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Dorothy Flatman explores the background to consulting with children and young people and summarises guidelines for ensuring their input to decision making at all levels. [ABSTRACT FROM AUTHOR]

Intracerebral haemorrhage is a debilitating stroke sub-type with high morbidity and mortality rates. For survivors, rehabilitation is a long process, and with no available therapeutics to limit the immediate pathophysiology of the haemorrhage, recovery is dependent on individual neuroplasticity. We have previously shown that zebrafish larvae can be used to model spontaneous brain haemorrhage. Zebrafish exhibit innate recovery mechanisms and are often used as a model system for investigation into regeneration after injury, including injury to the nervous system. Here, we investigate the spontaneous and immediate recovery in zebrafish larvae following an intracerebral haemorrhage at 2 days post-fertilisation, during pre-protected stages and over the first 3 weeks of life. We have shown that following the onset of bleed at ∼2 days post-fertilisation zebrafish are capable of clearing the haematoma through the ventricles. Brain cell damage associated with intracerebral haemorrhage is resolved within 48 h, and this recovery is associated with survival rates equal to wildtype and non-haemorrhaged sibling control animals. Larvae express more nestin-positive neural progenitor cells 24 h after injury when the most damage is observed, and through mass spectrometry analysis, we have determined that these cells are highly proliferative and may specially differentiate into oligodendrocytes. This study provides an insight into the haematoma resolution processes in a live, intact organism, and may suggest potential therapeutic approaches to support the recovery of intracerebral haemorrhage patients., Competing Interests: The authors have no competing interests to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Aims: Rare, deleterious genetic variants in FLT4 are associated with Tetralogy of Fallot (TOF), the most common cyanotic congenital heart disease. The distinct genetic variants in FLT4 are also an established cause of Milroy disease, the most prevalent form of primary hereditary lymphoedema. The phenotypic features of these two conditions are non-overlapping, implying pleiotropic cellular mechanisms during development., Methods and Results: In this study, we show that FLT4 variants identified in patients with TOF, when expressed in primary human endothelial cells, cause aggregation of FLT4 protein in the perinuclear endoplasmic reticulum, activating proteostatic and metabolic signalling, whereas lymphoedema-associated FLT4 variants and wild-type (WT) FLT4 do not. FLT4 TOF variants display characteristic gene expression profiles in key developmental signalling pathways, revealing a role for FLT4 in cardiogenesis distinct from its role in lymphatic development. Inhibition of proteostatic signalling abrogates these effects, identifying potential avenues for therapeutic intervention. Depletion of flt4 in zebrafish caused cardiac phenotypes of reduced heart size and altered heart looping. These phenotypes were rescued with coinjection of WT human FLT4 mRNA, but incompletely or not at all by mRNA harbouring FLT4 TOF variants., Conclusion: Taken together, we identify a pathogenic mechanism for FLT4 variants predisposing to TOF that is distinct from the known dominant negative mechanism of Milroy-causative variants. FLT4 variants give rise to conditions of the two circulatory subdivisions of the vascular system via distinct developmental pleiotropic molecular mechanisms., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: We sought to establish the effects of professionalism, which officially began in 1995, on the body mass and height of northern hemisphere male international rugby union (RU) players. We hypothesised that mass would significantly increase following professionalism. We also investigated the changes in size of players according to their playing position, and we compared changes to rugby league (RL) players and the public., Methods: The body mass and height of players representing their international team for that country's first game of the Five Nations in 1955, 1965, 1975, 1985 and 1995 and, for 2005 and 2015, the Six Nations, were collected from matchday programmes. RL players' data were collected from the Challenge Cup final games played in the same years., Results: International RU player body mass has significantly increased since 1995. In 1955 mean (±SD) player body mass was 84.8  kg (±8.2); in 2015, it was 105.4  kg (±12.1), an increase of 24.3%. Between 1955 and 2015, the body mass of forwards increased steadily, whereas that of backs has mostly gone up since 1995. RU player body mass gain has exceeded that of RL, but the age-matched difference between RU players and the public has remained relatively constant., Conclusions: The factors influencing the gain in body mass of rugby players are legion; however, we believe that the interpretation of the law relating to the scrum put-in and changes allowing substitutions have, at least in part, contributed to the observed changes. Injury severity is increasing, and this may be linked to greater forces (caused by greater body mass) occurring in contact. RU law makers should adjust the rules to encourage speed and skill at the expense of mass., Competing Interests: Competing interests: None declared.

Background: Two recent trials have shown that women's groups can reduce neonatal mortality in poor communities. We assessed the effectiveness of a scaled-up development programme with women's groups to address maternal and neonatal care in three rural districts of Bangladesh., Methods: 18 clusters (with a mean population of 27 953 [SD 5953]) in three districts were randomly assigned to either intervention or control (nine clusters each) by use of stratified randomisation. For each district, cluster names were written on pieces of paper, which were folded and placed in a bottle. The first three cluster names drawn from the bottle were allocated to the intervention group and the remaining three to control. All clusters received health services strengthening and basic training of traditional birth attendants. In intervention clusters, a facilitator convened 18 groups every month to support participatory action and learning for women, and to develop and implement strategies to address maternal and neonatal health problems. Women were eligible to participate if they were aged 15-49 years, residing in the project area, and had given birth during the study period (Feb 1, 2005, to Dec 31, 2007). Neither study investigators nor participants were masked to treatment assignment. In a population of 229 195 people (intervention clusters only), 162 women's groups provided coverage of one group per 1414 population. The primary outcome was neonatal mortality rate (NMR). Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN54792066., Findings: We monitored outcomes for 36 113 births (intervention clusters, n=17 514; control clusters, n=18 599) in a population of 503 163 over 3 years. From 2005 to 2007, there were 570 neonatal deaths in the intervention clusters and 656 in the control clusters. Cluster-level mean NMR (adjusted for stratification and clustering) was 33.9 deaths per 1000 livebirths in the intervention clusters compared with 36.5 per 1000 in the control clusters (risk ratio 0.93, 95% CI 0.80-1.09)., Interpretation: For participatory women's groups to have a significant effect on neonatal mortality in rural Bangladesh, detailed attention to programme design and contextual factors, enhanced population coverage, and increased enrolment of newly pregnant women might be needed., Funding: Women and Children First, the UK Big Lottery Fund, Saving Newborn Lives, and the UK Department for International Development., (Copyright 2010 Elsevier Ltd. All rights reserved.)

This article presents an overview of a three-year development project in Bangladesh and Nepal working in partnership with local non-governmental organisations (NGOs) to focus on improving services for mothers and their newborns.