We would like to thank R Marotta/IIT for support with IM-TEM and acknowledge Kim Mace for reviewing the manuscript. This work was supported by grants from Unilever, UK, and the NIHR Manchester BRC (BRC-1215-20007) "Inflammatory Hair Diseases" program.
The role of innate immunocytes such as mast cells, γδ T cells, NK cells and macrophages (MACs) in hair growth control under physiological and pathological conditions has recently begun to be re‐explored. Here, we revisit the role of resident perifollicular macrophages (pfMACs) located in the hair follicle (HF) mesenchyme (CTS). Substantial, stringently timed fluctuations in the number and localization of pfMACs were first observed long ago during murine HF morphogenesis and cycling. This already suggested some involvement of these innate immunocytes, with a recognized role in tissue remodelling and in hair growth control. The relatively recent demonstration of a Wnt signalling‐driven crosstalk between these immunocytes and HF epithelial stem cells in telogen HFs, which promotes anagen induction, has reinvigorated interest in the role that pfMAC plays in hair biology. Besides the apoptosis‐associated secretion of stem cell–activating Wnts and the differential secretion of HF‐targeting growth factors such as FGF‐5 and FGF5s from pfMACs, we also explore how MAC polarization, and thus function, may be influenced by the local metabolic and immune environment. Moreover, we examine how pfMACs may contribute to hair cycle–associated angiogenesis, vascular remodelling, HF immune privilege and immunopathology. On this basis, we discuss why targeting pfMACs may be relevant in the management of hair growth disorders. Finally, we argue that studying pfMACs offers an excellent, clinically relevant model system for characterizing and experimentally manipulating MAC interactions with an easily accessible mammalian, continuously remodelled (mini‐)organ under both physiological and pathological conditions.
PurposeWe sought to understand how best to teach medico-ethics, law and professionalism to undergraduate medical students using a student selected component.Materials and methodsStudents received small-group, seminar-based teaching from the module organiser and external representatives from organisations such as the General Medical Council and Medical Protection Society. Experiential learning was also facilitated through attendance at fitness to practice tribunals and Coroner’s court, followed by structured debrief sessions. Two cohorts of medical students(n=40) from Manchester University were surveyed before and after undergoing the placement, with qualitative interviews and thematic analysis for a subset of this group(n=16) and course leaders(n=4).ResultsThere were significant (p<0.05) improvements in students’ self-reported understanding of key medicolegal organisations and accessing guidance on professionalism. Thematic analysis uncovered increasing confidence in the role of the medicolegal system, barriers to challenging unprofessional behaviour, and a desire for this to be placed in the curricula.ConclusionsThis placement was well received and demonstrates an importance for this content to be taught effectively in the medical curricula. Having protected time to attend sessions while an undergraduate may reduce anxiety felt by doctors fearing medicolegal proceedings and help challenge unprofessional behaviours. Further work could explore mechanisms into how best to incorporate this into the medical curricula.
Based on molecular evidence that melanomas with unknown primary (MUPs) arise from the skin, we hypothesised that sites of MUPs are disproportionately on trunk and lower limbs, sites that are not readily visible to patients and clinicians. We tested this hypothesis by inferring the anatomic site of origin of MUPs from the corresponding known cutaneous sites of melanoma patients with known primary tumours (MKPs). We analysed data from three separate cohorts of patients from Brisbane, Australia (n = 236); Manchester, UK (n = 51) and Padova, Italy (n = 33), respectively, who first presented with stage III melanoma with lymph node metastases. We matched two MKP patients to each MUP patient based on lymph node dissection (LND) site, age and sex, and imputed cutaneous sites of origin of MUPs from their two matched MKPs for study countries, giving two possible sites for each MUP per centre. Overall, results showed that MUP patients were predominantly male, and trunk was the most likely origin, comprising around a third to a half of MUPs across the three cohorts. The remaining MUP inferred sites varied by country. In the Australian cohort, the legs accounted for a third of imputed sites of MUPs, while in the UK and Italian cohorts, the most frequent site was the arms followed by the legs. Our findings suggest the need for regular and thorough skin examination on trunk and limbs, especially in males, to improve early detection of cutaneous melanoma and reduce the risk of metastatic disease at the time of presentation.
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