Effect of a short-term HAART on SIV load in macaque tissues is dependent on time of initiation and antiviral diffusion

<p>Abstract</p> <p>Background</p> <p>HIV reservoirs are rapidly established after infection, and the effect of HAART initiated very early during acute infection on HIV reservoirs remains poorly documented, particularly in tissue known to actively replicate the virus. In this context, we used the model of experimental infection of macaques with pathogenic SIV to assess in different tissues: (i) the effect of a short term HAART initiated at different stages during acute infection on viral dissemination and replication, and (ii) the local concentration of antiviral drugs.</p> <p>Results</p> <p>Here, we show that early treatment with AZT/3TC/IDV initiated either within 4 hours after intravenous infection of macaques with SIVmac251 (as a post exposure prophylaxis) or before viremia peak (7 days post-infection [pi]), had a strong impact on SIV production and dissemination in all tissues but did not prevent infection. When treatment was initiated after the viremia peak (14 days pi) or during early chronic infection (150 days pi), significant viral replication persists in the peripheral lymph nodes and the spleen of treated macaques despite a strong effect of treatment on viremia and gut associated lymphoid tissues. In these animals, the level of virus persistence in tissues was inversely correlated with local concentrations of 3TC: high concentrations of 3TC were measured in the gut whereas low concentrations were observed in the secondary lymphoid tissues. IDV, like 3TC, showed much higher concentration in the colon than in the spleen. AZT concentration was below the quantification threshold in all tissues studied.</p> <p>Conclusions</p> <p>Our results suggest that limited antiviral drug diffusion in secondary lymphoid tissues may allow persistent viral replication in these tissues and could represent an obstacle to HIV prevention and eradication.</p

Report on the Fourth Excavation Season (2011) of the Madâ'in Sâlih Archaeological Project

This volume is the report on the results of the fourth excavation season of the Saudi-French Archaeological Project at Madâ'in Sâlih, ancient Hegra in the Nabataean kingdom, in north-west Saudi Arabia (MAEE, SCTA, CNRS, Univ Paris 1, IFPO). Apart from the results obtained in the different excavation areas (both in the residential area and in tomb IGN 117), the reader will find a study on the cairns/tumuli of the site (W. Abu-Azizeh) as well as intermediary reports on the geophysical detection (Chr. Benech), the fauna (J. Studer) and the pottery (C. Durand).Ce volume constitue le rapport sur les résultats de la quatrième campagne de fouilles de la mission archéologique franco-saoudienne de Madâ'in Sâlih, l'ancienne Hégra des Nabatéens, dans le nord-ouest de l'Arabie Saoudite (MAEE, SCTA, CNRS, Univ. Paris 1, IFPO). Outre les résultats obtenus dans les différents chantiers (dans la zone résidentielle et dans le tombeau IGN 117), le lecteur trouvera une étude synthétique sur les cairns/tumuli du site (W. Abu-Azizeh) ainsi que des rapports intermédiaires sur la détection géophysique (Chr. Benech), la faune (J. Studer) et la céramique (C. Durand)

Decision Support Systems for Weed Management

Editors: Guillermo R. Chantre, José L. González-Andújar.Weed management Decision Support Systems (DSS) are increasingly important computer-based tools for modern agriculture. Nowadays, extensive agriculture has become highly dependent on external inputs and both economic costs, as well the negative environmental impact of agricultural activities, demands knowledge-based technology for the optimization and protection of non-renewable resources. In this context, weed management strategies should aim to maximize economic profit by preserving and enhancing agricultural systems. Although previous contributions focusing on weed biology and weed management provide valuable insight on many aspects of weed species ecology and practical guides for weed control, no attempts have been made to highlight the forthcoming importance of DSS in weed management. This book is a first attempt to integrate 'concepts and practice' providing a novel guide to the state-of-art of DSS and the future prospects which hopefully would be of interest to higher-level students, academics and professionals in related areas

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Tryptophan metabolites get the gut moving

International audienceHow gut microbes can regulate the enteric nervous system and gut-brain communications is a field of intense research. In this issue of Cell Host & Microbe, Ye et al. demonstrate that bacteria can control intestinal motility and vagal neuronal activation via tryptophan catabolites through the receptor TrpA1 of enteroendocrine cells

Feasibility Study to Assess the Impact of a Lifestyle Intervention during Colorectal Cancer Screening in France

Current evidence suggests that 30–50% of cancers are attributable to established lifestyle risk factors. Cancer-screening has been identified as an opportunity for delivering advice on lifestyle behaviour change for cancer prevention. This study aimed to evaluate the feasibility and acceptance of promoting advice on the latest evidence-based lifestyle recommendations for cancer prevention at the time of colorectal cancer screening at two hospitals in Lyon, France. This feasibility study included 49 patients (20 men and 29 women) who were invited for colonoscopy. Patients received a leaflet with lifestyle recommendations for cancer prevention, accompanied with a logbook to plan and monitor their behavioural changes. Feedback from patients, hospital staff, and researchers was received via evaluation questionnaires (n = 26) completed after testing the educational material for at least two weeks and via two focus group discussions (n = 7 and n = 9 respectively) organized at the end of the study. All interviewed patients were interested in lowering their cancer risk, and the majority felt ready to change their lifestyle (88%), although most did not know how to decrease their risk of cancer (61%). All patients found the educational material easy to understand and sufficiently attractive and 50% of the patients reported having achieved at least one of the healthy behaviours recommended within the two weeks following the intervention. All hospital staff and almost all patients (92%) involved found that the screening program and the visits planned for colonoscopy was an appropriate moment to provide them with the educational material. This feasibility study has shown that the content, paper-based format, and time of delivery of the intervention were adequate. Health professionals seem to be willing to provide lifestyle recommendations, and patients appear interested in receiving advice for lowering their cancer risk during screening visits

Gut microbiota alterations are associated with phenotype and genotype in familial Mediterranean fever

International audienceAbstract Objective FMF is the most common monogenic autoinflammatory disease associated with MEFV mutations. Disease phenotype and response to treatment vary from one patient to another, despite similar genotype, suggesting the role of environmental factors. The objective of this study was to analyse the gut microbiota of a large cohort of FMF patients in relation to disease characteristics. Methods The gut microbiotas of 119 FMF patients and 61 healthy controls were analysed using 16 s rRNA gene sequencing. Associations between bacterial taxa, clinical characteristics, and genotypes were evaluated using multivariable association with linear models (MaAslin2), adjusting on age, sex, genotype, presence of AA amyloidosis (n = 17), hepatopathy (n = 5), colchicine intake, colchicine resistance (n = 27), use of biotherapy (n = 10), CRP levels, and number of daily faeces. Bacterial network structures were also analysed. Results The gut microbiotas of FMF patients differ from those of controls in having increased pro-inflammatory bacteria, such as the Enterobacter, Klebsiella and Ruminococcus gnavus group. Disease characteristics and resistance to colchicine correlated with homozygous mutations and were associated with specific microbiota alteration. Colchicine treatment was associated with the expansion of anti-inflammatory taxa such as Faecalibacterium and Roseburia, while FMF severity was associated with expansion of the Ruminococcus gnavus group and Paracoccus. Colchicine-resistant patients exhibited an alteration of the bacterial network structure, with decreased intertaxa connectivity. Conclusion The gut microbiota of FMF patients correlates with disease characteristics and severity, with an increase in pro-inflammatory taxa in the most severe patients. This suggests a specific role for the gut microbiota in shaping FMF outcomes and response to treatment

DART : modèle physique 3D d'images de télédétection et du bilan radiatif de paysages urbains et naturels

Le modèle DART (Discrete Anisotropic Radiative Transfer) simule le transfert radiatif optique dans le système "Terre - Atmosphère", du visible à l'infrarouge thermique, pour des paysages urbains et naturels (e.g., forêts multi-espèces), avec atmosphère et relief. Ses deux principales sorties sont : - images de télédétection spatiale (i.e., réflectance ou température directionnels), pour toute direction solaire et de visée, altitude du capteur, résolution spatiale, etc. - Bilan radiatif 3-D. ce bilan est utilisé pour simuler la photosynthèse ainsi que les bilans d'énergie et de masse des surfaces terrestres. DART génère aussi des séries de simulations où certains paramètres (e.g., LAI, temps, longueur d'onde) varient, ce qui permet de créer des courbes spectrales et temporelles. De plus, il inverse les images de télédétection pour calculer certains paramètres biophysiques (e.g., LAI, taux de couverture). DART simule les paysages en tant que matrices 3-D de cellules parallélépipédiques qui contiennent de la matière turbide et/ou des éléments de surface opaques ou translucides dotés de propriétés optiques isotropes (i.e., lambertien) ou non (e.g., spéculaire). Ces propriétés peuvent être spécifiées par des bases de données spectrales ou via le couplage de DART avec le modèle foliaire PROSPECT. Une interface graphique gère la simulation du paysage et l'affichage des résultats (e.g., images, spectres). Validé lors de l'expérience RAMI, puis breveté en 2003, DART est désormais un outil très utile pour analyser et interpréter les images de télédétection. Les scientifiques peuvent obtenir des licences gratuites auprès de l'Université Paul Sabatier