Cleft lip (CL) is a common malformation that has both genetic and exogenous causes. The main pharmaceutical cause is exposure to phenytoin during early facial development in the 5th to 6th weeks of gestation. Phenytoin also causes CL if administered to pregnant rats during the period of early facial development. Evidence is presented that in the pregnant rat, a teratogenic dose of phenytoin slows the early embryonic heart and causes a prolonged period of embryonic hypoxia. It is proposed that this hypoxia, through an undefined downstream mechanism, leads to the development of CL. The involvement of hypoxia in the pathogenesis of CL is in agreement with studies in mouse strains with a spontaneous rate of CL in which exposure to hypoxia has been shown to increase the rate and hyperoxia to decrease the rate. Other exogenous risk factors during pregnancy for human CL include maternal cigarette smoking, residence at high altitude and exposure to corticosteroids. It is suggested that these exposures all involve an increased risk of embryonic hypoxia. It has been proposed that phenytoin affects the embryonic heart by inhibition of the human-ether-a-go-go (HERG) potassium channel. Phenytoin also inhibits sodium and calcium channels and these properties may also be involved in the observed effect on the embryonic heart. Phenytoin-induced bradycardia leading to embryonic hypoxia may be an important mechanism by which phenytoin causes birth defects.

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Drugs that induce periods of bradycardia and/or arrhythmia of the embryonic heart and cause the embryo to become hypoxic are potential human teratogens.

Ultrasound is a useful technique to investigate the effect of maternally administered drugs on the embryonic HR in the rat. The results may provide more information about the safety of these drugs in pregnancy leading to better risk assessment for the human.

This study evaluates a cooperative learning approach for teaching anatomy to health science students incorporating small group and peer instruction based on the jigsaw method first described in the 1970's. Fifty-three volunteers participated in abdominal anatomy workshops. Students were given time to become an "expert" in one of four segments of the topic (sub-topics) by allocating groups to work-stations with learning resources: axial computerized tomography (CT) of abdominal structures, axial CT of abdominal blood vessels, angiograms and venograms of abdominal blood vessels and structures located within abdominal quadrants. In the second part of workshop, students were redistributed into "jigsaw" learning groups with at least one "expert" at each workstation. The "jigsaw" learning groups then circulated between workstations learning all sub-topics with the "expert" teaching others in their group. To assess abdominal anatomy knowledge, students completed a quiz pre- and post- workshop. Students increased their knowledge with significant improvements in quiz scores irrespective of prior exposure to lectures or practical classes related to the workshop topic. The evidence for long-term retention of knowledge, assessed by comparing end-semester examination performance of workshop participants with workshop nonparticipants, was less convincing. Workshop participants rated the jigsaw workshop highly for both educational value and enjoyment and felt the teaching approach would improve their course performance. The jigsaw method improved anatomy knowledge in the short-term by engaging students in group work and peer-led learning, with minimal supervision required. Reported outcomes suggest that cooperative learning approaches can lead to gains in student performance and motivation to learn. Anat Sci Educ 00: 000-000. © 2018 American Association of Anatomists.

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Hypoxia is a normal and essential part of embryonic development. However, this state may leave the embryo vulnerable to damage when oxygen supply is disturbed. Embryofetal response to hypoxia is dependent on duration and depth of hypoxia, as well as developmental stage. Early postimplantation rat embryos were resilient to hypoxia, with many surviving up to 1.5 hr of uterine clamping, while most mid-gestation embryos were dead after 1 hour of clamping. Survivors were small and many had a range of defects, principally terminal transverse limb reduction defects. Similar patterns of malformations occurred when embryonic hypoxia was induced by maternal hypoxia, interruption of uteroplacental flow, or perfusion and embryonic bradycardia. There is good evidence that high altitude pregnancies are associated with smaller babies and increased risk of some malformations, but these results are complicated by increased risk of pre-eclampsia. Early onset pre-eclampsia itself is associated with small for dates and increased risk of atrio-ventricular septal defects. Limb defects have clearly been associated with chorionic villus sampling, cocaine, and misoprostol use. Similar defects are also observed with increased frequency among fetuses who are homozygous for thalassemia. Drugs that block the potassium current, whether as the prime site of action or as a side effect, are highly teratogenic in experimental animals. They induce embryonic bradycardia, hypoxia, hemorrhage, and blisters, leading to transverse limb defects as well as craniofacial and cardiovascular defects. While evidence linking these drugs to birth defects in humans is not compelling, the reason may methodological rather than biological. Birth Defects Research 109:1358-1376, 2017.© 2017 Wiley Periodicals, Inc.