Absent expansion of AXIN2+ hepatocytes and altered physiology in Axin2CreERT2 mice challenges the role of pericentral hepatocytes in homeostatic liver regeneration.

BACKGROUND & AIMS: Mouse models of lineage tracing have helped to describe the important subpopulations of hepatocytes responsible for liver regeneration. However, conflicting results have been obtained from different models. Herein, we aimed to reconcile these conflicting reports by repeating a key lineage-tracing study from pericentral hepatocytes and characterising this Axin2CreERT2 model in detail. METHODS: We performed detailed characterisation of the labelled population in the Axin2CreERT2 model. We lineage traced this cell population, quantifying the labelled population over 1 year and performed in-depth phenotypic comparisons, including transcriptomics, metabolomics and analysis of proteins through immunohistochemistry, of Axin2CreERT2 mice to WT counterparts. RESULTS: We found that after careful definition of a baseline population, there are marked differences in labelling between male and female mice. Upon induced lineage tracing there was no expansion of the labelled hepatocyte population in Axin2CreERT2 mice. We found substantial evidence of disrupted homeostasis in Axin2CreERT2 mice. Offspring are born with sub-Mendelian ratios and adult mice have perturbations of hepatic Wnt/ß-catenin signalling and related metabolomic disturbance. CONCLUSIONS: We find no evidence of predominant expansion of the pericentral hepatocyte population during liver homeostatic regeneration. Our data highlight the importance of detailed preclinical model characterisation and the pitfalls which may occur when comparing across sexes and backgrounds of mice and the effects of genetic insertion into native loci. IMPACT AND IMPLICATIONS: Understanding the source of cells which regenerate the liver is crucial to harness their potential to regrow injured livers. Herein, we show that cells which were previously thought to repopulate the liver play only a limited role in physiological regeneration. Our data helps to reconcile differing conclusions drawn from results from a number of prior studies and highlights methodological challenges which are relevant to preclinical models more generally.

Dental neglect as a marker of broader neglect: a qualitative investigation of public health nurses' assessments of oral health in preschool children.

BACKGROUND: Child neglect is a pernicious child protection issue with adverse consequences that extend to adulthood. Simultaneously, though it remains prevalent, childhood dental caries is a preventable disease. Public health nurses play a pivotal role in assessing oral health in children as part of general health surveillance. However, little is known about how they assess dental neglect or what their thresholds are for initiating targeted support or instigating child protection measures. Understanding these factors is important to allow improvements to be made in care pathways. METHODS: We investigated public health nurses' assessment of oral health in preschool children in relation to dental neglect and any associations they make with child neglect more broadly. A qualitative study was conducted in Scotland during 2011/12. Sixteen public health nurses were recruited purposively from one health region. Individual, semi-structured interviews were undertaken and data were analyzed inductively using a framework approach. Categories were subsequently mapped to the research questions. RESULTS: Public health nurses assess oral health through proxy measures, opportunistic observation and through discussion with parents. Dental neglect is rarely an isolated issue that leads on its own to child protection referral. It tends to be other presenting issues that initiate a response. Threshold levels for targeted support were based on two broad indicators: social issues and concerns about child (and parental) dental health. Thresholds for child protection intervention were untreated dental caries or significant dental pain. Barriers to intervention are that dental neglect may be 'unseen' and 'unspoken'. The study revealed a communication gap in the care pathway for children where a significant dental problem is identified. CONCLUSIONS: Public health nurses take their child protection role seriously, but rarely make a link between dental caries and child neglect. Clear guidance on oral health assessment is required for public health nurses. Establishing formal communication pathways between child dental care providers and public health nurses may help close gaps in care pathways. However, further research is required into how these communication mechanisms can be improved.