Search Results (108)

Objective: The aim of this study was to propose a pathophysiological hypothesis for the occurrence of non-traumatic chylous effusions and Central Conducting Lymphatic Anomalies (CCLAs) related to lymphatic occlusion. Methods: We investigated the case of a 39-year-old woman managed at Nîmes University Hospital for chylous anasarca related to an endoluminal lymphatic occlusion. We then conducted a comprehensive review of the literature on CCLAs. Results: Lymphatic drainage is a dynamic process. Obstacles to lymphatic drainage via the thoracic duct can lead to chylous anasarca, depending on where the obstruction is. Lymphatic occlusion seems to be an explanation for certain CCLAs. Conclusions: Understanding CCLAs via the theory of lymph occlusion opens the way to new therapeutic options, but requires further investigation in order to personalize the patient’s treatment. Full article

TWIK-related K+ (TREK-1) channels are involved in pain perception and their pharmacological activation has potential for pain relief. The development of new pharmacological tools to study these channels and enrich our knowledge of structure–activity relationships is therefore important. We optimized a high throughput screening method based on thallium flux monitoring for the detection of TREK-1 activators in chemical libraries. We screened 1040 compounds from the French National Essential Chemical Library and identified LPS2336 as a potent TREK-1 activator with an EC₅₀ of 11.76 µM. Thirty-three LPS2336 analogs were subsequently tested but none of them retained activity on TREK-1. In vivo, LPS2336 produces antinociceptive activity when administered systemically and, to a lesser extent, intracerebroventricularly, but not intrathecally, showing that targeting peripheral TREK-1 channels may be important to produce pain relief, with the interest of reducing potential central adverse effects. LPS2336 was shown to produce sedation and hypothermia with a narrow therapeutic window. As these adverse effects are also observed in TREK-1 knock-out mice, they are likely mediated by off-targets. Our work provides key optimization steps for thallium-based assays and a new pharmacological tool for the study of TREK-1 channels. It also raises the importance of investigating adverse effects in vivo at early stages of drug discovery. Full article

Breast cancer (BC) is a heterogeneous disease with high metastasis potential, especially in the bones, liver, and lungs. Circulating tumor cells (CTCs), which emerge from active tumors, represent an early step toward metastasis and are associated with poor prognosis. CTCs of carcinoma origin are believed to express EpCAM and cytokeratins (CKs), common epithelial markers that are frequently used to identify them. However, in practice, the most aggressive CTCs lose the expression of those markers, leading to the partial loss of important information. Thus, finding some novel markers that identify CTCs regardless of their heterogeneity is crucial. A specific bioinformatics workflow integrating primary tumor and diverse BC cell lines transcriptomic expression analysis was developed and compared with single CTC transcriptomic analyses. We have identified a set of genes that are overexpressed in primary BC cells and are commonly upregulated among BC cell lines. Fifty of them were also found to be expressed in BC CTCs by single-cell transcriptomic analysis. Further in silico sorting narrowed this list to 12 genes. Using ScreenCell technology to isolate cancer cells spiked into normal blood, we tested the protein expression of all corresponding genes in vitro using the double immunocytochemistry method and validated MARCKSL1, SLC9A3R1, and RHOD as the most expressed markers. We then isolated the CTCs of 40 LN-invaded BC patients and 18 healthy donors using ScreenCell technology and showed that the combination of these three markers resulted in significantly better recognition of CTCs compared to EpCAM and CK conventional markers. Employing these novel markers, we found a clear distinction between blood samples from patients and healthy donors. In conclusion, through a specific bioinformatics workflow, in addition to in vitro and further clinical validations, we found three novel markers to precisely identify CTCs. These markers, when used together, enable a significantly more efficient identification of CTCs compared to conventional epithelial markers. Full article

Background/Objectives: Modern therapeutic strategies incorporating virtual reality (VR) have emerged as potential treatments for generalized anxiety disorder (GAD), a prevalent and debilitating condition that is challenging to cure. This study aimed to evaluate the efficacy of VR combined with relaxation techniques in patients with GAD by comparing VR-based relaxation with standard mental imagery (MI) relaxation. Methods: Fifty-eight patients with GAD participated in a randomized comparative trial. Specific virtual environments were created using an inexpensive game engine/level editor (GLE). Psychometric scales and physiological instruments were employed to assess the effects of relaxation therapy on anxiety, depression, quality of life, presence within virtual environments and cybersickness. Results: Both the VR and MI groups demonstrated statistically significant improvements in anxiety, worry and mental quality of life scores. However, no significant differences were observed between the two groups in pre–post comparisons of psychometric scores. The VR group exhibited a noticeably higher protocol completion rate and a significant increase in heart rate variability during the therapy. The level of presence in the VR group was satisfactory and significantly correlated with physiological improvements and anxiety reduction, while cybersickness remained low. Participants’ preferences for specific virtual environments for relaxation are also discussed. Conclusions: These findings suggest that teaching and practicing relaxation in VR holds therapeutic potential for the treatment of GAD. Further research leveraging advanced VR sensory equipment and artificial intelligence agents is warranted to enhance therapeutic outcomes and explore additional applications. Full article

The fluorescence index called the Transit Time index (TTi) is based on the fluorescence of natural organic matter in order to qualitatively assess the transit time of karst groundwater, using springs affected by human activities. This study aims to further evaluate the potential of fluorescent compounds as a natural tracer of transit time when applied to unsaturated zone flows with natural catchments, in contrast to the first study. For this purpose, a bi-monthly sampling of one year of monitoring for organic matter fluorescence, TOC, major elements and water-stable isotopes was performed. A conceptual model of the sources and fates of fluorescent compounds is built, emphasizing the allochthonous origin of humic-like C compounds, and the autochthonous production of humic-like M and protein-like compounds within the unsaturated zone. Fluorescent compound intensity interpretation according to this model reveals consistent relative transit times with flow behavior and also provides complementary information. The results also show the TTi’s ability to summarize fluorescent compounds, its consistency with relative transit time, and its higher sensitivity as compared to other natural tracers. However, prior to its use, a thorough assessment of soil organic matter, microbial activity, and potential anthropogenic contamination is required, encouraging interdisciplinary collaboration between hydrogeologists, microbiologists and soil scientists. Full article

This study investigated the low contact resistivity and Schottky barrier characteristics in p-GaN by modifying the thickness and doping levels of a p-InGaN cap layer. A comparative analysis with highly doped p-InGaN revealed the key mechanisms contributing to low-resistance contacts. Atomic force microscopy inspections showed that the surface roughness depends on the doping levels and cap layer thickness, with higher doping improving the surface quality. Notably, increasing the doping concentration in the p⁺⁺-InGaN cap layer significantly reduced the specific contact resistivity to 6.4 ± 0.8 × 10⁻⁶ Ω·cm², primarily through enhanced tunneling. Current–voltage (I–V) characteristics indicated that the cap layer’s surface properties and strain-induced polarization effects influenced the Schottky barrier height and reverse current. The reduction in barrier height by approximately 0.42 eV in the p⁺⁺-InGaN layer enhanced hole tunneling, further lowering the contact resistivity. Additionally, polarization-induced free charges at the metal–semiconductor interface reduced band bending, thereby enhancing carrier transport. A transition in current conduction mechanisms was also observed, shifting from recombination tunneling to space-charge-limited conduction across different voltage ranges. This research underscores the importance of doping, cap layer thickness, and polarization effects in achieving ultra-low contact resistivity, offering valuable insights for improving the performance of p-GaN-based power devices. Full article

This study aims to assess the diagnostic accuracy of non-contrast-enhanced 4D MR angiography (NCE-4D-MRA) compared to contrast-enhanced 4D MR angiography (CE-4D-MRA) for the detection and angioarchitectural characterisation of brain arteriovenous malformations (bAVMs). Utilising a retrospective design, we examined 54 MRA pairs from 43 patients with bAVMs, using digital subtraction angiography (DSA) as the reference standard. Both NCE-4D-MRA and CE-4D-MRA were performed using a 3-T MR imaging system. The primary objectives were to evaluate the diagnostic performance of NCE-4D-MRA against CE-4D-MRA and DSA and to assess concordance between imaging modalities in grading bAVMs according to four main scales: Spetzler–Martin, Buffalo, AVM embocure score (AVMES), and R2eDAVM. Our results demonstrated that NCE-4D-MRA had a higher accuracy and specificity compared to CE-4D-MRA (0.85 vs. 0.83 and 95% vs. 85%, respectively) and similar agreement, with DSA detecting shunts in bAVMs or residuals. Concordance in grading bAVMs was substantial between NCE-4D-MRA and DSA, particularly for the Spetzler–Martin and Buffalo scales, with CE-4D-MRA showing slightly higher kappa values for interobserver agreement. The study highlights the potential of NCE-4D-MRA as a diagnostic tool for bAVMs, offering comparable accuracy to CE-4D-MRA while avoiding the risks associated with gadolinium-based contrast agents. The safety profile of imaging techniques is a significant concern in the long-term follow up of bAVMs, and further prospective research should focus on NCE-4D-MRA protocol improvement for clinical use. Full article

Fermented foods, including cheeses, have garnered increased interest in recent years for their potential health benefits. This study explores the biological properties of eight French raw-milk cheeses—goat cheese, Saint-Nectaire, Cantal, Bleu d’Auvergne, Roquefort, Comté, Brie de Meaux, and Epoisses—on oxidative processes using both in vivo (Caenorhabditis elegans) and in vitro (human leukocytes) models. A cheese fractionation protocol was adapted to study four fractions for each cheese: a freeze-dried fraction (FDC) corresponding to whole cheese, an apolar (ApE), and two polar extracts (W40 and W70). We showed that all cheese fractions significantly improved Caenorhabditis elegans (C. elegans) survival rates when exposed to oxidative conditions by up to five times compared to the control, regardless of the fractionation protocol and the cheese type. They were also all able to reduce the in vivo accumulation of reactive oxygen species (ROS) by up to 70% under oxidative conditions, thereby safeguarding C. elegans from oxidative damage. These beneficial effects were explained by a reduction in ROS production up to 50% in vitro in human leukocytes and overexpression of antioxidant factor-encoding genes (daf-16, skn-1, ctl-2, and sod-3) in C. elegans. Full article

This article aims to investigate the atmospheric corrosion of carbon steel in a marine environment abundant in hydrogen sulfide (H₂S) resulting from the decomposition of Sargassum seaweed. To accomplish this, four sites with varying degrees of impact were chosen along the coast of Martinique. The corrosion rates of steel were evaluated through mass loss measurements. After one year of exposure, the corrosion rates were notably high, particularly in atmospheres rich in Cl⁻ ions and H₂S, ranging from 107 µm to 983 µm. Complementing these findings, surface and product morphologies were characterized using scanning electron microscopy (SEM) coupled with energy dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD). These analyses revealed a significant degradation of the corrosion surface in the most affected atmospheres compared to those unaffected by Sargassum seaweed strandings. Lepidocrocite (γFeOOH) was identified as the predominant product regardless of the exposure atmosphere. However, goethite (αFeOOH) was found to be present in atmospheres most impacted by H₂S. Full article

Power Electronics Converters (PEC) play a crucial role in the operation of many modern electrical systems and devices. Despite their widespread use, the lack of an efficient and cost-effective disassembly process can limit their repairability, refurbishability, remanufacturability and, ultimately, recyclability, thus hindering the circularity of products. In order to improve their circularity, it is important to assess their ease of disassembly. Therefore, this paper investigates the applicability of the “ease of Disassembly Metric” (eDiM), which is referenced in the material efficiency standards, Benelux repairability assessment method, and Repair Scoring System (RSS), to analyze the ease of disassembly of energy-related products. After identifying the limitations of the eDiM method, we refined and adapted it to make it more suitable for Printed Circuit Board (PCB)-based PEC, and thus propose a PCB-based disassemblability assessment method allowing the implementation of quantifiable requirements supporting their circularity. This standardized approach, at the PCB level, can improve the circularity of such products by facilitating design enhancements. With this approach, policymakers and designers can contribute more effectively to the transition to a circular economy in PCB electronics, particularly in the field of power electronics. Full article

Studying the spatial response of a single-axis magnetometer could be the key parameter to optimize the ultimate performances of magnetic heads of detection. Indeed, the problem of non-orthogonality, misalignment, and 3D spatial response could be improved based on the knowledge of the 3D sensor spatial response. In that way, we have investigated the latter for our giant magneto-impedance (GMI) magnetometer, as a far-field pattern, by using a three-axis Helmholtz coil system. Firstly, we calibrate our device and secondly, we apply a specific 3D magnetic field to obtain this pattern. The latter helps to observe the directional or angular dependence of the sensor sensitivity versus the applied magnetic field, as we exemplified. The results confirm the excellent directivity of our off-diagonal GMI magnetometer. The evaluation of the associated error compared to an ideal vector magnetometer is also given and discussed. Full article

Considering sustainability in Power Electronics (PE) is a relatively recent topic of interest. However, the existing regulatory and normative frameworks supposed to guide designers and industries in this direction have not been combined in an exhaustive way. This article aims to bridge the gap by conducting a literature review of the regulative and normative constraints for sustainability in PE. This study primarily addresses the framework at the European level, with a focus on French regulations and standards. In this study, a total of 63 relevant documents are collected and analyzed. A framework representing the overview of existing legislation and facultative guidelines for PE ecodesign is established. A collaborative online tool is developed to enable access to the inventory by PE stakeholders. The analysis of the framework outlines the limitations and challenges needing to be addressed, including the absence of constraints on environmental performance, the inadequacy of material efficiency standards for PE products, and the unclear methodology for ecodesign implementation. This work, undertaken at the European level with a detailed examination of the French context, is intended to serve as an inspiring analysis for other countries and for PE designers who are considering the regulatory framework of a European representative country. Full article

Human respiratory syncytial virus (hRSV) is the most common cause of bronchiolitis and pneumonia in newborns, with all children being infected before the age of two. Reinfections are very common throughout life and can cause severe respiratory infections in the elderly and immunocompromised adults. Although vaccines and preventive antibodies have recently been licensed for use in specific subpopulations of patients, there is still no therapeutic treatment commonly available for these infections. Here, we investigated the potential antiviral activity of Retro-2.2, a derivative of the cellular retrograde transport inhibitor Retro-2, against hRSV. We show that Retro-2.2 inhibits hRSV replication in cell culture and impairs the ability of hRSV to form syncytia. Our results suggest that Retro-2.2 treatment affects virus spread by disrupting the trafficking of the viral de novo synthetized F and G glycoproteins to the plasma membrane, leading to a defect in virion morphogenesis. Taken together, our data show that targeting intracellular transport may be an effective strategy against hRSV infection. Full article

Arboviruses represent a real public health problem globally and in the Central African subregion in particular, which represents a high-risk zone for the emergence and re-emergence of arbovirus outbreaks. Furthermore, an updated review on the current arbovirus burden and associated mosquito vectors is lacking for this region. To contribute to filling this knowledge gap, the current study was designed with the following objectives: (i) to systematically review data on the occurrence and distribution of arboviruses and mosquito fauna; and (ii) to identify potential spillover mosquito species in the Central African region in the last 30 years. A web search enabled the documentation of 2454 articles from different online databases. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) and the quality of reporting of meta-analyses (QUORUM) steps for a systematic review enabled the selection of 164 articles that fulfilled our selection criteria. Of the six arboviruses (dengue virus (DENV), chikungunya virus (CHIKV), yellow fever virus (YFV), Zika virus (ZIKV), Rift Valley fever virus (RVFV), and West Nile virus (WNV)) of public health concern studied, the most frequently reported were chikungunya and dengue. The entomological records showed >248 species of mosquitoes regrouped under 15 genera, with Anopheles (n = 100 species), Culex (n = 56 species), and Aedes (n = 52 species) having high species diversity. Three genera were rarely represented, with only one species included, namely, Orthopodomyia, Lutzia, and Verrallina, but individuals of the genera Toxorhinchites and Finlayas were not identified at the species level. We found that two Aedes species (Ae. aegypti and Ae. albopictus) colonised the same microhabitat and were involved in major epidemics of the six medically important arboviruses, and other less-frequently identified mosquito genera consisted of competent species and were associated with outbreaks of medical and zoonotic arboviruses. The present study reveals a high species richness of competent mosquito vectors that could lead to the spillover of medically important arboviruses in the region. Although epidemiological studies were found, they were not regularly documented, and this also applies to vector competence and transmission studies. Future studies will consider unpublished information in dissertations and technical reports from different countries to allow their information to be more consistent. A regional project, entitled “Ecology of Arboviruses” (EcoVir), is underway in three countries (Gabon, Benin, and Cote d’Ivoire) to generate a more comprehensive epidemiological and entomological data on this topic. Full article

Alzheimer’s disease (AD) is the most widespread form of senile dementia worldwide and represents a leading socioeconomic problem in healthcare. Although it is widely debated, the aggregation of the amyloid β peptide (Aβ) is linked to the onset and progression of this neurodegenerative disease. Molecules capable of interfering with specific steps in the fibrillation process remain of pharmacological interest. To identify such compounds, we have set up a small molecule screening process combining multiple experimental methods (UV and florescence spectrometry, ITC, and ATR-FTIR) to identify and characterise potential modulators of Aβ_1-42 fibrillation through the description of the biochemical interactions (molecule–membrane Aβ peptide). Three known modulators, namely bexarotene, Chicago sky blue and indomethacin, have been evaluated through this process, and their modulation mechanism in the presence of a biomembrane has been described. Such a well-adapted physico-chemical approach to drug discovery proves to be an undeniable asset for the rapid characterisation of compounds of therapeutic interest for Alzheimer’s disease. This strategy could be adapted and transposed to search for modulators of other amyloids such as tau protein. Full article