F1000Research
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Rho GTPases are crucial signaling molecules that regulate a plethora of biological functions. Traditional biochemical, cell biological, and genetic approaches have founded the basis of Rho GTPase biology. The development of biosensors then allowed measuring Rho GTPase activity with unprecedented spatio-temporal resolution. ⋯ In this review, we describe Rho GTPase activity patterns observed in different cell systems. We then discuss the growing body of evidence that upstream regulators such as guanine nucleotide exchange factors and GTPase-activating proteins shape these patterns by precisely controlling the spatio-temporal flux of Rho GTPase activity. Finally, we comment on additional mechanisms that might feed into the regulation of these signaling patterns and on novel technologies required to dissect this spatio-temporal complexity.
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Despite major research efforts leading to the recent approval of pirfenidone and nintedanib, the dismal prognosis of idiopathic pulmonary fibrosis (IPF) remains unchanged. The elaboration of international diagnostic criteria and disease stratification models based on clinical, physiological, radiological, and histopathological features has improved the accuracy of IPF diagnosis and prediction of mortality risk. Nevertheless, given the marked heterogeneity in clinical phenotype and the considerable overlap of IPF with other fibrotic interstitial lung diseases (ILDs), about 10% of cases of pulmonary fibrosis remain unclassifiable. ⋯ The development and validation of diagnostic and prognostic biomarkers are necessary to enable a more precise and earlier diagnosis of IPF and to improve prediction of future disease behaviour. The availability of approved antifibrotic therapies together with potential new drugs currently under evaluation also highlights the need for biomarkers able to predict and assess treatment responsiveness, thereby allowing individualised treatment based on risk of progression and drug response. This approach of disease stratification and personalised medicine is already used in the routine management of many cancers and provides a potential road map for guiding clinical care in IPF.
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Regional anaesthesia provides effective anaesthesia and analgesia in the perioperative setting. Central neuraxial blocks-that is, spinal and epidural blocks-are well established as an alternative or adjunct to general anaesthesia. Peripheral blocks may be used as part of multimodal anaesthesia/analgesia in perioperative practice, reducing the need for opioid analgesics and enhancing early recovery. ⋯ This article provides an overview of current evidence around quality of recovery, risk for delirium, long-term effects, and possible impact on cancer disease progression associated with the clinical use of local and regional anaesthetic techniques. In summary, there is still a lack of robust data that regional anaesthesia has a clinical impact beyond its well-acknowledged beneficial effects of reducing pain, reduced opioid consumption, and improved quality of early recovery. Further high-quality prospective studies on long-term outcomes are warranted.
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To pursue research, education, and health policy in one's career, broadly defined as academic medicine, is one of the most important decisions of a trainee doctor's career. Despite this, there is scant literature on which factors influence trainees' choices towards clinical work or academic research. ⋯ Conversely, long training periods, a lack of autonomy, and financial considerations are deterrents from a career in academic medicine. Insight into the decision-making process is provided by recent Canadian trainees in these respective fields, in a series of short interviews.
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The epidemics of Ebola virus in West Africa and Zika virus in America highlight how viruses can explosively emerge into new territories. These epidemics also exposed how unprepared we are to handle infectious disease emergencies. This is also true when we consider hypothesized new clinical features of infection, such as the associations between Zika virus infection and severe neurological disease, including microcephaly and Guillain-Barré syndrome. ⋯ Much of the recent panic regarding Zika virus has been about the Olympics in Brazil. We do not find any substantial evidence that the Olympics will result in a significant number of new Zika virus infections (~10 predicted) or that the Olympics will promote further epidemic spread over what is already expected. The Zika virus epidemic in the Americas is a serious situation and decisions based on solid scientific evidence - not hyped media speculations - are required for effective outbreak response.