[Folie à deux - Thrombosis and Infections]. / Folie à deux ­ Thrombose und Infektionen.

Folie à deux - Thrombosis and Infections Abstract: Although infections are not represented in the Revised Geneva or Wells score, they increase the risk of venous thromboembolism (VTE) similarly to the known risk factors (immobilization, major surgery, active neoplasia). This increased risk of VTE can persist for six to twelve months after infection; moreover, the more severe the infection, the higher the risk of VTE may be. In addition to VTEs, infections can promote arterial thromboembolism. For example, 20% of pneumonias are accompanied by an acute cardiovascular event (acute coronary syndrome, heart failure, atrial fibrillation). In the case of infection-associated atrial fibrillation, the CHA2DS2 VASc score remains an appropriate guide for the indication of anticoagulation.

USP47 deubiquitylates Groucho/TLE to promote Wnt-ß-catenin signaling.

The Wnt-ß-catenin signal transduction pathway is essential for embryonic development and adult tissue homeostasis. Wnt signaling converts TCF from a transcriptional repressor to an activator in a process facilitated by the E3 ligase XIAP. XIAP-mediated monoubiquitylation of the transcriptional corepressor Groucho (also known as TLE) decreases its affinity for TCF, thereby allowing the transcriptional coactivator ß-catenin to displace it on TCF. Through a genome-scale screen in cultured Drosophila melanogaster cells, we identified the deubiquitylase USP47 as a positive regulator of Wnt signaling. We found that USP47 was required for Wnt signaling during Drosophila and Xenopus laevis development, as well as in human cells, indicating evolutionary conservation. In human cells, knockdown of USP47 inhibited Wnt reporter activity, and USP47 acted downstream of the ß-catenin destruction complex. USP47 interacted with TLE3 and XIAP but did not alter their amounts; however, knockdown of USP47 enhanced XIAP-mediated ubiquitylation of TLE3. USP47 inhibited ubiquitylation of TLE3 by XIAP in vitro in a dose-dependent manner, suggesting that USP47 is the deubiquitylase that counteracts the E3 ligase activity of XIAP on TLE. Our data suggest a mechanism by which regulated ubiquitylation and deubiquitylation of TLE enhance the ability of ß-catenin to cycle on and off TCF, thereby helping to ensure that the expression of Wnt target genes continues only as long as the upstream signal is present.

Parents' vaccination information seeking, satisfaction with and trust in medical providers in Switzerland: a mixed-methods study.

OBJECTIVES: The aim of this study was to better understand parental trust in and satisfaction with information sources and medical providers regarding decision making about childhood vaccines. SETTING: The study was part of a Swiss national research programme investigating vaccine hesitancy and underimmunisation. PARTICIPANTS: We conducted qualitative interviews with 37 providers and 30 parents, observed 34 vaccination consultations, and then conducted quantitative surveys with 130 providers (both complementary and alternative medicine (CAM) oriented and biomedically oriented) and 1390 parents. MAIN OUTCOME MEASURES: Participants' vaccination information sources used in their decision-making process, parents' trust in and satisfaction with these sources and providers. RESULTS: Based on the Parent Attitudes about Childhood Vaccines scale, we considered 501 parents as vaccine-hesitant (VH) and 889 parents as non-VH. Whereas both groups mentioned providers as the most trusted source of information, VH-parents were less likely to mention paediatricians (N=358 (71%) vs N=755 (85%)) and public health authorities (N=101 (20%) vs N=333 (37%)) than non-VH-parents. VH-parents were more likely to have consulted another provider (N=196 (39%) vs N=173 (19%)) than non-VH-parents, to express less satisfaction with both their primary (N=342 (82%) vs N=586 (91%)) and other providers (N=82 (42%) vs N=142 (82%)) and less trust in their primary (N=368 (88%) vs N=632 (98%)) and other providers (N=108 (55%) vs N=146 (84%)). VH-parents were less likely to be satisfied with their biomedical primary provider than non-VH-parents (100 (69%) vs 467 (91%)). However, when the primary provider was CAM-oriented, there were similar levels of satisfaction among both groups (237 (89%) VH-parents vs 118 (89%) non-VH-parents). All differences were significant (p<0.05). CONCLUSIONS: While the provider remains the main information source, VH parents turn to additional sources and providers, which is likely related to VH parents being rather dissatisfied with and distrusting in obtained information and their provider. ETHICS: The local ethics committee (Ethikkommission Nordwest- und Zentralschweiz, EKNZ; project ID number 2017-00725) approved the study.