Nrg1 deficiency modulates the behavioural effects of prenatal stress in mice.

Little is known about the exact genes that confer vulnerability or resilience to environmental stressors during early neurodevelopment. Partial genetic deletion of neuregulin 1 (Nrg1) moderates the neurobehavioural effects of stressors applied in adolescence and adulthood, however, no study has yet examined its impact on prenatal stress. Here we examined whether Nrg1 deficiency in mice modulated the impact of prenatal stress on various behaviours in adulthood. Male heterozygous Nrg1 mice were mated with wild-type female mice who then underwent daily restraint stress from days 13 to 19 of gestation. Surprisingly, prenatal stress had overall beneficial effects by facilitating sensorimotor gating, increasing sociability, decreasing depressive-like behaviour, and improving spatial memory in adulthood. Such benefits were not due to any increase in maternal care, as prenatal stress decreased nurturing of the offspring. Nrg1 deficiency negated the beneficial behavioural effects of prenatal stress on all measures except sociability. However, Nrg1 deficiency interacted with prenatal stress to trigger locomotor hyperactivity. Nrg1 deficiency, prenatal stress or their combination failed to alter acute stress-induced plasma corticosterone concentrations. Collectively these results demonstrate that Nrg1 deficiency moderates the effects of prenatal stress on adult behaviour, but it does so in a complex, domain-specific fashion.

Incidence of allergic rhinitis in children with residual snoring and sleep symptoms after adenotonsillectomy.

BACKGROUND AND OBJECTIVES: Allergic rhinitis may contribute to sleep disordered breathing (SDB) in children. Although adenotonsillectomy is commonly performed to treat SDB, some patients will return to their primary practitioners with residual sleep symptoms. The aim of this study was to assess the incidence of allergic rhinitis via radioallergosorbent testing (RAST) in children undergoing adenotonsillectomy who had residual snoring or sleep symptoms. METHOD: A retrospective analysis of 500 patients post-adenotonsillectomy was undertaken. The incidence of residual snoring, residual sleep symptoms and results of RAST, as well as total immunoglobulin E (IgE) after surgical intervention, were documented. RESULTS: Children with positive RAST results or elevated total IgE had a significantly greater incidence of residual snoring post-adenotonsillectomy (P = 0.049) and residual sleep symptoms after surgery (P <0.0001). DISCUSSION: A positive RAST or elevated IgE in children with SDB was associated with incomplete resolution of snoring and residual sleep symptoms after adenotonsillectomy. Thus, there should be raised suspicion of allergic rhinitis in this population.

Is the cellular uptake of respiratory aerosols delivered from different devices equivalent?

The study focuses on the application of a cell integrated modified Andersen Cascade Impactor (ACI) as an in vitro lung model for the evaluation of aerosols' behaviour of different formulation devices, containing the same active drug, specifically nebuliser, pressurised metered dose inhaler (pMDI) and dry powder inhaler (DPI). Deposition and transport profiles of the three different inhaled salbutamol sulphate (SS) formulations with clinically relevant doses were evaluated using a modified ACI coupled with the air interface Calu-3 bronchial cell model. Reproducible amounts of SS were deposited on Snapwells for the different formulations, with no significant difference in SS deposition found between the standard ACI plate and modified plate. The transport of SS aerosols produced from pMDI formulation had similar transport kinetics to nebulised SS but significantly higher compared to the DPI, which could have led to the differences in clinical outcomes. Furthermore, drug absorption of different inhaled formulation devices of the same aerodynamic fraction was found not to be equivalent due to their physical chemical properties upon aerosolisation. This study has established an in vitro platform for the evaluation of the different inhaled formulations in physiologically relevant pulmonary conditions.