Accumbal Cholinergic Interneurons Differentially Influence Motivation Related to Satiety Signaling

Satiety, rather than all or none, can instead be viewed as a cumulative decrease in the drive to eat that develops over the course of a meal. The nucleus accumbens (NAc) is known to play a critical role in this type of value reappraisal, but the underlying circuits that influence such processes are unclear. Although NAc cholinergic interneurons (CINs) comprise only a small proportion of NAc neurons, their local impact on reward-based processes provides a candidate cell population for investigating the neural underpinnings of satiety. The present research therefore aimed to determine the role of NAc-CINs in motivation for food reinforcers in relation to satiety signaling. Through bidirectional control of CIN activity in mice, we show that when motivated by food restriction, increasing CIN activity led to a reduction in palatable food consumption while reducing CIN excitability enhanced food intake. These activity-dependent changes developed only late in the session and were unlikely to be driven by the innate reinforcer strength, suggesting that CIN modulation was instead impacting the cumulative change in motivation underlying satiety signaling. We propose that on a circuit level, an overall increase in inhibitory tone onto NAc output neurons played a role in the behavioral results, as activating NAc-CINs led to an inhibition of medium spiny neurons that was dependent on nicotinic receptor activation. Our results reveal an important role for NAc-CINs in controlling motivation for food intake and additionally provide a circuit-level framework for investigating the endogenous cholinergic circuits that signal satiety.Peer reviewe

Implementing paediatric appropriate use criteria for endotracheal suction to reduce complications in mechanically ventilated children with respiratory infections

BackgroundEndotracheal suction is used to maintain endotracheal tube patency. There is limited guidance to inform clinical practice for children with respiratory infections.ObjectiveThe objective of this study was to determine whether implementation of a paediatric endotracheal suction appropriate use guideline Paediatric AirWay Suction (PAWS) is associated with an increased use of appropriate and decreased use of inappropriate suction interventions.MethodsA mixed-method, pre-implementation–post-implementation study was conducted between September 2021 and April 2022. Suction episodes in mechanically ventilated children with a respiratory infection were eligible. Using a structured approach, we implemented the PAWS guideline in a single paediatric intensive care unit. Evaluation included clinical (e.g., suction intervention appropriateness), implementation (e.g., acceptability), and cost outcomes (implementation costs). Associations between implementation of the PAWS guideline and appropriateness of endotracheal suction intervention use were investigated using generalised linear models.ResultsData from 439 eligible suctions were included in the analysis. Following PAWS implementation, inappropriate endotracheal tube intervention use reduced from 99% to 58%, an absolute reduction (AR) of 41% (95% confidence interval [CI]: 25%, 56%). Reductions were most notable for open suction systems (AR: 48%; 95% CI: 30%, 65%), 0.9% sodium chloride use (AR: 23%; 95% CI: 8%, 38%) and presuction and postsuction manual bagging (38%; 95% CI: 16%, 60%, and 86%; 95% CI: 73%, 99%), respectively. Clinicians perceived PAWS as acceptable and suitable for use.ConclusionsImplementation of endotracheal tube suction appropriate use guidelines in a mixed paediatric intensive care unit was associated with a large reduction in inappropriate suction intervention use in paediatric patients with respiratory infections

Photoacclimation in Dunaliella tertiolecta reveals a unique NPQ pattern upon exposure to irradiance

Highly time-resolved photoacclimation patterns of the chlorophyte microalga Dunaliella tertiolecta during exposure to an off–on–off (block) light pattern of saturating photon flux, and to a regime of consecutive increasing light intensities are presented. Non-photochemical quenching (NPQ) mechanisms unexpectedly responded with an initial decrease during dark–light transitions. NPQ values started to rise after light exposure of approximately 4 min. State-transitions, measured as a change of PSII:PSI fluorescence emission at 77 K, did not contribute to early NPQ oscillations. Addition of the uncoupler CCCP, however, caused a rapid increase in fluorescence and showed the significance of qE for NPQ. Partitioning of the quantum efficiencies showed that constitutive NPQ was (a) higher than qE-driven NPQ and (b) responded to light treatment within seconds, suggesting an active role of constitutive NPQ in variable energy dissipation, although it is thought to contribute statically to NPQ. The PSII connectivity parameter p correlated well with F′, Fm′ and NPQ during the early phase of the dark–light transients in sub-saturating light, suggesting a plastic energy distribution pattern within energetically connected PSII centres. In consecutive increasing photon flux experiments, correlations were weaker during the second light increment. Changes in connectivity can present an early photoresponse that are reflected in fluorescence signals and NPQ and might be responsive to the short-term acclimation state, and/or to the actinic photon flux

Every child, every day, back to play: the PICUstars protocol - implementation of a nurse-led PICU liberation program

Background: As admissions to paediatric intensive care units (PICU) rise and mortality rates decline, the focus is shifting from survival to quality of survivorship. There is paucity of internationally accepted guidelines to manage complications like over-sedation, delirium, and immobility in the paediatric setting. These have a strong adverse impact on PICU recovery including healthcare costs and long-term functional disability. The A2F bundle (ABCDEF), or ICU Liberation, was developed to operationalise the multiple evidence-based guidelines addressing ICU-related complications and has been shown to improve clinical outcomes and health-care related costs in adult studies. However, there is little data on the effect of ICU Liberation bundle implementation in PICU. Methods: PICU-STARS will be a single centre before-and-after after trial and implementation study. It is designed to evaluate if the multidimensional, nurse-led ICU Liberation model of care can be applied to the PICU and if it is successful in minimising PICU-related problems in a mixed quaternary PICU. In a prospective baseline measurement, the present practises of care in the PICU will be assessed in order to inform the adaptation and implementation of the PICU Liberation bundle. To assess feasibility, implementation outcomes, and intervention effectiveness, the implementation team will use the Consolidated Framework for Implementation Research (CIFR) and process assessment (mixed methods). The implementation process will be evaluated over time, with focus groups, interviews, questionnaires, and observations used to provide formative feedback. Over time, the barriers and enablers for successful implementation will be analysed, with recommendations based on “lessons learned.” All outcomes will be reported using standard descriptive statistics and analytical techniques, with appropriate allowance for patient differentials in severity and relevant characteristics. Discussion: The results will inform the fine-tune of the Liberation bundle adaptation and implementation process. The expected primary output is a detailed adaptation and implementation guideline, including clinical resources (and investment) required, to adopt PICU-STARS in other children’s hospitals. Patient and public involvement statement: The authors thank the PICU education and Liberation Implementation team, and our patients and families for their inspiration and valuable comments on protocol drafts. Results will be made available to critical care survivors, their caregivers, relevant societies, and other researchers. Trial registration: ACTRN, ACTRN382863. Registered 19/10/2021 - Retrospectively registered. Study status: recruiting.</p