Knowledge of human pancreas development underpins our interpretation and exploitation of human pluripotent stem cell (PSC) differentiation toward a β-cell fate. However, almost no information exists on the early events of human pancreatic specification in the distal foregut, bud formation, and early development. Here, we have studied the expression profiles of key lineage-specific markers to understand differentiation and morphogenetic events during human pancreas development. The notochord was adjacent to the dorsal foregut endoderm during the fourth week of development before pancreatic duodenal homeobox-1 detection. In contrast to the published data from mouse embryos, during human pancreas development, we detected only a single-phase of Neurogenin 3 (NEUROG3) expression and endocrine differentiation from approximately 8 weeks, before which Nirenberg and Kim homeobox 2.2 (NKX2.2) was not observed in the pancreatic progenitor cell population. In addition to revealing a number of disparities in timing between human and mouse development, these data, directly assembled from human tissue, allow combinations of transcription factors to define sequential stages and differentiating pancreatic cell types. The data are anticipated to provide a useful reference point for stem cell researchers looking to differentiate human PSCs in vitro toward the pancreatic β-cell so as to model human development or enable drug discovery and potential cell therapy.
Heavy menstrual bleeding (HMB) accounts for approximately 20% of gynaecology referrals. The National Institute of Clinical Excellence (NICE) recommendations provide the framework for evidence-based management of HMB. Despite this, previous studies have highlighted significant variation in the investigation and management of HMB. This was an observational study of clinical practice performed by retrospective case note reviews of 43 women referred to the Royal Bolton NHS Foundation Trust with HMB between May and June 2011. The care that these women received was evaluated and compared with that currently recommended by clinical guidelines. The investigation and management of HMB in both primary and secondary care was variable, often failing to meet standards recommended by NICE. Greater awareness of NICE guidance may result in improved care. Educational sessions and information provision targeted at healthcare professionals who manage women with HMB, may be beneficial.
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