Paediatrics (RCH) - Research Publications
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ItemDecline in Physical Fitness From Childhood to Adulthood Associated With Increased Obesity and Insulin Resistance in Adults(AMER DIABETES ASSOC, 2009-04-01)OBJECTIVE: To examine how fitness in both childhood and adulthood is associated with adult obesity and insulin resistance. RESEARCH DESIGN AND METHODS: A prospective cohort study set in Australia in 2004-2006 followed up a cohort of 647 adults who had participated in the Australian Schools Health and Fitness Survey in 1985 and who had undergone anthropometry and cardiorespiratory fitness assessment during the survey. Outcome measures were insulin resistance and obesity, defined as a homeostasis model assessment index above the 75th sex-specific percentile and BMI >or=30 kg/m(2), respectively. RESULTS: Lower levels of child cardiorespiratory fitness were associated with increased odds of adult obesity (adjusted odds ratio [OR] per unit decrease 3.0 [95% CI 1.6-5.6]) and insulin resistance (1.7 [1.1-2.6]). A decline in fitness level between childhood and adulthood was associated with increased obesity (4.5 [2.6-7.7]) and insulin resistance (2.1 [1.5-2.9]) per unit decline. CONCLUSIONS: A decline in fitness from childhood to adulthood, and by inference a decline in physical activity, is associated with obesity and insulin resistance in adulthood. Programs aimed at maintaining high childhood physical activity levels into adulthood may have potential for reducing the burden of obesity and type 2 diabetes in adults.
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ItemDuration of Nocturnal Hypoglycemia Before Seizures(AMER DIABETES ASSOC, 2008-11-01)OBJECTIVE: Despite a high incidence of nocturnal hypoglycemia documented by the use of continuous glucose monitoring (CGM), there are no reports in the literature of nocturnal hypoglycemic seizures while a patient is wearing a CGM device. RESEARCH DESIGN AND METHODS: In this article, we describe four such cases and assess the duration of nocturnal hypoglycemia before the seizure. RESULTS: In the cases where patients had a nocturnal hypoglycemic seizure while wearing a CGM device, sensor hypoglycemia (<60 mg/dl) was documented on the CGM record for 2.25-4 h before seizure activity. CONCLUSIONS: Even with a subcutaneous glucose lag of 18 min when compared with blood glucose measurements, glucose sensors have time to provide clinically meaningful alarms. Current nocturnal hypoglycemic alarms need to be improved, however, since patients can sleep through the current alarm systems.
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ItemParadoxical myopic shift following cycloplegia in retinopathy of prematurity patients: a case series.(Springer Science and Business Media LLC, 2009-08-25)INTRODUCTION: Spectacle non-compliance is a significant problem in pediatric patients, and may have a variety of consequences. Non-compliance with myopic refractive correction could be secondary to a variety of issues, including age, discomfort, gender, urban vs. rural residence, presenting visual acuity, and degree of refractive error. We observed a phenomenon in our pediatric patients with retinopathy of prematurity that may add another possible explanation: incorrect prescription due to measures of increased, rather than decreased, myopia after cycloplegia. CASE PRESENTATION: An unmasked, prospective study of 8 consecutive patients seen in a single practice. Retinoscopic refraction measurements were obtained before and after pharmacologic cycloplegia. In all 13 eyes, there was either no change (2 eyes) or a myopic shift (11 eyes) in the measured refractive error. The average change in refraction was -1.58 and -1.54 for the right and left eyes, respectively (range 0 to -3.00 OD and 0 to -3.00 OS). CONCLUSIONS: The contribution of ocular components to refractive status differs between ROP and non-ROP eyes. Unanticipated myopic shift following cycloplegia in ROP patients may result in inappropriate glasses prescription with poor correction of visual acuity. This may contribute to spectacle noncompliance in this group.
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ItemUnravelling the molecular control of calvarial suture fusion in children with craniosynostosis.(Springer Science and Business Media LLC, 2007-12-12)BACKGROUND: Craniosynostosis, the premature fusion of calvarial sutures, is a common craniofacial abnormality. Causative mutations in more than 10 genes have been identified, involving fibroblast growth factor, transforming growth factor beta, and Eph/ephrin signalling pathways. Mutations affect each human calvarial suture (coronal, sagittal, metopic, and lambdoid) differently, suggesting different gene expression patterns exist in each human suture. To better understand the molecular control of human suture morphogenesis we used microarray analysis to identify genes differentially expressed during suture fusion in children with craniosynostosis. Expression differences were also analysed between each unfused suture type, between sutures from syndromic and non-syndromic craniosynostosis patients, and between unfused sutures from individuals with and without craniosynostosis. RESULTS: We identified genes with increased expression in unfused sutures compared to fusing/fused sutures that may be pivotal to the maintenance of suture patency or in controlling early osteoblast differentiation (i.e. RBP4, GPC3, C1QTNF3, IL11RA, PTN, POSTN). In addition, we have identified genes with increased expression in fusing/fused suture tissue that we suggest could have a role in premature suture fusion (i.e. WIF1, ANXA3, CYFIP2). Proteins of two of these genes, glypican 3 and retinol binding protein 4, were investigated by immunohistochemistry and localised to the suture mesenchyme and osteogenic fronts of developing human calvaria, respectively, suggesting novel roles for these proteins in the maintenance of suture patency or in controlling early osteoblast differentiation. We show that there is limited difference in whole genome expression between sutures isolated from patients with syndromic and non-syndromic craniosynostosis and confirmed this by quantitative RT-PCR. Furthermore, distinct expression profiles for each unfused suture type were noted, with the metopic suture being most disparate. Finally, although calvarial bones are generally thought to grow without a cartilage precursor, we show histologically and by identification of cartilage-specific gene expression that cartilage may be involved in the morphogenesis of lambdoid and posterior sagittal sutures. CONCLUSION: This study has provided further insight into the complex signalling network which controls human calvarial suture morphogenesis and craniosynostosis. Identified genes are candidates for targeted therapeutic development and to screen for craniosynostosis-causing mutations.
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ItemA cross-sectional survey of complementary and alternative medicine use by children and adolescents attending the University Hospital of Wales.(Springer Science and Business Media LLC, 2006-05-02)BACKGROUND: A high prevalence of CAM use has been documented worldwide in children and adolescents with chronic illnesses. Only a small number of studies, however, have been conducted in the United Kingdom. The primary aim of this study was to examine the use of CAM by children and adolescents with a wide spectrum of acute and chronic medical problems in a tertiary children's hospital in Wales. METHODS: Structured personal interviews of 100 inpatients and 400 outpatients were conducted over a 2-month period in 2004. The yearly and monthly prevalence of CAM use were assessed and divided into medicinal and non-medicinal therapies. This use was correlated with socio-demographic factors. RESULTS: There were 580 patients approached to attain 500 completed questionnaires. The use of at least one type of CAM in the past year was 41% (95% CI 37-46%) and past month 26% (95% CI 23-30%). The yearly prevalence of medicinal CAM was 38% and non-medicinal 12%. The users were more likely to have parents that were tertiary educated (mother: OR = 2.3, 95%CI 1.6-3.3) and a higher family income (Pearson chi-square for trend = 14.3, p < 0.001). The most common medicinal types of CAM were non-prescribed vitamins and minerals (23%) and herbal therapies (10%). Aromatherapy (5%) and reflexology (3%) were the most prevalent non-medicinal CAMs. None of the inpatient medical records documented CAM use in the past month. Fifty-two percent of medicinal and 38% of non-medicinal CAM users felt their doctor did not need to know about CAM use. Sixty-six percent of CAM users did not disclose the fact to their doctor. Three percent of all participants were using herbs and prescription medicines concurrently. CONCLUSION: There is a high prevalence of CAM use in our study population. Paediatricians need to ensure that they ask parents and older children about their CAM usage and advise caution with regard to potential interactions.CAM is a rapidly expanding industry that requires further evidence-based research to provide more information on the effectiveness and safety of many CAM therapies. Statutory or self-regulation of the different segments of the industry is important. Integration of CAM with allopathic western medicine through education and better communication is slowly progressing.
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ItemParental exercise is associated with Australian children's extracurricular sports participation and cardiorespiratory fitness: A cross-sectional study.(Springer Science and Business Media LLC, 2005-04-06)BACKGROUND: The relationship between parental physical activity and children's physical activity and cardiorespiratory fitness has not been well studied in the Australian context. Given the increasing focus on physical activity and childhood obesity, it is important to understand correlates of children's physical activity. This study aimed to investigate whether parental exercise was associated with children's extracurricular sports participation and cardiorespiratory fitness. METHODS: The data were drawn from a nationally representative sample (n = 8,484) of 7-15 year old Australian schoolchildren, surveyed as part of the Australian Schools Health and Fitness Survey in 1985. A subset of 5,929 children aged 9-15 years reported their participation in extracurricular sports and their parents' exercise. Cardiorespiratory fitness was measured using the 1.6 km (1-mile) run/walk and in addition for children aged 9, 12 or 15 years, using a physical work capacity test (PWC170). RESULTS: While the magnitude of the differences were small, parental exercise was positively associated with children's extracurricular sports participation (p < 0.001), 1.6 km run/walk time (p < 0.001) and, in girls only, PWC170 (p = 0.013). In most instances, when only one parent was active, the sex of that parent was not an independent predictor of the child's extracurricular sports participation and cardiorespiratory fitness. CONCLUSION: Parental exercise may influence their children's participation in extracurricular sports and their cardiorespiratory fitness levels. Understanding the correlates of children's extracurricular sport participation is important for the targeting of health promotion and public health interventions, and may influence children's future health status.
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ItemDeclining lung cancer mortality of young Australian women despite increased smoking is linked to reduced cigarette 'tar' yields.(Springer Science and Business Media LLC, 2001-02-02)Lung cancer data were examined to determine whether the mortality rates of young Australian women have continued to increase in line with the proportions of them who have smoked tobacco. Trends in annual age-specific lung cancer mortality were estimated for 1965-1998. Age-specific mortality rates and age-adjusted ratios of mortality rates were calculated for birth cohorts. Proportions of smokers in those cohorts were estimated from results of eight national surveys of smoking, and their mean ages of commencement and years of smoking were assessed from surveys of smokers in two states. Lung cancer mortality rates of 20-44-year-old Australian women peaked in 1986. Age-adjusted mortality rates are lower for women born in the 1950s and 1960s than for women born in the 1940s, despite higher proportions of smokers, younger age of commencement and longer duration of smoking by age 30 years in the more recent cohorts. Increased smoking has not resulted in higher lung cancer mortality for Australian women born in the 1950s and 1960s. Reductions in tar yields of Australian-made cigarettes, which would have affected primarily those born after the 1940s, may be responsible.
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ItemDifferences between Belgian and Brazilian Group A Streptococcus Epidemiologic Landscape(PUBLIC LIBRARY SCIENCE, 2006-12-20)BACKGROUND: Group A Streptococcus (GAS) clinical and molecular epidemiology varies with location and time. These differences are not or are poorly understood. METHODS AND FINDINGS: We prospectively studied the epidemiology of GAS infections among children in outpatient hospital clinics in Brussels (Belgium) and Brasília (Brazil). Clinical questionnaires were filled out and microbiological sampling was performed. GAS isolates were emm-typed according to the Center for Disease Control protocol. emm pattern was predicted for each isolate. 334 GAS isolates were recovered from 706 children. Skin infections were frequent in Brasília (48% of the GAS infections), whereas pharyngitis were predominant (88%) in Brussels. The mean age of children with GAS pharyngitis in Brussels was lower than in Brasília (65/92 months, p<0.001). emm-typing revealed striking differences between Brazilian and Belgian GAS isolates. While 20 distinct emm-types were identified among 200 Belgian isolates, 48 were found among 128 Brazilian isolates. Belgian isolates belong mainly to emm pattern A-C (55%) and E (42.5%) while emm pattern E (51.5%) and D (36%) were predominant in Brasília. In Brasília, emm pattern D isolates were recovered from 18.5% of the pharyngitis, although this emm pattern is supposed to have a skin tropism. By contrast, A-C pattern isolates were infrequently recovered in a region where rheumatic fever is still highly prevalent. CONCLUSIONS: Epidemiologic features of GAS from a pediatric population were very different in an industrialised country and a low incomes region, not only in term of clinical presentation, but also in terms of genetic diversity and distribution of emm patterns. These differences should be taken into account for designing treatment guidelines and vaccine strategies.
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ItemDifferentiating Protein-Coding and Noncoding RNA: Challenges and Ambiguities(PUBLIC LIBRARY SCIENCE, 2008-11-01)The assumption that RNA can be readily classified into either protein-coding or non-protein-coding categories has pervaded biology for close to 50 years. Until recently, discrimination between these two categories was relatively straightforward: most transcripts were clearly identifiable as protein-coding messenger RNAs (mRNAs), and readily distinguished from the small number of well-characterized non-protein-coding RNAs (ncRNAs), such as transfer, ribosomal, and spliceosomal RNAs. Recent genome-wide studies have revealed the existence of thousands of noncoding transcripts, whose function and significance are unclear. The discovery of this hidden transcriptome and the implicit challenge it presents to our understanding of the expression and regulation of genetic information has made the need to distinguish between mRNAs and ncRNAs both more pressing and more complicated. In this Review, we consider the diverse strategies employed to discriminate between protein-coding and noncoding transcripts and the fundamental difficulties that are inherent in what may superficially appear to be a simple problem. Misannotations can also run in both directions: some ncRNAs may actually encode peptides, and some of those currently thought to do so may not. Moreover, recent studies have shown that some RNAs can function both as mRNAs and intrinsically as functional ncRNAs, which may be a relatively widespread phenomenon. We conclude that it is difficult to annotate an RNA unequivocally as protein-coding or noncoding, with overlapping protein-coding and noncoding transcripts further confounding this distinction. In addition, the finding that some transcripts can function both intrinsically at the RNA level and to encode proteins suggests a false dichotomy between mRNAs and ncRNAs. Therefore, the functionality of any transcript at the RNA level should not be discounted.
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ItemRNAdb 2.0-an expanded database of mammalian non-coding RNAs(OXFORD UNIV PRESS, 2007-01-01)RNAdb is a comprehensive database of mammalian non-protein-coding RNAs (ncRNAs). There is increasing recognition that ncRNAs play important regulatory roles in multicellular organisms, and there is an expanding rate of discovery of novel ncRNAs as well as an increasing allocation of function. In this update to RNAdb, we provide nucleotide sequences and annotations for tens of thousands of non-housekeeping ncRNAs, including a wide range of mammalian microRNAs, small nucleolar RNAs and larger mRNA-like ncRNAs. Some of these have documented functions and/or expression patterns, but the majority remain of unclear significance, and include PIWI-interacting RNAs, ncRNAs identified from the latest rounds of large-scale cDNA sequencing projects, putative antisense transcripts, as well as ncRNAs predicted on the basis of structural features and alignments. Improvements to the database comprise not only new and updated ncRNA datasets, but also provision of microarray-based expression data and closer interface with more specialized ncRNA resources such as miRBase and snoRNA-LBME-db. To access RNAdb, visit http://research.imb.uq.edu.au/RNAdb.