Endocardite das válvulas das cavidades direitas: a importância da ecocardiografia na identificação da(s) estrutura(s) afectada(s)

A endocardite das válvulas das cavidades direitas do coração é rara. Ocorre geralmente em doentes com toxicofilia endovenosa, portadores de pacemaker (PMD), portadores de próteses valvulares ou cateter venoso central e ainda em doentes com cardiopatias congénitas. A Ecocardiografia constitui o gold standard na identificação da(s) estrutura(s) afetada (s) e permite a orientação terapêutica. Apesar de ser rara, a endocardite das cavidades direitas deve ser tida em conta durante a realização de ecocardiografia transtorácica e/ou transesofágica que vise o diagnóstico de endocardite. A profilaxia antibiótica deve ser sempre aplicada antes da realização de qualquer procedimento invasivo de acordo com as recomendações publicadas. Acentua-se a necessidade de educar a população, prevenindo-se assim complicações graves resultantes de procedimentos simples cada vez mais vulgares nas populações mais jovens, como a colocação de piercing. Os autores apresentam dois casos clínicos dessa patologia

A unique serum IgG glycosylation signature predicts development of Crohn’s disease and is associated with pathogenic antibodies to mannose glycan

Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the gut. There is growing evidence in Crohn’s disease (CD) of the existence of a preclinical period characterized by immunological changes preceding symptom onset that starts years before diagnosis. Gaining insight into this preclinical phase will allow disease prediction and prevention. Analysis of preclinical serum samples, up to 6 years before IBD diagnosis (from the PREDICTS cohort), revealed the identification of a unique glycosylation signature on circulating antibodies (IgGs) characterized by lower galactosylation levels of the IgG fragment crystallizable (Fc) domain that remained stable until disease diagnosis. This specific IgG2 Fc glycan trait correlated with increased levels of antimicrobial antibodies, specifically anti-Saccharomyces cerevisiae (ASCA), pinpointing a glycome–ASCA hub detected in serum that predates by years the development of CD. Mechanistically, we demonstrated that this agalactosylated glycoform of ASCA IgG, detected in the preclinical phase, elicits a proinflammatory immune pathway through the activation and reprogramming of innate immune cells, such as dendritic cells and natural killer cells, via an FcγR-dependent mechanism, triggering NF-κB and CARD9 signaling and leading to inflammasome activation. This proinflammatory role of ASCA was demonstrated to be dependent on mannose glycan recognition and galactosylation levels in the IgG Fc domain. The pathogenic properties of (anti-mannose) ASCA IgG were validated in vivo. Adoptive transfer of antibodies to mannan (ASCA) to recipient wild-type mice resulted in increased susceptibility to intestinal inflammation that was recovered in recipient FcγR-deficient mice. Here we identify a glycosylation signature in circulating IgGs that precedes CD onset and pinpoint a specific glycome–ASCA pathway as a central player in the initiation of inflammation many years before CD diagnosis. This pathogenic glyco-hub may constitute a promising new serum biomarker for CD prediction and a potential target for disease prevention.We wish to acknowledge the Gastroenterology Department of Centro Hospitalar Universitário de Santo António, in particular P. Lago, for providing samples from individuals with established CD. We kindly thank J. Rojo from the Instituto de Investigaciones Químicas (Universidad de Sevilla) for providing us with the di-GlcNAc glycodendrimer. We would also like to acknowledge J. V. Ravetch (Rockefeller University) and M. S. Cragg (University of Southampton) for kindly providing us with the FcγR-deficient mice used in the in vivo studies. S.S.P. acknowledges funding from the US Department of Defense, US Army Medical Research Acquisition Activity and FY18Peer-Reviewed Medical Research Program Investigator-Initiated Research Award (award number W81XWH1920053). S.S.P. also acknowledges funding from the European Crohn’s and Colitis Organisation (ECCO) Pioneer Award 2021, the International Organization for the study of Inflammatory Bowel Disease (IOIBD) and the Portuguese Foundation for Science and Technology (FCT; EXPL/MED-ONC/0496/2021). J.G. acknowledges funding from European Society of Clinical Microbiology and Infectious Diseases (ESCMID ResearchGrant 2022), European Crohn’s and Colitis Organisation (ECCO Grant 2023) and FCT (2020.00088.CEECIND). C.S.R. thanks FCT forfunding (2020.08422.BD). I.A. acknowledges funding from FCT (2022.00337.CEECIND) and the BIAL Foundation and PortugueseMedical Association (Maria de Sousa Award 2023). E.L.-G. thanks FCT for funding (UI/BD/152866/2022). F.P. and Z.H.G. were partially supported by the Kenneth-Rainin Foundation (20210021). B.C. acknowledges funding from FCT(CEECINST/00123/2021/CP1772/CT0001). J.T. acknowledges funding from the Portuguese Society of Gastroenterology and from Luz Saúde (Grupo dE iNvestIgação em Patologia Digestiva LUz Saúde LH.INV.F2019015). This study was also cofunded by the EuropeanUnion (GlycanTrigger, grant agreement number 101093997). The views and opinions expressed are, however, those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. This study was conducted under support of Peer-Reviewed Medical Research Program (PR180831P1). The views expressed in this article reflect the results of the research conducted by the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, the Henry M. Jackson Foundation for the Advancement of Military Medicine or the US Government. There are no restrictions on its use. This article was prepared while R.M.L. was employed at Henry M. Jackson Foundation for the Advancement of Military Medicine. The opinions expressed in this article are those of the authors and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services or the US Government. C.K.P. is an employee of the US Government. This work was prepared as part of official duties. Title 17 U.S.C. §105provides that ‘Copyright protection under this title is not available for any work of the United States Government.’ Title 17 U.S.C. §101 defines a US Government work as a work prepared by a military service member or employee of the US Government as part of that person’s official duties

The regularized visible fold revisited

The planar visible fold is a simple singularity in piecewise smooth systems. In this paper, we consider singularly perturbed systems that limit to this piecewise smooth bifurcation as the singular perturbation parameter $\epsilon\rightarrow 0$. Alternatively, these singularly perturbed systems can be thought of as regularizations of their piecewise counterparts. The main contribution of the paper is to demonstrate the use of consecutive blowup transformations in this setting, allowing us to obtain detailed information about a transition map near the fold under very general assumptions. We apply this information to prove, for the first time, the existence of a locally unique saddle-node bifurcation in the case where a limit cycle, in the singular limit $\epsilon\rightarrow 0$, grazes the discontinuity set. We apply this result to a mass-spring system on a moving belt described by a Stribeck-type friction law