Characterization of a vacuolar importer of secologanin in Catharanthus roseus.

Monoterpenoid indole alkaloid (MIA) biosynthesis in Catharanthus roseus is a paragon of the spatiotemporal complexity achievable by plant specialized metabolism. Spanning a range of tissues, four cell types, and five cellular organelles, MIA metabolism is intricately regulated and organized. This high degree of metabolic differentiation requires inter-cellular and organellar transport, which remains understudied. Here, we have characterized a vacuolar importer of secologanin belonging to the multidrug and toxic compound extrusion (MATE) family, named CrMATE1. Phylogenetic analyses of MATEs suggested a role in alkaloid transport for CrMATE1, and in planta silencing in two varieties of C. roseus resulted in a shift in the secoiridoid and MIA profiles. Subcellular localization of CrMATE1 confirmed tonoplast localization. Biochemical characterization was conducted using the Xenopus laevis oocyte expression system to determine substrate range, directionality, and rate. We can confirm that CrMATE1 is a vacuolar importer of secologanin, translocating 1 mM of substrate within 25 min. The transporter displayed strict directionality and specificity for secologanin and did not accept other secoiridoid substrates. The unique substrate-specific activity of CrMATE1 showcases the utility of transporters as gatekeepers of pathway flux, mediating the balance between a defense arsenal and cellular homeostasis.

A systematic review of subcutaneous versus intramuscular or intravenous routes of opioid administration on pain outcomes in cancer and post-surgical clinical populations - challenging current assumptions in palliative care practice.

Objective: The objective of this review is to investigate the use of the subcutaneous route of administration of analgesics, common practice within palliative medicine. Design: Systematic review using consensus approach, direct comparison of subcutaneous route with intravenous and intramuscular routes. Results: The limited available evidence demonstrates non-inferiority of the subcutaneous route in both cancer patients and those post-surgery. Pain management is comparable to other routes. Route-related side effects are rare and systemic side effects are comparable. Conclusion: Pain management is a critical role of palliative medicine. The subcutaneous route of administration offers a viable option for the delivery of parenteral analgesia within all settings, including the community. This review supports current practice, demonstrating equivalence with more invasive routes of administration.

Reporting on cyclist crashes in Australian newspapers.

OBJECTIVE: To assess information on cyclist crashes reported in Australian newspapers. METHODS: The Factiva news archive was searched for articles on cyclist crashes published in major Australian newspapers between 2010 and 2013. Information on the circumstances of cyclist crashes were extracted and coded. RESULTS: A total of 160 cyclist crashes were covered by 198 newspaper articles, with 44% of crashes resulting in cyclist fatalities. Crashes reported by more than one newspaper were more likely to involve public figures or protracted court cases. Individual characteristics of cyclists as well as the location of the crash were reported for more than 80% of crashes. The road user at fault was reported for more than half of crashes. In contrast, information on helmet use, alcohol and cycling lanes was mentioned for only about 10% of crashes. Fewer than one in five articles mentioned prevention strategies including education campaigns, legislative and infrastructure changes. CONCLUSION: Australian newspapers tend to focus on the most dramatic and more 'newsworthy' aspects of cyclist crashes. Cycling advocates need to work with journalists to improve the quality of this coverage. IMPLICATIONS: Better communication between cycling advocates and journalists is likely to have a positive impact on the safety and the uptake of cycling in the community.

Management of nausea and vomiting in palliative care.

Nausea and vomiting are common symptoms in palliative care and can be highly distressing to patients. This review discusses the mechanisms by which nausea and vomiting are triggered, using case studies to highlight the most common scenarios and how to manage these.