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One Sentence Summary: The circadian clock in fibroblasts determines the efficiency of wound healing through rhythmic regulation of actin cytoskeletal dynamics. 2 Abstract:Fibroblasts are primary cellular protagonists of wound healing. They also exhibit circadian timekeeping which imparts a ~24-hour rhythm to their biological function. We interrogated the functional consequences of the cell-autonomous clockwork in fibroblasts using a proteomewide screen for rhythmically expressed proteins. We observed temporal coordination of actin regulators that drives cell-intrinsic rhythms in actin dynamics. In consequence the cellular clock modulates the efficiency of actin-dependent processes such as cell migration and adhesion, which ultimately impact the efficacy of wound healing. Accordingly, skin wounds incurred during a mouse's active phase exhibited increased fibroblast invasion in vivo and ex vivo, as well as in cultured fibroblasts and keratinocytes. Our experimental results correlate with the observation that the time of injury significantly affects healing after burns in humans, with daytime wounds healing ~60% faster than night-time wounds. We suggest that circadian regulation of the cytoskeleton influences wound healing efficacy from the cellular to the organismal scale.Introduction:

ObjectiveTo describe, for the first time, distribution (by geography, age, sex) and time trends in burn injury in England and Wales over the period that the international Burn Injury Database (iBID) has been in place.SettingData from the iBID for the years 2003–2011 were used for a retrospective descriptive observational study of specialised services workload and admissions in England and Wales.ParticipantsAll patients who have been visited or admitted to the burn injury specialised health service of England and Wales during the time period 2003–2011. Data cleaning was performed omitting patients with incomplete records (missingness never exceeded 5%).Outcome measuresWorkload, admissions, mortality, length of stay (LOS), geographical distribution, sex differences, age differences, total burn surface area, mechanism of Injury.ResultsDuring 2003–2011, 81 181 patients attended the specialised burn service for assessment and admission in England and Wales. Of these, 57 801 were admitted to the services. Males accounted for 63% of the total workload in specialised burn injury services, and females for 37%. The median (IQR) burn surface area was 1.5% (3.5%). The most frequent reason for burn injury was scald (38%). The median (IQR) age for all the referred workload for both genders was 21 (40). The overall mortality of the admitted patients was 1.51% and the median (IQR) LOS was 1 (5) days.ConclusionsMortality from burn injuries in England and Wales is decreasing in line with western world trends. There is an observed increase in admissions to burn services but that could be explained in various ways. These results are vital for service development and planning, as well as the development and monitoring of prevention strategies and for healthcare commissioning.