Detection of abnormally shaped ears by a trained non-specialist allows for early non-surgical intervention.

INTRODUCTION: Many children are born with abnormally-shaped ears, including protruding ears or unusually-shaped outer ears. While the majority are benign, these may cause significant issues with self-esteem and bullying in childhood. Early molding can resolve some of these abnormalities, avoiding the need for future corrective surgery. However, newborns with these abnormalities are rarely identified early, within the first few days of life, when molding is most effective. In this study, we investigate whether a trained non-specialist can correctly identify ear shape abnormalities in newborns. METHODS: A non-specialist (medical student) was trained on normal and abnormal ear anatomy using photographs and descriptions. Newborns <72 h of age were recruited from maternity wards. Newborns' ears were photographed and these images were assessed independently by two specialists and the non-specialist. External ear shape was classified as either normal or abnormal based on pre-determined criteria. RESULTS: A total of 661 ears of 334 newborns were photographed and assessed. High inter-rater agreement was achieved with a kappa statistic of 0.863 (SE 0.078). The non-specialist detected abnormally-shaped ears with a sensitivity and specificity of 90.9% and 91.1% respectively. CONCLUSIONS: Our study illustrates that non-specialist can be trained to accurately detect newborn ear abnormalities, providing a cost-effective means of ensuring that these children's health care needs are met in a timely fashion. Specifically, we recommend the integration of ear shape assessment into currently established programs such as the newborn hearing screening program.

SOX9 modulates the expression of key transcription factors required for heart valve development.

Heart valve formation initiates when endothelial cells of the heart transform into mesenchyme and populate the cardiac cushions. The transcription factor SOX9 is highly expressed in the cardiac cushion mesenchyme, and is essential for heart valve development. Loss of Sox9 in mouse cardiac cushion mesenchyme alters cell proliferation, embryonic survival, and valve formation. Despite this important role, little is known about how SOX9 regulates heart valve formation or its transcriptional targets. Therefore, we mapped putative SOX9 binding sites by ChIP-Seq in E12.5 heart valves, a stage at which the valve mesenchyme is actively proliferating and initiating differentiation. Embryonic heart valves have been shown to express a high number of genes that are associated with chondrogenesis, including several extracellular matrix proteins and transcription factors that regulate chondrogenesis. Therefore, we compared regions of putative SOX9 DNA binding between E12.5 heart valves and E12.5 limb buds. We identified context-dependent and context-independent SOX9-interacting regions throughout the genome. Analysis of context-independent SOX9 binding suggests an extensive role for SOX9 across tissues in regulating proliferation-associated genes including key components of the AP-1 complex. Integrative analysis of tissue-specific SOX9-interacting regions and gene expression profiles on Sox9-deficient heart valves demonstrated that SOX9 controls the expression of several transcription factors with previously identified roles in heart valve development, including Twist1, Sox4, Mecom and Pitx2. Together, our data identify SOX9-coordinated transcriptional hierarchies that control cell proliferation and differentiation during valve formation.

A regulatory network controls nephrocan expression and midgut patterning.

Although many regulatory networks involved in defining definitive endoderm have been identified, the mechanisms through which these networks interact to pattern the endoderm are less well understood. To explore the mechanisms involved in midgut patterning, we dissected the transcriptional regulatory elements of nephrocan (Nepn), the earliest known midgut specific gene in mice. We observed that Nepn expression is dramatically reduced in Sox17(-/-) and Raldh2(-/-) embryos compared with wild-type embryos. We further show that Nepn is directly regulated by Sox17 and the retinoic acid (RA) receptor via two enhancer elements located upstream of the gene. Moreover, Nepn expression is modulated by Activin signaling, with high levels inhibiting and low levels enhancing RA-dependent expression. In Foxh1(-/-) embryos in which Nodal signaling is reduced, the Nepn expression domain is expanded into the anterior gut region, confirming that Nodal signaling can modulate its expression in vivo. Together, Sox17 is required for Nepn expression in the definitive endoderm, while RA signaling restricts expression to the midgut region. A balance of Nodal/Activin signaling regulates the anterior boundary of the midgut expression domain.