Neonatal Resuscitation Practices in Portuguese Delivery Rooms: A Cross-Sectional Study.

INTRODUCTION: Data from previous studies have demonstrated inconsistency between current evidence and delivery room resuscitation practices in developed countries. The primary aim of this study was to assess the quality of newborn healthcare and resuscitation practices in Portuguese delivery rooms, comparing current practices with the 2021 European Resuscitation Council guidelines. The secondary aim was to compare the consistency of practices between tertiary and non-tertiary centers across Portugal. METHODS: An 87-question survey concerning neonatal care was sent to all physicians registered with the Portuguese Neonatal Society via email. In order to compare practices between centers, participants were divided into two groups: Group A (level III and level IIb centers) and Group B (level IIa and I centers). A descriptive analysis of variables was performed in order to compare the two groups. RESULTS: In total, 130 physicians responded to the survey. Group A included 91 (70%) and Group B 39 (30%) respondents. More than 80% of participants reported the presence of a healthcare professional with basic newborn resuscitation training in all deliveries, essential equipment in the delivery room, such as a resuscitator with a light and heat source, a pulse oximeter, and an O2 blender, and performing delayed cord clamping for all neonates born without complications. Less than 60% reported performing team briefing before deliveries, the presence of electrocardiogram sensors, end-tidal CO2 detector, and continuous positive airway pressure in the delivery room, and monitoring the neonate's temperature. Major differences between groups were found regarding staff attending deliveries, education, equipment, thermal control, umbilical cord management, vital signs monitoring, prophylactic surfactant administration, and the neonate's transportation out of the delivery room. CONCLUSION: Overall, adherence to neonatal resuscitation international guidelines was high among Portuguese physicians. However, differences between guidelines and current practices, as well as between centers with different levels of care, were identified. Areas for improvement include team briefing, ethics, education, available equipment in delivery rooms, temperature control, and airway management. The authors emphasize the importance of continuous education to ensure compliance with the most recent guidelines and ultimately improve neonatal health outcomes.

Semaphorin heterodimerization in cis regulates membrane targeting and neocortical wiring.

Disruption of neocortical circuitry and architecture in humans causes numerous neurodevelopmental disorders. Neocortical cytoarchitecture is orchestrated by various transcription factors such as Satb2 that control target genes during strict time windows. In humans, mutations of SATB2 cause SATB2 Associated Syndrome (SAS), a multisymptomatic syndrome involving epilepsy, intellectual disability, speech delay, and craniofacial defects. Here we show that Satb2 controls neuronal migration and callosal axonal outgrowth during murine neocortical development by inducing the expression of the GPI-anchored protein, Semaphorin 7A (Sema7A). We find that Sema7A exerts this biological activity by heterodimerizing in cis with the transmembrane semaphorin, Sema4D. We could also observe that heterodimerization with Sema7A promotes targeting of Sema4D to the plasma membrane in vitro. Finally, we report an epilepsy-associated de novo mutation in Sema4D (Q497P) that inhibits normal glycosylation and plasma membrane localization of Sema4D-associated complexes. These results suggest that neuronal use of semaphorins during neocortical development is heteromeric, and a greater signaling complexity exists than was previously thought.

Protein translation rate determines neocortical neuron fate.

The mammalian neocortex comprises an enormous diversity regarding cell types, morphology, and connectivity. In this work, we discover a post-transcriptional mechanism of gene expression regulation, protein translation, as a determinant of cortical neuron identity. We find specific upregulation of protein synthesis in the progenitors of later-born neurons and show that translation rates and concomitantly protein half-lives are inherent features of cortical neuron subtypes. In a small molecule screening, we identify Ire1α as a regulator of Satb2 expression and neuronal polarity. In the developing brain, Ire1α regulates global translation rates, coordinates ribosome traffic, and the expression of eIF4A1. Furthermore, we demonstrate that the Satb2 mRNA translation requires eIF4A1 helicase activity towards its 5'-untranslated region. Altogether, we show that cortical neuron diversity is generated by mechanisms operating beyond gene transcription, with Ire1α-safeguarded proteostasis serving as an essential regulator of brain development.