Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling

Although concern remains about the athero-thrombotic risk posed by cyclo-oxygenase (COX)-2-selective inhibitors, recent data implicates rofecoxib, while celecoxib appears equivalent to NSAIDs naproxen and ibuprofen. We investigated the hypothesis that celecoxib activates AMP kinase (AMPK) signalling to enhance vascular endothelial protection. In human arterial and venous endothelial cells (EC), and in contrast to ibuprofen and naproxen, celecoxib induced the protective protein heme oxygenase-1 (HO-1). Celecoxib derivative 2,5-dimethyl-celecoxib (DMC) which lacks COX-2 inhibition also upregulated HO-1, implicating a COX-2-independent mechanism. Celecoxib activated AMPKα(Thr172) and CREB-1(Ser133) phosphorylation leading to Nrf2 nuclear translocation. Importantly, these responses were not reproduced by ibuprofen or naproxen, while AMPKα silencing abrogated celecoxib-mediated CREB and Nrf2 activation. Moreover, celecoxib induced H-ferritin via the same pathway, and increased HO-1 and H-ferritin in the aortic endothelium of mice fed celecoxib (1000 ppm) or control chow. Functionally, celecoxib inhibited TNF-α-induced NF-κB p65(Ser536) phosphorylation by activating AMPK. This attenuated VCAM-1 upregulation via induction of HO-1, a response reproduced by DMC but not ibuprofen or naproxen. Similarly, celecoxib prevented IL-1β-mediated induction of IL-6. Celecoxib enhances vascular protection via AMPK-CREB-Nrf2 signalling, a mechanism which may mitigate cardiovascular risk in patients prescribed celecoxib. Understanding NSAID heterogeneity and COX-2-independent signalling will ultimately lead to safer anti-inflammatory drugs

The nature and fate of natural resins in the geosphere XIII: a probable pinaceous resin from the early Cretaceous (Barremian), Isle of Wight

Terpenoid resin is produced by all families and most genera of the order Coniferales (the conifers), and the distribution of terpenes present in most conifer resins is characteristic of the originating family. Analyses of early Cretaceous (Barremian) amber (fossil resin) from the English Wealden, Isle of Wight, southern England, by pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS), indicate a terpene distribution dominated by abietane- and labdane-type terpenes. Similar distributions are observed in some species of the extant family Pinaceae. The Pinaceae are well represented within the Wealden deposits of southern England, by only one (known) species, Pityites solmsii (Seward) Seward, whereas the macro-fossil record of these deposits is dominated by the extinct conifer family Cheirolepidiaceae, for which no resin chemistry has been reported. By analogy with modern materials, it is probable that the ambers found in these deposits are derived from an extinct member of the Pinaceae, but given the absence of evidence concerning the chemotaxonomy of the Cheirolepidiaceae, this family cannot be excluded a priori as a possible paleobotanical source. These ambers may therefore be assigned to either the Pinaceae or to the Cheirolepidiaceae. These samples are the oldest ambers to date to yield useful chemotaxonomic data

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

The changing nature of teachers' work and its impact on wellbeing

The world is in the midst of an unprecedented technological revolution and changes are underway on a vast scale with digitalisation transforming economies, governments and societies in complex, interrelated and often unpredictable ways. These changes are fundamentally altering how people live, interact and work and are inevitably affecting how we do our work, thus requiring a transformation in design and delivery. Teaching is not immune to this revolution; in fact, it must play a critical part to prepare young people for innovative, productive and socially just futures. Yet teaching is a highly complex profession. Australia’s graduating teachers are entering the workforce at a time of unprecedented change, increased education opportunity and overwhelming complexity. They start their teaching degrees wanting to contribute positively to learning and engagement with young people but are often overwhelmed with the complexity of their roles and can grapple with professional identity, poor school literacy and numeracy and declines in student engagement in schools. We know that teaching is one of the most rewarding careers a person can encounter, yet it is one with increasing levels of workload; high levels of accountability, measurement and administration; is experiencing new challenges in student and parent behaviours; and is a rapid ever-changing digital and global sector. This chapter highlights that twenty-first-century skills are required to prepare today’s young people for New Work Smarts in 2030 and beyond, yet teachers’ health and wellbeing may be at risk because of this pursuit. Research in Australia and Canada has been undertaken on how well teachers feel they are prepared to manage their work by sampling early career teachers, mid-career teachers and those in leadership roles. A well-educated population is key to a nation’s prosperity, peace and human flourishing, and thus high-quality teachers must be attracted and retained, and the extent to which this is achieved is highly dependent on their wellbeing.Faye McCallu