Succinate accumulation drives ischaemia-reperfusion injury during organ transplantation.

During heart transplantation, storage in cold preservation solution is thought to protect the organ by slowing metabolism; by providing osmotic support; and by minimising ischaemia-reperfusion (IR) injury upon transplantation into the recipient1,2. Despite its widespread use our understanding of the metabolic changes prevented by cold storage and how warm ischaemia leads to damage is surprisingly poor. Here, we compare the metabolic changes during warm ischaemia (WI) and cold ischaemia (CI) in hearts from mouse, pig, and human. We identify common metabolic alterations during WI and those affected by CI, thereby elucidating mechanisms underlying the benefits of CI, and how WI causes damage. Succinate accumulation is a major feature within ischaemic hearts across species, and CI slows succinate generation, thereby reducing tissue damage upon reperfusion caused by the production of mitochondrial reactive oxygen species (ROS)3,4. Importantly, the inevitable periods of WI during organ procurement lead to the accumulation of damaging levels of succinate during transplantation, despite cooling organs as rapidly as possible. This damage is ameliorated by metabolic inhibitors that prevent succinate accumulation and oxidation. Our findings suggest how WI and CI contribute to transplant outcome and indicate new therapies for improving the quality of transplanted organs.Work in the M.P.M. laboratory was supported by the Medical Research Council UK (MC_U105663142) and by a Wellcome Trust Investigator award (110159/Z/15/Z) to M.P.M. Work in the C.F. laboratory was supported by the Medical Research Council (MRC_MC_UU_12022/6). Work in the K.S.P. laboratory was supported by the Medical Research Council UK. Work in the RCH lab laboratory was supported by a Wellcome Trust Investigator award (110158/Z/15/Z) and a PhD studentship for .L.P from the University of Glasgow. A.V.G. was supported by a PhD studentship funded by the National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Organ Donation and Transplantation at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT)

Preventing the Reintroduction of Malaria in Mauritius: A Programmatic and Financial Assessment

Sustaining elimination of malaria in areas with high receptivity and vulnerability will require effective strategies to prevent reestablishment of local transmission, yet there is a dearth of evidence about this phase. Mauritius offers a uniquely informative history, with elimination of local transmission in 1969, re-emergence in 1975, and second elimination in 1998. Towards this end, Mauritius's elimination and prevention of reintroduction (POR) programs were analyzed via a comprehensive review of literature and government documents, supplemented by program observation and interviews with policy makers and program personnel. The impact of the country's most costly intervention, a passenger screening program, was assessed quantitatively using simulation modeling