Nails are highly keratinized skin appendages that exhibit continuous growth under physiological conditions and full regeneration upon removal. These mini-organs are maintained by two autonomous populations of skin stem cells. The fast-cycling, highly proliferative stem cells of the nail matrix (nail stem cells (NSCs)) predominantly replenish the nail plate. Furthermore, the slow-cycling population of the nail proximal fold (nail proximal fold stem cells (NPFSCs)) displays bifunctional properties by contributing to the peri-nail epidermis under the normal homeostasis and the nail structure upon injury. Here, we discuss nail mini-organ stem cells’ location and their role in skin and nail homeostasis and regeneration, emphasizing their importance to orchestrate the whole digit tip regeneration. Such endogenous regeneration capabilities are observed in rodents and primates. However, they are limited to the region adjacent to the nail’s proximal area, indicating the crucial role of nail mini-organ stem cells in digit restoration. Further, we explore the molecular characteristics of nail mini-organ stem cells and the critical role of the bone morphogenetic protein (BMP) and Wnt signaling pathways in homeostatic nail growth and digit restoration. Finally, we investigate the latest accomplishments in stimulating regenerative responses in regeneration-incompetent injuries. These pioneer results might open up new opportunities to overcome amputated mammalian digits and limbs’ regenerative failures in the future.

IntroductionNoroviruses are the leading cause of acute gastroenteritis in all age groups, but illness is more severe and causes excess mortality in the elderly, particularly those in long-term care. The total burden of norovirus disease in the elderly in the UK is poorly defined; no current surveillance programmes systematically or accurately quantify norovirus infection in those living in care homes. The aim of this study is to evaluate an enhanced surveillance system for acute gastroenteritis among the elderly in care homes.Methods and analysisWe will conduct this prospective cohort study in care homes in North West England; residents and staff at study care homes will be asked to participate. We will prospectively enrol a cohort of participants in an enhanced surveillance system to capture the incidence of acute gastroenteritis and use multiplex PCR to detect pathogens. We will sample symptomatic and non-symptomatic participants to understand characteristics of norovirus disease and susceptibility to infection. We will generate novel data on transmission dynamics by collecting data on the pattern of interactions within care homes using electronic proximity sensors. Comparisons of outbreak and non-outbreak periods will be used to quantify the impact of norovirus outbreaks on care homes.Ethics and disseminationThe study has been approved by the North West–Greater Manchester South NHS Research Ethics Committee (REC Reference: 16/NW/0541). Study outputs will be disseminated through scientific conferences and peer-reviewed publications. This study will provide detailed insight on the burden and aetiology of acute gastroenteritis in care homes, in addition to generating novel data on transmission dynamics and risks. The study will identify areas for improving infection control practice and allow more accurate modelling of the introduction of interventions such as vaccination.

ObjectivesTo estimate the incidence of gastroenteritis in individuals in care homes.DesignProspective cohort study.SettingFive participating care homes in North West England, UK.ParticipantsResidents and staff present at the five study care homes between 15 August 2017 and 30 May 2019 (n=268).Outcome measuresWe calculated incidence rates for all gastroenteritis cases per 1000 person-years at risk and per 1000 bed-days at risk. We also calculated the incidence rate of gastroenteritis outbreaks per 100 care homes per year.ResultsIn total 45 cases were reported during the surveillance period, equating to 133.7 cases per 1000 person-years at risk. In residents the incidence rate was 0.62 cases per 1000 bed-days. We observed seven outbreaks in all care homes included in surveillance, a rate of 76.4 outbreaks per 100 care homes per year. 15 stool samples were tested; three were positive for norovirus, no other pathogens were detected.ConclusionsWe found that surveillance of infectious gastroenteritis disease in care homes based on outbreaks, the current general approach, detected a majority of cases of gastroenteritis. However, if policymakers are to estimate the burden of infectious gastroenteritis in this setting using only routine outbreak surveillance data and not accounting for non-outbreak cases, this study implies that the total burden will be underestimated.

Decades of research have shown that many, if not all, fully developed and differentiated organs and tissues contain a subpopulation of undifferentiated stem cells or progenitors of stem cells, which under natural or experimental conditions can self-renew and differentiate into specialised cells. These findings have opened countless possibilities of novel therapeutic applications for the treatment of adult and child diseases. The main sources of stem cells used in paediatric therapies are umbilical cord and umbilical cord blood, amniotic fluid, placenta, bone marrow, adipose tissue, urine, and induced pluripotent stem cells derived from the patient's cells. Here, we describe some of the paediatrically applicable stem cell therapies. We focus our attention on the therapeutic applications of mesenchymal stem cells in paediatric diseases. An important but negative effect of stem cell therapies is the risk of oncogenic potential of therapeutically applied stem cells. Under certain circumstances, these stem cells can lead to tumour development. In addition, the majority of adult and paediatric tumours contain a subpopulation of cancer stem cells which are privileged therapeutic targets for numerous paediatric cancers. In this article, we review these two opposite properties ("double face") of stem cells in general and paediatric medicine.

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