Combined regulation of pro-inflammatory cytokines production by STAT3 and STAT5 in a model of B. pertussis infection of alveolar macrophages

Bordetella pertussis is a highly contagious respiratory pathogen responsible for whooping-cough or pertussis. Despite high vaccination coverage worldwide, this gram-negative bacterium continues to spread among the population. B. pertussis is transmitted by aerosol droplets from an infected individual to a new host and will colonize its upper respiratory tract. Alveolar macrophages (AMs) are effector cells of the innate immune system that phagocytose B. pertussis and secrete both pro-inflammatory and antimicrobial mediators in the lungs. However, understanding their role in B. pertussis pathogenesis at the molecular level is hampered by the limited number of primary AMs that can be collected in vivo. In order to decipher the regulation of innate response induced by B. pertussis infection, we used for the first time self-renewing, non-transformed cells, called Max Planck Institute (MPI) cells, which are phenotypically and functionally very close to pulmonary AMs. Using optimized infection conditions, we characterized the entry and the clearance of B. pertussis within MPI macrophages. We showed that under these conditions, MPI cells exhibit a pro-inflammatory phenotype with the production of TNF, IL-1β, IL-6 and MIP-2α, similarly to primary AMs purified from broncho-alveolar fluids of mice. In addition, we explored the yet uncharacterized role of the signal transduction activator of transcription (STAT) proteins family in the innate immune response to B. pertussis infection and showed for the first time the parallel regulation of pro-inflammatory cytokines by STAT3 and STAT5 in MPI macrophages infected by B. pertussis. Altogether, this work highlights the interest of using MPI cells for experiments optimization and preliminary data acquisition to understand B. pertussis interaction with AMs, and thus significantly reduce the number of animals to be sacrificed

Livret pédagogique : Apprendre à programmer Poppy Ergo Jr en Snap!

Un livret composé d'activités pédagogiques pour apprendre les bases de la programmation (programmation séquentielles, boucles, conditions, variables etc.) et des idées de défis et de projets pour appliquer les connaissancesCe livret propose des activités et des petits défis à réaliser pour se familiariser avec le robot Poppy Ergo Jr et le langage de programmation Snap!

Intrinsic antibacterial activity of nanoparticles made of β-cyclodextrins potentiates their effect as drug nanocarriers against tuberculosis

Multi-drug-resistant tuberculosis (TB) is a major public health problem, concerning about half a million cases each year. Patients hardly adhere to the current strict treatment consisting of more than 10 000 tablets over a 2-year period. There is a clear need for efficient and better formulated medications. We have previously shown that nanoparticles made of cross-linked poly-β-cyclodextrins (pβCD) are efficient vehicles for pulmonary delivery of powerful combinations of anti-TB drugs. Here, we report that in addition to being efficient drug carriers, pβCD nanoparticles are endowed with intrinsic antibacterial properties. Empty pβCD nanoparticles are able to impair Mycobacterium tuberculosis (Mtb) establishment after pulmonary administration in mice. pβCD hamper colonization of macrophages by Mtb by interfering with lipid rafts, without inducing toxicity. Moreover, pβCD provoke macrophage apoptosis, leading to depletion of infected cells, thus creating a lung microenvironment detrimental to Mtb persistence. Taken together, our results suggest that pβCD nanoparticles loaded or not with antibiotics have an antibacterial action on their own and could be used as a carrier in drug regimen formulations effective against TB.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Prognostic impact of epidermal growth factor receptor (EGFR) expression on loco-regional recurrence after preoperative radiotherapy in rectal cancer

BACKGROUND: Epidermal growth factor receptor (EGFR) represents a major target for current radiosensitizing strategies. We wished to ascertain whether a correlation exists between the expression of EGFR and treatment outcome in a group of patients with rectal adenocarcinoma who had undergone preoperative radiotherapy (RT). METHODS: Within a six-year period, 138 patients underwent preoperative radiotherapy and curative surgery for rectal cancer (UICC stages II-III) at our institute. Among them, 77 pretherapeutic tumor biopsies were available for semi-quantitative immunohistochemical investigation evaluating the intensity and the number (extent) of tumor stained cells. Statistical analyses included Cox regression for calculating risk ratios of survival endpoints and logistic regression for determining odds ratios for the development of loco-regional recurrences. RESULTS: Median age was 64 years (range: 30–88). Initial staging showed 75% and 25% stage II and III tumors, respectively. RT consisted of 44-Gy pelvic irradiation in 2-Gy fractions using 18-MV photons. In 25 very low-rectal-cancer patients the primary tumor received a boost dose of up to 16 Gy for a sphincter-preservation approach. Concomitant chemotherapy was used in 17% of the cases. All patients underwent complete total mesorectal resection. Positive staining (EGFR+) was observed in 43 patients (56%). Median follow-up was 36 months (range: 6–86). Locoregional recurrence rates were 7 and 20% for EGFR extent inferior and superior to 25%, respectively. The corresponding locoregional recurrence-free survival rate at two years was 94% (95% confidence interval, CI, 92–98%) and 84% (CI 95%, 58–95%), respectively (P = 0.06). Multivariate analyses showed a significant correlation between the rate of loco-regional recurrence and three parameters: EGFR extent superior to 25% (hazard ratio = 7.18, CI 95%, 1.17–46, P = 0.037), rectal resection with microscopic residue (hazard ratio = 6.92, CI 95%, 1.18–40.41, P = 0.032), and a total dose of 44 Gy (hazard ratio = 5.78, CI 95%, 1.04–32.05, P = 0.045). CONCLUSION: EGFR expression impacts on loco-regional recurrence. Knowledge of expression of EGFR in rectal cancer could contribute to the identification of patients with an increased risk of recurrences, and to the prediction of prognosis

Trials

BACKGROUND: Postoperative upper gastrointestinal fistula (PUGIF) is a devastating complication, leading to high mortality (reaching up to 80%), increased length of hospital stay, reduced health-related quality of life and increased health costs. Nutritional support is a key component of therapy in such cases, which is related to the high prevalence of malnutrition. In the prophylactic setting, enteral nutrition (EN) is associated with a shorter hospital stay, a lower incidence of severe infectious complications, lower severity of complications and decreased cost compared to total parenteral nutrition (TPN) following major upper gastrointestinal (GI) surgery. There is little evidence available for the curative setting after fistula occurrence. We hypothesize that EN increases the 30-day fistula closure rate in PUGIF, allowing better health-related quality of life without increasing the morbidity or mortality. METHODS/DESIGN: The NUTRILEAK trial is a multicenter, randomized, parallel-group, open-label phase III trial to assess the efficacy of EN (the experimental group) compared with TPN (the control group) in patients with PUGIF. The primary objective of the study is to compare EN versus TPN in the treatment of PUGIF (after esophagogastric resection including bariatric surgery, duodenojejunal resection or pancreatic resection with digestive tract violation) in terms of the 30-day fistula closure rate. Secondary objectives are to evaluate the 6-month postrandomization fistula closure rate, time of first fistula closure (in days), the medical- and surgical treatment-related complication rate at 6 months after randomization, the fistula-related complication rate at 6 months after randomization, the type and severity of early (30 days after randomization) and late fistula-related complications (over 30 days after randomization), 30-day and 6-month postrandomization mortality rate, nutritional status at day 30, day 60, day 90 and day 180 postrandomization, the mean length of hospital stay, the patient's health-related quality of life (by self-assessment questionnaire), oral feeding time and direct costs of treatment. A total of 321 patients will be enrolled. DISCUSSION: The two nutritional supports are already used in daily practice, but most surgeons are reluctant to use the enteral route in case of PUGIF. This study will be the first randomized trial testing the role of EN versus TPN in PUGIF. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03742752. Registered on 14 November 2018.This research program is funded by the French Ministry of Health through Programme Hospitalier de Recherche Clinique 2016

Chirurgie des cancers de l'oesophage après radio-chimiothérapie concomitante (facteurs pronostiques fonctionnels et oncologiques)

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Lidar vent UV avec une architecture robuste comprenant un interféromètre Quadri Mach-Zehnder pour la calibration/validation et la future génération d'Aeolus

International audienceWind speed measurement with on-board system has many applications in aeronautics (Gust Load alleviation, Haps, etc.) and space (Weather forecast). The molecular wind lidar is developed for those purposes as it sent laser pulses into the atmosphere to determine, with a spectral analyzer, the wind speed from the Doppler shift induced by the molecules of the atmosphere. In this paper we present the lidar architecture developed at ONERA, that uses a Quadri Mach-Zehnder (QMZ) as a spectral analyzer and a UV fiber laser, designed for gust load alleviation application. We discuss about the advantages of such architecture for wind measurement from space. Simulations of the performances have been performed in the case of Calibration/Validation (Cal/Val) of Aeolus, showing standard deviation on wind speed measurement less than 2 m/s up to 17 km of altitude for the optimized hybrid fiber laser of 10 W laser average power and a pulse repetition frequency (PRF) of 5 kHz. Simulations that evaluates the performances for Aeolus measurement with minor changes in the lidar architecture have been computed, with results showing that requirements are fulfilled up to 22.5 km of altitude with the optimized hybrid fiber laser of 10 W and 3 kHz PRF.La mesure de la vitesse du vent avec système embarqué a de nombreuses applications en aéronautique (atténuation des charges de rafales, Haps, etc.) et spatial (Prévisions météorologiques). Le lidar vent moléculaire est développé dans ce but car il envoie des impulsions laser dans l'atmosphère pour déterminer, avec un analyseur spectral, la vitesse du vent à partir du décalage Doppler induite par les molécules de l’atmosphère. Dans cet article nous présentons l'architecture lidar développée à l'ONERA, qui utilise un Quadri Mach-Zehnder (QMZ) comme analyseur spectral et un laser à fibre UV, conçu pour l'allègement des charges de rafales. Nous discutons des avantages d’une telle architecture pour la mesure du vent depuis l’espace. Des simulations des performances ont été réalisées dans le cas de Calibration/Validation (Cal/Val) d'Aeolus, montrant un écart type sur la mesure de la vitesse du vent inférieur à 2 m/s jusqu'à 17 km d'altitude pour l'optimisation laser à fibre hybride d'une puissance moyenne laser de 10 W et d'une fréquence de répétition d'impulsions de 5 kHz. Des simulations qui évaluent les performances de la mesure d'Aeolus avec des changements mineurs dans l'architecture lidar ont été réalisées, avec des résultats montrant que les exigences sont remplies jusqu'à 22,5 km d'altitude avec le laser à fibre hybride de 10 W et 3 kHz PRF

An innovative far UV telescope for space weather and solar variability studies

International audienceSUAVE (Solar Ultraviolet Advanced Variability Experiment) is a far UV imaging solar telescope (Lyman Alpha, 121.6 nm, Herzberg continuum, 200-220 nm, etc.) of novel design for ultimate thermal stability and long lasting performances. SUAVE is a 80 mm Ritchey-Chrétien off-axis telescope with SiC mirrors and no entrance window for long and uncompromised observations in the UV (no coatings of mirrors, flux limited to less than 2 solar constants on filters to avoid degradation), associated with an ultimate thermal control (no central obscuration resulting in limited thermal gradients and easier heat evacuation, focus control, stabilization). Design and anticipated performances will be detailed as well as the realization process under way. Tests on a representative breadboard will be performed in 2018 (CNES R&T). SUAVE is the main instrument of the SUITS/SWUSV (Solar Ultraviolet Influence on Troposphere/Stratosphere / Space Weather and Ultraviolet Solar Variability) microsatellite mission

Sensitivity studies for the VeSUV/VenSpec-U instrument onboard ESA’s EnVision mission

International audienceThe next ESA mission to Venus, EnVision, aims to study the planet as a whole, including its various constituting parts as well as their interactions and coupling processes. Several instruments will therefore compose the payload: a synthetic aperture radar (VenSAR, NASA), a subsurface radar sounder and a suite of three spectrometers (VenSpec) will be embedded, and a radioscience experiment will be implemented. Among them, the UV channel of the spectrometer suite, VenSpec-U, will observe the atmosphere above the clouds and will focus on the characterisation of the sulphured gases SO2 and SO, the monitoring of the unknown UV absorber and dynamical processes. These four topics have been identified as the main science objectives of the instrument and have driven the elaboration of a preliminary design based on the requirements (e.g. spectral range, spectral and spatial resolution) that were formulated with respect to these goals. The compliance of the current design with respect to these requirements, regarding in particular the precision of the retrieved science data, can then be assessed. Sensitivity studies are therefore performed using the Radiative Transfer Model (RTM), updated from the one used for SPICAV-UV/Venus Express retrievals (Marcq et al., 2020), that allows to link atmospheric features and UV reflectance spectra. Two types of perturbations are considered : errors of random nature arising from the presence of noise on the signal, or systematic errors caused by various effects that induce biases on the measurements. The first ones can be characterised through the influence of the Signal-to-Noise Ratio (SNR) on the uncertainties associated to each retrieved parameter through the fitting algorithm. Limits in terms of SNR can then be defined in order to ensure the compliance with the specifications. The second ones are referring to the impact of biases on the retrievals’ accuracy, and evaluate more specifically the effects of the similarities between the spectral characteristics of these biases and those of the atmospheric components aiming to be detected. The implemented method is based on the Effective Spectral Radiometric Accuracy (ESRA) requirement, previously defined within the framework of the ESA Sentinel missions. It allows to study biases independently as well as potential compensations, so that allowable envelopes of residual errors can then be estimated for each of the considered biases

SUAVE, a disruptive off-axis SiC far UV Lyman-Alpha solar telescope for long term observations

International audienceSUAVE (Solar Ultraviolet Advanced Variability Experiment) is a far UV imaging solar telescope (Lyman Alpha, 121.6 nm, Herzberg continuum, 200-242 nm, etc.) of novel design for ultimate thermal stability and long lasting performances over several years instead of, often, a few weeks or months in this wavelength range. SUAVE is a 80 mm Ritchey-Chrétien off-axis telescope with "mushroom type" SiC mirrors and no entrance window for long and uncompromising observations in the UV (no coatings of mirrors, flux limited to less than 2 solar constants on filters to avoid their degradation), associated with an ultimate thermal control (no central obscuration resulting in limited thermal gradients and easier heat evacuation, focus control, stabilization). Design and performances will be detailed as well as results of thermal/optical tests performed on the SiC primary mirror and its regulated support plate also in SiC. Plans for the realization of a representative breadboard for testing of both optical and thermal properties are presented. SUAVE is the main instrument of the Solar/Climate microsatellite SoSWEET mission (Solar ultraviolet variability and Space Weather Extreme EvenTs)