Three-dimensional structure of basal body triplet revealed by electron cryo-tomography.

Basal bodies and centrioles play central roles in microtubule (MT)-organizing centres within many eukaryotes. They share a barrel-shaped cylindrical structure composed of nine MT triplet blades. Here, we report the structure of the basal body triplet at 33 Å resolution obtained by electron cryo-tomography and 3D subtomogram averaging. By fitting the atomic structure of tubulin into the EM density, we built a pseudo-atomic model of the tubulin protofilaments at the core of the triplet. The 3D density map reveals additional densities that represent non-tubulin proteins attached to the triplet, including a large inner circular structure in the basal body lumen, which functions as a scaffold to stabilize the entire basal body barrel. We found clear longitudinal structural variations along the basal body, suggesting a sequential and coordinated assembly mechanism. We propose a model in which δ-tubulin and other components participate in the assembly of the basal body

Sources of variation in under-5 mortality across sub-Saharan Africa: a spatial analysis

Background Detailed spatial understanding of levels and trends in under-5 mortality is needed to improve the targeting of interventions to the areas of highest need, and to understand the sources of variation in mortality. To improve this understanding, we analysed local-level information on child mortality across sub-Saharan Africa between 1980–2010. Methods We used data from 82 Demographic and Health Surveys in 28 sub-Saharan African countries, including the location and timing of 3·24 million childbirths and 393 685 deaths, to develop high-resolution spatial maps of under-5 mortality in the 1980s, 1990s, and 2000s. These estimates were at a resolution of 0·1 degree latitude by 0·1 degree longitude (roughly 10 km × 10 km). We then analysed this spatial information to distinguish within-country versus between-country sources of variation in mortality, to examine the extent to which declines in mortality have been accompanied by convergence in the distribution of mortality, and to study localised drivers of mortality diff erences, including temperature, malaria burden, and confl ict. Findings In our sample of sub-Saharan African countries from the 1980s to the 2000s, within-country diff erences in under-5 mortality accounted for 74–78% of overall variation in under-5 mortality across space and over time. Mortality diff ered signifi cantly across only 8–15% of country borders, supporting the role of local, rather than national, factors in driving mortality patterns. We found that by the end of the study period, 23% of the eligible children in the study countries continue to live in mortality hotspots—areas where, if current trends continue, the Sustainable Developent Goals mortality targets will not be met. In multivariate analysis, within-country mortality levels at each pixel were signifi cantly related to local temperature, malaria burden, and recent history of confl ict. Interpretation Our fi ndings suggest that sub-national determinants explain a greater portion of under-5 mortality than do country-level characteristics. Sub-national measures of child mortality could provide a more accurate, and potentially more actionable, portrayal of where and why children are still dying than can national statistics

Exercise prehabilitation in elective intra-cavity surgery: A role within the ERAS pathway? A narrative review

The Enhanced Recovery after Surgery (ERAS) model integrates several elements of perioperative care into a standardised clinical pathway for surgical patients. ERAS programmes aim to reduce the rate of complications, improve surgical recovery, and limit postoperative length of hospital stay (LOHS). One area of growing interest that is not currently included within ERAS protocols is the use of exercise prehabilitation (PREHAB) interventions. PREHAB refers to the systematic process of improving functional capacity of the patient to withstand the upcoming physiological stress of surgery. A number of recent systematic reviews have examined the role of PREHAB prior to elective intra-cavity surgery. However, the results have been conflicting and a definitive conclusion has not been obtained. Furthermore, a summary of the research area focussing exclusively on the therapeutic potential of exercise prior to intra-cavity surgery is yet to be undertaken. Clarification is required to better inform perioperative care and advance the research field. Therefore, this “review of reviews” provides a critical overview of currently available evidence on the effect of exercise PREHAB in patients undergoing i) coronary artery bypass graft surgery (CABG), ii) lung resection surgery, and iii) gastrointestinal and colorectal surgery. We discuss the findings of systematic reviews and meta-analyses and supplement these with recently published clinical trials. This article summarises the research findings and identifies pertinent gaps in the research area that warrant further investigation. Finally, studies are conceptually synthesised to discuss the feasibility of PREHAB in clinical practice and its potential role within the ERAS pathway