions the three beneficial soil organisms can establish nicely and are compatible, but their combined application provides no additional benefits. Further studies are required, also in other cropping systems, to fine-tune the functional interactions among beneficial soil organisms, crops, and the environment

Tracking CNS and systemic sources of oxidative stress during the course of chronic neuroinflammation

The functional dynamics and cellular sources of oxidative stress are central to understanding MS pathogenesis but remain elusive, due to the lack of appropriate detection methods. Here we employ NAD(P)H fluorescence lifetime imaging to detect functional NADPH oxidases (NOX enzymes) in vivo to identify inflammatory monocytes, activated microglia, and astrocytes expressing NOX1 as major cellular sources of oxidative stress in the central nervous system of mice affected by experimental autoimmune encephalomyelitis (EAE). This directly affects neuronal function in vivo, indicated by sustained elevated neuronal calcium. The systemic involvement of oxidative stress is mirrored by overactivation of NOX enzymes in peripheral CD11b(+) cells in later phases of both MS and EAE. This effect is antagonized by systemic intake of the NOX inhibitor and anti-oxidant epigallocatechin-3-gallate. Together, this persistent hyper-activation of oxidative enzymes suggests an "oxidative stress memory" both in the periphery and CNS compartments, in chronic neuroinflammation

A glial amino-acid transporter controls synapse strength and courtship in Drosophila

Mate choice is an evolutionarily critical decision that requires the detection of multiple sex-specific signals followed by central integration of these signals to direct appropriate behavior. The mechanisms controlling mate choice remain poorly understood. Here, we show that the glial amino-acid transporter genderblind controls whether Drosophila melanogaster males will attempt to mate with other males. Genderblind (gb) mutant males showed no alteration in heterosexual courtship or copulation, but were attracted to normally unappealing male species-specific chemosensory cues. As a result, genderblind mutant males courted and attempted to copulate with other Drosophila males. This homosexual behavior could be induced within hours using inducible RNAi, suggesting that genderblind controls nervous system function rather than its development. Consistent with this, and indicating that glial genderblind regulates ambient extracellular glutamate to suppress glutamatergic synapse strength in vivo, homosexual behavior could be turned on and off by altering glutamatergic transmission pharmacologically and/or genetically

A Model-Based Analysis of Chemical and Temporal Patterns of Cuticular Hydrocarbons in Male Drosophila melanogaster

Drosophila Cuticular Hydrocarbons (CH) influence courtship behaviour, mating, aggregation, oviposition, and resistance to desiccation. We measured levels of 24 different CH compounds of individual male D. melanogaster hourly under a variety of environmental (LD/DD) conditions. Using a model-based analysis of CH variation, we developed an improved normalization method for CH data, and show that CH compounds have reproducible cyclic within-day temporal patterns of expression which differ between LD and DD conditions. Multivariate clustering of expression patterns identified 5 clusters of co-expressed compounds with common chemical characteristics. Turnover rate estimates suggest CH production may be a significant metabolic cost. Male cuticular hydrocarbon expression is a dynamic trait influenced by light and time of day; since abundant hydrocarbons affect male sexual behavior, males may present different pheromonal profiles at different times and under different conditions

Mapping Neural Circuits with Activity-Dependent Nuclear Import of a Transcription Factor

Nuclear factor of activated T cells (NFAT) is a calcium-responsive transcription factor. We describe here an NFAT-based neural tracing method—CaLexA (calcium-dependent nuclear import of Lex A)—for labeling active neurons in behaving animals. In this system, sustained neural activity induces nuclear import of the chimeric transcription factor LexA-VP16-NFAT, which in turn drives green fluorescent protein (GFP) reporter expression only in active neurons. We tested this system in Drosophila and found that volatile sex pheromones excite specific neurons in the olfactory circuit. Furthermore, complex courtship behavior associated with multi-modal sensory inputs activated neurons in the ventral nerve cord. This method harnessing the mechanism of activity-dependent nuclear import of a transcription factor can be used to identify active neurons in specific neuronal population in behaving animals

Peripheral, Central and Behavioral Responses to the Cuticular Pheromone Bouquet in Drosophila melanogaster Males

Pheromonal communication is crucial with regard to mate choice in many animals including insects. Drosophila melanogaster flies produce a pheromonal bouquet with many cuticular hydrocarbons some of which diverge between the sexes and differently affect male courtship behavior. Cuticular pheromones have a relatively high weight and are thought to be — mostly but not only — detected by gustatory contact. However, the response of the peripheral and central gustatory systems to these substances remains poorly explored. We measured the effect induced by pheromonal cuticular mixtures on (i) the electrophysiological response of peripheral gustatory receptor neurons, (ii) the calcium variation in brain centers receiving these gustatory inputs and (iii) the behavioral reaction induced in control males and in mutant desat1 males, which show abnormal pheromone production and perception. While male and female pheromones induced inhibitory-like effects on taste receptor neurons, the contact of male pheromones on male fore-tarsi elicits a long-lasting response of higher intensity in the dedicated gustatory brain center. We found that the behavior of control males was more strongly inhibited by male pheromones than by female pheromones, but this difference disappeared in anosmic males. Mutant desat1 males showed an increased sensitivity of their peripheral gustatory neurons to contact pheromones and a behavioral incapacity to discriminate sex pheromones. Together our data indicate that cuticular hydrocarbons induce long-lasting inhibitory effects on the relevant taste pathway which may interact with the olfactory pathway to modulate pheromonal perception