Genetic diversity of Anaplasma Phagocytophilum, the causative agent of granulocytic anaplasmosis, implications for epidemiology and control in france

Anaplasma phagocytophilum is a tick-borne bacterium and the etiologic agent of granulocytic anaplasmosis, an emerging disease that affects a wide range of mammals. In this paper, we present the recent knowledge gained from studies on the genetic diversity of this pathogen in France. Multilocus sequence analysis (MLSA) was used to characterize the genetic diversity of A. phagocytophilum in populations of French cattle, horses, dogs, and roe deer. MLSA was based on nine loci (ankA, msp4, groESL, typA, pled, gyrA, recG, polA, and an intergenic region). Phylogenic analysis revealed three genetic clusters of bacterial variants in domesticated animals. The two principal clusters included 98% of the bacterial genotypes found in cattle, which were only distantly related to those in roe deer. One cluster comprised only cattle genotypes, while the second contained genotypes from cattle, horses, and dogs. The third contained all roe deer genotypes and three cattle genotypes. These results suggest that roe deer do not contribute to the spread of A. phagocytophilum in cattle in France. A Multiple-Locus Variable number tandem repeat (VNTR) Analysis typing technique was developed for A. phagocytophilum. Five VNTRs were selected based on the HZ human-derived strain genome, and were tested on the Webster human-derived strain and on 123 DNA samples. This study confirmed that A. phagocytophilum from roe deer or domestic ruminants belong to two different clusters, while A. phagocytophilum from red deer and domestic ruminants locate within the same cluster, questioning the respective roles of roe vs red deer as reservoir hosts for domestic ruminant strains in Europe. The molecular techniques recently developed have great potential to provide detailed information on A. phagocytophilum isolates,improving both epidemiological and phylogenic investigations, thereby helping in the development of relevant prevention and control measures.A. phagocytophilum, bactérie transmise par les tiques, est responsable de l’anaplasmose granulocytaire, une maladie émergente qui infecte une large gamme de mammifères dont l’homme. L’objectif de cet article est de présenter les nouvelles connaissances acquises sur la diversité génétique d’A. phagocytophilum chez différentes espèces d’hôtes en France, afin de déterminer quelles espèces participent au même cycle épidémiologique. Une analyse par séquençage multi-locus (MLSA) a été effectuée dans des populations de bovins, chevaux, chiens et chevreuils. Trois groupes de génotypes infectant les bovins ont été identifiés. Les deux groupes principaux incluent 98% des génotypes bactériens trouvés chez les bovins et sont éloignés de ceux des chevreuils. Un cluster ne comprenait que les génotypes de bovins, tandis que le second génotype contenant des bovins comprenait également des chevaux et des chiens. Le troisième cluster contenait tous les génotypes de chevreuils et trois génotypes de bovins. Ces résultats suggèrent que les chevreuils ne contribuent pas à la propagation d’A. phagocytophilum chez les bovins en France. Puis, une technique MLVA (Multiple Loci VNTR Analysis) a été développée pour A. phagocytophilum. Cinq VNTR ont été sélectionnés sur la base du génome de la souche d’origine humaine HZ, et ont été testés sur 123 échantillons d’ADN provenant d’animaux domestiques ou sauvages. Cette étude a confirmé que les souches d’A. phagocytophilum retrouvées chez les chevreuils et les ruminants domestiques appartiennent à deux groupes différents, alors que les souches identifiées chez les cerfs et les ruminants domestiques sont localisées dans le même cluster. Ces résultats remettent en question les rôles respectifs des chevreuils et des cerfs comme hôtes réservoirs pour les souches d’A. phagocytophilum de ruminants domestiques en Europe. Ces techniques moléculaires ont un grand potentiel pour améliorer nos connaissances sur les cycles épidémiologiques d’A. phagocytophilum, contribuant ainsi à l’élaboration de mesures de prévention et de contrôle pertinents

Higher risk for influenza-associated pulmonary aspergillosis (IAPA) in asthmatic patients: A Swiss multicenter cohort study on IAPA in critically ill influenza patients

Background: Influenza-associated pulmonary aspergillosis (IAPA) is an important complication of severe influenza with high morbidity and mortality. Methods: We conducted a retrospective multicenter study in tertiary hospitals in Switzerland during 2017/2018 and 2019/2020 influenza seasons. All adults with PCR-confirmed influenza infection and treatment on intensive-care unit (ICU) for >24 h were included. IAPA was diagnosed according to previously published clinical, radiological, and microbiological criteria. We assessed risk factors for IAPA and predictors for poor outcome, which was a composite of in-hospital mortality, ICU length of stay ≥7 days, mechanical ventilation ≥7 days, or extracorporeal membrane oxygenation. Results: One hundred fifty-eight patients (median age 64 years, 45% females) with influenza were included, of which 17 (10.8%) had IAPA. Asthma was more common in IAPA patients (17% vs. 4% in non-IAPA, P = 0.05). Asthma (OR 12.0 [95% CI 2.1-67.2]) and days of mechanical ventilation (OR 1.1 [1.1-1.2]) were associated with IAPA. IAPA patients frequently required organ supportive therapies including mechanical ventilation (88% in IAPA vs. 53% in non-IAPA, P = 0.001) and vasoactive support (75% vs. 45%, P = 0.03) and had more complications including ARDS (53% vs. 26%, P = 0.04), respiratory bacterial infections (65% vs. 37%, P = 0.04), and higher ICU-mortality (35% vs. 16.4%, P = 0.05). IAPA (OR 28.8 [3.3-253.4]), influenza A (OR 3.3 [1.4-7.8]), and higher SAPS II score (OR 1.07 [1.05-1.10]) were independent predictors of poor outcome. Interpretation: High clinical suspicion, early diagnostics, and therapy are indicated in IAPA because of high morbidity and mortality. Asthma is likely an underappreciated risk factor for IAPA. Keywords: asthma; influenza; influenza-associated aspergillosis; intensive care medicine; invasive aspergillosis

Higher risk for influenza-associated pulmonary aspergillosis (IAPA) in asthmatic patients: A Swiss multicenter cohort study on IAPA in critically ill influenza patients.

BACKGROUND Influenza-associated pulmonary aspergillosis (IAPA) is an important complication of severe influenza with high morbidity and mortality. METHODS We conducted a retrospective multicenter study in tertiary hospitals in Switzerland during 2017/2018 and 2019/2020 influenza seasons. All adults with PCR-confirmed influenza infection and treatment on intensive-care unit (ICU) for >24 h were included. IAPA was diagnosed according to previously published clinical, radiological, and microbiological criteria. We assessed risk factors for IAPA and predictors for poor outcome, which was a composite of in-hospital mortality, ICU length of stay ≥7 days, mechanical ventilation ≥7 days, or extracorporeal membrane oxygenation. RESULTS One hundred fifty-eight patients (median age 64 years, 45% females) with influenza were included, of which 17 (10.8%) had IAPA. Asthma was more common in IAPA patients (17% vs. 4% in non-IAPA, P = 0.05). Asthma (OR 12.0 [95% CI 2.1-67.2]) and days of mechanical ventilation (OR 1.1 [1.1-1.2]) were associated with IAPA. IAPA patients frequently required organ supportive therapies including mechanical ventilation (88% in IAPA vs. 53% in non-IAPA, P = 0.001) and vasoactive support (75% vs. 45%, P = 0.03) and had more complications including ARDS (53% vs. 26%, P = 0.04), respiratory bacterial infections (65% vs. 37%, P = 0.04), and higher ICU-mortality (35% vs. 16.4%, P = 0.05). IAPA (OR 28.8 [3.3-253.4]), influenza A (OR 3.3 [1.4-7.8]), and higher SAPS II score (OR 1.07 [1.05-1.10]) were independent predictors of poor outcome. INTERPRETATION High clinical suspicion, early diagnostics, and therapy are indicated in IAPA because of high morbidity and mortality. Asthma is likely an underappreciated risk factor for IAPA

Benefit and Risks of Aspirin in Addition to Ticagrelor in Acute Coronary Syndromes:A Post Hoc Analysis of the Randomized GLOBAL LEADERS Trial

Key PointsQuestionWhat are the benefits and risks of continuing aspirin in addition to P2Y12 receptor inhibition with ticagrelor among patients with acute coronary syndrome between 1 month and 12 months after percutaneous coronary intervention? FindingsIn this nonprespecified, post hoc analysis of the GLOBAL LEADERS randomized clinical trial, beyond 1 month after percutaneous coronary intervention in acute coronary syndrome, aspirin was associated with increased bleeding risk and appeared not to add to the benefit of ticagrelor on ischemic events. MeaningThe findings of this hypothesis-generating analysis pave the way for further trials evaluating aspirin-free antiplatelet strategies after percutaneous coronary intervention. ImportanceThe role of aspirin as part of antiplatelet regimens in acute coronary syndromes (ACS) needs to be clarified in the context of newer potent P2Y12 antagonists. ObjectiveTo evaluate the benefit and risks of aspirin in addition to ticagrelor among patients with ACS beyond 1 month after percutaneous coronary intervention (PCI). Design, Setting, and ParticipantsThis is a nonprespecified, post hoc analysis of GLOBAL LEADERS, a randomized, open-label superiority trial comparing 2 antiplatelet treatment strategies after PCI. The trial included 130 secondary/tertiary care hospitals in different countries, with 15991 unselected patients with stable coronary artery disease or ACS undergoing PCI. Patients had outpatient visits at 1, 3, 6, 12, 18, and 24 months after index procedure. InterventionsThe experimental group received aspirin plus ticagrelor for 1 month followed by 23-month ticagrelor monotherapy; the reference group received aspirin plus either clopidogrel (stable coronary artery disease) or ticagrelor (ACS) for 12 months, followed by 12-month aspirin monotherapy. In this analysis, we examined the clinical outcomes occurring between 31 days and 365 days after randomization, specifically in patients with ACS who, within this time frame, were assigned to receive either ticagrelor alone or ticagrelor and aspirin. Main Outcomes and MeasuresThe primary outcome was the composite of all-cause death or new Q-wave myocardial infarction. ResultsOf 15968 participants, there were 7487 patients with ACS enrolled; 3750 patients were assigned to the experimental group and 3737 patients to the reference group. Between 31 and 365 days after randomization, the primary outcome occurred in 55 patients (1.5%) in the experimental group and in 75 patients (2.0%) in the reference group (hazard ratio [HR], 0.73; 95% CI, 0.51-1.03; P=.07); investigator-reported Bleeding Academic Research Consortium-defined bleeding type 3 or 5 occurred in 28 patients (0.8%) in the experimental group and in 54 patients (1.5%) in the reference arm (HR, 0.52; 95% CI, 0.33-0.81; P=.004). Conclusions and RelevanceBetween 1 month and 12 months after PCI in ACS, aspirin was associated with increased bleeding risk and appeared not to add to the benefit of ticagrelor on ischemic events. These findings should be interpreted as exploratory and hypothesis generating; however, they pave the way for further trials evaluating aspirin-free antiplatelet strategies after PCI. Trial RegistrationClinicalTrials.gov identifier: NCT01813435. This secondary analysis of the GLOBAL LEADERS randomized clinical trial evaluates the benefit and risks of aspirin in addition to ticagrelor among patients with acute coronary syndrome beyond 1 month after percutaneous coronary intervention

Isolation of a natural DNA virus of <i>Drosophila melanogaster</i>, and characterisation of host resistance and immune responses

<div><p><i>Drosophila melanogaster</i> has played a key role in our understanding of invertebrate immunity. However, both functional and evolutionary studies of host-virus interaction in <i>Drosophila</i> have been limited by a dearth of native virus isolates. In particular, despite a long history of virus research, DNA viruses of <i>D</i>. <i>melanogaster</i> have only recently been described, and none have been available for experimental study. Here we report the isolation and comprehensive characterisation of Kallithea virus, a large double-stranded DNA virus, and the first DNA virus to have been reported from wild populations of <i>D</i>. <i>melanogaster</i>. We find that Kallithea virus infection is costly for adult flies, reaching high titres in both sexes and disproportionately reducing survival in males, and movement and late fecundity in females. Using the <i>Drosophila</i> Genetic Reference Panel, we quantify host genetic variance for virus-induced mortality and viral titre and identify candidate host genes that may underlie this variation, including <i>Cdc42-interacting protein 4</i>. Using full transcriptome sequencing of infected males and females, we examine the transcriptional response of flies to Kallithea virus infection and describe differential regulation of virus-responsive genes. This work establishes Kallithea virus as a new tractable model to study the natural interaction between <i>D</i>. <i>melanogaster</i> and DNA viruses, and we hope it will serve as a basis for future studies of immune responses to DNA viruses in insects.</p></div

Genetic architecture of subcortical brain structures in 38,851 individuals

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice

Utopies éducatives

International audienceCet ouvrage aborde aussi bien les utopies pédagogiques s’inscrivant dans des cadres scolaires ou institués que des projets de transformation globaux bouleversant l’éducation et la société. Ces deux modalités peuvent concerner des écrits utopiques classiques proposant un système inédit ou une cité idéale avec ses formes propres de transmission et de formation. On les rencontre aussi dans les analyses et propositions de philosophes comme Rousseau et Condorcet ou d’autres théoriciens moins connus. Cette approche se poursuit en revisitant des auteurs du XIXe siècle, républicains, positivistes et socialistes, qui offrent tantôt des systèmes complets de refondation de la société, tantôt des réflexions et expérimentations spécifiquement pédagogiques. On réinterroge des mouvements pédagogiques du XXe siècle ou des expériences d’éducation populaire. Enfin, l’ouvrage se termine par quelques ouvertures sur le devenir éclaté et problématique des utopies éducatives en ce début de XXIe siècle (éditeur

Dynamic headspace analysis of emmental aqueous phase as a method to quantify changes in volatile flavour compounds during ripening

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