Mutations within the LINC-HELLP non-coding RNA differentially bind ribosomal and RNA splicing complexes and negatively affect trophoblast differentiation

LINC-HELLP, showing chromosomal linkage with the pregnancy-specific HELLP syndrome in Dutch families, reduces differentiation from a proliferative to an invasive phenotype of first-trimester extravillous trophoblasts. Here we show that mutations in LINC-HELLP identified in HELLP families negatively affect this trophoblast differentiation either by inducing proliferation rate or by causing cell cycle exit as shown by a decrease in both proliferation and invasion. As LincRNAs predominantly function through interactions with proteins, we identified the directly interacting proteins using chromatin isolation by RNA purification followed by protein mass spectrometry. We found 22 proteins predominantly clustering in two functional networks, i.e. RNA splicing and the ribosome. YBX1, PCBP1, PCBP2, RPS6 and RPL7 were validated, and binding to these proteins was influenced by the HELLP mutations carried. Finally, we show that the LINC-HELLP transcript levels are significantly upregulated in plasma of women in their first trimester of pregnancy compared with non-pregnant women, whereas this upregulation seems absent in a pilot set of patients later developing pregnancy complications, indicative of its functional significance in vivo

A cytotoxic phenotype does not predict clinical outcome in anaplastic large cell lymphomas.

AIM: To investigate whether anaplastic large cell lymphomas (ALCL) expressing cytotoxic proteins have a relatively worse clinical outcome compared with ALCL lacking a cytotoxic phenotype. METHODS: 59 primary cases of ALCL originating from different sites were investigated by immunohistochemistry for the presence of the cytotoxic proteins T cell intracytoplasmic antigen (TIA-1) and granzyme B in the neoplastic cells. Since site of origin and expression of anaplastic lymphoma kinase (ALK) strongly influence prognosis, the presence of a cytotoxic phenotype was also investigated in relation to the primary site of origin (lymph node, gut, or skin) and ALK expression. The prognostic value was investigated by analysis of overall and relapse-free survival time, including Cox regression analysis. RESULTS: 39 of 59 ALCL (66%) appeared to have a cytotoxic phenotype as shown by expression of TIA-1 or granzyme B or both in the neoplastic cells. The presence of a cytotoxic phenotype did not have any influence on prognosis. Even when the survival data were corrected for site of origin and stage at presentation or were analysed separately for ALK positive and negative cases, no prognostic influence of a cytotoxic phenotype was observed. CONCLUSIONS: In primary biopsies of patients with ALCL, the presence of a cytotoxic phenotype is not related to clinical outcome of the disease

Red ROM als kwaliteitsinstrument [Save ROM as instrument for quality improvement]

In het recent verschenen rapport over de bekostiging van de curatieve ggz concludeert de Algemene Rekenkamer (2017): ‘informatie die met rom [routine outcome monitoring] wordt verkregen, heeft beperkingen en is van onvoldoende kwaliteit om te dienen als sturingsinformatie bij de zorginkoop’ (p. 14). Dit rapport is door een groep psychiaters en psychologen aangegrepen om de petitie ‘Stop benchmark met rom ’ (www.stoprom.com) in het leven te roepen, die inmiddels door ruim 6000 mensen getekend is. In dit artikel reageren wij op deze petitie. Wij onderschrijven dat rom geen basis mag zijn voor zorginkoop, maar vinden dat rom en benchmarking van grote waarde kunnen zijn voor het verbeteren van de kwaliteit van de behandeling en pleiten daarom voor inhoudelijke doorontwikkeling van benchmarking in plaats van deze te stoppen

Red ROM als kwaliteitsinstrument

FSW - Self-regulation models for health behavior and psychopathology - ou