Reverse genetic screening reveals poor correlation between morpholino-induced and mutant phenotypes in zebrafish.

The widespread availability of programmable site-specific nucleases now enables targeted gene disruption in the zebrafish. In this study, we applied site-specific nucleases to generate zebrafish lines bearing individual mutations in more than 20 genes. We found that mutations in only a small proportion of genes caused defects in embryogenesis. Moreover, mutants for ten different genes failed to recapitulate published Morpholino-induced phenotypes (morphants). The absence of phenotypes in mutant embryos was not likely due to maternal effects or failure to eliminate gene function. Consistently, a comparison of published morphant defects with the Sanger Zebrafish Mutation Project revealed that approximately 80% of morphant phenotypes were not observed in mutant embryos, similar to our mutant collection. Based on these results, we suggest that mutant phenotypes become the standard metric to define gene function in zebrafish, after which Morpholinos that recapitulate respective phenotypes could be reliably applied for ancillary analyses.

An investigation of the impact of regular use of the Wii Fit to improve motor and psychosocial outcomes in children with movement difficulties: a pilot study.

BACKGROUND: Children with Developmental Co-ordination Disorder (DCD) experience poor motor and psychosocial outcomes. Interventions are often limited within the healthcare system, and little is known about how technology might be used within schools or homes to promote the motor skills and/or psychosocial development of these children. This study aimed to evaluate whether short, regular school-based sessions of movement experience using a commercially available home video game console (Nintendo's Wii Fit) would lead to benefits in both motor and psychosocial domains in children with DCD. METHODS: A randomized crossover controlled trial of children with movement difficulties/DCD was conducted. Children were randomly assigned to an intervention (n = 10) or comparison (n = 8) group. The intervention group spent 10 min thrice weekly for 1 month using Wii Fit during the lunch break, while the comparison group took part in their regular Jump Ahead programme. Pre- and post-intervention assessments considered motor proficiency, self-perceived ability and satisfaction and parental assessment of emotional and behavioural problems. RESULTS: Significant gains were seen in motor proficiency, the child's perception of his/her motor ability and reported emotional well-being for many, but not all children. CONCLUSIONS: This study provides preliminary evidence to support the use of the Wii Fit within therapeutic programmes for children with movement difficulties. This simple, popular intervention represents a plausible method to support children's motor and psychosocial development. It is not possible from our data to say which children are most likely to benefit from such a programme and particularly what the dose and duration should be. Further research is required to inform across these and other questions regarding the implementation of virtual reality technologies in therapeutic services for children with movement difficulties.

Children's perception of breathlessness in acute asthma.

AIM: To determine whether asthmatic children who present to hospital with hypoxia perceive breathlessness less well than non-hypoxic presenters. METHODS: A total of 27 children aged 5-16 years (mean age 10) admitted with acute asthma had recordings of oxygen saturation (SaO(2)), clinical score, forced expiratory volume in one second (FEV(1)), and breathlessness score (HMP) at admission and at 5, 10, 24, 48, and 72 hours after admission. Those defined as hypoxic (SaO(2) <92%) at admission were compared with a non-hypoxic group. RESULTS: Twelve children were hypoxic at admission. Compared with the non-hypoxic group they were younger (8.6 (SD 2.8) v 11.2 (2. 8) y, p = 0.02), and had greater airway obstruction (FEV(1) 32.5 (10)% v 54.3 (26)%, p = 0.0073, 95% confidence interval (CI) -36.9 to -6.6) yet had a trend towards less breathlessness (median HMP 4 v 3, p = 0.062, CI -0.001 to 2.00) at admission. The hypoxic group had a smaller change in breathlessness from admission to discharge, despite a similar improvement in FEV(1), reflected in a lower ratio of change in HMP to change in FEV(1) (DeltaHMP/DeltaFEV(1)) (median DeltaHMP/DeltaFEV(1) 0.021%(-1) v 0.073%(-1), p = 0.0081, CI -0.075 to -0.016). Linear regression analysis showed a strong relation between DeltaHMP/DeltaFEV(1) and initial SaO(2) (p = 0.004, r = 0. 54). CONCLUSIONS: Asthmatic children who present to hospital hypoxic tend to perceive themselves as less breathless than non-hypoxic children. This may predispose to a future life threatening attack.

Management of acute childhood asthma: a prospective multicentre study.

Children with acute asthma account for a significant proportion of paediatric hospital admissions, and clear guidelines exist for their care. The aim of this study was to determine their management in the UK. Over 1 year (February 1995 to January 1996), children aged 1-14 yrs admitted with acute asthma were studied in both teaching and district general hospitals. An admission pro forma was used to collect data prospectively, with a computer-based information management system for the input of admissions in each centre. Ten centres collected data prospectively, with 1,578 admissions involving 1,352 children (median age 3.6 yrs). Sixty two per cent of children were <5 yrs of age. Sixty three per cent of admissions had initial arterial oxygen saturation (Sa,O2) recorded, and, in those older than 5 yrs, 36% had their initial peak expiratory flow rate recorded. Systemic steroids were given to 78%. An initial Sa,O2 of <92% was associated with a longer stay in hospital, and also with intravenous treatment. Preventative treatment increased from 42% on admission to 53% on discharge. The rates of documented education were low. This is the largest UK study following publication of national guidelines and shows that there is still room for improvement in the management of children admitted with acute asthma.