Search

Abstract Background Several randomized clinical trials have shown that non-invasive ventilation (NIV) applied immediately after extubation may prevent reintubation in patients at high-risk of extubation failure. However, most of studies included patients with chronic respiratory disorders as well as patients without underlying respiratory disease. To date, no study has shown decreased risk of reintubation with prophylactic NIV after extubation among patients with chronic obstructive pulmonary disease (COPD). We hypothesized that prophylactic NIV after extubation may decrease the risk of reintubation in COPD patients as compared with high-flow nasal oxygen. We performed a post hoc subgroup analysis of COPD patients included in a multicenter, randomized, controlled trial comparing prophylactic use of NIV alternating with high-flow nasal oxygen versus high-flow nasal oxygen alone immediately after extubation. Results Among the 651 patients included in the original study, 150 (23%) had underlying COPD including 86 patients treated with NIV alternating with high-flow nasal oxygen and 64 patients treated with high-flow nasal oxygen alone. The reintubation rate was 13% (11 out of 86 patients) with NIV and 27% (17 out of 64 patients) with high-flow nasal oxygen alone [difference, − 14% (95% CI − 27% to − 1%); p = 0.03]. Whereas reintubation rates were significantly lower with NIV than with high-flow nasal oxygen alone at 72 h and until ICU discharge, mortality in ICU did not differ between groups: 6% (5/86) with NIV vs. 9% (6/64) with high-flow nasal oxygen alone [difference − 4% (95% CI − 14% to 5%); p = 0.40]. Conclusions In COPD patients, prophylactic NIV alternating with high-flow nasal oxygen significantly decreased the risk of reintubation compared with high-flow nasal oxygen alone. Trial registration The study was registered at http://www.clinicaltrials.gov with the trial registration number NCT03121482 (20 April 2017)

Dengue virus (DENV) evolutionary dynamics are characterized by frequent DENV genotype/lineage replacements, potentially associated with changes in disease severity and human immunity. New Caledonia (NC) and Cambodia, two contrasted epidemiological settings, respectively experienced a DENV-1 genotype IV to I replacement in 2012 and a DENV-1 genotype I lineage 3–4 replacement in 2005–2007, both followed by a massive dengue outbreak. However, their underlying evolutionary drivers have not been elucidated. Here, we tested the hypothesis that these genotype/lineage switches reflected a higher transmission fitness of the replacing DENV genotype/lineage in the mosquito vector using in vivo competition experiments. For this purpose, field-derived Aedes aegypti from NC and Cambodia were orally challenged with epidemiologically relevant pairs of four DENV-1 genotype I and IV strains from NC or four DENV-1 genotype I lineage 3 and 4 strains from Cambodia, respectively. The relative transmission fitness of each DENV-1 genotype/lineage was measured by quantitative RT–PCR for infection, dissemination, and transmission rates. Results showed a clear transmission fitness advantage of the replacing DENV-1 genotype I from NC within the vector. A similar but more subtle pattern was observed for the DENV-1 lineage 4 replacement in Cambodia. Our results support the hypothesis that vector-driven selection contributed to the DENV-1 genotype/lineage replacements in these two contrasted epidemiological settings, and reinforce the idea that natural selection taking place within the mosquito vector plays an important role in DENV short-term evolutionary dynamics.

Abstract Background Although COPD patients are at higher risk for aspiration when breathing spontaneously, no information is available on the risk for microaspiration in invasively ventilated COPD patients. The aim of our study was to determine the relationship between COPD and abundant microaspiration in intubated critically ill patients. Methods This was a retrospective analysis of prospectively collected data, provided by 3 randomized controlled trials on microaspiration in critically ill patients receiving invasive mechanical ventilation for more than 48 h. Abundant microaspiration was defined as the presence of pepsin and or alpha-amylase at significant levels in tracheal aspirates. In all study patients, pepsin and alpha-amylase were quantitatively measured in all tracheal aspirates collected during a 48-h period. COPD was defined using spirometry criteria. Results Among the 515 included patients, 70 (14%) had proven COPD. Pepsin and alpha-amylase were quantitatively measured in 3873 and 3764 tracheal aspirates, respectively. No significant difference was found in abundant microaspiration rate between COPD and non-COPD patients (62 of 70 patients (89%) vs 366 of 445 (82%) patients, p = 0.25). Similarly, no significant difference was found in abundant microaspiration of gastric contents (53% vs 45%, p = 0.28), oropharyngeal secretions (71% vs 71%, p = 0.99), or VAP (19% vs 22%, p = 0.65) rates between the two groups. No significant difference was found between COPD and non-COPD patients in duration of mechanical ventilation, ICU length of stay, or ICU mortality. Conclusions Our results suggest that COPD is not associated with increased risk for abundant microaspiration in intubated critically ill patients.

Abstract Background Delayed intubation is associated with high mortality. There is a lack of objective criteria to decide the time of intubation. We assessed a recently described combined oxygenation index (ROX index) to predict intubation in immunocompromised patients. The study is a secondary analysis of randomized trials in immunocompromised patients, including all patients who received high-flow nasal cannula (HFNC). The first objective was to evaluate the accuracy of the ROX index to predict intubation for patients with acute respiratory failure. Results In the study, 302 patients received HFNC. Acute respiratory failure was mostly related to pneumonia (n = 150, 49.7%). Within 2 (1–3) days, 115 (38.1%) patients were intubated. The ICU mortality rate was 27.4% (n = 83). At 6 h, the ROX index was lower for patients who needed intubation compared with those who did not [4.79 (3.69–7.01) vs. 6.10 (4.48–8.68), p

Apelin and AVP have opposing effects water balance in humans and rodents. Here, the authors report that a metabolically stable apelin-17 analog, by acting at the kidney level, reduces AVP-induced antidiuresis and improves hyponatremia in rodents, demonstrating a potential approach for treating water metabolism disorders.

Abstract Background Oxytocin is effective in reducing labor duration, but can be associated with fetal and maternal complications such as neonatal acidosis and post-partum hemorrhage. When comparing discontinuing oxytocin in the active phase with continuing oxytocin infusion, previous studies were underpowered to show a reduction in neonatal morbidity. Thus, we aim at evaluating the impact of discontinuing oxytocin during the active phase of the first stage of labor on the neonatal morbidity rate. Methods STOPOXY is a multicenter, randomized, open-label, controlled trial conducted in 20 maternity units in France. The first participant was recruited January 17th 2020. The trial includes women with a live term (≥37 weeks) singleton, in cephalic presentation, receiving oxytocin before 4 cm, after an induced or spontaneous labor. Women aged 10 mmol/L and/or umbilical arterial lactates> 7 mmol/L and/or a 5 min Apgar score

Background/Aims Abnormal psychological profiles are frequently found in patients with functional gastrointestinal disorders (FGIDs). The present study aimed to evaluate the psychological profiles of FGID patients with irritable bowel syndrome (IBS), and IBS phenotypes. Methods In 608 FGID patients, including 235 with IBS, have filled a Rome III questionnaire and the French version of the Minnesota Multiphasic Personality Inventory 2. Data analysis was performed using univariate analysis and multivariate logistic regression. Results This study shows that IBS patients have abnormal psychological profiles with more significant symptom exaggeration and decreased test defensiveness than non-IBS patients. They have a significantly higher score for all clinical scales. Logistic regression analysis showed in IBS patients a decrease of body mass index (P= 0.002), and test defensiveness score K (P= 0.001) and an increase of Hypochondriasis (P< 0.001) and Masculinity-Femininity scale (P= 0.018). By comparison with non-IBS patients, IBS-constipation, IBS-diarrhea, and mixed IBS patients have increased Hypochondriasis value and Depression score, mixed IBS patients have higher Psychasthenia score and higher Hypomania score. No item was significantly different in the IBS-unspecified group. Conclusions This study shows that IBS patients have different psychological profiles than other FGID patients and that psychological characteristics are associated with IBS phenotypes except for patients with unsubtyped IBS.

Striatal dopaminoceptive neurons are molecularly and functionally heterogeneous. Here, the authors provide the translatome of D2R striatal neurons and identified hundreds of region specific molecular markers as well as testing their resource to shed light into function.

Climate change is a global challenge that also for glacier tourism. In the European Alps, glacial volume has decreased to one half since the end of the Little Ice Age. To confront with this evolution, local stakeholders are slowing adapting diversification on their tourism products and services. One of these adaptations concerns highlighting the scientific value of the glacier landscapes. Several Glacier Interpretation Centres (GIC) have been developed with the dual aim of spreading scientific knowledge and promoting glacier tourism destinations. Based on a qualitative approach and built in a historical and geographical perspective, this article aims to examine the territorial dynamics and the interaction of stakeholders which led to the creation of three of these centres: the Espace Glacialis (Champagny-le-Haut, France), the Glaciorium (Chamonix, France) and the World Nature Forum (Naters, Switzerland). Through a comparative analysis of these three GICs, the objective is to understand how the valorization of scientific knowledge contributes to the diversification of tourism in mountain areas. Although glacier tourism destinations are profoundly affected by climate change, the results show that local authorities have a strong will to continue to promote their glacier heritages through the creation and management of GICs, these centres undeniably contribute to the diversification of the tourism market and to the dynamisation of the tourism activity in their territories by relying on scientific knowledge and its mediation.

Climate change is a global challenge that also for glacier tourism. In the European Alps, glacial volume has decreased to one half since the end of the Little Ice Age. To confront with this evolution, local stakeholders are slowing adapting diversification on their tourism products and services. One of these adaptations concerns highlighting the scientific value of the glacier landscapes. Several Glacier Interpretation Centres (GIC) have been developed with the dual aim of spreading scientific knowledge and promoting glacier tourism destinations. Based on a qualitative approach and built in a historical and geographical perspective, this article aims to examine the territorial dynamics and the interaction of stakeholders which led to the creation of three of these centres: the Espace Glacialis (Champagny-le-Haut, France), the Glaciorium (Chamonix, France) and the World Nature Forum (Naters, Switzerland). Through a comparative analysis of these three GICs, the objective is to understand how the valorization of scientific knowledge contributes to the diversification of tourism in mountain areas. Although glacier tourism destinations are profoundly affected by climate change, the results show that local authorities have a strong will to continue to promote their glacier heritages through the creation and management of GICs, these centres undeniably contribute to the diversification of the tourism market and to the dynamisation of the tourism activity in their territories by relying on scientific knowledge and its mediation.

The rise of novel materials such as graphene compounds or carbon nanotubes recently revived the interest on the role of symmetries upon electrical properties. Among possible solids, symmetrical polytopes, widely realized in natural and artificial matter, deserve particular attention. When equal resistors are attached between neighbouring nodes of Perfect (Platonic) solids (PS) along the edges, the two-point resistance between any pair of nodes was established in the 1990s by van Steenwijk using an elegant and efficient method. Using van Steenwijk’s method, Moddy and Aravind subsequently derived the resistance values for two Archimedean and two Catalan solids. Here, with the same method, we derive the exact expression for the two-point resistance between any two nodes for resistor networks made of equal resistors placed along the edges of the thirteen Archimedean solids (AS). While the calculation remains elementary for the simplest AS, a dedicated method using computer assistance was developed for the Snub Cube, the Snub Dodecahedron and the three AS with three different rotation symmetries (the Great Rhombicuboctahedron, the Small Rhombicosidodecahedron and the Great Rhombicosidodecahedron). The largest resistance value (191/90) is obtained between the two opposite nodes of the Truncated Dodecahedron, and the second largest (42815/21114) is obtained between the two opposite nodes of the Great Rhombicosidodecahedron. The smallest resistance value (14137/38016) is obtained between some of the neighbouring nodes of the Snub Cube, whereas the resistance between neighbouring nodes of the Icosahedron (11/30) is slightly smaller. Some general symmetry relations between two-point resistances in AS networks are also derived, as well as some relations with two-point resistances in PS networks. The complete set of exact two-point resistance values for PS and AS networks can be used to check numerical codes or to evaluate the capacity of regular solids to provide appropriate models for given experimental situations.

Host proteins sense viral products and induce defence mechanisms, particularly in immune cells. Using cell-free assays and quantitative mass spectrometry, we determined the interactome of capsid-host protein complexes of herpes simplex virus and identified the large dynamin-like GTPase myxovirus resistance protein B (MxB) as an interferon-inducible protein interacting with capsids. Electron microscopy analyses showed that cytosols containing MxB had the remarkable capability to disassemble the icosahedral capsids of herpes simplex viruses and varicella zoster virus into flat sheets of connected triangular faces. In contrast, capsids remained intact in cytosols with MxB mutants unable to hydrolyse GTP or to dimerize. Our data suggest that MxB senses herpesviral capsids, mediates their disassembly, and thereby restricts the efficiency of nuclear targeting of incoming capsids and/or the assembly of progeny capsids. The resulting premature release of viral genomes from capsids may enhance the activation of DNA sensors, and thereby amplify the innate immune responses.

Abstract Higher education in evolutionary anthropology involves providing students with in‐depth knowledge of biological and cultural heritage sites and collections that are frequently inaccessible. Indeed, most sites, fossils, and archaeological remains can be visited or manipulated only rarely and solely by specialists with extensive experience. Owing to the development of 3D and medical imaging techniques, this fragile heritage is now more widely accessible, and in a dynamic way. However, exclusive adoption of virtual teaching and learning has a negative impact on student engagement and, naturally, on exchanges with instructors, and thus cannot be used without some reservations. In the ITAP (Immersion dans les Terrains de l’Anthropologie biologique et de la Préhistoire) project of the higher education STEP (Soutien à la Transformation et à l’Expérimentation Pédagogiques) transformation program at the University of Bordeaux, we combine student‐active teaching with Master's students fully immersed in ongoing fieldwork, laboratory study, and dissemination of research results in order to develop more individually shaped learning curricula and to foster both professional and new interdisciplinary skills. Here, we present examples of experiments conducted in the ITAP project using both authentic and virtual collections of archaeological, experimental, and reference materials that help to break down the barriers between research activities and higher education, as well as providing a more general appraisal of the appropriate use of virtual tools in higher education by combining them with real‐life situations.

Abstract Macrophage infiltration in mammary tumors is associated with enhanced tumor progression, metastasis, and poor clinical outcome, and considered as target for therapeutic intervention. By using different genetic mouse models, the authors show that ablation of the tyrosine kinase PYK2, either in breast cancer cells, only in the tumor microenvironment, or in both, markedly reduces the number of infiltrating tumor macrophages and concomitantly inhibits tumor angiogenesis and tumor growth. Strikingly, PYK2 ablation only in macrophages is sufficient to induce similar effects. These phenotypic changes are associated with reduced monocyte recruitment and a substantial decrease in tumor‐associated macrophages (TAMs). Mechanistically, the authors show that PYK2 mediates mutual communication between breast cancer cells and macrophages through critical effects on key receptor signaling. Specifically, PYK2 ablation inhibits Notch1 signaling and consequently reduces CCL2 secretion by breast cancer cells, and concurrently reduces the levels of CCR2, CXCR4, IL‐4Rα, and Stat6 activation in macrophages. These bidirectional effects modulate monocyte recruitment, macrophage polarization, and tumor angiogenesis. The expression of PYK2 is correlated with infiltrated macrophages in breast cancer patients, and its effects on macrophage infiltration and pro‐tumorigenic phenotype suggest that PYK2 targeting can be utilized as an effective strategy to modulate TAMs and possibly sensitize breast cancer to immunotherapy.

Diffusion Tensor Imaging (DTI) is a non-invasive neuroimaging method that has become the most widely employed MRI modality for investigations of white matter fiber pathways. DTI has proven especially valuable for improving our understanding of normative white matter maturation across the life span and has also been used to index clinical pathology and cognitive function. Despite its increasing popularity, especially in pediatric research, the majority of existing studies examining infant white matter maturation depend on regional or white matter skeleton-based approaches. These methods generally lack the sensitivity and spatial specificity of more advanced functional analysis options that provide information about microstructural properties of white matter along fiber bundles. DTI studies of early postnatal brain development show that profound microstructural and maturational changes take place during the first two years of life. The pattern and rate of these changes vary greatly throughout the brain during this time compared to the rest of the life span. For this reason, appropriate image processing of infant MR imaging requires the use of age-specific reference atlases. This article provides an overview of the pre-processing, atlas building, and the fiber tractography procedures used to generate two atlas resources, one for neonates and one for 1- to 2-year-old populations. Via the UNC-NAMIC DTI Fiber Analysis Framework, our pediatric atlases provide the computational templates necessary for the fully automatic analysis of infant DTI data. To the best of our knowledge, these atlases are the first comprehensive population diffusion fiber atlases in early pediatric ages that are publicly available.