Patients with Doublecortin (DCX) mutations have severe cortical malformations associated with mental retardation and epilepsy. Dcx knockout (KO) mice show no major isocortical abnormalities, but have discrete hippocampal defects. We questioned the functional consequences of these defects and report here that Dcx KO mice are hyperactive and exhibit spontaneous convulsive seizures. Changes in neuropeptide Y and calbindin expression, consistent with seizure occurrence, were detected in a large proportion of KO animals, and convulsants, including kainate and pentylenetetrazole, also induced seizures more readily in KO mice. We show that the dysplastic CA3 region in KO hippocampal slices generates sharp wave-like activities and possesses a lower threshold for epileptiform events. Video-EEG monitoring also demonstrated that spontaneous seizures were initiated in the hippocampus. Similarly, seizures in human patients mutated for DCX can show a primary involvement of the temporal lobe. In conclusion, seizures in Dcx KO mice are likely to be due to abnormal synaptic transmission involving heterotopic cells in the hippocampus and these mice may therefore provide a useful model to further study how lamination defects underlie the genesis of epileptiform activities.

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Objective. To identify specific health care areas whose optimization could improve population health in the Dutch Caribbean islands of Aruba and Curaçao. Methods. Comparative observational study using mortality and population data of the Dutch Caribbean islands and the Netherlands. Mortality trends were calculated, then analyzed with Joinpoint software, for the period 1988–2014. Life expectancies were computed using abridged life tables for the most recent available data of all territories (2005–2007). Life expectancy differences between the Dutch Caribbean and the Netherlands were decomposed into cause-specific contributions using Arriaga’s method. Results. During the period 1988–2014, levels of amenable mortality have been consistently higher in Aruba and Curaçao than in the Netherlands. For Aruba, the gap in amenable mortality with the Netherlands did not significantly change during the study period, while it widened for Curaçao. If mortality from amenable causes were reduced to similar levels as in the Netherlands, men and women in Aruba would have added, respectively, 1.19 years and 0.72 years to their life expectancies during the period 2005–2007. In Curaçao, this would be 2.06 years and 2.33 years. The largest cause-specific contributions were found for circulatory diseases, breast cancer, perinatal causes, and nephritis/nephrosis (these last two causes solely in Curaçao). Conclusions. Improvements in health care services related to circulatory diseases, breast cancer, perinatal deaths, and nephritis/nephrosis in the Dutch Caribbean could substantially contribute to reducing the gap in life expectancy with the Netherlands. Based on our study, we recommend more in-depth studies to identify the specific interventions and resources needed to optimize the underlying health care areas.