Geodesic acoustic modes in a fluid model of tokamak plasma : the effects of finite beta and collisionality

Starting from the Braginskii equations, relevant for the tokamak edge region, a complete set of nonlinear equations for the geodesic acoustic modes (GAM) has been derived which includes collisionality, plasma beta and external sources of particle, momentum and heat. Local linear analysis shows that the GAM frequency increases with collisionality at low radial wave number $k_{r}$ and decreases at high $k_{r}$. GAM frequency also decreases with plasma beta. Radial profiles of GAM frequency for two Tore Supra shots, which were part of a collisionality scan, are compared with these calculations. Discrepency between experiment and theory is observed, which seems to be explained by a finite $k_{r}$ for the GAM when flux surface averaged density $\langle n \rangle$ and temperature $\langle T \rangle$ are assumed to vanish. It is shown that this agreement is incidental and self-consistent inclusion of $\langle n \rangle$ and $\langle T \rangle$ responses enhances the disagreement more with $k_r$ at high $k_{r}$ . So the discrepancy between the linear GAM calculation, (which persist also for more "complete" linear models such as gyrokinetics) can probably not be resolved by simply adding a finite $k_{r}$

Learning curve for robot-assisted Roux-en-Y gastric bypass

Background: Robot-assisted Roux-en-Y gastric bypass (RYGBP) is rapidly evolving as an important surgical approach in the bariatric field. However, the specific learning curve associated with this new approach remains poorly investigated. This study aimed to evaluate the learning curve for robot-assisted RYGBP. Methods: A series of 64 consecutive robot-assisted RYGBP procedures were performed between December 2008 and December 2010 by a single surgeon already experienced in advanced laparoscopic procedures but not in bariatric surgery. All data were collected prospectively in a database and reviewed retrospectively. The learning curve was evaluated using the cumulative sum (CUSUM) method. Results: Women comprised 76.6% and men 23.4% of this series. These patients had a mean age of 43years and a mean body mass index (BMI) of 44.5kg/m2. The mean operative time (OT) was 238.1min (range, 150-400min). A total of six complications occurred (9.4%). The CUSUM learning curve consisted of two distinct phases: phase 1 (the initial 14 cases; mean OT, 288.9min) and phase 2 (the subsequent cases; mean OT, 223.6min), which represented the mastery phase, with a decrease in OT (P=0.0001). The two groups were similar in terms of gender, age, and BMI. The two phases did not differ in terms of complications or hospital stay. Conclusions: This series confirms previous study findings concerning the feasibility and the safety of robotic RYGBP even after a limited experience with laparoscopic RYGBP. The data reported in this article suggest that the learning phase for robot-assisted RYGBP can be achieved with 14 case

Robot-Assisted Roux-en-Y Gastric Bypass for Super Obese Patients: A Comparative Study

Superobese patients (SO) (body mass index (BMI) ≥ 50kg/m2) represent a real surgical challenge and the best management remains debatable. While the safety of a laparoscopic approach has been questioned for this population, robotics has been introduced in the armamentarium of the bariatric surgeon, yet its role remains poorly assessed, especially for a very high BMI. The study aim is thus to report our experience with robot-assisted Roux-en-Y gastric bypass (RYGB) for SO. From July 2006 to May 2012, 288 consecutive robot-assisted RYGB procedures have been performed at a single institution. All data were collected prospectively in a dedicated database. Among those patients, 41 were SO (14.2%). All the peri- and postoperative parameters were compared to the morbidly obese (MO) group (BMI < 50). Data have been reviewed retrospectively. The SO group presented a higher ASA score and more male patients. The operative time was similar between both groups, yet there were more conversions in the SO group (two versus one for MO; p = 0.05). The morbidity and mortality rates were similar between both groups. The length of stay was longer for the SO population (7 vs. 6days; p = 0.03). The percent BMI loss was similar at 1year (34 vs. 34%; p = 1), but the percent excess BMI loss was higher for the MO group (83 vs. 65% for the SO group; p = 0.0007). Robot-assisted RYGB can be performed safely for SO, with complication rates and functional results at 1year comparable to MO, yet this approach for SO has been associated with a slightly increased conversion rate and length of sta

Etude de la vascularisation utéro-placentaire par angiographie Doppler énergie tridimensionnelle (évaluations fondamentales de la technique sur modèles expérimentaux de brebis et lapines gestantes, et évaluations cliniques préliminaires chez la femme enceinte.)

Retard de croissance intra-utérin (RCIU) et prééclampsie (PE) sont des complications majeures de la grossesse humaine et sont le plus souvent due à une insuffisance de vascularisation utéro-placentaire. Notre objectif était d'évaluer l angiographie Doppler énergie tridimensionnelle (PDA) comme nouvel outil de dépistage de la PE et du RCIU et d étude de la fonction placentaire et du RCIU sur modèles animaux. La corrélation entre les indices Doppler 3D et l'écoulement de sang réel au sein de l'unité utéro-placentaires a d'abord été évaluée sur modèle de brebis gravide, ainsi que l'impact des réglages de la machine. Un degré de corrélation plus élevé a été observé pour VI et VFI (r = 0,86 et 0,82 respectivement, p <0,0001) que pour FI (r = 0,64, p <0,0001).L'intérêt de la technique a été ensuite démontré dans un modèle de RCIU chez le lapin (femelles traitées par du L-NAME).Troisièmement, la valeur prédictive du PDA comme test de dépistage du RCIU et de la PE a été démontrée par la réalisation d'une étude prospective multicentrique chez 70 femmes enceintes à bas risque (AUC 0,95, 100% VAN avec une spécificité de 85% pour un seuil de 36.784 FI placentaire).Intra-uterine growth retardation (IUGR) and preeclampsia (PE) are major complications of human pregnancy & are most often due to an insufficient utero-placental vascularization. Our aim was to evaluate the three-dimensional power Doppler angiography (PDA) as a new tool for the screening IUGR & PE & for the study placental function and IUGR in animal models. The correlation between 3D Doppler indices and the real blood flow within the utero-placental unit was first evaluated in the pregnant sheep model, as well as the impact of machine settings. A higher correlation degree was observed for VI and VFI (r = 0.86 and 0.82 respectively p<0.0001) than for FI (r = 0.64; p<0.0001).The interest of the technique was secondly demonstrated in a rabbit IUGR model (females treated with L-NAME).Thirdly, the predictive value of PDA as a screening test for IUGR & PE was demonstrated by conducting a prospective multicentric study in 70 low risk pregnant women (AUC 0.95, 100% NPV with a specificity of 85% for a 36.784 placental FI threshold).PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

Sporadic and genetic forms of paediatric somatotropinoma: a retrospective analysis of seven cases and a review of the literature

<p>Abstract</p> <p>Background</p> <p>Somatotropinoma, a pituitary adenoma characterised by excessive production of growth hormone (GH), is extremely rare in childhood. A genetic defect is evident in some cases; known genetic changes include: multiple endocrine neoplasia type 1 (MEN1<it>)</it>; Carney complex; McCune-Albright syndrome; and, more recently identified, aryl hydrocarbon receptor-interacting protein (AIP). We describe seven children with somatotropinoma with a special focus on the differences between genetic and sporadic forms.</p> <p>Methods</p> <p>Seven children who presented in our regional network between 1992 and 2008 were included in this retrospective analysis. First-type therapy was somatostatin (SMS) analogues or transsphenoidal surgery. Control was defined as when insulin-like growth factor-1 (IGF-1) levels were within the normal range for the patient's age at 6 months after therapy, associated with decreasing tumour volume.</p> <p>Results</p> <p>Patients were aged 5-17 years and the majority (n = 6) were male. Four patients had an identified genetic mutation (McCune-Albright syndrome: n = 1; MEN1: n = 1; AIP: n = 2); the remaining three cases were sporadic. Accelerated growth rate was reported as the first clinical sign in four patients. Five patients presented with macroadenoma; invasion was noted in four of them (sporadic: n = 1; genetic: n = 3). Six patients were treated with SMS analogues; normalisation of IGF-1 occurred in one patient who had a sporadic intrasellar macroadenoma. Multiple types of therapy were necessary in all patients with an identified genetic mutation (4 types: n = 1; 3 types: n = 2; 2 types: n = 1), whereas two of the three patients with sporadic somatotropinoma required only one type of therapy.</p> <p>Conclusions</p> <p>This is the first series that analyzes the therapeutic response of somatotropinoma in paediatric patients with identified genetic defects. We found that, in children, genetic somatotropinomas are more invasive than sporadic somatotropinomas. Furthermore, SMS analogues appear to be less effective for treating genetic somatotropinoma than sporadic somatotropinoma.</p

Molecular and functional characterization of a new X-linked chronic granulomatous disease variant (X91+) case with a double missense mutation in the cytosolic gp91phox C-terminal tail

AbstractWe report here two atypical cases of X-linked CGD patients (first cousins) in which cytochrome b558 is present at a normal level but is not functional (X91+). The mutations were localized by single-strand conformational polymorphism of reverse transcriptase–polymerase chain reaction amplified fragments and then identified by sequence analysis. They consisted in two base substitutions (C919 to A and C923 to G), changing His303 to Asn and Pro304 to Arg in the cytosolic gp91phox C-terminal tail. Mismatched polymerase chain reaction and genomic DNA sequencing showed that mothers had both wild-type and mutated alleles, confirming that this case was transmitted in an X-linked fashion. A normal amount of FAD was found in neutrophil membranes, both in the X91+ patients and their parents. Epstein–Barr virus-transformed B lymphocytes from the X91+ patients acidified normally upon stimulation with arachidonic acid, indicating that the mutated gp91phox still functioned as a proton channel. A cell-free translocation assay demonstrated that the association of the cytosolic factors p47phox and p67phox with the membrane fraction was strongly disrupted. We concluded that residues 303 and 304 are crucial for the stable assembly of the NADPH oxidase complex and for electron transfer, but not for its proton channel activity

PIXSIC: A Wireless Intracerebral Radiosensitive Probe in Freely Moving Rats

International audienceThe aim of this study was to demonstrate the potential of a wireless pixelated β+-sensitive intracerebral probe (PIXSIC) for in vivo positron emission tomographic (PET) radiopharmacology in awake and freely moving rodents. The binding of [ 11 C]raclopride to D 2 dopamine receptors was measured in anesthetized and awake rats following injection of the radiotracer. Competitive binding was assessed with a cold raclopride injection 20 minutes later. The device can accurately monitor binding of PET ligands in freely moving rodents with a high spatiotemporal resolution. Reproducible time-activity curves were obtained for pixels throughout the striatum and cerebellum. A significantly lower [ 11 C]raclopride tracer–specific binding was observed in awake animals. These first results pave the way for PET tracer pharmacokinetics measurements in freely moving rodents

Animal models of intrauterine growth retardation of vascular origin

Placental insufficiencies can complicate up to 7% of all pregnancies. They can lead to intrauterine growth retardation (IUGR) and preeclampsia, and represent a major public health concern. The pathophysiology of these placental anomalies is not yet fully understood. For obvious ethical reasons, studies in pregnant women are limited to non-invasive techniques, such as ultrasound scans and maternal blood tests. Therefore, animal models of IUGR play an important role in the study of this condition. Because the models using maternal undernutrition to induce foetal IUGR are not as appropriate to mimic the vascular IUGR observed in developed countries, we describe the animal models of vascular IUGR used currently: models based on an application of stress to the mother, genetic models, and surgical models. Finally, we describe briefly the controlled hypoperfusion model in non-anaesthetized ewes, currently developed in our laboratory.Les défauts de perfusion placentaire compliquent environ 7 % des grossesses. Ils peuvent entraîner un retard de croissance intra-utérin (RCIU) et une pré-éclampsie, et posent un problème majeur de santé publique. La physiopathologie de ces défauts n'est pas totalement connue. Les études chez la femme sont limitées à des examens non invasifs, échographiques et biologiques, pour des raisons éthiques évidentes. Il est donc important de disposer de modèles animaux expérimentaux pour appréhender cette pathologie. Nous n'abordons pas ici les modèles de sous-nutrition maternelle, qui ne nous semblent pas complètement appropriés pour reproduire les aspects physiopathologiques observés dans les pays développés. Les modèles animaux de RCIU d'origine vasculaire jusqu'ici utilisés sont décrits: modèles basés sur l'application d'un stress à la mère, modèles génétiques et modèles chirurgicaux. Enfin. Nous décrivons aussi brièvement le modèle d'hypoperfusion contrôlée chez la brebis vigile, actuellement mis au point au laboratoire

GW182-Free microRNA Silencing Complex Controls Post-transcriptional Gene Expression during Caenorhabditis elegans Embryogenesis

MicroRNAs and Argonaute form the microRNA induced silencing complex or miRISC that recruits GW182, causing mRNA degradation and/or translational repression. Despite the clear conservation and molecular significance, it is unknown if miRISC-GW182 interaction is essential for gene silencing during animal development. Using Caenorhabditis elegans to explore this question, we examined the relationship and effect on gene silencing between the GW182 orthologs, AIN-1 and AIN-2, and the microRNA-specific Argonaute, ALG-1. Homology modeling based on human Argonaute structures indicated that ALG-1 possesses conserved Tryptophan-binding Pockets required for GW182 binding. We show in vitro and in vivo that their mutations severely altered the association with AIN-1 and AIN-2. ALG-1 tryptophan-binding pockets mutant animals retained microRNA-binding and processing ability, but were deficient in reporter silencing activity. Interestingly, the ALG-1 tryptophan-binding pockets mutant phenocopied the loss of alg-1 in worms during larval stages, yet was sufficient to rescue embryonic lethality, indicating the dispensability of AINs association with the miRISC at this developmental stage. The dispensability of AINs in miRNA regulation is further demonstrated by the capacity of ALG-1 tryptophan-binding pockets mutant to regulate a target of the embryonic mir-35 microRNA family. Thus, our results demonstrate that the microRNA pathway can act independently of GW182 proteins during C. elegans embryogenesis

IL-26 inhibits hepatitis C virus replication in hepatocytes

Publisher Copyright: © 2021 European Association for the Study of the LiverBackground & Aims: Interleukin-26 (IL-26) is a proinflammatory cytokine that has properties atypical for a cytokine, such as direct antibacterial activity and DNA-binding capacity. We previously observed an accumulation of IL-26 in fibrotic and inflammatory lesions in the livers of patients with chronic HCV infection and showed that infiltrating CD3+ lymphocytes were the principal source of IL-26. Surprisingly, IL-26 was also detected in the cytoplasm of hepatocytes from HCV-infected patients, even though these cells do not produce IL-26, even when infected with HCV. Based on this observation and possible interactions between IL-26 and nucleic acids, we investigated the possibility that IL-26 controlled HCV infection independently of the immune system. Methods: We evaluated the ability of IL-26 to interfere with HCV replication in hepatocytes and investigated the mechanisms by which IL-26 exerts its antiviral activity. Results: We showed that IL-26 penetrated HCV-infected hepatocytes, where it interacted directly with HCV double-stranded RNA replication intermediates, thereby inhibiting viral replication. IL-26 interfered with viral RNA-dependent RNA polymerase activity, preventing the de novo synthesis of viral genomic single-stranded RNA. Conclusions: These findings reveal a new role for IL-26 in direct protection against HCV infection, independently of the immune system, and increase our understanding of the antiviral defense mechanisms controlling HCV infection. Future studies should evaluate the possible use of IL-26 for treating other chronic disorders caused by RNA viruses, for which few treatments are currently available, or emerging RNA viruses. Lay summary: This study sheds new light on the body's arsenal for controlling hepatitis C virus (HCV) infection and identifies interleukin-26 (IL-26) as an antiviral molecule capable of blocking HCV replication. IL-26, which has unique biochemical and structural characteristics, penetrates infected hepatocytes and interacts directly with viral RNA, thereby blocking viral replication. IL-26 is, therefore, a new player in antiviral defenses, operating independently of the immune system. It is of considerable potential interest for treating HCV infection and other chronic disorders caused by RNA viruses for which few treatments are currently available, and for combating emerging RNA viruses.Peer reviewe