METHODS: High-resolution fluorescent optical mapping of electrical activity and electrocardiogram measurements were used to characterize effects of UDCA on one-day-old neonatal and adult female Langendorff-perfused rat hearts. ICP was modelled by perfusion of taurocholic acid (TC, 400μM). Whole-cell calcium currents were recorded from neonatal rat and human fetal cardiomyocytes.
RESULTS: TC significantly prolonged the PR interval by 11.0±3.5% (P<0.05) and slowed ventricular conduction velocity (CV) by 38.9±5.1% (P<0.05) exclusively in neonatal and not in maternal hearts. A similar CV decline was observed with the selective T-type calcium current (ICa,T) blocker mibefradil 1μM (23.0±6.2%, P<0.05), but not with the L-type calcium current (ICa,L) blocker nifedipine 1μM (6.9±6.6%, NS). The sodium channel blocker lidocaine (30μM) reduced CV by 60.4±4.5% (P<0.05). UDCA co-treatment was protective against CV slowing induced by TC and mibefradil, but not against lidocaine. UDCA prevented the TC-induced reduction in the ICa,T density in both isolated human fetal (-10.2±1.5 versus -5.5±0.9 pA/pF, P<0.05) and neonatal rat ventricular myocytes (-22.3±1.1 versus -9.6±0.8 pA/pF, P<0.0001), whereas UDCA had limited efficacy on the ICa,L.
CONCLUSION: Our findings demonstrate that ICa,T plays a significant role in ICP-associated fetal cardiac conduction slowing and arrhythmogenesis, and is an important component of the fetus-specific anti-arrhythmic activity of UDCA.
METHOD: This study investigates three-dimensional (3D) soft-tissue craniofacial variation, with relation to ethnicity, sex and age variables in British and Irish white Europeans. This utilizes a geometric morphometric approach on a subsampled dataset comprising 292 scans, taken from a Liverpool-York Head Model database. Shape variation and analysis of each variable are tested using 20 anchor anatomical landmarks and 480 sliding semi-landmarks.
RESULTS: Significant ethnicity, sex, and age differences are observed for measurement covering major aspects of the craniofacial shape. The ethnicity shows subtle significant differences compared to sex and age; even though it presents the lowest classification accuracy. The magnitude of dimorphism in sex is revealed in the facial, nasal and crania measurement. Significant shape differences are also seen at each age group, with some distinct dimorphic features present in the age groups.
CONCLUSIONS: The patterns of shape variation show that white British individuals have a more rounded head shape, whereas white Irish individuals have a narrower head shape. White British persons also demonstrate higher classification accuracy. Regarding sex patterns, males are relatively larger than females, especially in the mouth and nasal regions. Females presented with higher classification accuracy than males. The differences in the chin, mouth, nose, crania, and forehead emerge from different growth rates between the groups. Classification accuracy is best for children and senior adult age groups.