Rodent models for the analysis of tissue clock function in metabolic rhythms research

The circadian timing system consists on a distributed network of cellular clocks that together coordinate 24-h rhythms of physiology and behavior. Clock function and metabolism are tightly coupled, from the cellular to the organismal level. Genetic and non-genetic approaches in rodents have been employed to study circadian clock function in the living organism. Due to the ubiquitous expression of clock genes and the intricate interaction between the circadian system and energy metabolism, genetic approaches targeting specific tissue clocks have been used to assess their contribution in systemic metabolic processes. However, special requirements regarding specificity and efficiency have to be met to allow for valid conclusions from such studies. In this review, we provide a brief summary of different approaches developed for dissecting tissue clock function in the metabolic context in rodents, compare their strengths and weaknesses, and suggest new strategies in assessing tissue clock output and the consequences of circadian clock disruption in vivo.Fil: Tsang, Anthony H.. University of Lübeck; Alemania. University of Cambridge; Reino UnidoFil: Astiz, Mariana. University of Lübeck; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Leinweber, Brinja. University of Lübeck; AlemaniaFil: Oster, Henrik. University of Lübeck; Alemani

Resonant Shattering of Neutron Star Crusts

The resonant excitation of neutron star (NS) modes by tides is investigated as a source of short gamma-ray burst (sGRB) precursors. We find that the driving of a crust-core interface mode can lead to shattering of the NS crust, liberating ~10^46-10^47 erg of energy seconds before the merger of a NS-NS or NS-black hole binary. Such properties are consistent with Swift/BAT detections of sGRB precursors, and we use the timing of the observed precursors to place weak constraints on the crust equation of state. We describe how a larger sample of precursor detections could be used alongside coincident gravitational wave detections of the inspiral by Advanced LIGO class detectors to probe the NS structure. These two types of observations nicely complement one another, since the former constrains the equation of state and structure near the crust-core boundary, while the latter is more sensitive to the core equation of state.Comment: 5 pages, 2 figures. Accepted to PR

'It's not one size fits all':A qualitative study of patients' and healthcare professionals' views of self-management for bronchiectasis

Background Bronchiectasis is a chronic respiratory condition that impacts significantly on individuals and healthcare services. Self-management is recommended in clinical guidelines for bronchiectasis as an intervention to enable patients to manage their condition, yet there is little evidence to support it.Methods Three face to face focus groups (17 adults with bronchiectasis) were conducted at three National Health Service (NHS) sites in North West England. Additionally, semi-structured telephone interviews were undertaken with 11 healthcare professionals (HCPs), including doctors, nurses and physiotherapists. Thematic analysis identified common themes and occurrences verified by independent audit.Findings Four common overarching themes were identified: the meaning of self-management; benefits; barriers and influencers to self-management; subthemes varied. Both groups recognised component interventions. Patients highlighted that self-management enabled them to learn what works and moderate behaviour. Aspects of delivery and structure were important to HCPs but a ‘make do’ culture was evident. Benefits for both groups included empowering patients. Common barriers for patients were time, mood and lack of access to support which could mitigate engagement with self-management. HCPs identified barriers including patient characteristics and lack of resources. Influencers for patients were peer, carer and psychosocial support, for HCPs influencers were individual patient attributes, including ability and motivation, and HCP characteristics such as knowledge and understanding about bronchiectasis.Summary This is the first study to explore patients’ and HCPs’ views of self-management for bronchiectasis. The need for an individual, flexible and responsive self-management programme specific to bronchiectasis was evident. Personal characteristics of patients and HCPs could affect the uptake and engagement with self-management and HCPs knowledge of the disease is a recognised precursor to effective self-management. The study identified key aspects for consideration during development, delivery and sustainability of self-management programmes and findings suggest that patients’ psychosocial and socioeconomic circumstances may affect adoption and activation of self-management behaviours

Improving musculoskeletal model scaling using an anatomical atlas:the importance of gender and anthropometric similarity to quantify joint reaction forces

Objective: The accuracy of a musculoskeletal model relies heavily on the implementation of the underlying anatomical dataset. Linear scaling of a generic model, despite being time and cost-efficient, produces substantial errors as it does not account for gender differences and inter-individual anatomical variations. The hypothesis of this study is that linear scaling to a musculoskeletal model with gender and anthropometric similarity to the individual subject produces similar results to the ones that can be obtained from a subject-specific model. Methods: A lower limb musculoskeletal anatomical atlas was developed consisting of ten datasets derived from magnetic resonance imaging of healthy subjects and an additional generic dataset from the literature. Predicted muscle activation and joint reaction force were compared with electromyography and literature data. Regressions based on gender and anthropometry were used to identify the use of atlas. Results: Primary predictors of differences for the joint reaction force predictions were mass difference for the ankle (p<0.001) and length difference for the knee and hip (p≤0.017) . Gender difference accounted for an additional 3% of the variance (p≤0.039) . Joint reaction force differences at the ankle, knee and hip were reduced by between 50% and 67% (p=0.005) when using a musculoskeletal model with the same gender and similar anthropometry in comparison with a generic model. Conclusion: Linear scaling with gender and anthropometric similarity can improve joint reaction force predictions in comparison with a scaled generic model. Significance: The scaling approach and atlas presented can improve the fidelity and utility of musculoskeletal models for subject-specific applications

CLUSTER searching approach to inform evidence syntheses: A methodological review

Background The CLUSTER model of searching was proposed as a systematic method of searching for studies for reviews of complex interventions. The method has not been evaluated before. Aim This methodological review identified and evaluated a sample of evidence syntheses that have used CLUSTER. Methods A forward citation search on the seed CLUSTER publication was conducted on Web of Science Core Collection using six journal citation indexes and Google Scholar in December 2020. Reviews which used the CLUSTER method were eligible for inclusion. A narrative synthesis was used to describe the types of evidence syntheses that used CLUSTER searching, the extent to which the CLUSTER approach has been operationalised within evidence syntheses and whether the value, benefits and limitations of CLUSTER were assessed by the reviewers. Findings A total of sixteen reviews were identified and eligible for synthesis. Six different review types that used CLUSTER were identified with realist reviews being the most prominent. The evaluation of complex interventions was the most common review topic area. The use of CLUSTER varied among reviews with the retrieval of sibling studies being the most common reason. ‘Citations’ and ‘Lead authors’ were the most followed elements of CLUSTER. Conclusions Evidence suggests that CLUSTER has been adopted for use in reviews of complex interventions. Its usage varied among the included reviews. It is imperative that future reviewers diligently report the elements and steps of CLUSTER that were utilised in order to provide a reproducible and transparent search strategy that can be reported with similar transparency to bibliographic database searches

Nutrient sensing in the nucleus of the solitary tract mediates non-aversive suppression of feeding via inhibition of AgRP neurons.

UNLABELLED: The nucleus of the solitary tract (NTS) is emerging as a major site of action for the appetite-suppressive effects of leading pharmacotherapies currently investigated to treat obesity. However, our understanding of how NTS neurons regulate appetite remains incomplete. OBJECTIVES: In this study, we used NTS nutrient sensing as an entry point to characterize stimulus-defined neuronal ensembles engaged by the NTS to produce physiological satiety. METHODS: We combined histological analysis, neuroanatomical assessment using inducible viral tracing tools, and functional tests to characterize hindbrain-forebrain circuits engaged by NTS leucine sensing to suppress hunger. RESULTS: We found that NTS detection of leucine engages NTS prolactin-releasing peptide (PrRP) neurons to inhibit AgRP neurons via a population of leptin receptor-expressing neurons in the dorsomedial hypothalamus. This circuit is necessary for the anorectic response to NTS leucine, the appetite-suppressive effect of high-protein diets, and the long-term control of energy balance. CONCLUSIONS: These results extend the integrative capability of AgRP neurons to include brainstem nutrient sensing inputs