The zebrafish is an outstanding model for intravital imaging of inflammation due to its optical clarity and the ability to express fluorescently labelled specific cell types by transgenesis. However, although several transgenic labelling myeloid cells exist, none allow distinction of macrophages from neutrophils. This prevents simultaneous imaging and examination of the individual contributions of these important leukocyte subtypes during inflammation. We therefore used Bacterial Artificial Chromosome (BAC) recombineering to generate a transgenic Tg(fms:GAL4.VP16)i186, in which expression of the hybrid transcription factor Gal4-VP16 is driven by the fms (CSF1R) promoter. This was then crossed to a second transgenic expressing a mCherry-nitroreductase fusion protein under the control of the Gal4 binding site (the UAS promoter), allowing intravital imaging of mCherry-labelled macrophages. Further crossing this compound transgenic with the neutrophil transgenic Tg(mpx:GFP)i114 allowed clear distinction between macrophages and neutrophils and simultaneous imaging of their recruitment and behaviour during inflammation. Compared with neutrophils, macrophages migrate significantly more slowly to an inflammatory stimulus. Neutrophil number at a site of tissue injury peaked around 6 hours post injury before resolving, while macrophage recruitment increased until at least 48 hours. We show that macrophages were effectively ablated by addition of the prodrug metronidazole, with no effect on neutrophil number. Crossing with Tg(Fli1:GFP)y1 transgenic fish enabled intravital imaging of macrophage interaction with endothelium for the first time, revealing that endothelial contact is associated with faster macrophage migration. Tg(fms:GAL4.VP16)i186 thus provides a powerful tool for intravital imaging and functional manipulation of macrophage behaviour during inflammation.

Cardiovascular disease (CVD) is the world’s leading cause of mortality. There is significant interest in using Artificial Intelligence (AI) to analyse data from novel sensors such as wearables to provide an earlier and more accurate prediction and diagnosis of heart disease. Digital health technologies that fuse AI and sensing devices may help disease prevention and reduce the substantial morbidity and mortality caused by CVD worldwide. In this review, we identify and describe recent developments in the application of digital health for CVD, focusing on AI approaches for CVD detection, diagnosis, and prediction through AI models driven by data collected from wearables. We summarise the literature on the use of wearables and AI in cardiovascular disease diagnosis, followed by a detailed description of the dominant AI approaches applied for modelling and prediction using data acquired from sensors such as wearables. We discuss the AI algorithms and models and clinical applications and find that AI and machine-learning-based approaches are superior to traditional or conventional statistical methods for predicting cardiovascular events. However, further studies evaluating the applicability of such algorithms in the real world are needed. In addition, improvements in wearable device data accuracy and better management of their application are required. Lastly, we discuss the challenges that the introduction of such technologies into routine healthcare may face.

Objective Massage is ubiquitous in elite sport and increasingly common at amateur level but the evidence base for this intervention has not been reviewed systematically. We therefore performed a systematic review and meta-analysis examining the effect of massage on measures of sporting performance and recovery. Design and eligibility We searched PubMed, MEDLINE and Cochrane to identify randomised studies that tested the effect of manual massage on measures of sporting performance and/or recovery. We performed separate meta-analyses on the endpoints of; strength, jump, sprint, endurance, flexibility, fatigue and delayed onset muscle soreness (DOMS). Results We identified 29 eligible studies recruiting 1012 participants, representing the largest examination of the effects of massage. We found no evidence that massage improves measures of strength, jump, sprint, endurance or fatigue, but massage was associated with small but statistically significant improvements in flexibility and DOMS. Conclusion Although our study finds no evidence that sports massage improves performance directly, it may somewhat improve flexibility and DOMS. Our findings help guide the coach and athlete about the benefits of massage and inform decisions about incorporating this into training and competition.

Rationale:: Blood flow–induced shear stress controls endothelial cell (EC) physiology during atherosclerosis via transcriptional mechanisms that are incompletely understood. The mechanosensitive transcription factor TWIST is expressed during embryogenesis, but its role in EC responses to shear stress and focal atherosclerosis is unknown. Objective:: To investigate whether TWIST regulates endothelial responses to shear stress during vascular dysfunction and atherosclerosis and compare TWIST function in vascular development and disease. Methods and Results:: The expression and function of TWIST1 was studied in EC in both developing vasculature and during the initiation of atherosclerosis. In zebrafish, twist was expressed in early embryonic vasculature where it promoted angiogenesis by inducing EC proliferation and migration. In adult porcine and murine arteries, TWIST1 was expressed preferentially at low shear stress regions as evidenced by quantitative polymerase chain reaction and en face staining. Moreover, studies of experimental murine carotid arteries and cultured EC revealed that TWIST1 was induced by low shear stress via a GATA4-dependent transcriptional mechanism. Gene silencing in cultured EC and EC-specific genetic deletion in mice demonstrated that TWIST1 promoted atherosclerosis by inducing inflammation and enhancing EC proliferation associated with vascular leakiness. Conclusions:: TWIST expression promotes developmental angiogenesis by inducing EC proliferation and migration. In addition to its role in development, TWIST is expressed preferentially at low shear stress regions of adult arteries where it promotes atherosclerosis by inducing EC proliferation and inflammation. Thus, pleiotropic functions of TWIST control vascular disease and development.