Burns and other traumatic injuries represent a substantial biomedical burden. The current standard of care for deep injuries is autologous split-thickness skin grafting (STSG), which frequently results in contractures, abnormal pigmentation, and loss of biomechanical function. Currently, there are no effective therapies that can prevent fibrosis and contracture after STSG. Here, we have developed a clinically relevant porcine model of STSG and comprehensively characterized porcine cell populations involved in healing with single-cell resolution. We identified an up-regulation of proinflammatory and mechanotransduction signaling pathways in standard STSGs. Blocking mechanotransduction with a small-molecule focal adhesion kinase (FAK) inhibitor promoted healing, reduced contracture, mitigated scar formation, restored collagen architecture, and ultimately improved graft biomechanical properties. Acute mechanotransduction blockade up-regulated myeloid CXCL10-mediated anti-inflammation with decreased CXCL14-mediated myeloid and fibroblast recruitment. At later time points, mechanical signaling shifted fibroblasts toward profibrotic differentiation fates, and disruption of mechanotransduction modulated mesenchymal fibroblast differentiation states to block those responses, instead driving fibroblasts toward proregenerative, adipogenic states similar to unwounded skin. We then confirmed these two diverging fibroblast transcriptional trajectories in human skin, human scar, and a three-dimensional organotypic model of human skin. Together, pharmacological blockade of mechanotransduction markedly improved large animal healing after STSG by promoting both early, anti-inflammatory and late, regenerative transcriptional programs, resulting in healed tissue similar to unwounded skin. FAK inhibition could therefore supplement the current standard of care for traumatic and burn injuries.

Crowding in Emergency Departments (EDs) has emerged as a global public health crisis. Current literature has identified causes and the potential harms of crowding in recent years. The way crowding is measured has also been the source of emerging literature and debate. We aimed to synthesize the current literature of the causes, harms, and measures of crowding in emergency departments around the world. The review is guided by the current PRIOR statement, and involved Pubmed, Medline, and Embase searches for eligible systematic reviews. A risk of bias and quality assessment were performed for each review, and the results were synthesized into a narrative overview. A total of 13 systematic reviews were identified, each targeting the measures, causes, and harms of crowding in global emergency departments. Key among the results is that the measures of crowding were heterogeneous, even in geographically proximate areas, and that temporal measures are being utilized more frequently. It was identified that many measures are associated with crowding, and the literature would benefit from standardization of these metrics to promote improvement efforts and the generalization of research conclusions. The major causes of crowding were grouped into patient, staff, and system-level factors; with the most important factor identified as outpatient boarding. The harms of crowding, impacting patients, healthcare staff, and healthcare spending, highlight the importance of addressing crowding. This overview was intended to synthesize the current literature on crowding for relevant stakeholders, to assist with advocacy and solution-based decision making. Supplementary Information The online version contains supplementary material available at 10.1007/s11739-023-03239-2.

In the 1920s in Canada, the Federal Government's Division of Child Welfare issued the nation's first dietary guidelines aimed at encouraging women to breastfeed and also, somewhat ambivalently, encouraging women to feed cow's milk to babies over nine months of age. The early 1920s was a time of transition in milk processing and distribution. Some cities and provinces had strong sanitary hygiene laws to ensure that milk was free of disease and contamination but others did not so that general national guidelines promoting the use of cow's milk were problematic. These guidelines were promulgated at a time when many public health officials had begun to shift from vilifying milk, because of its potential to harbour dirt and bacteria and because of its well-known links to infant mortality, to extolling its virtues because of its newly discovered rich vitamin and mineral content. The shift in milk's status as an unhealthy liquid to the quintessential protective food for children, both in the public's mind and in the mind of many public health practitioners, particularly those from cities that had managed to clean up their milk supply, was rapid and occurred while much of the nation's milk supply was in fact not safe. The promulgation of dietary guidelines promoting the consumption of cow's milk for babies over nine months at this time was inconsistent and probably quite dangerous, particularly as Canada during the 1920s had the highest infant mortality rates among industrialized nations. The guideline was issued at a time of scientific enthusiasm over the new value of milk in protecting against under-nutrition and promoting optimal health. The dairy industry and the Federal Department of Agriculture unabashedly promoted the protective benefits of milk in large national campaigns overwhelming the ability of the Division of Child Welfare to deliver the best possible dietary guidelines for the times. The relatively weak guidelines developed by the Division in the 1920s demonstrate how, in the absence of a strong nutrition policy centre, inappropriate and perhaps unhealthy nutrition advice was too easily modified by the dairy industry and its representative in the federal government, the Department of Agriculture.

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