Overexpression of the E2 ubiquitin–conjugating enzyme UbcH10 causes chromosome missegregation and tumor formation

An overabundance of UbcH10 disrupts mitotic checkpoint signaling as a result of a degradation of cyclin B, increasing spontaneous and carcinogen-induced tumor formation in transgenic mice

Hip fractures in elderly people:Surgery or no surgery? A systematic review and meta-analysis

Iintroduction:  Increasing numbers of patients with hip fractures also have advanced comorbidities. A majority are treated surgically. However, a significantly increasing percentage of medically unfit patients with unacceptably high risk of perioperative death are treated nonoperatively. Important questions about patients' prefracture quality of life (QOL) and future perspectives should be asked before considering different treatment options to assess what kind of treatment is advisable in frail elderly high-risk patients with a hip fracture. Objective:  The aim of this review was to provide an overview of differences in mortality, health-related QOL [(HR)QOL], functional outcome, and costs between nonoperative management (NOM) and operative management (OM) of hip fractures in patients above 65 years. Methods:  A systematic literature search was performed in EMBASE, OvidSP, PubMed, Cochrane Central, and Web of Science for observational studies and trials. Observational studies and randomized controlled trials comparing NOM with OM in hip fracture patients were selected. The methodological quality of the selected studies was assessed according to the Methodological Index for Nonrandomized Studies (MINORS) or Furlan checklist. Results:  Seven observational studies were included with a total of 1189 patients, of whom 242 (20.3%) were treated conservatively. The methodological quality of the studies was moderate (mean: 14.7, standard deviation [SD]: 1.5). The 30-day and 1-year mortalities were higher in the nonoperative group (odds ratio [OR]: 3.95, 95% confidence interval [CI]: 1.43-10.96; OR: 3.84, 95% CI: 1.57-9.41). None of the included studies compared QOL, functional outcome, or health-care costs between the 2 groups. Conclusion:  This systematic review and meta-analysis demonstrated that only a few studies with small number of patients comparing NOM with OM were published. A significantly higher 30-day and 1-year mortality was revealed in nonoperatively treated hip fracture patients. No data were found examining (HR)QOL and costs. Further work is needed to enable shared decision-making and to initiate NOM in frail elderly patients with advanced comorbidity and limited life expectancy

Cdc20 hypomorphic mice fail to counteract de novo synthesis of cyclin B1 in mitosis

Low expression levels of Cdc20 result in chromatin bridging and chromosome misalignment, revealing a requirement for Cdc20 in efficient sister chromosome separation and chromosome–microtubule attachment

Second intravenous immunoglobulin dose in patients with Guillain-Barre syndrome with poor prognosis (SID-GBS):a double-blind, randomised, placebo-controlled trial

Background Treatment with one standard dose (2 g/kg) of intravenous immunoglobulin is insufficient in a proportion of patients with severe Guillain-Barre syndrome. Worldwide, around 25% of patients severely affected with the syndrome are given a second intravenous immunoglobulin dose (SID), although it has not been proven effective. We aimed to investigate whether a SID is effective in patients with Guillain-Barre syndrome with a predicted poor outcome. Methods In this randomised, double-blind, placebo-controlled trial (SID-GBS), we included patients (>= 12 years) with Guillain-Barre syndrome admitted to one of 59 participating hospitals in the Netherlands. Patients were included on the first day of standard intravenous immunoglobulin treatment (2 g/kg over 5 days). Only patients with a poor prognosis (score of >= 6) according to the modified Erasmus Guillain-Barre syndrome Outcome Score were randomly assigned, via block randomisation stratified by centre, to SID (2 g/kg over 5 days) or to placebo, 7-9 days after inclusion. Patients, outcome adjudicators, monitors, and the steering committee were masked to treatment allocation. The primary outcome measure was the Guillain-Barre syndrome disability score 4 weeks after inclusion. All patients in whom allocated trial medication was started were included in the modified intention-to-treat analysis. Findings Between Feb 16, 2010, and June 5, 2018, 327 of 339 patients assessed for eligibility were included. 112 had a poor prognosis. Of those, 93 patients with a poor prognosis were included in the modified intention-to-treat analysis: 49 (53%) received SID and 44 (47%) received placebo. The adjusted common odds ratio for improvement on the Guillain-Barre syndrome disability score at 4 weeks was 1.4 (95% CI 0.6-3.3; p=0.45). Patients given SID had more serious adverse events (35% vs 16% in the first 30 days), including thromboembolic events, than those in the placebo group. Four patients died in the intervention group (13-24 weeks after randomisation). Interpretation Our study does not provide evidence that patients with Guillain-Barre syndrome with a poor prognosis benefit from a second intravenous immunoglobulin course; moreover, it entails a risk of serious adverse events. Therefore, a second intravenous immunoglobulin course should not be considered for treatment of Guillain-Barre syndrome because of a poor prognosis. The results indicate the need for treatment trials with other immune modulators in patients severely affected by Guillain-Barre syndrome. Funding Prinses Beatrix Spierfonds and Sanquin Plasma Products. Copyright (C) 2021 Elsevier Ltd. All rights reserved

Bub1 overexpression induces aneuploidy and tumor formation through Aurora B kinase hyperactivation

Hyperactivated Aurora B kinase is a primary mediator of Bub1 overexpression-induced aneuploidy and tumorigenesis in mice

An alternative allergen risk management approach

Protein components in food can trigger immune-mediated response in susceptible individuals. International law requires risk assessment to be undertaken by competent individuals to minimize food safety risk to consumers. Historically, allergen control legislation has been food focused and on the requirement for on pack labeling, and the need for formal food recalls in the event of misleading or inappropriate labeling. In order to develop a mechanism for decision makers when assessing allergenic risk from plant derived materials, the aim of this research was to consider a more holistic risk assessment method whereby rather than just using the food-based approach, an additive element in terms of considering the families of proteins is included. This approach reflects the need for food professionals to fully understand the role of proteins in triggering an allergic response to plant material and the health risk to individuals who show cross-reactivity to such proteins

Ran-dependent docking of importin-β to RanBP2/Nup358 filaments is essential for protein import and cell viability

RanBP2 captures RanGTP–importin-β complexes at cytoplasmic fibrils to ensure adequate classical NLS–mediated protein import and cell viability