Opportunistic screening to detect atrial fibrillation in Aboriginal adults in Australia.

INTRODUCTION: There is a 10-year gap in life expectancy between Aboriginal and non-Aboriginal Australians. The leading cause of death for Aboriginal Australians is cardiovascular disease, including myocardial infarction and stroke. Although atrial fibrillation (AF) is a known precursor to stroke there are no published studies about the prevalence of AF for Aboriginal people and limited evidence about AF in indigenous populations globally. METHODS AND ANALYSIS: This mixed methods study will recruit and train Aboriginal health workers to use an iECG device attached to a smartphone to consecutively screen 1500 Aboriginal people aged 45 years and older. The study will quantify the proportion of people who presented for follow-up assessment and/or treatment following a non-normal screening and then estimate the prevalence and age distribution of AF of the Australian Aboriginal population. The study includes semistructured interviews with the Aboriginal health workers about the effectiveness of the iECG device in their practice as well as their perceptions of the acceptability of the device for their patients. Thematic analysis will be undertaken on the qualitative data collected in the study. If the device and approach are acceptable to the Aboriginal people and widely adopted, it may help prevent the effects of untreated AF including ischaemic stroke and early deaths or impairment in Aboriginal people. ETHICS AND DISSEMINATION: This mixed methods study received ethics approval from the Aboriginal Health and Medical Research Council (1135/15) and the Australian Health Council of Western Australia (HREC706). Ethics approval is being sought in the Northern Territory. The findings of this study will be shared with Aboriginal communities, in peer reviewed publications and at conferences. There are Aboriginal investigators in each state/territory where the study is being conducted who have been actively involved in the study. They will also be involved in data analysis, dissemination and research translation. TRIAL REGISTRATION NUMBER: ACTRN12616000459426.

Endothelial and hematopoietic cell fate of human embryonic stem cells originates from primitive endothelium with hemangioblastic properties.

The cellular organization and relationships among precursors that initiate embryonic angiogenesis and hematopoiesis in the human have yet to be characterized. Here, we identify a subpopulation of primitive endothelial-like cells derived from human embryonic stem cells (hESCs) that express PECAM-1, Flk-1, and VE-cadherin, but not CD45 (CD45negPFV cells), and that are uniquely responsible for endothelial and hematopoietic development. Molecular profiling of CD45negPFV cells is consistent with endothelial and hematopoietic competency. Clonal isolation demonstrates that the CD45negPFV population includes bipotent cells with endothelial and hematopoietic capacity. We suggest that human hematopoiesis and endothelial maturation originate exclusively from a subset of embryonic endothelium that possesses hemangioblastic properties and offers a model system to study these lineage relationships in the human.

Human embryonic stem cells possess immune-privileged properties.

Human embryonic stem cells (hESCs) are envisioned to be a major source for cell-based therapies. Efforts to overcome rejection of hESCs include nuclear transfer and collection of hESC banks representing the broadest diversity of major histocompatability complex (MHC) polymorphorisms. Surprisingly, immune responses to hESCs have yet to be experimentally evaluated. Here, injection of hESCs into immune-competent mice was unable to induce an immune response. Undifferentiated and differentiated hESCs failed to stimulate proliferation of alloreactive primary human T cells and inhibited third-party allogeneic dendritic cell-mediated T-cell proliferation via cellular mechanisms independent of secreted factors. Upon secondary rechallenge, T cells cocultured with hESCs were still responsive to allogeneic stimulators but failed to proliferate upon re-exposure to hESCs. Our study demonstrates that hESCs possess unique immune-privileged characteristics and provides an unprecedented opportunity to further investigate the mechanisms of immune response to transplantation of hESCs that may avoid immune-mediated rejection.