Rheumatoid arthritis response to treatment across IgG1 allotype - anti-TNF incompatibility: a case-only study.

INTRODUCTION: We have hypothesized that incompatibility between the G1m genotype of the patient and the G1m1 and G1m17 allotypes carried by infliximab (INX) and adalimumab (ADM) could decrease the efficacy of these anti-tumor necrosis factor (anti-TNF) antibodies in the treatment of rheumatoid arthritis (RA). METHODS: The G1m genotypes were analyzed in three collections of patients with RA totaling 1037 subjects. The first, used for discovery, comprised 215 Spanish patients. The second and third were successively used for replication. They included 429 British and Greek patients and 393 Spanish and British patients, respectively. Two outcomes were considered: change in the Disease Activity Score in 28 joint (ΔDAS28) and the European League Against Rheumatism (EULAR) response criteria. RESULTS: An association between less response to INX and incompatibility of the G1m1,17 allotype was found in the discovery collection at 6 months of treatment (P = 0.03). This association was confirmed in the replications (P = 0.02 and 0.08, respectively) leading to a global association (P = 0.001) that involved a mean difference in ΔDAS28 of 0.4 units between compatible and incompatible patients (2.3 ± 1.5 in compatible patients vs. 1.9 ± 1.5 in incompatible patients) and an increase in responders and decrease in non-responders according to the EULAR criteria (P = 0.03). A similar association was suggested for patients treated with ADM in the discovery collection, but it was not supported by replication. CONCLUSIONS: Our results suggest that G1m1,17 allotypes are associated with response to INX and could aid improved therapeutic targeting in RA

Diabetic Gastroparesis Modeling and Observer Design

Type 1 diabetes results from the lack of endogenous production of insulin by the pancreas. According to various references, 4% to 12% of diabetic patients are affected by gastroparesis which delays the digestion process. Gastroparesis is characterized by a constellation of gastrointestinal symptoms in association with delayed gastric emptying (GE). For the first time, a mathematical model is introduced to describe the glycemia dynamics for this significant class of patients. It is shown to yield to a nonlinear time delay model designed for estimation and control

Dynamic force measurements on swimming Chlamydomonas cells using micropipette force sensors

Flagella and cilia are cellular appendages that inherit essential functions of microbial life including sensing and navigating the environment. In order to propel a swimming microorganism they displace the surrounding fluid by means of periodic motions, while precisely timed modulations of their beating patterns enable the cell to steer towards or away from specific locations. Characterizing the dynamic forces, however, is challenging and typically relies on indirect experimental approaches. Here, we present direct in vivo measurements of the dynamic forces of motile Chlamydomonas reinhardtii cells in controlled environments. The experiments are based on partially aspirating a living microorganism at the tip of a micropipette force sensor and optically recording the micropipette’s position fluctuations with high temporal and sub-pixel spatial resolution. Spectral signal analysis allows for isolating the cell-generated dynamic forces caused by the periodic motion of the flagella from background noise. We provide an analytic, elasto-hydrodynamic model for the micropipette force sensor and describe how to obtain the micropipette’s full frequency response function from a dynamic force calibration. Using this approach, we measure the amplitude of the oscillatory forces during the swimming activity of individual Chlamydomonas reinhardtii cells of 26 ± 5 pN, resulting from the coordinated flagellar beating with a frequency of 49 ± 5 Hz. This dynamic micropipette force sensor technique generalizes the applicability of micropipettes as force sensors from static to dynamic force measurements, yielding a force sensitivity in the piconewton range. In addition to measurements in bulk liquid environment, we study the dynamic forces of the biflagellated microswimmer in the vicinity of a solid/liquid interface. As we gradually decrease the distance of the swimming microbe to the interface, we measure a significantly enhanced force transduction at distances larger than the maximum extent of the beating flagella, highlighting the importance of hydrodynamic interactions for scenarios in which flagellated microorganisms encounter surfaces

[Effects of delay in onset of revascularisation strategies in the acute phase of myocardial infarction].

International audiencethrombolysis (THL) and primary percutaneous coronary intervention (PCI) are therapeutic options in acute myocardial infarction (MI). These strategies have similar efficiency, particularly in the early phase. However, in these randomized studies, different times to treatment (TT) threshold are recognized as discriminant

Severe early-onset axonal neuropathy with homozygous and compound heterozygous MFN2 mutations

OBJECTIVE: Severe early-onset axonal neuropathy (SEOAN) is a heterogeneous phenotype first delineated by Ouvrier et al., characterized by progressive axonal degeneration with gait problems often progressing to wheelchair requirement and later respiratory involvement. Most cases are sporadic single cases. Some have heterozygous mitofusin 2 (MFN2) mutations, many of which are de novo dominant mutations. The aim of this study was to investigate the mode of inheritance in three individuals with severe early-onset axonal neuropathy and homozygous or compound heterozygous MFN2 mutations. METHODS: The clinical and molecular findings in the parents of three individuals with SEOAN with homozygous or compound heterozygous MFN2 mutations were examined. RESULTS: All parents were asymptomatic or mildly symptomatic with some signs of peripheral neuropathy indicating a minimal phenotype. Two had hearing problems. All parents carried the relevant single base (heterozygous) MFN2 variations. CONCLUSION: Severe early-onset axonal neuropathy due to MFN2 mutations can present as an apparently recessively inherited neuropathy but the minimal phenotype in the parents suggests a semi-dominant mechanism.4 page(s

Oculo-dento-digital dysplasia: lack of genotype-phenotype correlation for GJA1 mutations and usefulness of neuro-imaging.

International audienceOculo-dento-digital dysplasia (ODDD) is an autosomal dominant disorder with complete penetrance and high intra- and interfamilial phenotypic variability. The key features in this syndrome are microphthalmia, enamel hypoplasia and syndactyly of the 4th-5th fingers. ODDD is caused by mutations in the connexin 43 gene (GJA1). We report here four patients from three families with GJA1 mutations, one of them diagnosed prenatally. The three mutations (c.52T > C/p.Ser18Pro, c.689_690delTA/p.Tyr230CysfsX6, c.442C > G/p.Arg148Gly) have been reported once before. Two patients had white matter hypersignal anomalies, associated in one case with mental retardation, but asymptomatic in the other one, an observation that leads us to discuss systematic neuroradiological imaging for ODDD. One case has optic atrophy, another has hypospadias. The patient carrying a truncating mutation of Cx43 did not have palmoplantar keratoderma, in contradiction with the previously suggested genotype-phenotype correlation between truncating mutation and skin involvement

Les productions avicoles biologiques en France : état des lieux, verrous, atouts et perspectives

La France est actuellement au premier rang des productions européennes de poulets et d’œufs biologiques. Ces productions ne représentent toutefois au mieux que quelques pourcents de la production nationale. Elles sont en régression pour le poulet ou stable pour l’œuf et ne couvrent pas les besoins du marché intérieur. Dans un contexte à la fois de demande du citoyen, d’une volonté politique nationale affichée et d’évolution du règlement européen, l’aviculture biologique française pourrait reprendre sa croissance en saisissant ces opportunités pour se développer. Aussi nous proposons d’analyser les atouts et les verrous qui caractérisent ce mode de production. Les analyses multicritères de ces productions restent à conduire à l’échelle du territoire. Elles devront prendre en compte les différentes composantes biotechniques, depuis la gestion agronomique des sols jusqu’au produit terminal, en passant par la production territorialisée des matières premières végétales, de même que les composantes économiques, sociétales ou politiques. Au-delà des images positives que les produits biologiques véhiculent en termes de bien-être, de qualité des produits ou de bilan environnemental, certaines contraintes déjà identifiées sont autant d’obstacles à leurs développements. Il convient donc de les analyser finement et de les prendre en compte afin de définir de nouveaux itinéraires de production et de ommercialisation. Ceux-ci devront permettre de concilier un développement cohérent et durable, répondant à des attentes sociétales complexes, de produire des produits de qualité, respectueux de l’environnement, accessibles au plus grand nombre et favorisant l’emploi rural et le développement des territoires. Cette problématique complexe constitue l’objet de deux programmes de recherches pluriannuels complémentaires initiés en 2009, AlterAviBio et AviBio