Bilberry anthocyanin-rich extract exerts atheroprotective property through complex molecular mechanism of action

International audienceBackground: Anthocyanins are water-soluble plant pigments that belong to the large group of polyphenols and more specifically to the subclass of flavonoids. They are abundant in the human diet due to their wide occurrence in fruits, such as berries, and fruit-based beverages. Bilberry is one of the richest sources of anthocyanins, with an anthocyanin glycoside content of 300–600 mg/100 g of fresh weight. Once ingested, anthocyanin glycosides are rapidly absorbed in both the stomach and small intestine and appear in blood and urine as intact, methylated, glucurono- and/or sulfoconjugated forms. Dietary intake of anthocyanin-rich foods has been associated with a reduced risk of coronary heart disease in the Iowa Women’s Health Study, a prospective study of postmenopausal women (Mink et al., AJCN 2007.) Reduction of atherosclerotic lesions has been previously reported after supplementation of apolipoprotein E-deficient (apo E-/-) mice with anthocyanin-rich extracts from black rice and purple sweet potato (Miyazak et al., JAFC 2000). However, little is known about the molecular mechanisms underlying the cardiovascular protective effect of anthocyanins. In vitro experiments suggest that anthocyanins may affect the expression of genes in endothelial cells or macrophages, such as those encoding the cholesterol transporter ABCA-1, the pro-inflammatory enzyme COX-2 or the scavenger receptor CD36. Aim: The aim of our studies was (1) to evaluate the effects of a bilberry anthocyanin-rich extract, when supplemented in the diet at a nutritional dose, on the development of atherosclerosis in apo E-/- mice and (2) to explore the in vivo mechanisms of action using a global transcriptomic approach. Dragan Milenkovic Ph.D. INRA/Centre de Recherche de Clemont – Ferrand/Theix, France Methods: Male apo E-/- mice at 8 weeks of age received a diet supplemented with 0.02% of anthocyanin-rich extract from bilberry. The atherosclerotic plaque was quantified in the aortic sinus by histomorphometry. Total cholesterol, triglyceride and anti-oxidant capacity were measured in plasma and liver. Impact of anthocyanins on the expression of genes has been performed using pangenomic microarrays for both liver and aorta. Results: Bilberry extract is a purified anthocyanin-rich extract and the supplementation of the diet with 0.02% of this extract may correspond to an equivalent human intake of about 30 mg of anthocyanins per day; intake estimated to vary from 12.5 mg/day in the United States to 47 mg/day in Finland After a 16-week supplementation period, a significant reduction of atherosclerotic plaques was observed as compared to the control one (-15 %,). Consumption of the bilberry extracts did not modified the plasma antioxidant capacity, measured by the ORAC assay, nor the levels of markers of lipid oxidation (aortic F2-isoprostanes, hepatic TBARS). All these data support the hypothesis that the antiatherogenic effects of bilberry extracts are independent of their antioxidant capacity in this animal model. Microarray analyses performed on the aortas of apoE -/- mice revealed that the bilberry extract-supplemented diet affected the expression of 1261 genes, with 554 genes up-regulated and 707 down-regulated. Bioinformatic analyses indicated that these differentially expressed genes are involved in the regulation of processes underlying atherosclerosis development, such as cell adhesion, migration, communication, inflammation, as well as angiogenesis and cell proliferation through vascular endothelial growth factor (VEGF) and WNT signalling pathways. The obtained gene expression profile could be related to increased inter-cellular adhesion, and decreased monocyte recruitment, cellular contractility and their regulating signalling pathways, thereby improving endothelial function and consequently lesser atherosclerosis development. In the liver, the anthocyanin-rich extract affected the expression of 2,289 genes with 1,331 genes identified as up-regulated and 958 down-regulated. These genes are involved in various molecular and cellular pathways, such as cholesterol metabolism, VLDL removal, reverse cholesterol transport, but also inflammatory responses in the liver known to play a role in atherogenesis through the production of the pro-inflammatory cytokines. The expression profile of these genes after bilberry extract supplementation could explain the observed reduction of plasma cholesterol level via an increased elimination as bile acids, and the reduction of triglycerides in the liver via a decrease in hepatic lipogenesis. Furthermore this gene expression profile suggests a lower inflammatory status via a decrease in the expression of pro-inflammatory genes. Conclusion: Supplementation of the diet with bilberry anthocyanin-rich extract led to a significant inhibition of plaque development in apolipoprotein E deficient mice without an effect on oxidative stress parameters, suggesting the implication of other mechanisms of action. The use of holistic transcriptomic approach provided new data and a global integrative view of molecular mechanisms involved in the preventive action of bilberry anthocyanin-rich extract against atherosclerosis. Globally, bilberry extract induced changes in gene expression to an anti-inflammatory profile, which could be related to its anti-atherogenic properties

Direct Diagnosis of Echovirus 12 Meningitis Using Metagenomic Next Generation Sequencing

International audienceThe current point-of-care diagnosis of enterovirus meningitis does not identify the viral genotype, which is prognostic. In this case report, more than 81% of an Echovirus 12 genome were detected and identified by metagenomic next-generation sequencing, directly from the cerebrospinal fluid collected in a 6-month-old child with meningeal syndrome and meningitis: introducing Echovirus 12 as an etiological agent of acute meningitis in the pediatric population

Bilberry anthocyanin-rich extract alters expression of genes related to atherosclerosis development in aorta of apo E-deficient mice

Intake of anthocyanin-rich foods has been associated with a reduced risk of cardiovascular diseases. We recently reported that a nutritional supplementation with a bilberry anthocyanin-rich extract (BE) attenuates atherosclerotic lesion development in apolipoprotein E-deficient (apoE−/−) mice. However, the mechanism(s) of their preventive action are not completely understood. Anthocyanins may alter mRNA levels of genes related to atherosclerosis in cultured macrophages and endothelial cells, but in vivo studies remain scarce. The aim of the present study was to explore the in vivo mechanisms of action of the same bilberry extract, administered by supplementation at a nutritional level, in the aorta of apo E−/− mice using a global transcriptomic approach. This study focused on the early stage of atherosclerosis development for better assessment of BE action on initiation mechanisms of this pathology. After a two week period, plasma lipid and antioxidant capacity were evaluated and the global genomic analysis was carried out using pangenomic microarrays. BE supplementation significantly improved hypercholesterolemia whereas the plasmatic antioxidant status remained unchanged. Nutrigenomic analysis identified 1261 genes which expression was modulated by BE in the aorta. Bioinformatic analysis revealed that these genes are implicated in different cellular processes such as oxidative stress, inflammation, transendothelial migration and angiogenesis, processes associated with atherosclerosis development/protection. Some of the most significantly down-regulated genes included genes coding for AOX1, CYP2E1 or TXNIP implicated in the regulation of oxidative stress, JAM-A coding for adhesion molecules or VEGFR2 implicate in regulation of angiogenesis. Other genes were up-regulated, such as CRB3, CLDN14 or CDH4 potentially associated with increased cell-cell adhesion and decreased paracellular permeability. These results provide a global integrated view of the mechanisms involved in the preventive action of bilberry anthocyanin-rich extract against atherosclerosis

Seek and Find! PCR analyses of skin infections in West-European travelers returning from abroad with an eschar

International audienceBackground: Skin infections are among the leading causes of diseases in travelers. Diagnosing pathogens could be difficult. Method: We applied molecular assays for the diagnostic of a large collection of skin biopsies and swabs from travelers with suspected skin infections. All samples were tested by qPCR for Coxiella burnetti, Bartonella sp., Rickettsia sp., Borrelia sp., Ehrlichia sp., Trophetyma whipplei, Francisella tularensis, Mycobacteria sp., Staphylococcus aureus, Streptococcus pyogenes, Leishmania spp., Ortho poxvirus and Para poxvirus and then screened for the presence of bacteria by PCR amplification and sequencing, targeting the 16S rRNA gene. Results: From January 2009 to January 2017, 100 international travelers presenting with a suspected skin infection were enrolled. We detected 51 patients with an identified pathogen on skin samples. Travelers presenting with eschars were more likely to have a positive PCR sample (n = 44/76, 57.9%) compared to other patients (n = 7/24, 29.2%). Spotted fever group Rickettsia (n = 28) was the most frequently detected pathogens (19 R. africae, 6 R. conorii, 3 R. mongolitimonae); S. aureus were detected in 11 patients; S. pyogenes in 3; Leishmania sp.; M. leprae and B. henselae in 1 patient, respectively. Conclusion: By targeting the most commonly encountered causative agents of travel-related skin infections, our strategy provides a sensitive and rapid diagnostic method

Human Bacterial Repertoire of the Urinary Tract: a Potential Paradigm Shift

International audienceThe aim of this article is to review the human repertoire of bacteria in urine already described by culture and metagenomic techniques and published in the literature. Our study led us to compare this repertoire with other available human repertoires. We followed automatic and manual bibliographical methods and found 562 bacterial species reported in the literature as part of the human urinary microbiota. Of the 562 species, 322 were described only by culture, 101 by both culture and metagenomics, and 139 only by metagenomics. A total of 352 species (62.6%) have been associated with at least one case report of human infection, of which 225 (40.0%) have been described as causative agents of urinary tract infection. The urinary tract bacterial repertoire contains 21.4% of the known prokaryotic diversity associated with human beings (464 species in common), and it shares 23.6% species with the human gut microbiota (350 species in common, 62.3% of the urine species). The urinary repertoire shares a significant difference in aerointolerant species compared with those of the gut microbiota (100/562 [17.8%] and 505/1,484 [34.0%], respectively; P < 0.001; odds ratio [OR] = 9.0 [7.0 to 11.4]). Studies using high-throughput sequencing show a higher proportion of aerointolerant bacteria in urine (74/240 [30.8%]) than studies using culture techniques (40/423 [9.5%]). Most pathogenic bacteria are part of the commensal human urinary tract bacteria, and their pathogenicity may occur following any imbalance of this microbiota. The restoration of urinary tract health can occur following a fecal transplantation. The potential gut origin of the human bacterial microbiota has to be explored

Les services écosystémiques face au changement climatique

National audienc

Integrated approaches to health : concepts and experiences in framing, integration and evaluation of One Health and EcoHealth

Integrated approaches to health address health challenges arising from the intertwined spheres of humans, animals and ecosystems. This eBook is the product of an interdisciplinary effort to establish how One Health, EcoHealth and other integrated approaches to health are conceptualized, framed, implemented and evaluated today. It supplements the handbook for the evaluation of One Health, published by the COST Action “Network for Evaluation of One Health (NEOH)” with in depth reflections on the theory behind integrated approaches to health and One Health more specifically, a brief version of the NEOH evaluation framework, a supplementary evaluation approach, and eight case studies in which the NEOH framework was applied. The eBook is intended for practitioners, researchers, evaluators as well as funders of integrated approaches to health and beyond. Without the outstanding support and leadership from the management committee, this work would not have been achieved. Our gratitude goes to Maria-Eleni Filippitzi (BE), Véronique Renault (BE), Nihad Fejzic (BA), Sabina Seric-Haracic (BA), Nenad Turk (HR), Relia Beck (HR), Luca Guardabassi (DK), Liza Rosenbaum Nielsen (DK) Flavie Goutard (FR), Vladimir Grosbois (FR), Brigitte Petersen (DE), Martin Hamer (DE), Elias Papadopoulos (GR), Ilias Chaligiannis (GR), Gábor Földvári (HU), Anthony Staines (IE), Helen O’Shea (IE), Shimon Harrus (IL), Gad Baneth (IL), Valeria Grieco (IT), Maurizio Aragrande (vice chair, IT), Jovita Mažeikienė (LT), Sandra Buttigieg (MT), Elaine Lautier (MT), Helmut Saatkamp (NL), Kitty Maassen (NL), Vlatko Ilieski (MK), Mijalce Santa (MK), Merete Hofshagen (NO), Yngvild Wasteson (NO), Paulo Roriz (PT), Jorge Torgal (PT), Andrei D. Mihalca (RO), Razvan Chereches (RO), Dragan Milićević (RS), Sara Savic (RS), Joze Staric (SI), Mojca Juričič (SI), Pedro Soto-Acosta (ES), Francisco Giménez Sánchez (ES), Ann Lindberg (SE), Josef Järhult (SE), Jakob Zinsstag (CH), Simon Rüegg (CH), Barbara Häsler (chair, UK), K. Marie McIntyre (UK), Martha Betson (UK), Marieta Braks (NL), Chinwe Ifejika Speranza (DE), Spela Sinigoj (SI), Martijn Bouwknegt (NL), Andras Lakos (HU) and their substitutes Merel Postma (BE), Semra Cavaljuga (BA), Estella Prukner Radovcic (HR), Maria Vang Johansen (DK), Elena Boriani (DK), Ricarda Schmithausen (DE), Maryla Hanna Obszarski (DE), Smaragda Sotiraki (GR), Theofilos Papadopoulos (GR), Barry McMahon (IE), Massimo Canali (IT), Fabrizio Ceciliani (IT), Daniele De Meneghi (IT), Dalia Jurevičiūtė (LT), Miroslav Radeski (MK), Toni Vekov (MK); Manuela Vilhena (PT), Carla Maia (PT), Alexandru Coman (RO), Branka Vidic (RS), Gospava Lazić (RS), Ksenija Sinigoj Gacnik (SI), Juan Gabriel Cegarra Navarro (ES), Asta Tvarijonaviciute (ES), José Cerón (ES), Helene Wahlström (SE), Karin Artursson (SE), Laura Cornelsen (UK), Jonathan Rushton (UK). We also would like to thank the 240+ researchers that have engaged with the COST Action throughout and participated actively. Our gratitude also goes to the Royal Veterinary College in London, who acted as a grant holder.peer-reviewe

Child with liver transplant recovers from COVID-19 infection. A case report

International audienceWe present the case of a 55-month-old girl who recovered from coronavirus disease 2019 (COVID-19) infection 5 months after undergoing liver transplantation; she had a co-infection with Epstein-Barr virus (EBV). To the best of our knowledge, this is the first case report of a COVID-19 infection in a pediatric patient with liver transplantation. Additionally, this is also the first report of confirmed co-infection between COVID-19 and EBV. On the basis of this case, we suggest that liver transplantation is not associated with COVID-19 symptom severity and development. Moreover, COVID-19 and EBV co-infections do not seem to aggravate the clinical outcome. (C) 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved

Similar patterns of [18F]-FDG brain PET hypometabolism in paediatric and adult patients with long COVID: a paediatric case series

International audienc

Pediatr Nephrol

BACKGROUND: Schistosomiasis affects approximately 230 million people worldwide. There is an increased incidence of schistosomiasis cases in France acquired from outside the country. This increases the risk of schistosomiasis outbreaks as observed in Corsica. Clinicians from non-endemic regions are not accustomed to diagnosing and managing this pathology. The objective of this study is to provide a better description of the clinical and paraclinical characteristics and disease evolution of affected children. METHODS: Through the French Pediatric Nephrology Society and the Pediatric Infectious Pathology Group, we contacted all French pediatric centers that may have treated children with urinary schistosomiasis between 2013 and 2019. Age, sex, comorbidities, and clinical, biological, and radiological data (at discovery and follow-up) were collected retrospectively. RESULTS: A total of 122 patients from 10 different centers were included. The median age was 14 years and the sex ratio M/F was 4:1. Hematuria was present in 82% of the patients while urinary tract abnormality was found in 36% of them. Fourteen patients (11%) displayed complicated forms of urinary schistosomiasis including 10 patients with chronic kidney disease. A total of 110 patients received treatment with praziquantel, which was well-tolerated and led to clinical resolution of symptoms in 98% of cases. CONCLUSION: Patients with schistosomiasis present frequent kidney, urinary, or genital involvement. Systematic screening of patients returning from endemic areas is therefore recommended, especially since treatment with antiparasitic drugs is effective and well-tolerated. Enhancing medical knowledge of this pathology among all practitioners is essential to improve care and outcomes