Multicentric Atrial Strain COmparison between Two Different Modalities: MASCOT HIT Study

Two methods are currently available for left atrial (LA) strain measurement by speckle tracking echocardiography, with two different reference timings for starting the analysis: QRS (QRS-LASr) and P wave (P-LASr). The aim of MASCOT HIT study was to define which of the two was more reproducible, more feasible, and less time consuming. In 26 expert centers, LA strain was analyzed by two different echocardiographers (young vs senior) in a blinded fashion. The study population included: healthy subjects, patients with arterial hypertension or aortic stenosis (LA pressure overload, group 2) and patients with mitral regurgitation or heart failure (LA volume–pressure overload, group 3). Difference between the inter-correlation coefficient (ICC) by the two echocardiographers using the two techniques, feasibility and analysis time of both methods were analyzed. A total of 938 subjects were included: 309 controls, 333 patients in group 2, and 296 patients in group 3. The ICC was comparable between QRS-LASr (0.93) and P-LASr (0.90). The young echocardiographers calculated QRS-LASr in 90% of cases, the expert ones in 95%. The feasibility of P-LASr was 85% by young echocardiographers and 88% by senior ones. QRS-LASr young median time was 110 s (interquartile range, IR, 78-149) vs senior 110 s (IR 78-155); for P-LASr, 120 s (IR 80-165) and 120 s (IR 90-161), respectively. LA strain was feasible in the majority of patients with similar reproducibility for both methods. QRS complex guaranteed a slightly higher feasibility and a lower time wasting compared to the use of P wave as the reference

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

The future of road transport

A perfect storm of new technologies and new business models is transforming not only our vehicles, but everything about how we get around, and how we live our lives. The JRC report “The future of road transport - Implications of automated, connected, low-carbon and shared mobility” looks at some main enablers of the transformation of road transport, such as data governance, infrastructures, communication technologies and cybersecurity, and legislation. It discusses the potential impacts on the economy, employment and skills, energy use and emissions, the sustainability of raw materials, democracy, privacy and social fairness, as well as on the urban context. It shows how the massive changes on the horizon represent an opportunity to move towards a transport system that is more efficient, safer, less polluting and more accessible to larger parts of society than the current one centred on car ownership. However, new transport technologies, on their own, won't spontaneously make our lives better without upgrading our transport systems and policies to the 21st century. The improvement of governance and the development of innovative mobility solutions will be crucial to ensure that the future of transport is cleaner and more equitable than its car-centred present.JRC.C.4-Sustainable Transpor

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Vectorization of photodynamic therapy using extracellular vesicles in the treatment of peritoneal metastasis. Preclinical data

Les métastases péritonéales (MP) sont particulières tant par leur nombre que par leur dispersion à l'ensemble de la cavité péritonéale. Elles surviennent à un stade avancé des cancers digestifs et ovariens, et le pronostic des patients est limité malgré une cytoréduction complète. La thérapie photodynamique (PDT), du fait de la faible sélectivité tumorale des photosensibilisateurs (PS), a vu son développement freiné dans le traitement des MP. La nanovectorisation, notamment liposomale, a récemment démontré l'optimisation de la biodistribution intra tumorale des médicaments. L'intégration de la méta-tétra(hydroxyphényl)chlorine (mTHPC), l'un des PS les plus utilisés en clinique, au sein des vésicules extracellulaires issues de cellules souches mésenchymateuses (EVs), a permis in vitro et dans un modèle murin de xénogreffe sous cutanée, l'amélioration de l'efficacité de la PDT. L'objectif de ce travail était d'évaluer la nanovectorisation vésiculaire de la mTHPC (EVs-mTHPC) dans un modèle murin de MP d'origine colique, et de la comparer à la vectorisation liposomale (Foslip®). La reproductibilité était analysée dans un modèle ovarien de MP. Les EVs ciblaient les MP, avec une concentration intra tumorale de mTHPC 24h après injection intra péritonéale de EVs-mTHPC, 3 et 8 fois supérieure par rapport à la formulation libre et vectorisée par des liposomes respectivement (p<0.01). Le ratio moyen de mTHPC dans les tumeurs/tissus non tumoraux était de 44 pour la formulation vésiculaire vs 1.5 et 5.5 pour les formulations libres, et liposomales respectivement. En moyenne le ciblage tumoral par les EVs était 8 fois plus important. La vectorisation vésiculaire potentialisait la cytotoxicité tumorale de la PDT (55 % des nodules tumoraux nécrotiques versus 18 % pour Foslip, p < 0,0001) sans affecter les tissus sains, et modulait le microenvironnement tumoral. Elle favorisait une réponse immunitaire antitumorale, principalement pro-inflammatoire M1-like CD80+ et lymphocytaire T CD8+, dans les modèles immunocompétents de MP. De plus, la PDT vectorisée par les EVs réduisait significativement la prolifération intratumorale et prolongeait la survie des souris (KI67 : 9% vs 48, 26 et 18%, p<0.0001; et médiane survie : 28, vs 22,16 et 26 jours pour la PDT vectorisée par les EVs, vs les contrôles, la PDT non vectorisée et la PDT vectorisée par les liposomes, respectivement, p<0.0001). La sélectivité tumorale des EVs était confirmée dans un modèle ovarien de MP. Notamment dans l'ascite, on observait des clusters de cellules tumorales avec colocalisation du signal de fluorescence de la mTHPC. L'ensemble de ces résultats présente les EVs comme un nanovecteur biologique efficace de la mTHPC, supérieur aux liposomes, permettant une PDT sélective et efficace dans un modèle murin de MP.Peritoneal metastasis (PM) are particular both in their number and in their dispersion throughout the peritoneal cavity. PM occur in advanced digestive and ovarian cancers, and the prognosis of patients is limited despite complete cytoreduction. The development of photodynamic therapy (PDT) in PM treatment was not important, due to the low tumor selectivity of photosensitizers (PS). Nanovectorization, especially with liposome, recently demonstrate the optimization of tumor accumulation of drugs. The integration of meta(tetrahydroxyphenyl)-chlorin (mTHPC), one of the most clinically used PS, into extracellular nanovesicles derived from mesenchymal stem/stromal cells (EVs), improved PDT efficacy in vitro and in mouse xenograft model. The objective of this work was to evaluate the vesicular vectorization of mTHPC (EVs-mTHPC) in a mouse model of PM from colic origin, and to compare with liposomal vectorization (Foslip®). These analyzes were reproduced in an ovarian model of PM. The EVs targeted the PM. mTHPC tumoral concentration, 24 hours after intraperitoneal injection of EVs-mTHPC, was 3 and 8 times higher compared to the free and liposomal formulations respectively (p <0.01). The mean ratio of mTHPC in tumor/non-tumor tissue was 44 for EVs formulation vs 1.5 and 5.5 for the free and liposomal formulations respectively. Tumor targeting by EVs was approximately 8 times higher. EVs vectorization potentiated PDT cytotoxicity at the tumor site (55% of necrotic tumor nodules versus 18% for Foslip, p <0.0001) without affecting healthy tissues, and modulated the tumor microenvironment of immunocompetent colorectal and ovarian carcinomatosis models. EVs promoted antitumor immune cell infiltration, mainly proinflammatory M1-like CD80+ and CD8+ T cell effector. In addition, intratumor proliferation was significantly decreased after PDT with EVs-mTHPC (KI67: 9% vs 48, 26 and 18%, p <0.0001 for EVs-mTHPC, vs controls, free PDT and Foslip®, respectively). Overall EVs vectorization of mTHPC afforded important tumor selectivity while overcoming the PDT toxicity of the free drug and prolonged mice survival in the colorectal carcinomatosis model (median survival: 28, vs 22, 16 and 26 days for for EVs-mTHPC, vs controls, free PDT and Foslip®, respectively, p <0.0001). Tumor selectivity of EVs was confirmed in an ovarian model of MP. Particularly, mice presented important ascitis. Tumor cells observed on ascitis smears were mainly observed as clusters and colocalized with a mTHPC fluorescence signal, in favor of PS internalization in tumor cells present in ascites. EVs appears like the clinically relevant fourth-generation PDT vehicle to overcome current limitations of PDT in the treatment of PM and promote a hot tumor immune environment in PM. EVs tumor selectivity appears superior to liposomal targetting

Immune Reprogramming Precision Photodynamic Therapy of Peritoneal Metastasis by Scalable Stem-Cell-Derived Extracellular Vesicles

International audienc

Liaisons dangereuses: cross-border gene flow and dispersal of insecticide resistance-associated genes in the mosquito Aedes aegypti from Brazil and French Guiana

Submitted by Sandra Infurna ([email protected]) on 2020-03-20T18:28:31Z No. of bitstreams: 1 AdemirJesus_Martins_etal_IOC_2019.pdf: 2425759 bytes, checksum: 39d921c3e77e581a867423b06d9c12a4 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2020-03-20T18:36:59Z (GMT) No. of bitstreams: 1 AdemirJesus_Martins_etal_IOC_2019.pdf: 2425759 bytes, checksum: 39d921c3e77e581a867423b06d9c12a4 (MD5)Made available in DSpace on 2020-03-20T18:36:59Z (GMT). No. of bitstreams: 1 AdemirJesus_Martins_etal_IOC_2019.pdf: 2425759 bytes, checksum: 39d921c3e77e581a867423b06d9c12a4 (MD5) Previous issue date: 2019Universidade Nova de Lisboa. Global Health and Tropical Medicine Centre. Instituto de Higiene e Medicina Tropical. Lisboa, Portugal.Institut Pasteur de la Guyane. Vectopole Amazonien Emile Abonnenc. Vector Control and Adaptation Unit. Cayenne, France.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Fisiologia e Controle de Artrópodes Vetores. Rio de Janeiro, RJ, Brasil.Instituto de Pesquisas Científicas e Tecnológicas do Estado do Amapá. Amapá, AP, Brasil.Universidade Nova de Lisboa. Global Health and Tropical Medicine Centre. Instituto de Higiene e Medicina Tropical. Lisboa, Portugal.Institut Pasteur de la Guyane. Vectopole Amazonien Emile Abonnenc. Vector Control and Adaptation Unit. Cayenne, France.Institut Pasteur de la Guyane. Vectopole Amazonien Emile Abonnenc. Vector Control and Adaptation Unit. Cayenne, France.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Fisiologia e Controle de Artrópodes Vetores. Rio de Janeiro, RJ, Brasil.Institut Pasteur de la Guyane. Vectopole Amazonien Emile Abonnenc. Vector Control and Adaptation Unit. Cayenne, France / Institut National de la Recherche Scientifique. Centre Armand Frappier Santé Biotechnologie. Laval, QC, Canada.In recent years, South America has suffered the burden of continuous high impact outbreaks of dengue, chikungunya and Zika. Aedes aegypti is the main mosquito vector of these arboviruses and its control is the only solution to reduce transmission

Diet and feeding pattern modulate diurnal dynamics of the ileal microbiome and transcriptome.

Compositional oscillations of the gut microbiome are essential for normal peripheral circadian rhythms, both of which are disrupted in diet-induced obesity (DIO). Although time-restricted feeding (TRF) maintains circadian synchrony and protects against DIO, its impact on the dynamics of the cecal gut microbiome is modest. Thus, other regions of the gut, particularly the ileum, the nexus for incretin and bile acid signaling, may play an important role in entraining peripheral circadian rhythms. We demonstrate the effect of diet and feeding rhythms on the ileal microbiome composition and transcriptome in mice. The dynamic rhythms of ileal microbiome composition and transcriptome are dampened in DIO. TRF partially restores diurnal rhythms of the ileal microbiome and transcriptome, increases GLP-1 release, and alters the ileal bile acid pool and farnesoid X receptor (FXR) signaling, which could explain how TRF exerts its metabolic benefits. Finally, we provide a web resource for exploration of ileal microbiome and transcriptome circadian data