Abstract:Bath-applied serotonin (5-HT) induces competent larvae of the marine snail Ilyanassa obsoleta to metamorphose. Previously, the mode of action of 5-HT, whether as an external ligand or as an internal neurotransmitter, was unknown. Larvae were injected with 10 -4 M 5-HT and other pharmacological agents to provide evidence that serotonergic neurons are necessary for metamorphosis in Ilyanassa larvae and that serotonin functions as a neurotransmitter or neuromodulator during this process. About 50% of 5-HT-injected animals metamorphose within 48 hours. Fluoxetine, a 5-HT re-uptake inhibitor, and alpha-methy1-5-hydroxytryptamine (αm5HT), a 5-HT agonist, were also effective inducers of metamorphosis. Gramine (3-[dimethyl-aminomethyl]indole), a 5-HT antagonist, inhibited the inductive activity of 5-HT, while the amino acid gamma-aminobutyric acid (GABA) resulted in rates of morphological restructuring similar to those of controls. Collectively, the results of our experiments support the idea that serotonergic neurons are active during larval metamorphosis of Ilyanassa and that 5-HT does not induce metamorphosis by binding to epidermal chemoreceptors.

BackgroundAcute exacerbations of asthma are common in children, however, treatment decisions for severe exacerbations are challenging due to a lack of robust evidence. In order to create more robust research, a core set of outcome measures needs to be developed. In developing these outcomes, it is important to understand the views of clinicians who care for these children in particular, views that relate to outcome measures and research priorities.MethodsTo determine the views of clinicians, a total of 26 semistructured interviews based on the theoretical domains framework were conducted. These included experienced clinicians from emergency, intensive care and inpatient paediatrics across 17 countries. The interviews were recorded, and later transcribed. All data analyses were conducted in Nvivo by using thematic analysis.ResultsThe length of stay in hospital and patient-focused parameters, such as timing to return to school and normal activity, were the most frequently highlighted outcome measures, with clinicians identifying the need to achieve a consensus on key core outcome measure sets. Most research questions focused on understanding the best treatment options, including the role of novel therapies and respiratory support.ConclusionOur study provides an insight into what research questions and outcome measures clinicians view as important. In addition, information on how clinicians define asthma severity and measure treatment success will assist with methodological design in future trials. The current findings will be used in parallel with a further Paediatric Emergency Research Network study focusing on the child and family perspectives and will contribute to develop a core outcome set for future research.

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