The reference site collaborative network of the european innovation partnership on active and healthy ageing

Seventy four Reference Sites of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) have been recognised by the European Commission in 2016 for their commitment to excellence in investing and scaling up innovative solutions for active and healthy ageing. The Reference Site Collaborative Network (RSCN) brings together the EIP on AHA Reference Sites awarded by the European Commission, and Candidate Reference Sites into a single forum. The overarching goals are to promote cooperation, share and transfer good practice and solutions in the development and scaling up of health and care strategies, policies and service delivery models, while at the same time supporting the action groups in their work. The RSCN aspires to be recognized by the EU Commission as the principal forum and authority representing all EIP on AHA Reference Sites. The RSCN will contribute to achieve the goals of the EIP on AHA by improving health and care outcomes for citizens across Europe, and the development of sustainable economic growth and the creation of jobs

Are oral deformities in tadpoles accurate indicators of anuran chytridiomycosis?

© 2018 Navarro-Lozano et al.We evaluated the use of oral deformities as reliable proxies for determining Batrachochytrium dendrobatidis (Bd) infection in tadpoles of six anuran species of the Atlantic Forest in southeastern Brazil. We examined oral discs of 2156 tadpoles of six species of anurans collected in 2016: Aplastodiscus albosignatus, Boana albopunctata, Boana faber, Scinax hayii, Crossodactylus caramaschii, and Physalaemus cuvieri. Three oral deformities were recognized: lack of keratinization only in upper and/or lower jaw sheaths, lack of keratinization only in upper or lower tooth rows, and both deformities together. A subsample composed of all the individuals possessing oral deformities (N = 195) plus randomly selected individuals without oral deformities (N = 184) were tested for Bd via qPCR. Oral deformities were observed in all six species, but only five were infected with Bd. Since we found that dekeratinization of tooth rows was not associated with the presence of Bd in any of the studied species we used a new proxy (jaw sheaths dekeratinization with or without dekeratinization in tooth rows: JSD-proxy) for Bd detection. Our results showed a nonrandom relationship between Bd infection and JSD-proxy in three species of the family Hylidae. However, the use of JSD-proxy for Bd detection in these species resulted in up to 30.8% false positives and up to 29.3% false negatives. The use of the JSD-proxy in species for which no relationship was found reached 100% of false positives. We conclude that the use of oral dekeratinization as a generalized proxy for Bd detection in tadpoles should not be used as a single diagnosis technique.ANL thanks Asociación Universitaria Iberoamericana de Postgrado for doctoral fellowship (www.auip.org); DSD thanks Coordenação de Aperfeiçoamento de Pessoal de Nível Superior for doctoral fellowship (#1518162) (www.capes.gov.br); DCRF thanks Conselho Nacional de Desenvolvimento Científico e Tecnológico for the research fellowship (303522/2013-5) and (563075/2010-4) (www.cnpq.br), and Fundação de Amparo à Pesquisa do Estado de São Paulo (#2010/52321-7) (www.fapesp.br); JB thanks Fundación BBVA (www.fbbva.es); RJS thanks Fundação de Amparo à Pesquisa do Estado de São Paulo (#2014/23677-9), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (304929/2015-8).Peer Reviewe

Are oral deformities in tadpoles accurate indicators of anuran chytridiomycosis?

We evaluated the use of oral deformities as reliable proxies for determining Batrachochytrium dendrobatidis (Bd) infection in tadpoles of six anuran species of the Atlantic Forest in southeastern Brazil. We examined oral discs of 2156 tadpoles of six species of anurans collected in 2016: Aplastodiscus albosignatus, Boana albopunctata, Boana faber, Scinax hayii, Crossodactylus caramaschii, and Physalaemus cuvieri. Three oral deformities were recognized: lack of keratinization only in upper and/or lower jaw sheaths, lack of keratinization only in upper or lower tooth rows, and both deformities together. A subsample composed of all the individuals possessing oral deformities (N = 195) plus randomly selected individuals without oral deformities (N = 184) were tested for Bd via qPCR. Oral deformities were observed in all six species, but only five were infected with Bd. Since we found that dekeratinization of tooth rows was not associated with the presence of Bd in any of the studied species we used a new proxy (jaw sheaths dekeratinization with or without dekeratinization in tooth rows: JSD-proxy) for Bd detection. Our results showed a nonrandom relationship between Bd infection and JSD-proxy in three species of the family Hylidae. However, the use of JSD-proxy for Bd detection in these species resulted in up to 30.8% false positives and up to 29.3% false negatives. The use of the JSD-proxy in species for which no relationship was found reached 100% of false positives. We conclude that the use of oral dekeratinization as a generalized proxy for Bd detection in tadpoles should not be used as a single diagnosis technique

Example of oral deformities found among the studied tadpoles.

<p>(A) and (B) = normal tadpoles; (C) = tadpole with dekeratinized jaw sheaths (black arrows) and generalized dekeratinization in tooth rows; (D) = tadpole with dekeratinized upper jaw sheath (black arrow). Upper images <i>Boana albopunctata</i>, and lower images <i>Scinax hayii</i>.</p

Oral deformities and related <i>Batrachochytrium dendrobatidis (Bd)</i> infections of tadpoles of six species of Atlantic Forest anurans in southeastern Brazil.

<p>Oral deformities and related <i>Batrachochytrium dendrobatidis (Bd)</i> infections of tadpoles of six species of Atlantic Forest anurans in southeastern Brazil.</p

Cases of false positives and false negatives for the detection of <i>Batrachochytrium dendrobatidis (Bd)</i> infection produced by the use of the three oral deformities studied as proxies (JS, TR and JT) and for the JSD-proxy.

<p>Cases of false positives and false negatives for the detection of <i>Batrachochytrium dendrobatidis (Bd)</i> infection produced by the use of the three oral deformities studied as proxies (JS, TR and JT) and for the JSD-proxy.</p

Experimental and computational biophysics to identify vasodilator drugs targeted at TRPV2 using agonists based on the probenecid scaffold

CatedresAltres ajuts: Ministerio de Universidades Margarita Salas Award (MGSD2021-10 to M.L.-M.); Universitat Autònoma De Barcelona Predoctoral Fellowship (B21P0033 to E.C.-H.); the Royal Society of Chemistry for Financial Support through a RS International Exchanges award (IES\R\193089 to C.D.); Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) through the collaborative research center 1507 “Membrane-associated Protein Assemblies, Machineries, and Supercomplexes” – Project ID 450648163 (to UAH); Cluster of Excellence “Balance of the Microverse” EXC2051 – Project-ID 390713860 (to UAH).TRP channels are important pharmacological targets in physiopathology. TRPV2 plays distinct roles in cardiac and neuromuscular function, immunity, and metabolism, and is associated with pathologies like muscular dystrophy and cancer. However, TRPV2 pharmacology is unspecific and scarce at best. Using in silico similarity-based chemoinformatics we obtained a set of 270 potential hits for TRPV2 categorized into families based on chemical nature and similarity. Docking the compounds on available rat TRPV2 structures allowed the clustering of drug families in specific ligand binding sites. Starting from a probenecid docking pose in the piperlongumine binding site and using a Gaussian accelerated molecular dynamics approach we have assigned a putative probenecid binding site. In parallel, we measured the EC50 of 7 probenecid derivatives on TRPV2 expressed in Pichia pastoris using a novel medium-throughput Ca influx assay in yeast membranes together with an unbiased and unsupervised data analysis method. We found that 4-(piperidine-1-sulfonyl)-benzoic acid had a better EC50 than probenecid, which is one of the most specific TRPV2 agonists to date. Exploring the TRPV2-dependent anti-hypertensive potential in vivo, we found that 4-(piperidine-1-sulfonyl)-benzoic acid shows a sex-biased vasodilator effect producing larger vascular relaxations in female mice. Overall, this study expands the pharmacological toolbox for TRPV2, a widely expressed membrane protein and orphan drug target

Combined effects of landscape composition and agrochemicals on frog communities amid sugarcane-dominated agroecosystems

Global demand for crops will continue increasing over the next few decades to cover both food and biofuel needs. This demand will put further pressure to expand arable land and replace natural habitats. However, we are only beginning to understand the combined effects of agrochemicals and land use change on tropical freshwater biodiversity. Here, we analyzed how pond-dwelling anuran larvae respond to pond characteristics, landscape composition, and agrochemical contamination in a sugarcane-dominated agroecosystem in Brazil. Then, we used an information theoretical approach with generalized linear models to relate species richness and abundance to predictor variables. The variation in tadpole abundance was associated with both agrochemical concentration (e.g., Ametryn, Diuron, and Malathion) and landscape variables (e.g., percentage of forest, percentage of agriculture, and distance to the closest forest). The relationship between species abundance and agrochemicals was species-specific. For example, the abundance of Scinax fuscovarius and Physalaemus nattereri were negatively associated with Ametryn, and Dendropsophus nanus was negatively associated with Tebuthiuron, while that of Leptodactylus fuscus was positively associated with Malathion. Conversely, species richness was associated with distance to forest fragments and aquatic vegetation heterogeneity, but not agrochemicals. Although we were unable to assign a specific mechanism to the variation in tadpole abundance based on field observations, the lower abundance of three species in ponds with high concentrations of agrochemicals suggest they negatively impact some frog species inhabiting agroecosystems. We recommend conserving ponds near forest fragments, with abundant stratified vegetation, and far from agrochemical runoffs to safeguard more sensitive pond-breeding species.D.S.D was supported with a doctoral fellowship from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES, Finance Code 001, #1518162), in association with the Integrated Ph.D. Program in Bioenergy (PIPG-Bioen) and the Bioenergy Research Institute (IPBEN). A.N.L. was supported by Asociación Universitaria Iberoamericana de Postgrado. DCRF has been continuously supported by a CNPq fellowship (#302328/2017-3). F.R.S. and C.C.M were supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (#2013/50714-0; 2014/24740-6). DBP was supported by a grant from CNPq (#407318/2021-6)

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P &lt; 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)