Immunoscintigraphic localization of inflammatory lesions: concept, radiolabelling and in vitro testing of a granulocyte specific antibody.

Current nuclear medicine techniques for the localization of inflammatory processes are based on injection of 111In labelled autologous granulocytes which need to be isolated and radiolabelled in vitro before reinjection. A new technique is presented here that obviates the need for cell isolation by the direct intravenous injection of a granulocyte specific 123I labelled monoclonal antibody. In this publication the basic parameters of the antibody granulocyte interaction are described. Antibody binding does not inhibit vital functions of the granulocytes, such as chemotaxis and superoxide generation. Scatchard analysis of binding data reveals an apparent affinity of the antibody for granulocytes of 6.8 X 10(9) l/mol and approximately 7.1 X 10(4) binding sites per cell. Due to the high specificity of the antibody, the only expected interference is from CEA producing tumors.

The concept of instability: a French perspective on the concept of ADHD.

Historical references to the emergence of the current concept of ADHD typically cite descriptions from medical textbooks by Weikard (1775) and Crichton (An inquiry into the nature and origin of mental derangement: Comprehending a concise system of the physiology and pathology of the human mind and a history of the passion and their affects. Cardell Jr and Davies, Londres, 1798) on attention disorders, poems of Hoffman on hyperactive and impulsive behaviors (Der Struwwelpeter. Frankfurt am Main, Literarische Anstalt, 1843), as well as the work of Still (Lancet 1:1008-1012, 1077-1082, 1163-1168, 1902a, Lancet 159(4102):1008-1013, 1902b, Lancet 159(4103):1077-1082, 1902c, Lancet 159(4104):1163-1168, 1902d) on impulsive behaviors and defective moral regulation of behavior. The notion of "instability" developed by French physicians between 1887 and 1910 is rarely mentioned and often ignored. Writings from this period show that in France, the emergence of the concept of ADHD according to modern terminology comes from the notion of "mental instability" introduced in the 1890s under the leadership of Désiré-Magloire Bourneville at the Hospital Bicêtre in Paris, based on his observations of children and adolescents who had been labeled "abnormal" and placed in medical and educational institutions. In the early twentieth century, elaborating on the observations of Bourneville, Jean Phillipe and Georges Paul-Boncour showed the presence of a subgroup of "unstable" children who suffered from a disease entity in its own right within the population of "abnormal" schoolchildren (the terminology of the time). This new pathological entity included symptoms of hyperactivity, impulsivity and inattention, corresponding to today's classic triad of ADHD symptoms. While noting the lack of behavioral inhibition, clinical descriptions of Bourneville, Philip and Paul-Boncour also considered the notion of "moral disorder" which at that time played an important role in psychopathology. This resulted in some degree of confusion between impulsive symptoms and major behavioral disturbances often associated with ADHD.

Genome-Wide Prediction Methods in Highly Diverse and Heterozygous Species: Proof-of-Concept through Simulation in Grapevine.

Nowadays, genome-wide association studies (GWAS) and genomic selection (GS) methods which use genome-wide marker data for phenotype prediction are of much potential interest in plant breeding. However, to our knowledge, no studies have been performed yet on the predictive ability of these methods for structured traits when using training populations with high levels of genetic diversity. Such an example of a highly heterozygous, perennial species is grapevine. The present study compares the accuracy of models based on GWAS or GS alone, or in combination, for predicting simple or complex traits, linked or not with population structure. In order to explore the relevance of these methods in this context, we performed simulations using approx 90,000 SNPs on a population of 3,000 individuals structured into three groups and corresponding to published diversity grapevine data. To estimate the parameters of the prediction models, we defined four training populations of 1,000 individuals, corresponding to these three groups and a core collection. Finally, to estimate the accuracy of the models, we also simulated four breeding populations of 200 individuals. Although prediction accuracy was low when breeding populations were too distant from the training populations, high accuracy levels were obtained using the sole core-collection as training population. The highest prediction accuracy was obtained (up to 0.9) using the combined GWAS-GS model. We thus recommend using the combined prediction model and a core-collection as training population for grapevine breeding or for other important economic crops with the same characteristics.

Réanimation cardio-pulmonaire et travail en équipe : réflexion autour du concept aéronautique de "Crew Resource Management"

La prise en charge intra-hospitalière des arrêts cardio-respiratoires s'appuie sur une application précoce des gestes de base de la réanimation cardio- pulmonaire (massage cardiaque, ventilation pulmonaire, défibrillation) par les soignants. À l'heure actuelle, les formations à la réanimation cardio-pulmonaire impliquent uniquement l'apprentissage de gestes techniques et de connaissances théoriques, mais omettent totalement les aspects relationnels, ainsi que les problèmes de communication et de travail en équipe. Au travers d'une revue critique de la littérature médicale et aéronautique, nous proposons une nouvelle piste de formation dans le domaine de la réanimation cardio-pulmonaire. En s'appuyant sur les travaux réalisés dans l'aviation, dans les domaines de l'erreur humaine et du travail en équipe, nous offrons finalement une adaptation du "Crew Resource Management" ainsi qu'une série de recommandations, visant à intégrer les éléments relationnels et le facteur humain dans les cours de réanimations cardio-pulmonaires.

Reshaping the remodelled left ventricle: a new concept.

OBJECTIVE: Based on the law of Laplace, transventricular tension members were designed to diminish wall stress by changing the left ventricle (LV) globular shape to a bilobular one, thus reducing the ventricular wall radius of curvature. This concept was tested in a model of congestive heart failure. METHODS: Seven calves were used for the study (74.3+/-4.2 kg). Treatment efficacy was assessed with sonomicrometric wall motion analysis coupled with intraventricular pressure measurement. Preload increase was applied stepwise with tension members in released and tightened position. RESULTS: Tightening of the tension members improved systolic function for CVP>10 mmHg (dP/dt: 828+/-122 vs. 895+/-112 mmHg/s, P=0.019, for baseline and 20% stress level reduction respectively; wall thickening: 11.6+/-1.5 vs. 13.3+/-1.7%, P<0.001) and diastolic function (LV end-diastolic pressure: 15.9+/-4.8 vs. 13.6+/-2.7 mmHg, P<0.001, for CVP>10 mmHg; peak rate of wall thinning: -12.2+/-2.2 vs. -14+/-2.3 cm(2)/s, P<0.001 and logistic time constant of isovolumic relaxation: 48.4 +/-10.9 vs. 39.8+/-9.6ms, P<0.001, for CVP>5 mmHg). CONCLUSIONS: This less aggressive LV reduction method significantly improves contractility and relaxation parameters in this model of congestive heart failure.

Ecological assembly rules in plant communities--approaches, patterns and prospects.

Understanding how communities of living organisms assemble has been a central question in ecology since the early days of the discipline. Disentangling the different processes involved in community assembly is not only interesting in itself but also crucial for an understanding of how communities will behave under future environmental scenarios. The traditional concept of assembly rules reflects the notion that species do not co-occur randomly but are restricted in their co-occurrence by interspecific competition. This concept can be redefined in a more general framework where the co-occurrence of species is a product of chance, historical patterns of speciation and migration, dispersal, abiotic environmental factors, and biotic interactions, with none of these processes being mutually exclusive. Here we present a survey and meta-analyses of 59 papers that compare observed patterns in plant communities with null models simulating random patterns of species assembly. According to the type of data under study and the different methods that are applied to detect community assembly, we distinguish four main types of approach in the published literature: species co-occurrence, niche limitation, guild proportionality and limiting similarity. Results from our meta-analyses suggest that non-random co-occurrence of plant species is not a widespread phenomenon. However, whether this finding reflects the individualistic nature of plant communities or is caused by methodological shortcomings associated with the studies considered cannot be discerned from the available metadata. We advocate that more thorough surveys be conducted using a set of standardized methods to test for the existence of assembly rules in data sets spanning larger biological and geographical scales than have been considered until now. We underpin this general advice with guidelines that should be considered in future assembly rules research. This will enable us to draw more accurate and general conclusions about the non-random aspect of assembly in plant communities.

Growth Arrest-Specific Gene 6 product modulates innate immunity in sepsis

Background: Growth Arrest-Specific Gene 6 product (Gas6) is, like anticoagulant protein C, a vitamin K-dependent protein. Our aim was to determine whether Gas6 plays a role in sepsis. Materials and methods: We submitted mice lacking Gas6 (Gas6)/)) or one of its receptors (Axl)/), Tyro3)/) or Mertk)/)) to LPS-induced endotoxemia and peritonitis (cecal ligation and puncture (CLP) and inoculation of E. coli). In addition, we measured Gas6 or its soluble receptors in plasma of eight volunteers that received LPS, 13 healthy subjects, 28 patients with severe sepsis, and 18 patients with non-infectious inflammatory diseases. Results: Gas6 and its soluble receptor sAxl raised in mice models and TNF-a was more elevated in Gas6)/) mice than in wild-type (WT). Protein array showed that before and after LPS injection, titers of 62 cytokines were more elevated in plasma of Gas6)/) than WT mice. Endotoxemia-induced mortality was higher in Gas6)/), Axl)/), Tyro3)/) and Mertk)/) compared to WT mice and mortality subsequent to CLP was amplified in Gas6)/) mice. LPS-stimulated Gas6)/) macrophages produced more cytokines than WT macrophages. This production was dampened by recombinant Gas6. Phosphorylation of Akt in Gas6)/) macrophages was reduced, but p38 phosphorylation and NF-jB translocation were increased. In human, Gas6 raised in plasma after LPS (2 ng/kg). Gas6 and sAxl were higher in patients with severe sepsis than in healthy subjects or control patients, and there was a non-significant trend for higher Gas6 in the survival group. Conclusions: Our data point to Gas6 as a major modulator of innate immunity and provide thereby novel insights into the mechanism of sepsis. Thus Gas6 and its receptors might constitute potential therapeutic targets for the development of new immunomodulating drugs.

Investigations on hydrogen isotope ratios of endogenous urinary steroids: reference-population-based thresholds and proof-of-concept.

Carbon isotope ratio (CIR) analysis has been routinely and successfully used in sports drug testing for many years to uncover the misuse of endogenous steroids. One limitation of the method is the availability of steroid preparations exhibiting CIRs equal to endogenous steroids. To overcome this problem, hydrogen isotope ratios (HIR) of endogenous urinary steroids were investigated as a potential complement; results obtained from a reference population of 67 individuals are presented herein. An established sample preparation method was modified and improved to enable separate measurements of each analyte of interest where possible. From the fraction of glucuronidated steroids; pregnanediol, 16-androstenol, 11-ketoetiocholanolone, androsterone (A), etiocholanolone (E), dehydroepiandrosterone (D), 5α- and 5β-androstanediol, testosterone and epitestosterone were included. In addition, sulfate conjugates of A, E, D, epiandrosterone and 17α- and 17β-androstenediol were considered and analyzed after acidic solvolysis. The obtained results enabled the calculation of the first reference-population-based thresholds for HIR of urinary steroids that can readily be applied to routine doping control samples. Proof-of-concept was accomplished by investigating urine specimens collected after a single oral application of testosterone-undecanoate. The HIR of most testosterone metabolites were found to be significantly influenced by the exogenous steroid beyond the established threshold values. Additionally, one regular doping control sample with an extraordinary testosterone/epitestosterone ratio of 100 without suspicious CIR was subjected to the complementary methodology of HIR analysis. The HIR data eventually provided evidence for the exogenous origin of urinary testosterone metabolites. Despite further investigations on HIR being advisable to corroborate the presented reference-population-based thresholds, the developed method proved to be a new tool supporting modern sports drug testing procedures.

The concept of the inflammasome and its rheumatologic implications.

The inflammasome is a proteolytic complex that regulates IL1β and IL-18 secretion in macrophages and dendritic cells. Its plays a vital role in the control of the inflammatory and cellular responses to infectious and danger signals and is an essential part of the innate immune system. Four different inflammasomes have been identified so far, and the NLRP3-inflammasome has been the best-studied in relation to human disease. Activation of the NLRP3-inflammasome by microcrystals, such as monosodium urate (MSU) and basic calcium phosphate (BCP) crystals, leads to IL1β release, which in turn triggers local inflammation. Dysfunction of the NLRP3-inflammasome due to mutations of the NLRP3 gene is the cause of the auto-inflammatory syndrome CAPS. The symptoms and signs of inflammation in both conditions respond to IL1 blockade. IL1 inhibitors have also been used successfully in other idiopathic inflammatory diseases, suggesting that dysregulated inflammasome activity contributes to the pathogenesis of multiple diseases, but the precise underlying mechanisms remain to be identified.

A modular magnetic anastomotic device for minimally invasive digestive anastomosis: proof of concept and preliminary data in the pig model.

BACKGROUND: The aim of our study was to assess the feasibility of minimally invasive digestive anastomosis using a modular flexible magnetic anastomotic device made up of a set of two flexible chains of magnetic elements. The assembly possesses a non-deployed linear configuration which allows it to be introduced through a dedicated small-sized applicator into the bowel where it takes the deployed form. A centering suture allows the mating between the two parts to be controlled in order to include the viscerotomy between the two magnetic rings and the connected viscera. METHODS AND PROCEDURES: Eight pigs were involved in a 2-week survival experimental study. In five colorectal anastomoses, the proximal device was inserted by a percutaneous endoscopic technique, and the colon was divided below the magnet. The distal magnet was delivered transanally to connect with the proximal magnet. In three jejunojejunostomies, the first magnetic chain was injected in its linear configuration through a small enterotomy. Once delivered, the device self-assembled into a ring shape. A second magnet was injected more distally through the same port. The centering sutures were tied together extracorporeally and, using a knot pusher, magnets were connected. Ex vivo strain testing to determine the compression force delivered by the magnetic device, burst pressure of the anastomosis, and histology were performed. RESULTS: Mean operative time including endoscopy was 69.2 ± 21.9 min, and average time to full patency was 5 days for colorectal anastomosis. Operative times for jejunojejunostomies were 125, 80, and 35 min, respectively. The postoperative period was uneventful. Burst pressure of all anastomoses was ≥ 110 mmHg. Mean strain force to detach the devices was 6.1 ± 0.98 and 12.88 ± 1.34 N in colorectal and jejunojejunal connections, respectively. Pathology showed a mild-to-moderate inflammation score. CONCLUSIONS: The modular magnetic system showed enormous potential to create minimally invasive digestive anastomoses, and may represent an alternative to stapled anastomoses, being easy to deliver, effective, and low cost.