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A 16-element 140–160-GHz phased array transceiver is reported. The chipset is fabricated using STMicroelectronics’ 55-nm SiGe BiCMOS process. Five different chips are implemented: a 4-channel transmitter with a maximum gain per channel of 15 dB and 0-dBm saturated output power; a 4-channel receiver with a maximum gain of 8 dB, a − 10.4-dBm input 1-dB compression point (IP 1dB ), and a minimum noise figure (NF) of 15.6 dB per channel; a 0–1-GHz to 140–160-GHz I/Q up-converter with integrated frequency doubler, exhibiting a − 13.5-dB conversion gain (CG) and − 6-dBm output 1-dB compression point using a 70–80-GHz local oscillator (LO); a 140–160-GHz to 0–1-GHz I/Q down-converter with integrated frequency doubler, exhibiting a CG of 0 dB and IP 1dB of 0 dBm using a 70–80-GHz LO and an 11.67–13.33-GHz to 70–80-GHz x6 frequency multiplier for the LO, delivering 5.6-dBm maximum output power. The chips are assembled together with 16 cavity-backed aperture-coupled patch antennas using a high-performance and low-cost commercial PCB, supported over a heat sink. The main challenges encountered during the integration of the proposed system are also discussed. The complete system is used to build a wireless radio link in the laboratory, demonstrating 2-D beam steering in a range of ± 30 ∘ .

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BACKGROUND: Oxygen uptake (V̇O2) kinetics have been shown to be slowed in adolescents with cystic fibrosis (CF) during heavy-intensity cycling and maximal exercise testing. OBJECTIVES: This study investigated V̇O2 kinetics in adolescents with CF compared to control adolescents (CON) during a treadmill-walking exercise. METHODS: Eight adolescents with CF and mild-to-moderate pulmonary obstruction (5 girls; 13.1 ± 2.5 years; FEV1 67.8 ± 21.4%) and 18 CON adolescents (10 girls; 13.8 ± 1.8 years) were recruited. Pulmonary gas exchange and ventilation were measured during a single transition of 10 min of treadmill walking and a 5 min seated recovery period. Participant's walking speed was determined during a one-minute self-paced walking task along a 50-m corridor. A six-parameter, non-linear regression model was used to describe the changes in V̇O2 function during the treadmill walking and recovery, with monoexponential curve fitting used to describe the mean response time (MRT1) at the onset of exercise, and the half-life (T1/2V̇O2) at the offset of exercise. V̇O2 baseline and amplitude, minute ventilation and respiratory equivalents were recorded. RESULTS: V̇O2 kinetics were slower in CF group compared to CON group during the treadmill walking with a greater MRT1 (32 ± 14 s vs 21 ± 16 s; p = .04, effect size = 0.75). The T1/2V̇O2 was prolonged during recovery in CF group compared to CON group (86 ± 24 s vs 56 ± 22 s; p = .04, effect size = 1.31). The mean VE/V̇CO2 during exercise was the only parameter significantly greater in CF group compared to CON group (32.9 ± 2.3 vs 29.0 ± 2.4; p < .01, effect size = 1.66). CONCLUSION: V̇O2 kinetics were found to be slowed in adolescents with CF during treadmill walking.

Accurate testing of muscle function is essential in individuals with cystic fibrosis (CF). A literature search was conducted in MEDLINE, CENTRAL, CINAHL, PEDro, ScienceDirect and Web of Science according to PRISMA and COSMIN guidelines from inception to September 2019 to investigate the clinimetric properties of muscle tests in individuals with CF. The search identified 37 studies (1310 individuals) and 34 different muscle tests. Maximal inspiratory pressure, inspiratory work capacity and quadriceps strength measured by computerised dynamometry were identified as reliable tests of muscle function. The one-minute sit-to-stand test was found to have high reliability but its validity to measure quadriceps strength is unknown. The clinimetric properties of other routinely used tests have not been reported in people with CF. Very different measurement procedures were identified. Inspiratory muscle and quadriceps testing can be considered as reliable but high-quality studies evaluating tests of other muscles function (e.g. muscle endurance) are lacking.

Hepatic fibrosis is a major consequence of chronic liver disease such as non-alcoholic steatohepatitis which is undergoing a dramatic evolution given the obesity progression worldwide, and has no treatment to date. Hepatic stellate cells (HSCs) play a key role in the fibrosis process, because in chronic liver damage, they transdifferentiate from a “quiescent” to an “activated” phenotype responsible for most the collagen deposition in liver tissue. Here, using a diet-induced liver fibrosis murine model (choline-deficient amino acid-defined, high fat diet), we characterized a specific population of HSCs organized as clusters presenting simultaneously hypertrophy of retinoid droplets, quiescent and activated HSC markers. We showed that hypertrophied HSCs co-localized with fibrosis areas in space and time. Importantly, we reported the existence of this phenotype and its association with collagen deposition in three other mouse fibrosis models, including CCl4-induced fibrosis model. Moreover, we have also shown its relevance in human liver fibrosis associated with different etiologies (obesity, non-alcoholic steatohepatitis, viral hepatitis C and alcoholism). In particular, we have demonstrated a significant positive correlation between the stage of liver fibrosis and HSC hypertrophy in a cohort of obese patients with hepatic fibrosis. These results lead us to conclude that hypertrophied HSCs are closely associated with hepatic fibrosis in a metabolic disease context and may represent a new marker of metabolic liver disease progression.

OBJECTIVES: Monitoring psychosocial, emotional, and hedonic aspects of food behavior is important to understand cancer patients’ distress and help to reduce risks of malnutrition. However, to date, there is no specific tool to measure the impact of diet, eating behavior, and chemotherapy side effects on patients’ food-related quality of life during cancer and its treatments. The objective was to develop and validate a questionnaire that aims to assess the food-related quality of life in cancer patients undergoing chemotherapy. METHODS: Relevant items from the existing food-related quality of life assessment tools were selected to compose the present 46-item questionnaire. The validation of the questionnaire was conducted in 276 healthy volunteers and 173 cancer patients. Exploratory Factor Analysis (EFA) was performed in both groups, construct and discriminant validity, and test-retest reliability were calculated. RESULTS: The questionnaire was perceived as clear and required less than14 minutes for completion (93% complete responses) in a pre-test (n = 156). The EFA allowed the inclusion of 9 dimensions in the food-related quality of life questionnaire. Common patterns between patients and healthy volunteers (factor loadings ≥ 0.4 in both groups) were used to calculate scores by dimension. Scores in the dimensions of adapting diet and sensorial discomfort (taste/odor) were higher in cancer patients, whilst scores in the dimension of discomfort in satiety were higher in healthy volunteers. Among patients with cancer, the total scores in sensorial discomfort, digestive discomfort, and discomfort in satiety were higher under chemotherapy than no treatment. Reproducibility after one week was in increasing order; digestive discomfort 0.6, adapting diet 0.61, products’ quality 0.67, cooking 0.75, healthy diet 0.76, eating and pleasure 0.80, discomfort in satiety 0.82, and sensorial discomfort 0.85. CONCLUSIONS: This 46-item questionnaire can discriminate cancer patients versus healthy volunteers, and patients receiving vs those not receiving chemotherapy. A good to very good reproducibility was found for the most important factors of food-related quality of life of patients with cancer, i.e, eating and pleasure, sensorial discomfort, and discomfort in satiety. FUNDING SOURCES: This study is funded by La Région Auvergne Rhône-Aples and La Métropôle de Lyon.

BACKGROUND: It is unclear whether asthma may affect susceptibility or severity of coronavirus disease 2019 (COVID-19) in children and how pediatric asthma services worldwide have responded to the pandemic. OBJECTIVE: To describe the impact of the COVID-19 pandemic on pediatric asthma services and on disease burden in their patients. METHODS: An online survey was sent to members of the Pediatric Asthma in Real Life think tank and the World Allergy Organization Pediatric Asthma Committee. It included questions on service provision, disease burden, and the clinical course of confirmed cases of COVID-19 infection among children with asthma. RESULTS: Ninety-one respondents, caring for an estimated population of more than 133,000 children with asthma, completed the survey. COVID-19 significantly impacted pediatric asthma services: 39% ceased physical appointments, 47% stopped accepting new patients, and 75% limited patients' visits. Consultations were almost halved to a median of 20 (interquartile range, 10-25) patients per week. Virtual clinics and helplines were launched in most centers. Better than expected disease control was reported in 20% (10%-40%) of patients, whereas control was negatively affected in only 10% (7.5%-12.5%). Adherence also appeared to increase. Only 15 confirmed cases of COVID-19 were reported among the population; the estimated incidence is not apparently different from the reports of general pediatric cohorts. CONCLUSIONS: Children with asthma do not appear to be disproportionately affected by COVID-19. Outcomes may even have improved, possibly through increased adherence and/or reduced exposures. Clinical services have rapidly responded to the pandemic by limiting and replacing physical appointments with virtual encounters. (C) 2020 American Academy of Allergy, Asthma & Immunology.

International audience; We consider in review current state-of-the-art fluorescence microscopy for investigating the host-pathogen interface. Our perspective is honed from years with literally thousands of microbiologists using the variety of imaging technologies available within our dedicated BSL2/BSL3 optical imaging research service facilities at the Institut Pasteur Paris founded from scratch in 2001. During fifteen years learning from the success and failures of introducing different fluorescence imaging technologies, methods, and technical development strategies we provide here a synopsis review of our experience to date and a synthesis of how we see the future in perspective for fluorescence imaging at the host-pathogen interface.

Magnetic resonance imaging (MRI) is the diagnostic cornerstone for precisely identifying acute ischaemic strokes and locating vascular occlusions, especially since mechanical thrombectomy has become a reference treatment. We observed that a post-contrast three-dimensional turbo-spin-echo T1-weighted sequence showed striking post-contrast vascular hyperintensities (PCVH) in ischaemic territories. We aimed to evaluate the prevalence and the meaning of this finding. This retrospective single centre study included 130 consecutive patients admitted for acute ischaemic stroke with a 3-T MRI performed in the first 12 h of symptom onset from September 2014 through September 2016. Two neuroradiologists blinded to clinical data analysed the first MRI assessments. The association between PCVH and clinical, radiological and follow-up findings was assessed, as well as inter- and intra-observer agreements. Of 130 patients, 105 (81%) had PCVH in the ischaemic territory. PCVH were associated with the presence of thrombus on susceptibility weighted imaging (p < 0.0001) and vascular occlusions on MR angiography (p < 0.0001). All patients with a visible thrombus had PCVH closely surrounding the clot. PCVH were associated with higher initial (p < 0.01) and follow-up (p < 0.01) National Institutes of Health Stroke Scale score, and higher mRS score (p < 0.05). Thrombectomy was the reference treatment for all patients with arterial occlusions. Inter- and intra-observer agreements for the detection of PCVH were excellent (κ = 0.95 and κ = 0.91, respectively). PCVH during acute strokes are a striking sensitive and reproducible tool for diagnosing and locating vascular occlusions. It may help triage patients who can benefit from thrombectomy. • Post-contrast vascular hyperintensities (PCVH) are a sensitive MR finding in acute stroke • PCVH are strongly associated with the presence and location of arterial occlusions • Inter- and intra-observer agreements for the detection of PCVH are excellent • PCVH are visible even in the case of significant motion artefacts • PCVH may help triage patients who can benefit from mechanical thrombectomy

BackgroundEndovascular venous access is increasingly used for the treatment of many cerebrovascular diseases. The quality of venous roadmapping through arterial injection can be problematic because of contrast media dilution, slow flow velocity, and unilateral opacification of the venous system.ObjectiveTo describe our experience with the VesselNavigator (Philips Healthcare, Best, The Netherlands) in performing live 3D roadmapping for intracranial venous procedures.Material and methodsLive 3D roadmapping is an image-processing technique that allows dynamic roadmapping of vessels with immediate adaptation to the C-arm movements without the need for contrast injection. For this purpose, 3D MR venography is overlaid on live fluoroscopy images after semiautomatic coregistration. The technique was applied to cases of idiopathic venous stenosis and arteriovenous fistula.ResultsThe process of coregistration was performed by the principal operator in ConclusionOur preliminary experience suggests that it is a feasible and safe technique for intracranial venous navigation and procedures. The potential lowering of overall radiation dose and contrast media use needs to be verified with further studies.

International audience; Background: Cerebral small-vessel disease (CSVD) is a chronic disease accounting for one-third of strokes and the second etiology of dementia. Despite sustained immunovirological control, CSVD prevalence is doubled in middle-aged persons living with HIV (PLHIVs), even after adjustment for traditional cardiovascular risk factors. We aimed to investigate whether exposure to any antiretroviral drug class could be associated with an increasing risk of CSVD.Methods: The MicroBREAK-2 case-control study (NCT02210130) enrolled PLHIVs aged 50 years and older, treated with combined antiretroviral therapy for ≥5 years, with plasma HIV load controlled for ≥12 months. Cases were PLHIVs with radiologically defined CSVD, and controls were CSVD-free PLHIVs matched for age (±5 years), sex, and year of HIV diagnosis (±5 years). Multivariable conditional logistic regression analyses focused on cumulative exposure to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and/or exposure to integrase inhibitors (yes or no), adjusted for hypertension, CD4 nadir, current CD4/CD8 ratio, and HIV transmission group.Results: Between May 2014 and April 2017, 77 cases and 77 controls (85.7% males) were recruited. PLHIVs' median age was 57.6 years, and median HIV diagnosis year was 1992. The increasing risk of CSVD was not associated with exposure to any ART class.Conclusion: No deleterious effect of ART class exposure on the risk of CSVD was found for middle-aged treated PLHIVs.

This paper presents a study of the D-band radio solutions, with beam-steering functionality, intended for use in the reconfigurable meshed network. The regulation and radio network constraints defining the specifications of a D-Band transceiver are reviewed. The architecture of the radio link is proposed and key enabling technologies needed to build the D-band transceiver are presented. The proposed solutions can be used for plenty of different radio connections, since they can provide a capacity level up to 100 Gbps over 160 meter and, at reduced capacity, hop lengths exceeding 1 km.

Background Functional exercise capacity assessment is recommended in children with cystic fibrosis (CF). The six-minute walk test (6MWT) is a valid evaluation of exercise capacity but can be technically complex. Inversely, the sit-to-stand test (STST) is a simple method to evaluate exercise capacity, and is validated in healthy children and adults with CF. This study aimed to evaluate STST measurement properties in children and adolescents with CF. Methods In this multicenter study, children with CF (6 to 18 years) performed two iterations of both the STST and the 6MWT in a randomized order. Criterion validity was determined by assessing correlations between STST repetitions and 6MWT distance (6MWD). Intra-rater reliability, test-retest repeatability, mean bias and limits of agreement were also assessed. Relationships with other outcomes (i.e. respiratory and quadriceps muscle strength) and cardio-respiratory responses were analysed for both tests. Results Thirty-six children with CF were included (mean age 12.0 ±3.5 years and FEV1 95.8 ±25.0%). On average, 39.6 ±10.5 repetitions were performed during the STST and mean 6MWD was 596.0 ±102.6 meters. STST number of repetitions was significantly correlated with 6MWD (r = 0.48; pSTST = 0.91 (95%CI 0.76–0.96) and ICC6MWT = 0.94 (95%CI 0.85–0.97)), and a significant test-retest learning effect. The number of STST repetitions was not correlated with quadriceps or respiratory muscle strength test, and the STST induced fewer cardio-respiratory responses than the 6MWT. Conclusions The STST is an easy-to-use functional test with moderate criterion validity when compared to the 6MWT in children with CF, probably because both tests measure different components of functional exercise capacity. The STST is useful when the 6MWT is unfeasible, however further investigations are required to explore the clinical implications of STST results in children with CF. Clinical trial registration NCT03069625.

BackgroundSusceptibility vessel sign (SVS) can be a useful MRI biomarker of an occlusion but its relationship with clinical outcomes of acute ischemic stroke (AIS) is yet to be fully elucidated.ObjectiveTo investigate SVS in relation to the clinical outcomes after mechanical thrombectomy using a stent retriever (SR) as first-line approach in patients with AIS.Material and methodsWe included patients with a first-line SR approach for anterior AIS from the the Contact Aspiration vs Stent Retriever for Successful Revascularization (ASTER) and THRombectomie des Artères CErebrales (THRACE) trials when both baseline imaging of SVS and 90-day modified Rankin Scale (mRS) scores were available. Patients were assigned to two groups based on the presence of an SVS (independent core laboratory), and the overall distributions of the mRS score at 90 days (shift analysis) and clinical independence (mRS score ≤2) were compared.Results217 patients were included and SVS was diagnosed in 76.0% of cases (n=165, 95% CI 70.4% to 81.7%). After adjustment for potential confounders, SVS+ was significantly associated with 90-day mRS improvement (adjusted common OR=2.75; 95% CI 1.44 to 5.26) and favorable outcome (adjusted common OR=2.76; 95% CI 1.18 to 6.45).ConclusionBased on results for patients of the ASTER and THRACE trials receiving first-line SR treatment, SVS was associated with lower disability at 3 months. Large prospective studies using MRI-based thrombus evaluation are warranted.

Background Skeletal muscle has the capacity to adapt to environmental changes and regenerate upon injury. To study these processes, most experimental methods use quantification of parameters obtained from images of immunostained skeletal muscle. Muscle cross-sectional area, fiber typing, localization of nuclei within the muscle fiber, the number of vessels, and fiber-associated stem cells are used to assess muscle physiology. Manual quantification of these parameters is time consuming and only poorly reproducible. While current state-of-the-art software tools are unable to analyze all these parameters simultaneously, we have developed MuscleJ, a new bioinformatics tool to do so. Methods Running on the popular open source Fiji software platform, MuscleJ simultaneously analyzes parameters from immunofluorescent staining, imaged by different acquisition systems in a completely automated manner. Results After segmentation of muscle fibers, up to three other channels can be analyzed simultaneously. Dialog boxes make MuscleJ easy-to-use for biologists. In addition, we have implemented color in situ cartographies of results, allowing the user to directly visualize results on reconstituted muscle sections. Conclusion We report here that MuscleJ results were comparable to manual observations made by five experts. MuscleJ markedly enhances statistical analysis by allowing reliable comparison of skeletal muscle physiology-pathology results obtained from different laboratories using different acquisition systems. Providing fast robust multi-parameter analyses of skeletal muscle physiology-pathology, MuscleJ is available as a free tool for the skeletal muscle community. Electronic supplementary material The online version of this article (10.1186/s13395-018-0171-0) contains supplementary material, which is available to authorized users.

Objectives To determine frequency and syndrome specificity of novel and known nervous system (NS)-directed antibodies in a large, unbiased cohort of SLE patients in the Swiss SLE Cohort Study. Methods This retrospective pilot study included 174 patients in a cross-sectional and 102 in a longitudinal study. Antibodies against 12 NS antigens [myelin oligodendrocyte glycoprotein (MOG), neurofascin 186 (NF186), aquaporin-4 (AQP4), N-methyl-D-aspartate receptor (subunit NR1) (NMDAR-NR1), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (subunits 1 and 2) (AMPAR1/2), gamma-aminobutyric acid B receptor (subunits B1 and B2) (GABABR1/2), glutamate decarboxylase 65 (GAD65), glycine receptor (GlyR), contactin-associated protein-like 2 (CASPR2), leucine-rich glioma-inactivated 1 (LGI1), metabotropic glutamate receptor 5 (mGluR5) and dipeptidyl-peptidase-like protein 6 (DPPX)] were screened with validated cell-based assays and correlated with clinical and diagnostic findings. Results Twenty-three of one hundred and seventy-four (13.2%) patients harboured antibodies against MOG (n = 14), NF186 (n = 6), GAD65 (n = 2), AQP4 and GlyR (n = 1). Anti-MOG antibodies were most frequently found in the cohort (8%). Thirteen of the anti-NS antibody-positive patients showed clinical symptoms of NS involvement, a subgroup of which (n = 8) resembled the syndrome associated with the antibody. Nine patients harboured antibodies without neurological symptoms and one patient was lost to follow-up. The frequency of NPSLE was significantly higher in the anti-NS antibody-positive patients (13/23, 56.5%: MOG 6/14, 42.9%; NF186 5/6, 83.3%; GAD65 2/2, 100%; AQP4/GlyR 0/1, 0%) compared with the antibody-negative cohort (21/151, 13.9%) (chi-square test, P < 0.0001). Conclusion Anti-NS antibodies, most prevalently anti-MOG antibodies, are significantly associated with NPSLE and manifest with the distinct neurological syndrome associated with the antibody in a subgroup. Follow-up studies in large, independent cohorts will reveal whether these anti-NS antibodies could serve as a diagnostic and prognostic biomarker for NPSLE and enable tailored treatment decisions in this challenging and diverse patient cohort.

Resume Le terme tumeurs orbitaires recouvre un large spectre de pathologies benignes et malignes, touchant les composants orbitaires ou developpees a leur contact. Elles sont decouvertes de maniere fortuite ou recherchees dans le bilan d’une affection generale ou devant des signes orbitaires (exophtalmie, douleurs…). Le scanner, l’IRM et l’echographie avec Doppler couleur (EDC) jouent un role qui varie en fonction de la presentation clinique et de la pathologie recherchee. Cet article, fruit d’une longue experience dans un centre referent, n’a pas la volonte d’etre exhaustif. Nous avons prefere aborder ces tumeurs sous l’angle de leur presentation usuelle, en insistant sur les causes les plus frequentes et les tableaux radiocliniques qui permettent d’y penser (exophtalmie progressive ou brutale, enfant ou adulte, lesions des glandes lacrymales, lesions periorbitaires, enophtalmie). Nous detaillerons en particulier les atteintes musculaires (maladie de Basedow, tumeurs), les lesions vasculaires (hemangiome caverneux, varices, lymphangiome kystique), les lesions de l’enfant, les hematomes orbitaires. Nous proposons des protocoles d’exploration simples et des diagnostics differentiels utiles. Les references bibliographiques permettront a ceux qui veulent aller plus loin de completer leurs connaissances dans ce domaine passionnant.

The term orbital tumor covers a wide range of benign and malignant diseases affecting specific component of the orbit or developing in contact with them. They are found incidentally or may be investigated as part of the assessment of a systemic disorder or because of orbital signs (exophthalmos, pain, etc.). Computed tomography, MRI and Color Doppler Ultrasound (CDU), play a varying role depending on the clinical presentation and the disease being investigated. This article reflects long experience in a reference center but does not claim to be exhaustive. We have chosen to consider these tumors from the perspective of their usual presentation, emphasizing the most common causes and suggestive radiological and clinical presentations (progressive or sudden-onset exophthalmos, children or adults, lacrimal gland lesions, periorbital lesions and enophthalmos). We will describe in particular muscle involvement (thyrotoxicosis and tumors), vascular lesions (cavernous sinus hemangioma, orbital varix, cystic lymphangioma), childhood lesions and orbital hematomas. We offer straightforward useful protocols for simple investigation and differential diagnosis. Readers who wish to go further to extend their knowledge in this fascinating area can refer to the references in the bibliography.

Introduction: Backpack carrying restricts lung function and exercise capacity in healthy children. However, schoolbag consequences are unclear in a chronic respiratory disease context like school-aged cystic fibrosis (CF) children. Objectives: Our main aim was to compare forced vital capacity (FVC) change according to backpack carriage and straps position in children with CF and healthy controls. Secondary objectives were to assess other lung function parameters and track ventilatory response while walking with a backpack. Methods: Lung function was tested in three conditions: without backpack (control condition) and while carrying a 12.5% of child’s body weight backpack with bilateral strap (BB) or with unilateral strap (UB). Ventilatory responses were quantified while performing a mild intensity 10 minutes walking period. Results: Nine CF children (age 13.3±2.6 years and FEV1 66±22% predicted value) and 18 healthy controls (age 13.8±1.8 years) participated in this study. Similar FVC reduction was found in CF children and healthy controls. FVC was lower in UB when compared to NB (68.5±23.3% vs 72.1±24.3%, p=0.024) in CF group. CF children underwent a greater diminution on FEV1 (-6.5±4.3% vs -2.4±3.6%, p=0.017) and maximal inspiratory pressure (-12.5±16 vs -6±11.8cmH2O, p=0,048) with UB compared to their healthy peers. Walking with UB induced greater oxygen consumption, respiratory rate and minute ventilation in CF group than in control group. Conclusion: Unilateral backpack carrying leads to greater change on lung function parameters and ventilatory response in CF children than in healthy children. This position may be discouraged for CF school-aged children.

Arthropod-borne virus (arbovirus) infections cause several emerging and resurgent infectious diseases in humans and animals. Chikungunya-affected areas often overlap with dengue-endemic areas. Concurrent dengue virus (DENV) and chikungunya virus (CHIKV) infections have been detected in travelers returning from regions of endemicity. CHIKV and DENV co-infected Aedes albopictus have also been collected in the vicinity of co-infected human cases, emphasizing the need to study co-infections in mosquitoes. We thus aimed to study the pathogen-pathogen interaction involved in these co-infections in DENV/CHIKV co-infected Aedes aegypti mosquitoes. In mono-infections, we detected CHIKV antigens as early as 4 days post-virus exposure in both the midgut (MG) and salivary gland (SG), whereas we detected DENV serotype 2 (DENV-2) antigens from day 5 post-virus exposure in MG and day 10 post-virus exposure in SG. Identical infection rates were observed for singly and co-infected mosquitoes, and facilitation of the replication of both viruses at various times post-viral exposure. We observed a higher replication for DENV-2 in SG of co-infected mosquitoes. We showed that mixed CHIKV and DENV infection facilitated viral replication in Ae. aegypti. The outcome of these mixed infections must be further studied to increase our understanding of pathogen-pathogen interactions in host cells.

Background and Purpose Fast, safe and stable endovascular access is crucial for mechanical thrombectomy in acute ischemic stroke. We investigated the feasability of a MRI based anatomic and geometric characterization of aortic arch and supra-aortic vessels and correlated these findings with time metrics to access the clot in patients treated for a large intracranial vessel occlusion. Methods Patients with MRA as a part of the diagnostic imaging in the settings of an acute ischemic stroke by middle cerebral artery occlusion were included. Level Set segmentation of DICOM MRI Datasets was used to create 3D geometric model (surface mesh and centerlines) and automatic analysis of parameters known to affect the endovascular access to intracranial vasculature: Aortic arch Classification; length of carotid arteries from ostium to intracranial carotid termination, tortuosity indexes, angle of take off of left common carotid artery and brachiocephalic trunk (BCT) from aortic arch (AA) and number of changes of direction along the path of the vessel (reverse curves). Those parameters were correlated with time from femoral puncture to clot contact. Results Analyses were performed in 27 patients. Aortic arch type were I: 17 patients, II: 5 patients and III: 5 patients. Mean length of carotid arteries from ostium to intracranial carotid termination was 285 mm for left side and 299 mm for right side (Including BCT). Mean tortuosity indexes were 1.32 on the left and 1.36 on the right side, mean take off angles of arteries from AA were 109 for the left and 123 for BCT, number of reverse curves were found 12/27 on left side and 15/27 on right side. Length of procedures was impacted by aortic arch type. Conclusion MRI based morphometric characterization of factors affecting endovascular access to the intracranial circulation is feasible in the settings of acute ischemic stroke imaging and could be helpful for interventional procedures or future developments of vascular access devices. Disclosures R. Blanc: None. G. Ciccio: None. S. Smajda: None. H. Redjem: None. J. Desilles: None. R. Fahed: None. M. Mazighi: None. P. Roux: None. M. Piotin: None.

Introduction Venous access is being increasingly used for the endovascular treatment of many cerebrovascular diseases (Intracranial hypertension, dural cavernous fistulas, Arteriovenous malformations). Venous roadmapping through arterial injection can be problematic because of contrast media dilution and slow flow velocity leading to moderate quality of veins visualization or necessity to repeat injections. Live 3D roadmapping is an image-processing technique which allows dynamic vessels roadmapping which immediately adapts to the C-arm movements without the need for any contrast medium injection. This technique involves the coregistration of a previously obtained magnetic resonance angiography with live fluoroscopy in order to create a combined roadmap of the vessels. Objective To report our preliminary experience with Vessel navigator (Philips, Best, the Netherlands) for guidance of endovascular venous procedures at the intracranial level.Results After semi automatic coregistration, live 3D roadmapping of the 3D MR venography overlaid on the live fluoroscopy images was used for cases of Venous pressure measurement, intracranial venous stenting and arteriovenous dural malformations endovascular treatments. Conclusion Our preliminary experience suggests that it is a feasible and safe technique for venous navigation and performance of and for intracranial venous procedures from the jugular vein to the intracranial sinuses. The accuracy of the coregistration is satisfactory. The potential to lower overall radiation dose and contrast medium use needs to be verified with further studies. Disclosures R. Blanc: None. R. Fahed: None. S. Smajda: None. H. Redjem: None. J. Desilles: None. P. Roux: None. M. Mazighi: None. G. Ciccio: None. M. Piotin: None.

Background Microglial cells are tissue-resident macrophages of the central nervous system. They are extremely dynamic, sensitive to their microenvironment and present a characteristic complex and heterogeneous morphology and distribution within the brain tissue. Many experimental clues highlight a strong link between their morphology and their function in response to aggression. However, due to their complex “dendritic-like” aspect that constitutes the major pool of murine microglial cells and their dense network, precise and powerful morphological studies are not easy to realize and complicate correlation with molecular or clinical parameters. Methods Using the knock-in mouse model CX3CR1GFP/+, we developed a 3D automated confocal tissue imaging system coupled with morphological modelling of many thousands of microglial cells revealing precise and quantitative assessment of major cell features: cell density, cell body area, cytoplasm area and number of primary, secondary and tertiary processes. We determined two morphological criteria that are the complexity index (CI) and the covered environment area (CEA) allowing an innovative approach lying in (i) an accurate and objective study of morphological changes in healthy or pathological condition, (ii) an in situ mapping of the microglial distribution in different neuroanatomical regions and (iii) a study of the clustering of numerous cells, allowing us to discriminate different sub-populations. Results Our results on more than 20,000 cells by condition confirm at baseline a regional heterogeneity of the microglial distribution and phenotype that persists after induction of neuroinflammation by systemic injection of lipopolysaccharide (LPS). Using clustering analysis, we highlight that, at resting state, microglial cells are distributed in four microglial sub-populations defined by their CI and CEA with a regional pattern and a specific behaviour after challenge. Conclusions Our results counteract the classical view of a homogenous regional resting state of the microglial cells within the brain. Microglial cells are distributed in different defined sub-populations that present specific behaviour after pathological challenge, allowing postulating for a cellular and functional specialization. Moreover, this new experimental approach will provide a support not only to neuropathological diagnosis but also to study microglial function in various disease models while reducing the number of animals needed to approach the international ethical statements. Electronic supplementary material The online version of this article (doi:10.1186/s12974-016-0614-7) contains supplementary material, which is available to authorized users.

Summary The extracellular matrix (ECM) and its role in the outcome of infectious diseases have been poorly investigated. In this study, we determined the impact of the collagen fibres architecture on the invasive process of the enteric parasite Entam- oeba histolytica. The behaviour of E. histolytica wild-type and silenced for the cysteine protease A5 (CP-A5) were compared on a three-dimensional collagen matrix and within human colon fragments for fibrillar collagen cleavage and migration. The interstitial collagen fibres within the connective tissue of the human colon, visualized by multipho- ton and second harmonic generation signals imaging, presented a dense scaffold at the subepi- thelial level and a loose meshwork within the chorion. To penetrate the tissue, E. histolytica migrated on the dense scaffold that remained intact, reached the crypt of Lieberkhun, migrated along and then disorganized the loose scaffold to escape into the mucosa. Interestingly, in vitro, CP-A5 was not required for collagenase activity and migration through the matrix but was neces- sary within the tissue environment for collagen meshwork remodelling and subsequent invasion. The data point out that further step of invasion relay with ECM destruction that requires human components induced or activated in the presence of CP-A5.

Mice are exquisitely sensitive to infection with encapsulated B. anthracis strains, even in the absence of toxins. Bioluminescence imaging shows that the lungs are the terminals targets before death, whatever the route of infection: cutaneous, inhalational or digestive. In this study, we addressed the pathophysiological mechanisms of this phenomenon during a cutaneous infection in the absence of toxins. Ultrastructural analysis before the appearance of any clinical signs shows a high density of encapsulated bacteria colonizing the alveolar capillary network. Histological analysis when clinical signs were patent, just before death, showed lung tissue damage, with bacteria localized in alveolar capillaries and spaces along alveolar cells. Bronchiolar epithelium injury and intra-alveolar hemorrhages were also observed. Using functional approaches, we detected hypoxia of blood vessel endothelial cells in the lung, and multifocal hypoxic zones in the brain parenchyma, associated with neurological signs at the time of death. During the bacteriemic phase of infection, we determined that the bacteria circulating in blood presented as chains of circa 13 μm in length with a mean of 4 bacteria per chain. To address the mechanisms of lung colonization, we mimicked this phase of infection by intravenous inoculation of bioluminescent bacteria of a similar chain length; the bacteria were immediately trapped within the lung capillary network. Encapsulated bacteria of shorter length were not sequestered and trapping was decreased in the absence of the capsule surrounding the bacilli. In conclusion, we show that the high pathogenicity of B. anthracis in the absence of toxins is most probably linked to physical sequestration of blood-circulating encapsulated bacilli of a given length. Clearly, in the case of anthrax, the toxins produced by the trapped encapsulated B. anthracis will add locally their deleterious effects. Controlling the lung-targeted pathology would be beneficial for the prognosis of anthrax infection.

Introduction La sclerose en plaque est une maladie inflammatoire du systeme nerveux central, caracterisee par la presence de plaques de demyelinisation. L’exploration de l’atteinte medullaire, habituellement etudiee en ponderation T2, est difficile compte tenu de la petite taille de cette structure et de nombreux artefacts. De nouvelles sequences (STIR, DIR, PSIR, MPRAGE) [1] , [2] , [3] , [4] , [5] ont montre une meilleure sensibilite de detection des lesions, dans de petites series. L’objectif de notre etude etait de comparer les performances de detection de la sequence 3D PSIR par rapport a une sequence T2. Materiel et methode Cette etude retrospective monocentrique approuvee par un comite d’ethique local a inclus 100 patients ayant beneficie d’une IRM medullaire avec des sequences T2 et 3D PSIR. Deux lecteurs (senior et junior) ont analyse les sequences en insu des informations cliniques, selon un ordre independant, aleatoire, avec lecture en consensus si discordance. Le critere de jugement principal portait sur la detection et la quantification du nombre de lesions medullaires, les criteres secondaires sur la mesure du degre de certitude et la concordance interobservateur. Les tests statistiques non parametriques de Wilcoxon et le kappa de Cohen ont ete utilises. Resultats Cent patients ont ete inclus (âge median = 41, sex-ratio = 3F/2 M). La sequence 3D PSIR etait fortement plus sensible que le sagittal T2 seul (480 plaques visualisees versus 168 respectivement, p = 6 10–13). Treize patients sans plaque decelable en T2 avaient au moins une plaque visible en 3D PSIR. Le degre de confiance etait nettement superieur avec le 3D PSIR (2,56 contre 2,21), p = 3,10–11. La concordance interobservateurs etait bonne (kappa = 0,7). Conclusion La sensibilite de detection de lesions medullaires etait significativement meilleure avec une sequence 3D PSIR comparativement a une sequence sagittale T2.

The fungal pathogen Candida albicans forms therapeutically challenging biofilms on biomedical implants. Using a transcript profiling approach genes whose expression is favoured upon biofilm growth compared with planktonic growth have been previously identified. Knock-out mutants for 38 of these genes were constructed, six of which showed a specific defect in biofilm formation. Among these genes, TYE7 that encodes a transcriptional activator of glycolytic genes in planktonic and biofilm growth conditions was identified as being required for the cohesiveness of biofilms. Biofilms formed by the tye7Δ knock-out mutant showed a hyperfilamentous morphology, and growth of this mutant on solid medium under hypoxia was also associated with the production of hyphae. Similar to TYE7 inactivation, inhibition of glycolysis or ATP synthesis using oxalate or an uncoupler, respectively, triggered morphogenesis when a wild-type strain was grown under hypoxia. These treatments also induced the formation of weakly cohesive, hyper-filamentous biofilms by a wild-type strain. Our data indicate that a hypoxic environment is generated within C. albicans biofilms and that continued biofilm development requires a Tye7p-dependent upregulation of glycolytic genes necessary to adapt to hypoxia and prevent uncontrolled hyphal formation. Thus, adaptation to hypoxia is an integral component of biofilm formation in C. albicans.

Objective To characterise recurrence of multiple sclerosis (MS) inflammatory activity during the year following natalizumab (NTZ) cessation. Methods Thirty-two patients with MS were included in a monocentric cohort study. Data were collected prospectively during and after NTZ, with serial clinical and MRI evaluations. The first relapse occurring after interrupting NTZ was the primary outcome measure. The numbers of gadolinium-enhancing lesions before, during and after NTZ treatment, were compared. Results During the year following NTZ cessation, the cumulative probability of relapses was estimated at 52.9% and an unusually high MRI inflammation was noticed. It was defined by a number of gadolinium-enhancing lesions >5 and exceeding the gadolinium lesions existing before NTZ initiation. Rebound of MS activity after NTZ cessation was characterised by association of relapses and unusual MRI inflammation. Cumulative probability of rebound was estimated at 39% and mostly occurring between 3 months and 9 months after interrupting NTZ. Risk of rebound appears related with a higher annualised relapse rate and a lower Expanded Disability Status Scale score before NTZ initiation. Rebound was associated with severe recurring relapses in 9% of the patients. Conclusions This study identifies rebound after NTZ cessation as an association of relapses and high MRI activity.

Background Backpack carrying impacts lung function in healthy children but the effect in children with cystic fibrosis (CF) is unknown. Methods Three backpack positions were tested: no backpack (NB), a 12.5% body-weight backpack carried bilaterally (BB) or unilaterally (UB), at rest and during a 10 minute walk. Primary outcome was forced vital capacity (FVC). Secondary outcomes included comparison of cardio-respiratory variables within and between groups. Results Nine children with CF (13.3±2.6 years; FEV1 66±22%) and 18 healthy children (13.8±1.8 years; FEV1 107±30%) were included. FVC was reduced with UB compared to NB (68.5±23.3% vs 72.1±24.3%, p = 0.024) in children with CF. FEV1, MIP and MEP decreased more with UB in children with CF than in healthy peers. Increases in VO2, VCO2 and minute ventilation with UB were greater in the CF group during walking. Conclusions Unilateral backpack wearing affects FVC in children with CF and requires greater cardio-respiratory adjustments compared to healthy peers.

International audience; After cell entry, HIV undergoes rapid transport toward the nucleus using microtubules and microfilaments. Neither the cellular cytoplasmic components nor the viral proteins that interact to mediate transport have yet been identified. Using a yeast two-hybrid screen, we identified four cytoskeletal components as putative interaction partners for HIV-1 p24 capsid protein: MAP1A, MAP1S, CKAP1, and WIRE. Depletion of MAP1A/MAP1S in indicator cell lines and primary human macrophages led to a profound reduction in HIV-1 infectivity as a result of impaired retrograde trafficking, demonstrated by a characteristic accumulation of capsids away from the nuclear membrane, and an overall defect in nuclear import. MAP1A/MAP1S did not impact microtubule network integrity or cell morphology but contributed to microtubule stabilization, which was shown previously to facilitate infection. In addition, we found that MAP1 proteins interact with HIV-1 cores both in vitro and in infected cells and that interaction involves MAP1 light chain LC2. Depletion of MAP1 proteins reduced the association of HIV-1 capsids with both dynamic and stable microtubules, suggesting that MAP1 proteins help tether incoming viral capsids to the microtubular network, thus promoting cytoplasmic trafficking. This work shows for the first time that following entry into target cells, HIV-1 interacts with the cytoskeleton via its p24 capsid protein. Moreover, our results support a role for MAP1 proteins in promoting efficient retrograde trafficking of HIV-1 by stimulating the formation of stable microtubules and mediating the association of HIV-1 cores with microtubules.

The flavivirus nonstructural protein NS1 is expressed as three discrete species in infected mammalian cells: an intracellular, membrane-associated form essential for viral replication, a cell surface-associated form that may be involved in signal transduction, and a secreted form (sNS1), the biological properties of which remain elusive. To determine the distribution of the dengue virus (DEN) sNS1 protein in vivo, we have analyzed by immunohistological means the tissue tropism of purified DEN sNS1 injected intravenously into adult mice. The sNS1 protein was found predominantly associated with the liver, where hepatocytes appeared to represent a major target cell. We further showed that sNS1 could be efficiently endocytosed by human Huh7 and HepG2 hepatocytes in vitro. After its internalization, the protein was detected intracellularly for at least 48 h without being substantially degraded. Colocalization studies of sNS1 with markers of the endolysosomal compartments revealed that the protein was specifically targeted to lysobisphosphatidic acid-rich structures reminiscent of late endosomes, as confirmed by electron microscopy. Intracellular accumulation of sNS1 in Huh7 cells enhanced the fluid phase uptake of rhodamine-labeled dextran. Furthermore, preincubation of Huh7 cells with sNS1 increased dengue virus production after infection with the homologous strain of DEN-1 virus. Our results demonstrate that the accumulation of DEN sNS1 in the late endosomal compartment of hepatocytes potentializes subsequent dengue virus infection in vitro, raising the possibility that sNS1 may contribute to viral propagation in vivo.

The protozoan parasite Entamoeba histolytica colonizes the human large bowel. Invasion of the intestinal epithelium causes amoebic colitis and opens the route for amoebic liver abscesses. The parasite relies on its dynamic actomyosin cytoskeleton and on surface adhesion molecules for dissemination in the human tissues. Here we show that the galactose/ N -acetylgalactosamine (Gal/GalNAc) lectin clusters in focal structures localized in the region of E. histolytica that contacts monolayers of enterocytes. Disruption of myosin II activity impairs the formation of these structures and renders the trophozoites avirulent for liver abscess development. Production of the cytoplasmic domain of the E. histolytica Gal/GalNAc lectin in engineered trophozoites causes reduced adhesion to enterocytes. Intraportal delivery of these parasites to the liver leads to the formation of a large number of small abscesses with disorganized morphology that are localized in the vicinity of blood vessels. The data support a model for invasion in which parasite motility is essential for establishment of infectious foci, while the adhesion to host cells modulates the distribution of trophozoites in the liver and their capacity to migrate in the hepatic tissue.