Association of FCGR3A and FCGR3B haplotypes with rheumatoid arthritis and primary Sjögren's syndrome [POSTER PRESENTATION]

Background Rheumatoid arthritis (RA) is an autoimmune disease that is thought to arise from a complex interaction between multiple genetic factors and environmental triggers. We have previously demonstrated an association between a Fc gamma receptor (FcγR) haplotype and RA in a cross-sectional cohort of RA patients. We have sought to confirm this association in an inception cohort of RA patients and matched controls. We also extended our study to investigate a second autoanti-body associated rheumatic disease, primary Sjögren's syndrome (PSS). Methods The FCGR3A-158F/V and FCGR3B-NA1/NA2 functional polymorphisms were examined for association in an inception cohort of RA patients (n = 448), and a well-characterised PSS cohort (n = 83) from the United Kingdom. Pairwise disequilibrium coefficients (D') were calculated in 267 Blood Service healthy controls. The EHPlus program was used to estimate haplotype frequencies for patients and controls and to determine whether significant linkage disequilibrium was present. A likelihood ratio test is performed to test for differences between the haplotype frequencies in cases and controls. A permutation procedure implemented in this program enabled 1000 permutations to be performed on all haplotype associations to assess significance. Results There was significant linkage disequilibrium between FCGR3A and FCGR3B (D' = -0.445, P = 0.001). There was no significant difference in the FCGR3A or FCGR3B allele or genotype frequencies in the RA or PSS patients compared with controls. However, there was a significant difference in the FCGR3A-FCGR3B haplotype distributions with increased homozygosity for the FCGR3A-FCGR3B 158V-NA2 haplotype in both our inception RA cohort (odds ratio = 2.15, 95% confidence interval = 1.1–4.2 P = 0.027) and PSS (odds ratio = 2.83, 95% confidence interval = 1.0–8.2, P = 0.047) compared with controls. The reference group for these analyses comprised individuals who did not possess a copy of the FCGR3A-FCGR3B 158V-NA2 haplotype. Conclusions We have confirmed our original findings of association between the FCGR3A-FCGR3B 158V-NA2 haplotype and RA in a new inception cohort of RA patients. This suggests that there may be an RA-susceptibility gene at this locus. The significant increased frequency of an identical haplotype in PSS suggests the FcγR genetic locus may contribute to the pathogenesis of diverse autoantibody-mediated rheumatic diseases

Minimal immersions of closed surfaces in hyperbolic three-manifolds

We study minimal immersions of closed surfaces (of genus $g \ge 2$) in hyperbolic 3-manifolds, with prescribed data $(\sigma, t\alpha)$, where $\sigma$ is a conformal structure on a topological surface $S$, and $\alpha dz^2$ is a holomorphic quadratic differential on the surface $(S,\sigma)$. We show that, for each $t \in (0,\tau_0)$ for some $\tau_0 > 0$, depending only on $(\sigma, \alpha)$, there are at least two minimal immersions of closed surface of prescribed second fundamental form $Re(t\alpha)$ in the conformal structure $\sigma$. Moreover, for $t$ sufficiently large, there exists no such minimal immersion. Asymptotically, as $t \to 0$, the principal curvatures of one minimal immersion tend to zero, while the intrinsic curvatures of the other blow up in magnitude.Comment: 16 page

Pan-European early switch/early discharge opportunities exist for hospitalised patients with methicillin-resistant <em>Staphylococcus</em> <em>aureus</em> complicated skin and soft-tissue infections

AbstractThe objective of this study was to document pan-European real-world treatment patterns and healthcare resource use and estimate opportunities for early switch (ES) from intravenous (IV) to oral antibiotics and early discharge (ED) in hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft tissue infections (cSSTIs). This retrospective observational medical chart review study enrolled 342 physicians across 12 European countries who collected data from 1542 patients with documented MRSA cSSTI who were hospitalized (July 2010 to June 2011) and discharged alive (by July 2011). Data included clinical characteristics and outcomes, hospital length of stay (LOS), MRSA-targeted IV and oral antibiotic use, and ES and ED eligibility according to literature-based and expert-validated criteria. The most frequent initial MRSA-active antibiotics were vancomycin (50.2%), linezolid (15.1%), clindamycin (10.8%), and teicoplanin (10.4%). Patients discharged with MRSA-active antibiotics (n = 480) were most frequently prescribed linezolid (42.1%) and clindamycin (19.8%). IV treatment duration (9.3 ± 6.5 vs. 14.6 ± 9.9 days; p <0.001) and hospital LOS (19.1 ± 12.9 vs. 21.0 ± 18.2 days; p 0.162) tended to be shorter for patients switched from IV to oral treatment than for patients who received IV treatment only. Of the patients, 33.6% met ES criteria and could have discontinued IV treatment 6.0 ± 5.5 days earlier, and 37.9% met ED criteria and could have been discharged 6.2 ± 8.2 days earlier. More than one-third of European patients hospitalized for MRSA cSSTI could be eligible for ES and ED, resulting in substantial reductions in IV days and bed-days, with potential savings of €2000 per ED-eligible patient

Comorbidité lèpre et tuberculose: à propos de six cas

Objectif : Rapporter 6 observations de co-infection de la lèpre et de la tuberculose. Méthodes : Il s’agissait d’une série rétrospective transversale à visée descriptive réalisée au Centre Hospitalier de l’Ordre de Malte à Dakar (Sénégal) sur une période de 15 ans (2001-2016).Résultats : Six dossiers étaient étudiés. La moyenne d’âge des patients était de 29 ans ± 10,4 [15 - 42 ans] avec un sex ratio H/F de 2 (4 hommes pour 2 femmes). Quatre patients avaient une lèpre lépromateuse et deux une lèpre borderline (boderline lépromateuse). Le délai médian d’évolution entre la tuberculose et la lèpre était de 32 mois [5 mois- 48 mois]. Les formes de tuberculose retrouvées étaient des formes purement pulmonaires dans 4 cas et multifocale (pleural et ganglionnaire ; pleural puis neurologique) dans 2 cas. Les facteurs de risque de survenue de la tuberculose étaient la corticothérapie générale au long cours, la malnutrition, l’anémie, le tabagisme et la grossesse. La sérologie antirétrovirale à VIH était négative chez tous les patients. Les traitements de la lèpre et de la tuberculose étaient prescrits selon les protocoles de l’OMS. Tous les patients étaient déclarés guéris de la lèpre et de la tuberculose.Conclusion : la survenue de la lèpre dans sa forme multibacillaire sur un terrain immunitaire déficitaire pourrait favoriser soit la réactivation d'une tuberculose latente sous-jacente ou une surinfection de la lèpre par Mycobacterium tuberculosis. Il paraît donc important de rechercher activement la tuberculose durant le screening des patients atteints de lèpre surtout lépromateus

Epstein-Barr virus nuclear protein EBNA3C directly induces expression of AID and somatic mutations in B cells

Activation-induced cytidine deaminase (AID), the enzyme responsible for induction of sequence variation in immunoglobulins (Igs) during the process of somatic hypermutation (SHM) and also Ig class switching, can have a potent mutator phenotype in the development of lymphoma. Using various Epstein-Barr virus (EBV) recombinants, we provide definitive evidence that the viral nuclear protein EBNA3C is essential in EBV-infected primary B cells for the induction of AID mRNA and protein. Using lymphoblastoid cell lines (LCLs) established with EBV recombinants conditional for EBNA3C function, this was confirmed, and it was shown that transactivation of the AID gene (AICDA) is associated with EBNA3C binding to highly conserved regulatory elements located proximal to and upstream of the AICDA transcription start site. EBNA3C binding initiated epigenetic changes to chromatin at specific sites across the AICDA locus. Deep sequencing of cDNA corresponding to the IgH V-D-J region from the conditional LCL was used to formally show that SHM is activated by functional EBNA3C and induction of AID. These data, showing the direct targeting and induction of functional AID by EBNA3C, suggest a novel role for EBV in the etiology of B cell cancers, including endemic Burkitt lymphoma

Chemical composition and migration levels of packaging adhesives

Includes bibliographical referencesAvailable from British Library Document Supply Centre- DSC:5332. 177(557) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo