Services déconcentrés d'appui à la recherche Nouvelle-Aquitaine-Bordeaux

Abstract Metabolomics plays a pivotal role in systems biology, and NMR is a central tool with high precision and exceptional resolution of chemical information. Most NMR metabolomic studies are based on 1H 1D spectroscopy, severely limited by peak overlap. 13C NMR benefits from a larger signal dispersion but is barely used in metabolomics due to ca. 6000-fold lower sensitivity. We introduce a new approach, based on hyperpolarized 13C NMR at natural abundance, that circumvents this limitation. A new untargeted NMR-based metabolomic workflow based on dissolution dynamic nuclear polarization (d-DNP) for the first time enabled hyperpolarized natural abundance 13C metabolomics. Statistical analysis of resulting hyperpolarized 13C data distinguishes two groups of plant (tomato) extracts and highlights biomarkers, in full agreement with previous results on the same biological model. We also optimize parameters of the semiautomated d-DNP system suitable for high-throughput studies.

Abstract. Canopy structure is one of the most important vegetation characteristics for land–atmosphere interactions, as it determines the energy and scalar exchanges between the land surface and the overlying air mass. In this study we evaluated the performance of a newly developed multi-layer energy budget in the ORCHIDEE-CAN v1.0 land surface model (Organising Carbon and Hydrology In Dynamic Ecosystems – CANopy), which simulates canopy structure and can be coupled to an atmospheric model using an implicit coupling procedure. We aim to provide a set of acceptable parameter values for a range of forest types. Top-canopy and sub-canopy flux observations from eight sites were collected in order to conduct this evaluation. The sites crossed climate zones from temperate to boreal and the vegetation types included deciduous, evergreen broad-leaved and evergreen needle-leaved forest with a maximum leaf area index (LAI; all-sided) ranging from 3.5 to 7.0. The parametrization approach proposed in this study was based on three selected physical processes – namely the diffusion, advection, and turbulent mixing within the canopy. Short-term sub-canopy observations and long-term surface fluxes were used to calibrate the parameters in the sub-canopy radiation, turbulence, and resistance modules with an automatic tuning process. The multi-layer model was found to capture the dynamics of sub-canopy turbulence, temperature, and energy fluxes. The performance of the new multi-layer model was further compared against the existing single-layer model. Although the multi-layer model simulation results showed few or no improvements to both the nighttime energy balance and energy partitioning during winter compared with a single-layer model simulation, the increased model complexity does provide a more detailed description of the canopy micrometeorology of various forest types. The multi-layer model links to potential future environmental and ecological studies such as the assessment of in-canopy species vulnerability to climate change, the climate effects of disturbance intensities and frequencies, and the consequences of biogenic volatile organic compound (BVOC) emissions from the terrestrial ecosystem.

Reducing production of type B trichothecenes by Fusarium graminearum on cereals is necessary to control contamination, prevent yield reduction and protect human and animal health. Thus, an understanding of how trichothecene biosynthesis is induced is essential. The effect of ambient pH on fungal growth, toxin biosynthesis and expression of TRI genes was studied during in vitro liquid culture of F. graminearum on minimal medium. Fungal development stopped at day 3 after a sharp pH drop in the medium. At the same time, induction of TRI gene expression was observed and toxin began accumulating 1 day later. Acidification seems a determinant of induction, as neither the toxin nor the TRI genes were detected when the pH was maintained neutral. Shifting from neutral to acidic pH by mycelium transfer induced TRI gene expression and toxin accumulation. The regulation of toxin production by ambient pH appears to be specific to some TRI genes since TRI5, located in the core FgTRI5 cluster, showed an immediate induction while TRI101, located elsewhere in the genome, showed a more progressive response. The regulation of trichothecene biosynthesis by the ambient pH appears to be a general mechanism, independent of strain or chemotype, as all tested strains, including F. graminearum and F. culmorum species, showed a regulation of toxin production in response to the ambient pH. We conclude that, in vitro, external acidification is required for induction of TRI gene expression.

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Skin conditions such as acne, atopic dermatitis, skin toxicity from oncology treatment, and scars are among the most common health conditions and negatively impact quality of life (QoL). Yet the physician perception of this impact often varies greatly from the patient perception. This is important because patient illness perception is closely linked with seeking help and treatment adherence behaviors. The objective of this review is to better understand the impact of these four highly prevalent skin conditions on QoL including their health-related economic factors to improve treatment outcomes. The literature search included literature published on QoL with acne, atopic dermatitis, scars (from any cause) and skin toxicities on PubMed between 2015 and 2020. We found that patients with skin conditions have a much higher frequency of altered QoL and psychological distress than those without. Also, skin conditions negatively impact self-image and can cause feelings of isolation, loneliness, lower self-esteem, and lower body satisfaction. Additionally, physical discomfort adds to the psychological distress. These physical and psychological impacts are an enormous financial burden on patients, their families and society. We found evidence that holistic treatment including treating the skin condition itself, providing wider peer and psychological support as well as shared decision-making, therapeutic patient education and dermatologist involvement improves outcomes. Holistic history-taking, checklists, or the use of more formal QoL scoring tools can be incorporated into routine consultations to better assess patient well-being and provide clinicians with important information for adapting treatment to individual patient requirements. In conclusion, this review highlights the overall impact of skin conditions (including psychological and QoL impacts) and the importance of providing holistic care to optimize treatment outcomes. A comprehensive QoL screening tool would be useful to help provide patient-centered treatment.

Stable aqueous dispersions of fatty acids can now be obtained and yield multiple applications.

OBJECTIVE: To characterize the role of interleukin-1β (IL-1β) and microvascular endothelial cells (MVECs) in the generation of alternatively activated macrophages in the skin, and to explore their role in the development of skin fibrosis in patients with systemic sclerosis (SSc; scleroderma). METHODS: Conditioned medium prepared with MVECs purified from the skin of healthy donors and the skin of SSc patients was used to generate monocyte-derived macrophages. Flow cytometry, multiplex protein assessment, real-time quantitative polymerase chain reaction, and tissue immunofluorescence were used to characterize MVEC-induced polarization of alternatively activated macrophages. Coculture experiments were conducted to assess the role of MVEC-induced alternatively activated macrophages in fibroblast activation. Alternatively activated macrophages were characterized in the skin of healthy donors and SSc patients using multiparametric immunofluorescence and multiplex immunostaining for gene expression. Based on our in vitro data, we defined a supervised macrophage gene signature score to assess correlation between the macrophage score and clinical features in patients with SSc, using the Spearman's test. RESULTS: IL-1β-activated MVECs from SSc patients induced monocytes to differentiate into DC-SIGN+ alternatively activated macrophages producing high levels of CCL18, CCL2, and CXCL8 but low levels of IL-10. DC-SIGN+ alternatively activated macrophages showed significant enhancing effects in promoting the production of proinflammatory fibroblasts and were found to be enriched in perivascular regions of the skin of SSc patients who had a high fibrosis severity score. A novel skin transcriptomic macrophage signature, defined from our in vitro findings, correlated with the extent of skin fibrosis (Spearman's r = 0.6, P = 0.0018) and was associated with early disease manifestations and lung involvement in patients with SSc. CONCLUSION: Our findings shed new light on the vicious circle implicating unabated IL-1β secretion, MVEC activation, and the generation of DC-SIGN+ alternatively activated macrophages in the development of skin fibrosis in patients with SSc.

Decision-making in humans is known to be subject to several biases. For instance, when facing bets, humans demonstrate some asymmetry concerning their preference for the riskiest option depending on whether stakes involve potential gains or potential losses. They are indeed risk-averse for bets involving gains but risk seeking for bets involving losses. They also exhibit a distorted perception of probabilities. It is not clear whether non-human primates exhibit the same biases. Setting up a protocol that allowed two rhesus monkeys to make choices between lotteries involving either gains or losses, we demonstrated that rhesus monkeys facing bets exhibited an asymmetry in the treatment of gains and losses comparable with that of humans.

We aimed to estimate the prevalence of depressive disorder in people living with HIV (PLWH) and evaluate its association with non-HIV-specific and HIV-specific factors in PLWH and in PLWH compared to the general population (GP). We used cross-sectional data from the QuAliV study, conducted within the ANRS-CO3 Aquitaine-AQUIVIH-NA cohort of PLWH in Nouvelle-Aquitaine (2018-2020), and a nationally-representative survey in the GP (EHIS-ESPS, 2014-2015), we included all participants aged ≥ 18 years old who had completed the Patient Health Questionnaire-8 (PHQ-8). Depressive disorder was defined as Patient Health Questionnaire-8 score greater or equal to 10. Its association with non-HIV-specific (demographic, socio-economic, behavioral, health status), HIV-specific factors (immuno-viral markers, antiretrovirals, level of perceived HIV-stigma), and HIV-status was assessed using Poisson regression models with robust variance in women and men separately. We included 914 PLWH (683 men/231 women). More than one in five PLWH had depressive disorder. It was strongly associated with being younger and experiencing severe pain in both sexes. Unemployment in women, being single, and lack of family ties in men were also associated with depressive disorder. More than 30% of our sample reported HIV-stigma, with a dose-response relationship between level of perceived HIV-stigma and depressive disorder. The crude prevalence of depressive disorder was 2.49 (95%CI 1.92-3.22) and 4.20 (95%CI 3.48-5.05) times higher in women and men living with HIV respectively compared to GP counterparts and 1.46 (95%CI 1.09-1.95) and 2.45 (95%CI 1.93-3.09) times higher after adjustment for non-HIV specific factors. The adjusted prevalence ratio of depressive disorder was not significantly different in HIV-stigma free women, but remained twice as high in HIV-stigma free men. The prevalence of depressive disorder compared to the GP tended to decrease with age in PLWH. Excess depressive disorder remains a major concern in PLWH. Our findings reaffirm the importance of regular screening. Tackling social inequalities and HIV-stigma should be prioritized to ensure that PLWH achieve good mental as well as physical health outcomes.

Highly prevalent comorbidities associated with metabolic syndrome, such as abdominal obesity, nonalcoholic fatty liver disease (NAFLD) and insulin-resistance/Type 2 diabetes (IR/T2D) share alterations in gut microbiota composition as a potential triggering factor. Recent studies put the attention in the potential usage of postbiotics (inactivated probiotics) on these metabolic alterations. This review summarizes the current evidence regarding the efficacy of postbiotic administration in both, preclinical and clinical studies, for the management of obesity, NAFLD and IR/T2D. Data from preclinical studies (rodents) suggest that postbiotic administration effectively prevents obesity, whereas clinical studies corroborate these benefits also in overweight/obese subjects receiving inactivated bacteria. As for NAFLD, although preclinical studies indicate that postbiotic administration improves different liver markers, no data obtained in humans have been published so far since all the studies are ongoing clinical trials. Finally, while the administration of inactivated bacteria demonstrated to be a promising approach for the management of IR/T2D in rodents, data from clinical trials indicates that in humans, this approach is more effective on IR than in T2D. In conclusion, the available scientific data indicate that postbiotic administration not only is safer, but also as effective as probiotic administration for the management of obesity associated prevalent metabolic alterations.

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Résumé On examine quelques emplois d’indéfinis à polarité et « free choice » du français dans la perspective de la scalarité. Cette investigation montre que le caractère premier de ces séries lexicales est l’indétermination et l’interchangeabilité des référents. Cependant des inférences pragmatiques peuvent orienter vers la périphérie du domaine et donner lieu à des interprétations d’extrémité d’échelle, souvent dépréciatives. Les FC sont en plus utilisables de façon attributive, indépendamment de leur interprétation quantitative, souvent mais pas exclusivement de façon dépréciative. La valeur sémantique de base reste l’interchangeabilité du référent, sans scalarité.

Marine ecosystems are affected by diverse pressures and consequently may undergo significant changes that can be interpreted as regime shifts. In this study we used integrated trend analysis (ITA) that combines multivariate statistics and methodologies to identify abrupt changes in time-series, in order to test a hypothesis about the occurrence of regime shifts in the Portuguese continental shelf ecosystem (PCSE). We used two types of data describing ecosystem drivers (fishing mortality and environmental/climatic indices) and ecosystem state (observed and modelled biomass and ecosystem indices). Modelled biomass and ecosystem indices were outputs of Ecopath with Ecosim temporal model parametrised for PSCE between 1986 and 2017. The analyses indicated that the regime shifts in the PCSE have occurred during three periods in the last three decades: “early regime” until the mid-1990s, followed by “transition regime” in-between and “late regime” since the mid-2010s. The detected regime shifts are characterised by changes in the pelagic community that became more dominant when compared to the demersal community and shifted from sardine, the main fishing resource, abundant in the “early regime”, to other less valuable pelagic fishes such as chub mackerel that dominated the “late regime”. The “early regime” was characterised by high catch, a larger proportion of demersal species, and higher diversity while, the “late regime” was represented by lower catch, an increase in higher trophic level (TL) predatory fish and lower diversity. Moreover, the “late regime” showed lower resilience and reduced maturity when compared to the “early regime”. Changes described in the ecosystem were probably related to (1) the shift in the north Atlantic environmental conditions that affected small pelagic fish (SPF) and lower TLs groups, (2) reduction in fishing pressure, and (3) internal triggers, related to the indirect trophic interactions that might have benefited higher TL fish and impacted the pelagic community. In the context of PCSE management, this study highlighted a need to consider the possibility of regime shifts in the management process. For example, regime specific harvest rates and environmental reference points should be considered when an indication of abrupt change in the ecosystem exists.

OBJECTIVE: The aim of this study was to compare differences in clinical response, drug survival, and adverse event rates between anakinra and canakinumab in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. METHODS: This multicenter international study includes patients with VEXAS from France, Israel, and Italy treated with interleukin-1 inhibition. Global response (GR) was defined as the absence of inflammatory symptoms and ≥50% decrease in steroid dose and C-reactive protein. Multiple regression analysis was performed to identify associated variables. Drug survival was analyzed using Kaplan-Meier plots and log-rank test, with Cox regression models for associated factors. RESULTS: We included 47 male patients with VEXAS; 44 received anakinra and 9 received canakinumab, with 6 patients using both at different time points. GR at 1 month was 34% for anakinra and 100% for canakinumab (P < 0.001) and 22% and 78% at 3 months, respectively (P = 0.001). Treatment with canakinumab was associated with a higher odds ratio (OR) of achieving GR at 3 months (OR 28.8, 95% confidence interval 3.0-273.9; P = 0.004) in a multivariable analysis. Median drug survival was 54 (interquartile range [IQR] 30-56) months for canakinumab at 300 mg/month compared with 7 (IQR 4-8) months for canakinumab 150 mg/month and 1 (IQR 1-2.5) months for anakinra (P = 0.01). Injection-site reactions were only recorded for the anakinra group (47 vs 0%; P = 0.006), whereas infections were more frequent in the anakinra group (31% and 11%; P = 0.3). CONCLUSION: Canakinumab demonstrated superior clinical response and drug survival with fewer adverse events compared with anakinra. Monthly canakinumab 300 mg may be considered as an effective steroid-sparing therapeutic option for patients with VEXAS.

Understanding food webs environmental condition is a challenging task since evaluations are limited by data on key ecosystem elements, by the availability of indicators that incorporate relevant guilds and by the difficulty in establishing cause-effect relations between pressures and health status, as multiple overlapping pressures can affect taxonomic elements differently. The present work aims to investigate food webs assessment under the Marine Strategy Framework Directive (MSFD), revealing gaps and future research needs in the North Eastern Atlantic. To understand reporting patterns, information on the criteria employed and the resulting assessment trends of Descriptor 4—Food webs were surveyed from the MSFD reports. A multivariate analysis was applied to food webs assessment status and spatially overlapping anthropogenic pressures to understand if the assessment was detecting pressures, considering fish elements. Results revealed that reporting strategies varied between Member States. High reporting effort was exhibited by the United Kingdom in opposition to Ireland or France. Reporting of other groups other than fish and plankton was limited to the United Kingdom due to the availability of monitoring programs and data. The analysis applied to criteria considering fish elements reinforced that reporting strategies and trends differed between countries, although some similarities were found for the Bay of Biscay and Iberian coast and the Celtic Seas. Food webs assessment trends for fish were variable in Spain and were stable or increased in Portugal and the United Kingdom. Anthropogenic drivers significantly influencing food web trends for fish elements were fishing, and climate anomalies in the southern Bay of Biscay and Iberian coast, while eutrophication and chemical contamination had effects on trends in the Celtic Sea and the North Sea. Results allowed to establish a relation between anthropogenic effects and food web patterns, however, these were limited since food webs assessment is incongruent in terms of criteria used and data is still limited at relevant scales. This study reinforced the necessity to increase Member States harmonization and calibration to improve our understanding of food webs environmental status.

INTRODUCTION: Systemic sclerosis (SSc) is a rare autoimmune disease currently classified into two subgroups based on skin extension. The aim of this study was to determine in a large cohort whether the determination of autoantibody (AAb) profile among a full antinuclear AAbs panel including nine specificities had a higher impact than skin phenotype on stratifying the risk of organ involvement and mortality in SSc. METHODS: Data for patients with SSc followed in seven French university hospitals were retrospectively analysed in terms of skin phenotype, AAbs (anti-topoisomerase I (ATA), anticentromere (ACA), anti-RNA polymerase III (anti-RNAPIII), anti-U1RNP, anti-U3RNP, anti-Pm/Scl, anti-Ku, anti-Th/To, anti-NOR90), organ involvement and mortality. Multivariate analyses were performed to identify independent factors associated with organ involvement and mortality. RESULTS: We included 1605 patients with SSc (367 with diffuse cutaneous SSc). On multivariate analysis, ATAs were associated with interstitial lung disease and mortality (OR=3.27 (95% CI 2.42 to 4.42); HR=1.9 (95% CI 1.01 to 3.58)), anti-RNAPIII with scleroderma renal crisis and mortality (OR=7.05 (95% CI 2.98 to 16.72); HR=2.35 (95% CI 1.12 to 4.93)), anti-U1RNP with arthritis (OR=3.79 (95% CI 2.16 to 6.67)), anti-Pm/Scl and anti-Ku with myositis (OR=7.09 (95% CI 3.87 to 12.98) and 7.99 (95% CI 2.41 to 26.46)). The skin phenotype was not associated with survival or organ involvement on multivariate analysis without stepwise selection. CONCLUSION: This study unravels, by contrast with skin phenotype, a strong association between AAbs specificities, organ involvement and outcome in SSc and suggests that patients' classification based on only skin extension is not sufficient for defining prognosis and phenotype.

Raising awareness on marine environmental issues is crucial to deepen students’ knowledge on ocean sustainability. Nonetheless, ocean-related topics have not been adequately addressed through formal education curricula, thus non-formal learning activities were developed to promote Ocean Literacy among students. These include visits to the local fish market and hands-on activities of fish biological sampling. A mixed methodology with closed and open-self questionnaires and interviews, was used to assess the activities’ effect in student’s learning and to evaluate their implementation and importance. Results showed the activities contribution to the increased learning while promoting a more active citizenship regarding ocean conservancy.

PURPOSE: To evaluate the real-world effectiveness of intravitreal ranibizumab 0.5 mg (Lucentis) in improving visual acuity (VA) in adults with decreased VA due to diabetic macular edema (DME). PATIENTS AND METHODS: Real-world prospective observational 24-month study. Ranibizumab-naïve patients (n=116) were enrolled, treated and followed up according to investigators' usual procedures. Outcomes included change from baseline to month 24 in best-corrected VA (BCVA; primary outcome), central retinal thickness (CRT), treatment exposure and safety. RESULTS: Overall, 62.9% of patients completed the study per protocol, 68.6% completed the induction phase (first three injections one month apart). On average, patients had 12.5 ophthalmologist visits and 5.74 injections in year 1, decreasing to 4.6 visits and 1.94 injections in year 2. Mean baseline BCVA was 58.4 letters, mean gain at M24 was +6.08 letters (95% CI: 2.95, 9.21). Gains were higher for patients who completed induction, and for patients who did not switch treatment. Mean CRT improved by 149.17 μm at M24. There were no new safety signals. BCVA variation of ≥6 letters by M3 was predictive of BCVA gains at M24 (p=0.007), as was hypertension medication at baseline (p=0.022). CONCLUSION: Real-world ranibizumab treatment improved VA in DME patients, despite fewer injections than recommended.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common treatable disease often diagnosed in patients with risk factors after a prolonged period with suggestive symptoms. Our qualitative study aimed to identify barriers to establishing diagnosis in the natural history of this condition. METHODS: An inductive thematic analysis was performed on structured interviews with patients, general practitioners (GPs) and pulmonologists in France. Inclusion depended on criteria to generate two purposive samples (patients and physicians). Recruitment occurred online. Data collection proceeded until 15 patients and 15 physicians (eight pulmonologists, seven GPs) were interviewed. Data saturation was checked and achieved. The interviews were transcribed and coded in NVivo and triangulated between two researchers. The article respects the consolidated criteria for reporting qualitative research guidelines. RESULTS: Three phases in the patients' clinical pathway to diagnosis and 12 barriers were found: Phase 1 (symptoms before consultation; n=4), lack of COPD knowledge, symptom denial, fear of lung cancer, and delayed general practice consultations; Phase 2 (primary care; n=3), letting bronchitis become chronic, priority to diseases with similar symptoms and/or more serious diseases, lack of COPD screening devices, time and curative treatments; Phase 3 (specialised medicine; n=5), treatment before diagnosis, late referral to pulmonologists, difficulty in accessing specialists and examination results, patient's reluctance to undergo further examinations, and need for additional tests to confirm a diagnosis. CONCLUSION: People unaware of their COPD condition can encounter up to 12 barriers, which may combine before obtaining a formal diagnosis. Patients, GPs, pulmonologists and the state health authorities share responsibility for addressing these barriers and enhancing the care pathway.

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