Children with severe neurological impairment (SNI) have central nervous system disorders that arise in childhood and result in motor and cognitive impairment as well as complex developmental disability that requires much assistance with activities of daily living. 1 Some children with SNI receive home mechanical ventilation (HMV), defined as invasive ventilatory support with a tracheostomy and therefore clinician counseling must include relevant information about its known risks and benefits. 2,3 Counseling about HMV for children with SNI depends on many factors and is challenging for both parents and clinicians. 4,5 Children with SNI often have overlapping chronic

We previously discovered that oxidative cleavage of docosahexaenoate (DHA), which is especially abundant in the retinal photoreceptor rod outer segments and retinal pigmented endothelial (RPE) cells, generates 4-hydroxy-7-oxo-5-heptenoate (HOHA) lactone, and that HOHA lactone can enter RPE cells that metabolize it through conjugation with glutathione (GSH). The consequent depletion of GSH results in oxidative stress. We now find that HOHA lactone induces upregulation of the antioxidant transcription factor Nrf2 in ARPE-19 cells. This leads to expression of GCLM, HO1, and NQO1, three known Nrf2-responsive antioxidant genes. Besides this protective response, HOHA lactone also triggers a countervailing inflammatory activation of innate immunity. Evidence for a contribution of the complement pathway to age-related macular degeneration (AMD) pathology includes the presence of complement proteins in drusen and Bruch's membrane from AMD donor eyes, and the identification of genetic susceptibility loci for AMD in the complement pathway. In eye tissues from a mouse model of AMD, accumulation of complement protein in Bruch's membrane below the RPE suggested that the complement pathway targets this interface, where lesions occur in the RPE and photoreceptor rod outer segments. In animal models of AMD, intravenous injection of NaIO to induce oxidative injury selectively destroys the RPE and causes secretion of factor C3 from the RPE into areas directly adjacent to sites of RPE damage. However, a molecular-level link between oxidative injury and complement activation remained elusive. We now find that sub-micromolar concentrations of HOHA lactone foster expression of C3, CFB, and C5 in ARPE-19 cells and induce a countervailing upregulation of CD55, an inhibitor of C3 convertase production and complement cascade amplification. Ultimately, HOHA lactone causes membrane attack complex formation on the plasma membrane. Thus, HOHA lactone provides a molecular-level connection between free-radical-induced oxidative cleavage of DHA and activation of the complement pathway in AMD pathology.

Aim Paediatric emergency departments (ED) nationwide experience a shared burden of boarding mental health patients. Whilst boarding, some patients have a change in disposition from hospitalization to discharge home. This phenomenon raises concern because EDs often have scarce resources for mental health patients. We sought to understand which patient and clinical factors are associated with a change in disposition outcome. Methods A nested age‐sex‐race frequency‐matched case–control study was conducted including paediatric patients who presented to an urban PED for mental healthcare over a 36‐month period. Control patients included patients admitted to an inpatient psychiatric facility, whilst case patients were those discharged home. Descriptive statistics and multivariable logistic regression analyses were performed to compare groups. Results Case patients were more likely to receive intramuscular Haloperidol (OR 2.2 [CI 1.1–4.4]) for agitation and a psychiatric consult (OR 2.3 [1.4–3.9]) whilst boarding. Case patients were also more likely to present with behavioural concerns (OR 1.8 [CI 1.1–3.1]) and have additional complexities such as medical comorbidities (OR 1.8 [CI 1.1–2.9]) or suicidal ideation/attempt (OR 2.6 [CI 1.1–6.1]). Amongst the most common themes for disposition change was improved patient status (58.8%). Conclusion These findings suggest that boarding mental health patients have different disposition outcomes and thus may benefit from patient‐specific treatment interventions. Given that patients' statuses may change during the boarding period prompting discharge to home, more focus should be directed to developing brief evidence‐based practises that may be implemented in the ED and effectively bridge the gap to outpatient mental health services.