Regulated secretion by glands and neurons involves release of signalling molecules and enzymes selectively concentrated in dense-core granules (DCGs). Although we understand how many secretagogues stimulate DCG release, how DCG biogenesis is then accelerated to replenish the DCG pool remains poorly characterised. Here we demonstrate that each prostate-like secondary cell (SC) in the paired adult Drosophila melanogaster male accessory glands contains approximately ten large DCGs, which are loaded with the Bone Morphogenetic Protein (BMP) ligand Decapentaplegic (Dpp). These DCGs can be marked in living tissue by a glycophosphatidylinositol (GPI) lipid-anchored form of GFP. In virgin males, BMP signalling is sporadically activated by constitutive DCG secretion. Upon mating, approximately four DCGs are typically released immediately, increasing BMP signalling, primarily via an autocrine mechanism. Using inducible knockdown specifically in adult SCs, we show that secretion requires the Soluble NSF Attachment Protein, SNAP24. Furthermore, mating-dependent BMP signalling not only promotes cell growth, but is also necessary to accelerate biogenesis of new DCGs, restoring DCG number within 24 h. Our analysis therefore reveals an autocrine BMP-mediated feedback mechanism for matching DCG release to replenishment as secretion rates fluctuate, and might explain why in other disease-relevant systems, like pancreatic β-cells, BMP signalling is also implicated in the control of secretion.

Background Mobile health (mHealth) apps are increasingly used postoperatively to monitor, educate, and rehabilitate. The usability of mHealth apps is critical to their implementation. Objective This systematic review evaluates the (1) methodology of usability analyses, (2) domains of usability being assessed, and (3) results of usability analyses. Methods The A Measurement Tool to Assess Systematic Reviews checklist was consulted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline was adhered to. Screening was undertaken by 2 independent reviewers. All included studies were assessed for risk of bias. Domains of usability were compared with the gold-standard mHealth App Usability Questionnaire (MAUQ). Results A total of 33 of 720 identified studies were included for data extraction. Of the 5 included randomized controlled trials (RCTs), usability was never the primary end point. Methodology of usability analyses included interview (10/33), self-created questionnaire (18/33), and validated questionnaire (9/33). Of the 3 domains of usability proposed in the MAUQ, satisfaction was assessed in 28 of the 33 studies, system information arrangement was assessed in 11 of the 33 studies, and usefulness was assessed in 18 of the 33 studies. Usability of mHealth apps was above industry average, with median System Usability Scale scores ranging from 76 to 95 out of 100. Conclusions Current analyses of mHealth app usability are substandard. RCTs are rare, and validated questionnaires are infrequently consulted. Of the 3 domains of usability, only satisfaction is regularly assessed. There is significant bias throughout the literature, particularly with regards to conflicts of interest. Future studies should adhere to the MAUQ to assess usability and improve the utility of mHealth apps.

Background Phyllodes tumours represent less than 1% of all UK breast neoplasms. Histological features allow classification into benign, borderline or malignant, which has a significant impact on prognosis and recurrence. Currently, there is no consensus for the optimal surgical excision margin. This systematic review aims to provide a comparative summary of outcomes (local recurrence, metastasis and survival) for borderline and malignant phyllodes tumours resected with either ≥1cm or <1cm margins. Methods MEDLINE and Embase were systematically searched (1990 to July 2019), in line with PRISMA guidelines. Study quality was assessed using the Newcastle–Ottawa scale. Results Ten retrospective studies were included (Newcastle–Ottawa scale mean score: 5.6, range: 8–4). Nine reported local recurrence rates, four reported distant metastasis and four reported survival. Meta-analysis pooling demonstrated no statistically significant difference between <1cm and ≥1cm margins in terms of local recurrence rates (relative risk [RR] 1.43, 95% confidence interval [95% CI] 0.70 – 2.93; p=0.33, n=456), distant metastasis (RR 1.93, 95% CI 0.35 – 10.63; p=0.45, n=72) or mortality (RR 1.93, 95% CI 0.42 – 8.77; p=0.40, n=58) for borderline and malignant tumours. Additionally, two studies demonstrated no significant difference in local recurrence for borderline tumours excised with <0.1cm margins compared to ≥1cm. Conclusion Current evidence suggests that margins <1cm may provide adequate tumour excision. This could enable breast conservation in patients with smaller breast-to-tumour volume ratios, with improved cosmetic outcomes and patient satisfaction. A prospective, multi-institutional trial would be appropriate to further elucidate the safety of smaller margins.

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