Anatomie du nerf laryngé externe et ses applications chirurgicales

Objectif : La lésion de la branche externe du nerf laryngé supérieur (BeNLS) , non rare lors de la chirurgie thyroïdienne, est responsable de modifications de la voix et de troubles de la déglutition. Mais ses différentes variantes anatomiques ainsi que les faibles taux de son identification ont découragé les chirurgiens de son repérage systématique.Le but de notre travail est de faire une description anatomique des variantes de la BeNLS , d’estimer la fréquence des nerfs à risque et de décrire les techniques chirurgicales de son identification pour proposer une approche systématique de sa préservation.Matériel et méthodes: Il s’agit d’une étude prospective portant sur 10 patients ayant eu une chirurgie thyroïdienne et chez qui on a procédé à un repérage systématique de la BeNLS dans l’espace avasculaire de Reeve. On a utilisé la classification de Cernea pour regrouper les variations anatomiques rencontrées.Résultats : On a procédé à la dissection de 13 nerfs. Le taux  d’identification de la BeNLS était de 84% , 38% sont de Type 2a , 46% sont de Type 2b. Des complications ont été notées chez 3 patients dont 2 qui présentent une BeNLS de Type Ni.Conclusion : On pense que la variante anatomique de la BeNLS de type 2 présente un risque de blessure car le chirurgien manipule le pédicule supérieur au niveau du centimètre critique situé au-dessus du pôle supérieur de la thyroïde. Le sous-type 2b , le plus fréquent dans notre série , est une variante à haut risque. L’identification du nerf lors de la chirurgie thyroïdienne est la solution de choix.Mots-clés : Branche externe du nerf laryngé supérieur, anatomie, muscle crico-thyroïdien, chirurgie thyroïdienne, voix

Leomyosarcome du larynx

Le leiomyosarcome laryngé est une tumeur musculaire lisse maligne rare. Il représente moins de 1% de toutes les tumeurs malignes laryngées. Nous rapportons un nouveau cas chez un patient de 63 ans. Le traitement a consisté en une laryngectomie totale avec curage ganglionnaire suivie de radiothérapie. A travers ce cas et une revue de la littérature, nous discutons les aspects épidémiologiques, cliniques et étiopathogéniques de ce sarcome rare du larynx.Mots clés : Léiomyosarcome, larynx, radiothérapie, chirurgie

Insight into the Optimization of Implementation Time in Cob Construction: Field Test and Compressive Strength Versus Drying Kinetics

Mastering construction times is of paramount importance in making vernacular earth construction techniques attractive to modern clients. The work presented here is a contribution towards the optimization of the construction time of cob buildings. Therefore, this paper follows the evolution of a cob’s mechanical properties during its drying process in the case of a double-walling CobBauge system. Laboratory tests and in situ measurements were performed, and further results were described. Volumetric water content sensors were immersed in the walls of a CobBauge prototype building during its construction. The evolution of the cob layer’s compressive strength and Clegg Impact Value (CIV) as a function of its water content has been experimentally studied and discussed. These studies showed that compressive strength and CIV are correlated with water content, and both properties decrease exponentially with time. In this study, a new tool to evaluate cob’s mechanical performances in situ has been proposed, Clegg Impact Soil Tester. This was linked to compressive strength, and a linear relationship between these two properties was found. Finally, appropriate values of compressive strength and CIV to satisfy before formwork stripping and re-lifting were proposed. For this study’s conditions, these values are reached after approximately 27 days

Machine Learning-Based Indoor Relative Humidity and CO2 Identification Using a Piecewise Autoregressive Exogenous Model: A Cob Prototype Study

The population of developed nations spends a significant amount of time indoors, and the implications of poor indoor air quality (IAQ) on human health are substantial. Many premature deaths attributed to exposure to indoor air pollutants result from diseases exacerbated by poor indoor air. CO2, one of these pollutants, is the most prevalent and often serves as an indicator of IAQ. Indoor CO2 concentrations can be significantly higher than outdoor levels due to human respiration and activity. The primary objective of this research was to numerically investigate the indoor relative humidity and CO2 in cob buildings through the CobBauge prototype, particularly during the first months following the building delivery. Both in situ experimental studies and numerical predictions using an artificial neural network were conducted for this purpose. The study presented the use of a piecewise autoregressive exogenous model (PWARX) for indoor relative humidity (RH) and CO2 content in a building constructed with a double walling system consisting of cob and light earth. The model was validated using experimental data collected over a 27-day period, during which indoor RH and CO2 levels were measured alongside external conditions. The results indicate that the PWARX model accurately predicted RH levels and categorized them into distinct states based on moisture content within materials and external conditions. However, while the model accurately predicted indoor CO2 levels, it faced challenges in finely classifying them due to the complex interplay of factors influencing CO2 levels in indoor environments

Impact of concomitant administration of gastric acid-suppressive agents and pazopanib on outcomes in soft-tissue sarcoma patients treated within the EORTC 62043/62072 trials

Purpose: Pazopanib is active in soft-tissue sarcoma (STS). Because pazopanib absorption is pH-dependent, coadministration with gastric acid-suppressive (GAS) agents such as proton pump inhibitors could affect exposure of pazopanib, and thereby its therapeutic effects.Experimental Design: The EORTC 62043 and 62072 were single-arm phase II and placebo-controlled phase III studies, respectively, of pazopanib in advanced STS. We first compared the outcome of patients treated with pazopanib with or without GAS agents for ≥80% of treatment duration, and subsequently using various thresholds. The impact of concomitant GAS therapy was assessed on progression-free survival (PFS) and overall survival (OS) using multivariate Cox models, exploring and comparing also the potential effect on placebo-treated patients.Results: Of 333 eligible patients, 59 (17.7%) received concomitant GAS therapy for >80% of pazopanib treatment duration. Median PFS was shorter in GAS therapy users versus nonusers: 2.8 vs. 4.6 months, respectively [HR, 1.49; 95% confidence interval (CI), 1.11-1.99; P = 0.01]. Concomitant administration of GAS therapy was also associated with a shorter median OS: 8.0 vs. 12.6 months (HR, 1.81; 95% CI, 1.31-2.49; P < 0.01). The longer the overlapping use of GAS agents and pazopanib, the worse the outcome with pazopanib. These effects were not observed in placebo-treated patients (HR, 0.82; 95% CI, 0.51-1.34; P = 0.43 for PFS and HR, 0.84; 95% CI, 0.48-1.48; P = 0.54 for OS).Conclusions: Coadministration of long-term GAS therapy with pazopanib was associated with significantly shortened PFS and OS. Withdrawal of GAS agents must be considered whenever possible. Therapeutic drug monitoring of pazopanib plasma concentrations may be helpful for patients on pazopanib and GAS therapy

Caveolin-1 protects B6129 mice against Helicobacter pylori gastritis.

Caveolin-1 (Cav1) is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract. Chronic infection of gastric epithelial cells by Helicobacter pylori (H. pylori) is a major risk factor for human gastric cancer (GC) where Cav1 is frequently down-regulated. However, the function of Cav1 in H. pylori infection and pathogenesis of GC remained unknown. We show here that Cav1-deficient mice, infected for 11 months with the CagA-delivery deficient H. pylori strain SS1, developed more severe gastritis and tissue damage, including loss of parietal cells and foveolar hyperplasia, and displayed lower colonisation of the gastric mucosa than wild-type B6129 littermates. Cav1-null mice showed enhanced infiltration of macrophages and B-cells and secretion of chemokines (RANTES) but had reduced levels of CD25+ regulatory T-cells. Cav1-deficient human GC cells (AGS), infected with the CagA-delivery proficient H. pylori strain G27, were more sensitive to CagA-related cytoskeletal stress morphologies ("humming bird") compared to AGS cells stably transfected with Cav1 (AGS/Cav1). Infection of AGS/Cav1 cells triggered the recruitment of p120 RhoGTPase-activating protein/deleted in liver cancer-1 (p120RhoGAP/DLC1) to Cav1 and counteracted CagA-induced cytoskeletal rearrangements. In human GC cell lines (MKN45, N87) and mouse stomach tissue, H. pylori down-regulated endogenous expression of Cav1 independently of CagA. Mechanistically, H. pylori activated sterol-responsive element-binding protein-1 (SREBP1) to repress transcription of the human Cav1 gene from sterol-responsive elements (SREs) in the proximal Cav1 promoter. These data suggested a protective role of Cav1 against H. pylori-induced inflammation and tissue damage. We propose that H. pylori exploits down-regulation of Cav1 to subvert the host's immune response and to promote signalling of its virulence factors in host cells

Extreme events and predictability of catastrophic failure in composite materials and in the Earth

Despite all attempts to isolate and predict extreme earthquakes, these nearly always occur without obvious warning in real time: fully deterministic earthquake prediction is very much a ‘black swan’. On the other hand engineering-scale samples of rocks and other composite materials often show clear precursors to dynamic failure under controlled conditions in the laboratory, and successful evacuations have occurred before several volcanic eruptions. This may be because extreme earthquakes are not statistically special, being an emergent property of the process of dynamic rupture. Nevertheless, probabilistic forecasting of event rate above a given size, based on the tendency of earthquakes to cluster in space and time, can have significant skill compared to say random failure, even in real-time mode. We address several questions in this debate, using examples from the Earth (earthquakes, volcanoes) and the laboratory, including the following. How can we identify ‘characteristic’ events, i.e. beyond the power law, in model selection (do dragon-kings exist)? How do we discriminate quantitatively between stationary and non-stationary hazard models (is a dragon likely to come soon)? Does the system size (the size of the dragon’s domain) matter? Are there localising signals of imminent catastrophic failure we may not be able to access (is the dragon effectively invisible on approach)? We focus on the effect of sampling effects and statistical uncertainty in the identification of extreme events and their predictability, and highlight the strong influence of scaling in space and time as an outstanding issue to be addressed by quantitative studies, experimentation and models

Assessing the efficiency and significance of Methylated DNA Immunoprecipitation (MeDIP) assays in using in vitro methylated genomic DNA

<p>Abstract</p> <p>Background</p> <p>DNA methylation contributes to the regulation of gene expression during development and cellular differentiation. The recently developed Methylated DNA ImmunoPrecipitation (MeDIP) assay allows a comprehensive analysis of this epigenetic mark at the genomic level in normal and disease-derived cells. However, estimating the efficiency of the MeDIP technique is difficult without previous knowledge of the methylation status of a given cell population. Attempts to circumvent this problem have involved the use of <it>in vitro </it>methylated DNA in parallel to the investigated samples. Taking advantage of this stratagem, we sought to improve the sensitivity of the approach and to assess potential biases resulting from DNA amplification and hybridization procedures using MeDIP samples.</p> <p>Findings</p> <p>We performed MeDIP assays using <it>in vitro </it>methylated DNA, with or without previous DNA amplification, and hybridization to a human promoter array. We observed that CpG content at gene promoters indeed correlates strongly with the MeDIP signal obtained using <it>in vitro </it>methylated DNA, even when lowering significantly the amount of starting material. In analyzing MeDIP products that were subjected to whole genome amplification (WGA), we also revealed a strong bias against CpG-rich promoters during this amplification procedure, which may potentially affect the significance of the resulting data.</p> <p>Conclusion</p> <p>We illustrate the use of <it>in vitro </it>methylated DNA to assess the efficiency and accuracy of MeDIP procedures. We report that efficient and reproducible genome-wide data can be obtained via MeDIP experiments using relatively low amount of starting genomic DNA; and emphasize for the precaution that must be taken in data analysis when an additional DNA amplification step is required.</p

High Prevalence of Extended-Spectrum Beta Lactamases among Salmonella enterica Typhimurium Isolates from Pediatric Patients with Diarrhea in China

We investigated the extended-spectrum beta lactamases among 62 Salmonella enterica Typhimurium isolates recovered from children with diarrhea in a Chinese pediatric hospital. A large proportion of S. enterica Typhimurium isolates were resistant to multiple antimicrobial agents, including ampicillin (90.3%), tetracycline (80.6%), trimethoprim/sulfamethoxazole (74.2%), chloramphenicol (66.1%), cefotaxime (27.4%). Forty-nine (79.0%) of S. enterica Typhimurium isolates were positive for blaTEM-1b and resistant to ampicillin. Thirteen S. enterica Typhimurium isolates (21.0%) were positive for blaCTX-M-1-group and blaCTX-M-9-group, and all isolates harboring blaCTX-M genes were positive for ISEcp1. Two main clones (PFGE type A and D) accounted for nearly 70% of S. enterica Typhimurium isolates, and 7 CTX-M-producing isolates belonged to PFGE type D. Collectively, our data reveal multi-drug resistance and a high prevalence of extended spectrum beta lactamases among S. enterica Typhimurium isolates from children in China. In addition, we report the first identification of blaCTX-M-55 within Salmonella spp. Our data also suggest that clonal spread is responsible for the dissemination of S. enterica Typhimurium isolates