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AimsIn response to the COVID-19 pandemic, the UK was placed under strict lockdown measures on 23 March 2020. The aim of this study was to quantify the effects on physical activity (PA) levels using data from the prospective Triage-HF Plus Evaluation study.MethodsThis study represents a cohort of adult patients with implanted cardiac devices capable of measuring activity by embedded accelerometery via a remote monitoring platform. Activity data were available for the 4 weeks pre-implementation and post implementation of ‘stay at home’ lockdown measures in the form of ‘minutes active per day’ (min/day).ResultsData were analysed for 311 patients (77.2% men, mean age 68.8, frailty 55.9%. 92.2% established heart failure (HF) diagnosis, of these 51.2% New York Heart Association II), with comorbidities representative of a real-world cohort.Post-lockdown, a significant reduction in median PA equating to 20.8 active min/day was seen. The reduction was uniform with a slightly more pronounced drop in PA for women, but no statistically significant difference with respect to age, body mass index, frailty or device type. Activity dropped in the immediate 2-week period post-lockdown, but steadily returned thereafter. Median activity week 4 weeks post-lockdown remained significantly lower than 4 weeks pre-lockdown (p≤0.001).ConclusionsIn a population of predominantly HF patients with cardiac devices, activity reduced by approximately 20 min active per day in the immediate aftermath of strict COVID-19 lockdown measures.Trial registration numberNCT04177199.

Aims/Objectives/BackgroundThere is broad involvement of emergency medicine (EM) practitioners in global EM (GEM) research. However this work is often siloed, reducing efficiency of collaboration and impeding healthy critical appraisal. The purpose of this novel longitudinal study is to identify the GEM research undertaken by those in EM. Quantifying, displaying and understanding the ‘who’, ‘what’ and ‘where’ of such research is a key step to facilitate collaboration and highlight important gaps to ultimately drive quality in GEM research as a whole.Methods/DesignThe Global Emergency Medicine Literature Review (GEMLR) is an annual summary of the top-ranked GEM literature. A spreadsheet of all papers identified by each initial search (before ranking) is freely available. We searched the past six years of GEMLR’s 3,634 initial titles to identify authors with EM affiliations. We also collected data on author institutions, country focus, topic, funding sources and if co-authorship included local collaborators.Results/ConclusionsFrom 2014–2019 the GEMLR found over 800 individual papers with at least one EM affiliated author. Authors were from over 600 different institutions (see figure 1) and research focused on over 100 countries.Abstract 833 Figure 1Author spreadApproximately 60% had no funding/documented and 5% papers did not include a local author.There are limitations, including the GEMLR search strategy and EM practitioners omitting their EM affiliations (a take home message, if we wish to strengthen EM’s perceived research presence). However this study serves as a robust start-point to map GEM research engagement. Interestingly, the study demonstrates a modest UK author slice with 20 being identified, contributing to 12 papers over 6 years.Further analysis will target the sociodemographic association between the most/least researched countries, expanding to include further years of data. Using a data visualisation strategy we will make the work accessible online to provide leverage in areas of much-needed GEM research growth.

Fatty acid uptake and metabolism are often dysregulated in cancer cells. Fatty acid activation is a critical step that allows these biomolecules to enter cellular metabolic pathways such as mitochondrial β-oxidation for ATP generation or the lipogenic routes that generate bioactive lipids such as the inositol phospholipids. Fatty acid activation by the addition of coenzyme A is catalysed by a family of enzymes called the acyl CoA synthetase ligases (ACSL). Furthermore, enhanced expression of particular ACSL isoforms, such as ACSL4, is a feature of some more aggressive cancers and may contribute to the oncogenic phenotype. This study focuses on ACSL3 and ACSL4, closely related structural homologues that preferentially activate palmitate and arachidonate fatty acids, respectively. In this study, immunohistochemical screening of multiple soft tissue tumour arrays revealed that ACSL3 and ACSL4 were highly, but differentially, expressed in a subset of leiomyosarcomas, fibrosarcomas and rhabdomyosarcomas, with consistent cytoplasmic and granular stainings of tumour cells. The intracellular localisations of endogenously expressed ACSL3 and ACSL4 were further investigated by detailed subcellular fractionation analyses of HT1080 fibrosarcoma and MCF-7 breast cancer cells. ACSL3 distribution closely overlapped with proteins involved in trafficking from the trans-Golgi network and endosomes. In contrast, the ACSL4 localisation pattern more closely followed that of calnexin which is an endoplasmic reticulum resident chaperone. Confocal immunofluorescence imaging of MCF-7 cells confirmed the intracellular localisations of both enzymes. These observations reveal new information regarding the compartmentation of fatty acid metabolism in cancer cells. Electronic supplementary material The online version of this article (10.1007/s11010-018-3332-x) contains supplementary material, which is available to authorized users.

Long-chain fatty acyl CoA synthetases (ACSLs) activate fatty acids by CoA addition thus facilitating their intracellular metabolism. Dysregulated ACSL expression features in several cancers and can affect processes such as ferroptosis, fatty acid β-oxidation, prostaglandin biosynthesis, steroidogenesis and phospholipid acyl chain remodelling. Here we investigate long chain acyl-CoA synthetase 3 (ACSL3) and long chain acyl-CoA synthetase 4 (ACSL4) expression in liver malignancies. The expression and subcellular localisations of the ACSL3 and ACSL4 isoforms in hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA) and hepatic metastases were assessed by immunohistochemical analyses of multiple tumour tissue arrays and by subcellular fractionation of cultured HepG2 cells. The expression of both enzymes was increased in HCC compared with normal liver. Expression of ACSL3 was similar in HCC and hepatic metastases but lower in healthy tissue. Increased ACSL3 expression distinguished HCC from CCA with a sensitivity of 87.2% and a specificity of 75%. ACSL4 expression was significantly greater in HCC than in all other tumours and distinguished HCC from normal liver tissue with a sensitivity of 93.8% and specificity of 93.6%. Combined ACSL3 and ACSL4 staining scores distinguished HCC from hepatic metastases with 80.1% sensitivity and 77.1% specificity. These enzymes had partially overlapping intracellular distributions, ACSL4 localised to the plasma membrane and both isoforms associated with lipid droplets and the endoplasmic reticulum (ER). In conclusion, analysis of ACSL3 and ACSL4 expression can distinguish different classes of hepatic tumours.