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The aim of this study was to adapt and evaluate laser Doppler perfusion monitoring (LDPM) together with custom-designed brain probes and software for continuous recording of cerebral microcirculation in patients undergoing neurosurgery. The LDPM system was used to record perfusion and backscattered light (TLI). These parameters were displayed together with the extracted heart rate (HR), pulsatility index (PI) and signal trends from adjustable time intervals. Technical evaluation was done on skin during thermal provocation. Clinical measurements were performed on ten patients undergoing brain tumour surgery. Data from 76 tissue sites were captured with a length varying between 10 s to 15 min. Statistical comparisons were done using Mann–Whitney tests. Grey and tumour tissue could be separated from white matter using the TLI signal ( p  < 0.05). The perfusion was significantly higher in grey and tumour tissue compared to white matter ( p  < 0.005). LDPM was successfully used as an intraoperative tool for monitoring local blood flow and additional parameters linked to cerebral microcirculation (perfusion, TLI, HR and PI) during tumour resection. The systems stability opens up for studies in the postoperative care of patients with, for example, traumatic brain injury or subarachnoid haemorrhage.

Retinoblastoma is a rare, intraocular paediatric cancer that originates in the neural retina and is most frequently caused by bi-allelic loss of RB1 gene function. Other oncogenic mutations, such as amplification and increased expression of the MYCN gene, have been found even with proficient RB1 function. In this study, we investigated whether MYCN over-expression can drive carcinogenesis independently of RB1 loss-of-function mutations. The aim was to elucidate the events that result in carcinogenesis and identify the cancer cell-of-origin. We used the chicken retina, a well-established model for studying retinal neurogenesis, and established human embryonic stem cell-derived retinal organoids as model systems. We over-expressed MYCN by electroporation of piggyBac genome-integrating expression vectors. We found that over-expression of MYCN induced tumorigenic growth with high frequency in RB1-proficient chicken retinas and human organoids. In both systems, the tumorigenic cells expressed markers for undifferentiated cone photoreceptor/horizontal cell progenitors. The over-expression resulted in metastatic retinoblastoma within 7–9 weeks in chicken. Cells expressing MYCN could be grown in vitro and, when orthotopically injected, formed tumours that infiltrated the sclera and optic nerve and expressed markers for cone progenitors. Investigation of the tumour cell phenotype determined that the potential for neoplastic growth was embryonic stage-dependent and featured a cell-specific resistance to apoptosis in the cone/horizontal cell lineage, but not in ganglion or amacrine cells. We conclude that MYCN over-expression is sufficient to drive tumorigenesis and that a cell-specific resistance to apoptosis in the cone/horizontal cell lineage mediates the cancer phenotype.