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To explore variation in treatment-related-decisions for severe caries in children among dentists in the Public Dental Service (PDS) in Norway. It was also to evaluate the treatment choices in relation to the best interest of children and a child’s rights to enjoy the highest standard of health care. A pre-coded questionnaire was sent electronically to all general dental practitioners (GDPs) working in the PDS in eight counties in Norway (n= 611). The questionnaire included two case scenarios to reflect common dental conditions related to severe caries among 5-year-old children. Paediatric dentists and paediatric students were invited to validate the different treatment options. Frequency distributions and statistical analyses were carried out using Chi square statistics. The response rate was 65% (n= 391) among the GDPs. A majority of the GDPs preferred a new appointment with behaviour management techniques (BMT) to a child presenting pulpitis and pain. Dentists educated outside the Nordic region would use restraint more often as a treatment alternative when the child was in pain than Nordic-educated dentists (p< 0.05). Dentists with less than 10 years of experience preferred BMT and sedation more often when the child was in pain than their older colleagues, who, however, preferred a waiting approach and no immediate treatment if the child was not in pain (p< 0.05). Use of BMT and sedation is related to region of education and years of experience. Awareness of ethical principles with the child´s best interest in mind, should receive increased attention.

Colorectal cancer (CRC) is a complex disease with still unsatisfactory prognosis even in western societies, although substantial progress has been made in pre-screening programs, surgical techniques and targeted therapy options. Mediator of motility-1 (Memo-1) was previously recognized as an important effector of cell migration downstream of receptor tyrosine kinase signaling in breast cancer. This study identified Memo-1 as frequently overexpressed in CRC and established a close link between extracellular HER2 activation, AhR/ARNT transcriptional activity and Memo-1 expression. Dissection of the hMemo-1gene promoter using reporter assays and chromatin IP techniques revealed recruitment of Aryl hydrocarbon receptor (AhR)/Aryl hydrocarbon receptor nuclear-translocator (ARNT) complex, which positively influenced Memo-1expression in cancer cells. We found that Memo-1 depletion negatively influenced the cellular actin network and that its expression is required for HER2-mediated cell migration and invasion. Moreover, analyses of Memo-1 expression in primary CRC revealed correlation with clinical parameters that point to Memo-1 as a new prognostic factor of aggressive disease in CRC patients. Altogether, these observations demonstrate that Memo-1 is an important downstream regulator of HER2-driven CRC cell migration and invasion through connecting extracellular signals from membrane to the cytoskeletal actin network.

Levosimendan is approved for use as an intravenous agent to treat temporarily patients with severe systolic heart failure. It is thought, but hitherto never tested in isolated human cardiac tissue, that the main metabolite of levosimendan, called OR 1896, might cause the positive inotropic effect of levosimendan in patients. For comparison, we studied mouse atrial preparations. OR alone (up to 10 µM) failed to increase force of contraction in mouse atrial preparations while in the presence of the phosphodiesterase (PDE) IV–inhibitor rolipram (0.1 µM) profound positive inotropic effects and positive chronotropic effects of OR 1895 were recorded in mouse atrial preparations. In contrast to mouse atrium, we noticed that OR 1896 alone (0.01 µM to 10 µM cumulatively applied) exerted time– and concentration–dependent positive inotropic effects 1 µM increase by 72 ± 14.7%, p<0.05, n=7) and shortened the time of relaxation (by 7 .3 %, p<0.05, n=7) in isolated electrically paced human right atrial muscle preparations (obtained during cardiac surgery), that started at 0.1 µM and plateaued at 1 µM OR 1896. The positive inotropic effect of OR 1896 was antagonized by 10 µM propranolol. The positive inotropic effect of OR 1896 in mouse atrial preparations and human right atrial preparations was less effective than that of 1 µM isoprenaline (human atrium by 154 %). The positive inotropic effect of OR 1896 was diminished by pre–incubation of the samples with the PDE III inhibitor cilostamide (10 µM). EMD 57033 (10 µM), a calcium sensitizer, increased force of contraction further in the additional presence of 1 µM OR 1896. Our data suggest that OR 1896 is indeed a positive inotropic agent in the human heart and that OR 1896 acts mainly as a PDE III – inhibitor because the effect of OR 1896 was attenuated by a β–adrenoceptor antagonist and thus OR 1896 is unlikely to act as a calcium sensitizer in the human heart.