Furthermore, protein stability and cell viability assays using two distinct proteasome inhibitor anticancer drugs, the 20S proteasome inhibitor bortezomib and the ubiquitin activating enzyme E1 inhibitor TAK-243, which show that upregulation of the NRF3-POMP axis leads to ubiquitin-independent proteolysis of p53 and Rb, and to impaired sensitivity to bortezomib, but not TAK-243.  https://www.selleckchem.com/products/sb290157-tfa.html  More importantly, the NRF3-POMP axis supports tumorigenesis and metastasis, with higher NRF3/POMP expression correlating with poor prognosis in patients with colorectal or rectal adenocarcinoma. These results suggest the NRF3-POMP-20S proteasome assembly axis is significant for cancer development via ubiquitin-independent proteolysis of tumor suppressor proteins. Copyright © 2020 Waku et al.BACKGROUND AND PURPOSE Stroke recurrence is high in patients with symptomatic intracranial stenosis despite best medical treatment. Based on evidence from past studies using previous stent generations, elective intracranial stenting (eICS) is considered in a minority of patients. This study aims to report on experience performing eICS with a novel device combination. METHODS We retrospectively reviewed data from three high volume stroke centers and analyzed patients that were treated with eICS for symptomatic intracranial stenosis using the Acclino® (flex) stent and the NeuroSpeed® balloon catheter (Acandis GmbH, Pforzheim, Germany). Study endpoints were periprocedural rates of stroke regardless of territory or death at discharge and at the time of follow-up after eICS. Safety evaluation included asymptomatic and symptomatic intracranial hemorrhage, serious adverse events related to the intervention, and evaluation of stent patency at the time of follow-up. RESULTS The median age of patients that met the inclusion criteria (n=76) was 69 years. Target vessels were located in the anterior circulation in 55.3% (42/76) of patients. The periprocedural stroke rate was 6.5% (fatal stroke 2.6%; non-fatal stroke 3.9%) at discharge after eICS. Asymptomatic intracranial hemorrhage was observed in 5.2% (4/76) of patients. Follow-up DSA revealed in-stent restenosis of 25% (15/60), and percutaneous transluminal angioplasty was performed again in 11.6% (7/60) of patients. CONCLUSION Stenting for symptomatic intracranial stenosis with the Acclino® (flex)/NeuroSpeed balloon® catheter seemed to be safe and reinforces eICS as an endovascular therapy option for secondary stroke prevention. Future studies are warranted to confirm these findings and investigate antithrombotic strategies and in-stent restenosis to minimize periprocedural complications and guarantee long term stent patency. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.This paper describes a series of critically ill patients who were cared for at a UK military field hospital during Op TRENTON 4, in support of the United Nations Mission in South Sudan. These cases highlight the potential challenges in managing the critically ill patient during contingency operations that take place in an austere resource-limited environment. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.The United Nations Mission in South Sudan has a mandate to protect civilians and support the delivery of humanitarian assistance. Recognising this during Operation TRENTON, UK staff of the UN level 2 hospital were able to support the people of Bentiu through initiatives to develop local health services with on-the-ground civil-military cooperation. The Bentiu State Hospital Medical Training Programme was developed to train and mentor staff associated with healthcare in Bentiu, to help improve service delivery, support local health services with on-the-ground non-governmental organisation/military coordination and to create a platform to facilitate the sharing of information to support local health services with the overall humanitarian response. It was recognised how important it was to deliver a programme that carefully understood the unique challenging limitations, circumstances and environment. Hence careful tailoring of the programme was essential to ensure that the training was valuable, implementable and durable, long beyond the operational deployment of TRENTON. Despite the logistical and practical complexities, the programme was very positively received, and the training team believed that the development and progress made would build a small part of the future infrastructure of healthcare delivery in the region. Future contingency operations are likely to take place in the resource- limited austere environment. As reflected in this deployed initiative, local health training activity providing key knowledge to build resilience for the current and immediate future is a precious and important defence engagement utility. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.INTRODUCTION The 2016 Interim Report on the Health Risks to Women in Ground Close Combat Roles highlighted an increased risk of skeletal injury and significant physiological changes, including increased ligament laxity and decreased bone mineral content, during the postpartum period. The report called for further research and a re-evaluation of postpartum policy to optimise the return of female Service personnel to arduous employment. The purpose of this study was to determine whether returning to duty is at greater risk of injury and illness in the first year postpartum than they were prepregnancy. METHODS Fifty-five female UK Army Service personnel aged 18-41 years, who had given birth in the previous 4 years, completed a lifestyle questionnaire and gave written consent for a review of their medical records. The number of working days lost (WDL) due to illness, injury and combined illness and injury was obtained from medical records, for 1 year prepregnancy and 1 year postpartum. Female Service personnel returned to duty at different time-points postpartum, so data were expressed as WDL/week. RESULTS WDL/week due to illness and combined illness and injury were higher postpartum compared with prepregnancy (p less then 0.05). WDL/week due to combined illness and injury was significantly lower prepregnancy (p less then 0.05) and at 0-26 weeks postpartum (p less then 0.05), compared with 26-52 weeks postpartum. CONCLUSIONS Postpartum female UK Army Service personnel are at greater risk of illness and a combination of illness and injury in the year after giving birth, compared with prepregnancy. The study suggests female Service personnel are unprepared for the demands of full active duty in the first year postpartum. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.