96 research outputs found

    Onzekere pensioenuitkomsten verhogen kans van opname ‘bedrag ineens’

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    Vanaf 2023 mogen pensioendeelnemers bij pensionering eenmalig (maximaal) tien procent van hun opgebouwde pensioenvermogen opnemen. In hoeverre speelt het vertrouwen in de beloftes van pensioenuitvoerders een rol bij de interesse om gebruik te maken van deze eenmalige uitkering? IN HET KORT ● Van de oudere werknemers zegt 25 procent gebruik te willen maken van de eenmalige opname van pensioenvermogen. ● Onzekere verwachtingen over pensioenuitkomsten vergroten de behoefte aan de keuze voor opname. ● Vooral hogere inkomens en goed geïnformeerde pensioendeelnemers hebben veel belangstelling

    Duplication of the IL2RA locus causes excessive IL-2 signaling and may predispose to very early onset colitis

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    Single genetic mutations predispose to very early onset inflammatory bowel disease (VEO-IBD). Here, we identify a de novo duplication of the 10p15.1 chromosomal region, including the IL2RA locus, in a 2-year-old girl with treatment-resistant pancolitis that was brought into remission by colectomy. Strikingly, after colectomy while the patient was in clinical remission and without medication, the peripheral blood CD4:CD8 ratio was constitutively high and CD25 expression was increased on circulating effector memory, Foxp3(+), and Foxp3(neg) CD4(+) T cells compared to healthy controls. This high CD25 expression increased IL-2 signaling, potentiating CD4(+) T-cell-derived IFN gamma secretion after T-cell receptor (TCR) stimulation. Restoring CD25 expression using the JAK1/3-inhibitor tofacitinib controlled TCR-induced IFN gamma secretion in vitro. As diseased colonic tissue, but not the unaffected duodenum, contained mainly CD4(+) T cells with a prominent IFN gamma-signature, we hypothesize that local microbial stimulation may have initiated colonic disease. Overall, we identify that duplication of the IL2RA locus can associate with VEO-IBD and suggest that increased IL-2 signaling predisposes to colonic intestinal inflammation.Transplantation and immunomodulatio
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