Radical c–h18f-difluoromethylation of heteroarenes with [18f]difluoromethyl heteroaryl-sulfones by visible light photoredox catalysis

peer reviewedThe18F-labeling of CF2H groups has been recently studied in radiopharmaceutical chemistry owing to the favorable nuclear and physical characteristics of the radioisotope18F for positron emission tomography (PET). Following up on the reported efficiency of the [18F]difluoromethyl benzothiazolyl-sulfone ([18F]1) as a18F-difluoromethylating reagent, we investigated the influence of structurally-related [18F]difluoromethyl heteroaryl-sulfones in the reactivity toward the photoredox C–H18F-difluoromethylation of heteroarenes under continuous-flow conditions. In the present work, six new [18F]difluoromethyl heteroaryl-sulfones [18F]5a–[18F]5f were prepared and, based on the overall radiochemical yields (RCYs), three of these reagents ([18F]5a, [18F]5c, and [18F]5f) were selected for the fully automated radiosynthesis on a FASTlab™ synthesizer (GE Healthcare) at high level of starting radioactivity. Subsequently, their efficiency as 18 F-difluoromethylating reagents was evaluated using the antiherpetic drug acyclovir as a model substrate. Our results showed that the introduction of molecular modifications in the structure of [18F]1 influenced the amount of fac-IrIII(ppy)3 and the residence time needed to ensure a complete C– H18F-difluoromethylation process. The photocatalytic C–H18F-difluoromethylation reaction with the reagents [18F]5a, [18F]5c, and [18F]5f was extended to other heteroarenes. Radical-trapping experiments demonstrated the likely involvement of radical species in the C–H 18 F-difluoromethylation process

Étude des complémentarités entre gestion dynamique à la ferme et gestion statique en collection: Cas de la variété de blé Rouge de Bordeaux

National audienceWhile on-farm conservation was considered minor in the development of the National Charter on Genetic Resources in 1998, there is increasing recognition of its important role in the conservation of genetic diversity. In addition to amateur gardening associations that save and exchange seeds, farmers in France have formed networks around systems of shared seed conservation and exchanges, with the goal of protecting the diversity of cultivated species. Parallel to this, the contribution of farmers to the dynamic management of agricultural biodiversity has been recognized by many scientific studies and in international treaties. These developments led us to examine the complementary nature of on-farm and gene-bank conservation efforts in terms of the management of genetic resources. This study, which combines ethnobotanical and genetic approaches, was conducted on bread wheat, for which France has a national collection of 10 000 accessions. There is also an active network of farmers who cultivate historic varieties and landraces, including the Rouge de Bordeaux, which was chosen for a detailed study. By conducting individual interviews with farmers, we were able to understand better their management practices, seed exchanges with other farmers and with the national collection, and strategies for maintaining and selecting this variety on their own farms. We characterized the genetic diversity conserved by several farmers and in the samples preserved in the national collection for Rouge de Bordeaux by using a comparative genetic analysis of samples obtained from farmers and from the collection, in light of the management practices and exchange networks that exist among farmers and between farmers and the national collection. Our results demonstrate that the diversity of these populations is far from being redundant. While certain samples are quite homogeneous and similar to samples from the national collection, others are highly heterogeneous. There is also a high degree of genetic differentiation among populations, with clear groupings of populations identified. The structure of the diversity may be explained by the structure of exchanges and the development of local adaptation within the populations to environmental conditions and management practices, and by differing strategies of selection and conservation. Further analysis will help us understand more precisely what defines a variety and what type of genetic diversity or phenotypic traits are conserved with different management strategies. Our results also support a greater degree of seed circulation between farmers' fields and the national collection, to conserve the adaptive potential and a broader range of genetic diversity for each variety.Considérée comme mineure lors de la rédaction de la Charte nationale des ressources génétiques en 1998, la gestion à la ferme a depuis gagné en importance et en reconnaissance. En effet, après les associations de jardiniers amateurs, des réseaux d'agriculteurs se sont fédérés en France autour de systèmes mutualistes de sélection/conservation de la diversité cultivée. Parallèlement, la contribution des paysans à la gestion dynamique de l'agrobiodiversité a été scientifiquement et institutionnellement reconnue. Ces éléments nous ont conduit à examiner les complémentarités dans la gestion des ressources génétiques à la ferme et en collection. Cette étude, qui croise des approches ethnobotanique et génétique, a été menée sur le blé tendre pour lequel il existe en France une collection nationale de 10 000 accessions et un réseau actif d'agriculteurs-collectionneurs de variétés. Pour la variété Rouge de Bordeaux, nous avons tenté de caractériser la diversité dans les champs et en collection, en procédant à une analyse génétique d'échantillons obtenus auprès d'agriculteurs et auprès de la collection. Nos résultats montrent que les ressources génétiques conservées dans les deux compartiments sont loin d'être redondantes. La structuration de la diversité s'explique par les réseaux d'échanges de semences (entre paysans, et entre les paysans et la collection), par l'adaptation locale des populations aux conditions du milieu et aux pratiques de culture, et par les pratiques de sélection/conservation. Ces résultats appellent des analyses complémentaires pour comprendre précisément ce qui est conservé/cultivé sous un nom variétal donné, et plaident en faveur d'une circulation accrue des semences entre champs et collection

Prevalence of tick-borne pathogens in ticks collected from the wild mountain ungulates mouflon and chamois in 4 regions of France

Ticks are major vectors of various pathogens of health importance, such as bacteria, viruses and parasites. The problems associated with ticks and vector-borne pathogens are increasing in mountain areas, particularly in connection with global climate change. We collected ticks (n = 2,081) from chamois and mouflon in 4 mountainous areas of France. We identified 6 tick species: Ixodes ricinus, Rhipicephalus bursa, Rh. sanguineus s.l., Haemaphysalis sulcata, H. punctata and Dermacentor marginatus. We observed a strong variation in tick species composition among the study sites, linked in particular to the climate of the sites. We then analysed 791 ticks for DNA of vector-borne pathogens: Babesia/Theileria spp., Borrelia burgdorferi s.l., Anaplasma phagocytophilum, A. marginale, A. ovis, and Rickettsia of the spotted fever group (SFG). Theileria ovis was detected only in Corsica in Rh. bursa. Babesia venatorum (2 sites), Borrelia burgdorferi s.l. (B. afzelii and B. garinii; 2 sites) and Anaplasma phagocytophilum (3 sites) were detected in I. ricinus. Anaplasma ovis was detected at one site in I. ricinus and Rh. sanguineus s.l. SFG Rickettsia were detected at all the study sites: R. monacensis and R. helvetica in I. ricinus at the 3 sites where this tick is present; R. massiliae in Rh. sanguineus s.l. (1 site); and R. hoogstraalii and Candidatus R. barbariae in Rh. bursa in Corsica. These results show that there is a risk of tick-borne diseases for humans and domestic and wild animals frequenting these mountain areas

Molecular prevalence, genetic characterization and patterns of Toxoplasma gondii infection in domestic small mammals from Cotonou, Benin

Toxoplasmosis, one of the most prevalent parasitic infections in humans and animals, is caused by the intracellular protozoan parasite Toxoplasma gondii. Small mammals play a key role as intermediate reservoir hosts in the maintenance of the T. gondii life cycle. In this study, we estimated the molecular prevalence and provide genetic diversity data for T. gondii in 632 small mammals sampled in four areas of Cotonou city, Benin. Both the brain and heart of each individual were screened through T. gondii-targeting qPCR, and positive samples were then genotyped using a set of 15 T. gondii-specific microsatellites. Prevalence data were statistically analyzed in order to assess the relative impact of individual host characteristics, spatial distribution, composition of small mammal community, and urban landscape features. An overall T. gondii molecular prevalence of 15.2% was found and seven genotypes, all belonging to the Africa 1 lineage, could be retrieved from the invasive black rat Rattus rattus and the native African giant shrew Crocidura olivieri. Statistical analyses did not suggest any significant influence of the environmental parameters used in this study. Rather, depending on the local context, T. gondii prevalence appeared to be associated either with black rat, shrew, or mouse abundance or with the trapping period. Overall, our results highlight the intricate relationships between biotic and abiotic factors involved in T. gondii epidemiology and suggest that R. rattus and C. olivieri are two competent reservoirs for the Africa 1 lineage, a widespread lineage in tropical Africa and the predominant lineage in Benin

Systems medicine and integrated care to combat chronic noncommunicable diseases

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems

Lutte contre la pauvreté et sécurité alimentaire au Québec: comparaison de la logique d'intervention gouvernementale et du discours des acteurs du terrain

Duns le cadre d'une e'tude de cas sur la pertinence des interventions en se'curite' alimentaire, des acteurs oeuvrant auprks de la population de Que'bec touche'e par l'inse'curite' alimentaire ont expime' en entrevue des solutions pour ame'liorer la situation. L'objet de cet article est d'examiner si celles-ci cmespondent h la logique d'intervention sous-jacente h la strate'gie que'be'coise de lutte contre la pauvrete'. Alors que les parties penantes interviewe'es pre'conisent une approche globale pour s'attaquer aux de'terminants socio-e'conomiques de l'inse'curite' alimentaire notamment par des mesures sociaks pour re'soudre l'insuffisance de revenu, les dicideurs gouuernementaux s'en remettent essentielbment h l'insertion .en emploi, h l'aide alimentaire ponctuelle et aux projets communautaires ayant pour objectif de responsabiliser les individus et favoriser leur propre prise en charge. Au nom de l'incitation au travail, le gouvernement rnaintient les prestations d'aide sociale h un niveau trks faible, risqwznt de limiter l'accks aux aliments de nombreux me'nages. Les auteurs suggkrent de remettre en perspective la tension entre l'objectif d'assurer h chaque citoyen un revenu &cent pour satisfaire les besoins essentiels et l'objectif de valoriser le travail. . Pour faire progresser le &bat, ils appellent. les acteurs du terrain et les chercheurs h examiner dans quelle mesure l'inse'curite' alimentaire peut constituer un obstacle h lJintigration en emploi des personnes exclues du march4 du travail. Les auteurs insistent enfin sur l'importance de &welopper des re'ponses spe'cijiques h l'inse'curite' alimentaire qui &passent le cadre de la lutte contre la pauvrete'. In a case study of the relevance of interventions to increase food security, Quebec City stakeholders were interviewed about perceived solutions to improve household food security. The paper examines whether their solutions correspond to the Quebec government's strategy to fight poverty and social exclusion. The stakeholders suggest an overall approach to address the so~io-economic determinants of food insecurity, especially social measures to eliminate income insuficiency. However, government decision-makers focus on employment policies, emergency food programs, and community programs promoting individual responsibility and self-help. To encourage employment integration, the govemment maintains social assistance benefits at a low level; this compromises the ability to afford adequate food in many households. The authors suggest a more detailed exumination of the conflict between the objective of adequute income to fulfill essential needs, and the objective to promote re-entry to the labour market. The authors recommend that field workers and researchers e m i n e the extent towhich food insecurity constitutes an obstacle to job integration for persons excluded from the labour market. Finally, the authors emphasize the importance of responses specific to food insecurity, beyond the framework of fighting poverty

Evaluation of a new [18F] labeled tracer targeting synaptic vesicle protein 2C by ex vivo autoradiography and in vivo PET study in rat brain.

Introduction The synaptic vesicle protein 2 (SV2) family is a group of integral membrane glycoproteins homologous to the major facilitator superfamily and could be involved in several neuronal diseasesa. The binding of the novel, no-carrier-added, [18F] labeled compound [18F]UCB-F to the SV2C isoform was evaluated in rat brain. Methods Radiochemistry No-carrier added [18F]UCB-F was obtained following the method shown in Fig. 1. The identity and purity of the tracer were evaluated by radioUPLC and chiral radioHPLC. Autoradiography Sprague Dawley rat brain sections were incubated at RT with buffered [18F]UCB-F solutions and exposed on film. Matching sections were stained with cresyl violet for structural identification. PET studies PET studies (Siemens Concorde Focus 120 µPET) were performed under isoflurane anesthesia. The tracer was injected as a bolus via the tail vein. After a 10-min transmission scan to correct for attenuation, dynamic emission data was recorded for a total of 60 min. The impact of P-glycoprotein (P-gp) activity on tracer uptake in the brain was evaluated using cyclosporine (50 mg/kg SC). Metabolite analysis During PET studies, arterial blood samples were taken for the measurement of tracer metabolites. Plasma was separated by centrifugation and proteins were acid-precipitated. Metabolites were detected using HPLC and confirmed by gamma counting. Results The tracer was obtained with a decay corrected yield of ±10%. Specific activity ranged from 10 GBq/µmol to 40 GBq/µmol. Ex vivo autoradiography showed that the binding of [18F]UCB-F to SV2C closely matched the expected distribution b (Fig.2). In vivo PET studies revealed that [18F]UCB-F briefly entered the brain, but exhibited extremely rapid washout. A large accumulation in the liver and intestines was observed. Metabolite analysis in the plasma revealed high protein binding and rapid metabolism. Inhibition of P-gp transport with cyclosporin had no clear effect on the rapid washout from the brain. Conclusions Despite a close match between [18F]UCB-F SV2C binding and the expected brain distribution, the pharmacokinetics in rat brain appear unfavorable for the use of this tracer to quantify SV2C in vivo. Acknowledgement / References a Lynch & al (2004) Proc. Natl. Acad. Sci. USA 101:9861 b Janz & Sudhof (1999) Neuroscience 94:1279 c The authors thank the Walloon Region and the FRNS Belgium for financial support

Un trouble temporo-mandibulaire particulier : l’ankylose. Notions fondamentales et cliniques

L’ankylose temporo-mandibulaire touche préférentiellement l’enfant et l’adulte jeune. Malgré sa rareté, c’est une pathologie extrêmement invalidante dont les conséquences au niveau de la croissance, du développement morphologique et du développement personnel sont majeures. La connaissance de ses étiologies, de ses formes anatomiques et de ses signes cliniques est indispensable à sa prise en charge. De ces connaissances va découler également le choix de la thérapeutique la plus adaptée, qui pourra présenter malgré tout des échecs et des récidives, nécessitant une réhabilitation prothétique