RESUMEN
BACKGROUND: Aspiration lung disease (ALD) is a common cause of respiratory morbidity in children and adults with severe neurodisability (sND). Recent studies suggest that chronic microaspiration of gastric contents is associated with mild rather than low, airway acidification. We investigated inflammatory responses to infection by airway epithelial cells (AECs) exposed to weakly acidic media. METHODS: Using pH measurements from children with sND at high risk of ALD as a guide, we incubated AECs in weakly acidic (pH5.5-7.4) media alone; in combination with lipopolysaccharide (LPS); or prior to LPS stimulation at normal pH. Interleukin (IL) -6 and IL-8 expression were measured. RESULTS: IL-6/8 expression in AECs simultaneously exposed to weakly acidic media and LPS for 4 h was reduced with no effect on cell viability. Pre-incubation of AECs at weakly acidic pH also reduced subsequent LPS-induced cytokine expression. Suppression of inflammation was greatest at lower pHs (pH 5.5-6.0) for prolonged periods (16/24 h), but this also adversely affected cell viability. CONCLUSION: AEC inflammatory responses to bacterial stimuli is markedly reduced in a mildly acidic environment.
Asunto(s)
Enfermedades del Sistema Nervioso Central/complicaciones , Células Epiteliales/metabolismo , Mediadores de Inflamación/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Pulmón/metabolismo , Aspiración Respiratoria de Contenidos Gástricos/etiología , Línea Celular , Supervivencia Celular , Enfermedades del Sistema Nervioso Central/inmunología , Enfermedades del Sistema Nervioso Central/metabolismo , Regulación hacia Abajo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/inmunología , Humanos , Concentración de Iones de Hidrógeno , Mediadores de Inflamación/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Interleucina-8/genética , Interleucina-8/inmunología , Lipopolisacáridos/farmacología , Pulmón/efectos de los fármacos , Pulmón/inmunología , Aspiración Respiratoria de Contenidos Gástricos/inmunología , Aspiración Respiratoria de Contenidos Gástricos/fisiopatología , Factores de TiempoRESUMEN
X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4(-/-) mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases.
Asunto(s)
Variación Genética , Discapacidad Intelectual Ligada al Cromosoma X/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Adolescente , Adulto , Animales , Células Cultivadas , Canales de Cloruro/genética , Canales de Cloruro/metabolismo , Estudios de Cohortes , Quinasas Ciclina-Dependientes/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Histona Acetiltransferasas/genética , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Masculino , Ratones Noqueados , Proteínas de Microfilamentos/genética , Neuronas/metabolismo , Neuronas/patología , Proteínas Nucleares/genética , ARN Mensajero/metabolismo , Factores Asociados con la Proteína de Unión a TATA/genética , Factor de Transcripción TFIID/genética , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
Recent evidence suggests that early changes in postural control may be discernible among females with premutation expansions (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene at risk of developing fragile X-associated tremor ataxia syndrome (FXTAS). Cerebellar dysfunction is well described in males and females with FXTAS, yet the interrelationships between cerebellar volume, CGG repeat length, FMR1 messenger RNA (mRNA) levels and changes in postural control remain unknown. This study examined postural sway during standing in a cohort of 22 males with the FMR1 premutation (ages 26-80) and 24 matched controls (ages 26-77). The influence of cerebellar volume, CGG repeat length and FMR1 mRNA levels on postural sway was explored using multiple linear regression. The results provide preliminary evidence that increasing CGG repeat length and decreasing cerebellar volume were associated with greater postural sway among premutation males. The relationship between CGG repeat length and postural sway was mediated by a negative association between CGG repeat size and cerebellar volume. While FMR1 mRNA levels were significantly elevated in the premutation group and correlated with CGG repeat length, FMR1 mRNA levels were not significantly associated with postural sway scores. These findings show for the first time that greater postural sway among males with the FMR1 premutation may reflect CGG repeat-mediated disruption in vulnerable cerebellar circuits implicated in postural control. However, longitudinal studies in larger samples are required to confirm whether the relationships between cerebellar volume, CGG repeat length and postural sway indicate greater risk for neurological decline.
Asunto(s)
Ataxia/genética , Ataxia/patología , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/patología , Equilibrio Postural/genética , Temblor/genética , Temblor/patología , Sustancia Blanca/patología , Sustancia Blanca/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , ARN Mensajero/genética , Sustancia Blanca/anatomía & histologíaRESUMEN
BACKGROUND: To investigate changes in intakes of 'negative' and 'positive' foods, fruit, vegetables, and salad in serial cohorts of 9-10-year-old children from 2000-2001 to 2010-2011. METHODS: For this serial, cross-sectional study, children in school year 5 (9-10 years of age) completed the SportsLinx Lifestyles Survey [n = 30,239 (15,336 boys and 14,903 girls)]. Changes in positive and negative food scores, and the proportion of boys and girls reportedly consuming fruit, vegetables and salad on the previous day to surveying, were investigated annually from 2000 to 2011. RESULTS: The consumption of negative foods declined and positive foods increased significantly compared to baseline. Positive changes in fruit, vegetables and salad consumption were observed over time, with the most recent cohort more likely to consume fruit, vegetables and salad compared to the 2000-2001 baseline. Girls displayed more favourable positive and negative food scores and were more likely to consume fruit, salad and vegetables across several study years compared to boys. CONCLUSIONS: The consumption of negative and positive foods, fruit, vegetables, and salad has improved over the last 10 years. In addition, girls appear to have better positive and negative food scores, and were more likely to consume fruit, vegetables and salad, across a number of study years or cohorts compared to boys. These encouraging findings suggest that children's food intake has improved since 2000. Furthermore, the data indicate that boys and girls may require separate or different healthy eating messages to further improve food intake.
Asunto(s)
Dieta/tendencias , Frutas , Verduras , Niño , Fenómenos Fisiológicos Nutricionales Infantiles , Estudios de Cohortes , Estudios Transversales , Conducta Alimentaria , Femenino , Preferencias Alimentarias , Promoción de la Salud , Humanos , Lactuca , Masculino , Factores SexualesRESUMEN
Mice incapable of synthesizing the myelin lipid sulfatide form paranodes that deteriorate with age. Similar instability also occurs in mice that lack contactin, contactin-associated protein or neurofascin155 (Nfasc155), the proteins that cluster in the paranode and form the junctional complex that mediates myelin-axon adhesion. In contrast to these proteins, sulfatide has not been shown to be enriched in the paranode nor has a sulfatide paranodal binding partner been identified; thus, it remains unclear how the absence of sulfatide results in compromised paranode integrity. Using an in situ extraction procedure, it has been reported that the absence of the myelin sphingolipids, galactocerebroside and sulfatide, increased the susceptibility of Nfasc155 to detergent extraction. Here, employing a similar approach, we demonstrate that in the presence of galactocerebroside but in the absence of sulfatide Nfasc155 is susceptible to detergent extraction. Furthermore, we use this in situ approach to show that stable association of myelin-associated glycoprotein (MAG) with the myelin membrane is sulfatide dependent while the membrane associations of myelin/oligodendrocyte glycoprotein, myelin basic protein and cyclic nucleotide phosphodiesterase are sulfatide independent. These findings indicate that myelin proteins maintain their membrane associations by different mechanisms. Moreover, the myelin proteins that cluster in the paranode and require sulfatide mediate myelin-axon adhesion. Additionally, the apparent dependency on sulfatide for maintaining Nfasc155 and MAG associations is intriguing since the fatty acid composition of sulfatide is altered and paranodal ultrastructure is compromised in multiple sclerosis. Thus, our findings present a potential link between sulfatide perturbation and myelin deterioration in multiple sclerosis.
Asunto(s)
Moléculas de Adhesión Celular/metabolismo , Detergentes/química , Vaina de Mielina/química , Glicoproteína Asociada a Mielina/metabolismo , Factores de Crecimiento Nervioso/metabolismo , Animales , Western Blotting , Moléculas de Adhesión Celular/aislamiento & purificación , Ratones Noqueados , Glicoproteína Asociada a Mielina/aislamiento & purificación , Factores de Crecimiento Nervioso/aislamiento & purificación , Esfingolípidos/metabolismo , Sulfoglicoesfingolípidos/metabolismoRESUMEN
Craniosynostosis is one of the most common craniofacial disorders encountered in clinical genetics practice, with an overall incidence of 1 in 2,500. Between 30% and 70% of syndromic craniosynostoses are caused by mutations in hotspots in the fibroblast growth factor receptor (FGFR) genes or in the TWIST1 gene with the difference in detection rates likely to be related to different study populations within craniofacial centers. Here we present results from molecular testing of an Australia and New Zealand cohort of 630 individuals with a diagnosis of craniosynostosis. Data were obtained by Sanger sequencing of FGFR1, FGFR2, and FGFR3 hotspot exons and the TWIST1 gene, as well as copy number detection of TWIST1. Of the 630 probands, there were 231 who had one of 80 distinct mutations (36%). Among the 80 mutations, 17 novel sequence variants were detected in three of the four genes screened. In addition to the proband cohort there were 96 individuals who underwent predictive or prenatal testing as part of family studies. Dysmorphic features consistent with the known FGFR1-3/TWIST1-associated syndromes were predictive for mutation detection. We also show a statistically significant association between splice site mutations in FGFR2 and a clinical diagnosis of Pfeiffer syndrome, more severe clinical phenotypes associated with FGFR2 exon 10 versus exon 8 mutations, and more frequent surgical procedures in the presence of a pathogenic mutation. Targeting gene hot spot areas for mutation analysis is a useful strategy to maximize the success of molecular diagnosis for individuals with craniosynostosis.
Asunto(s)
Acrocefalosindactilia/genética , Disostosis Craneofacial/genética , Craneosinostosis/genética , Acrocefalosindactilia/diagnóstico , Acrocefalosindactilia/patología , Australia , Disostosis Craneofacial/diagnóstico , Disostosis Craneofacial/patología , Craneosinostosis/clasificación , Craneosinostosis/diagnóstico , Craneosinostosis/patología , Humanos , Mutación , Nueva Zelanda , Proteínas Nucleares/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Proteína 1 Relacionada con Twist/genéticaAsunto(s)
Cromosomas Humanos X , Enfermedades Genéticas Ligadas al Cromosoma X , Predisposición Genética a la Enfermedad/genética , Discapacidad Intelectual/genética , Mutación/genética , Proteínas/genética , Proteínas Portadoras/metabolismo , Estudios de Casos y Controles , Estudios de Cohortes , Proteínas de Unión al ADN , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Proteínas Nucleares/metabolismo , Fenotipo , ARN Mensajero/metabolismoRESUMEN
The nonsense-mediated mRNA decay (NMD) pathway was originally discovered by virtue of its ability to rapidly degrade aberrant mRNAs with premature termination codons. More recently, it was shown that NMD also directly regulates subsets of normal transcripts, suggesting that NMD has roles in normal biological processes. Indeed, several NMD factors have been shown to regulate neurological events (for example, neurogenesis and synaptic plasticity) in numerous vertebrate species. In man, mutations in the NMD factor gene UPF3B, which disrupts a branch of the NMD pathway, cause various forms of intellectual disability (ID). Using Epstein Barr virus-immortalized B cells, also known as lymphoblastoid cell lines (LCLs), from ID patients that have loss-of-function mutations in UPF3B, we investigated the genome-wide consequences of compromised NMD and the role of NMD in neuronal development and function. We found that ~5% of the human transcriptome is impacted in UPF3B patients. The UPF3B paralog, UPF3A, is stabilized in all UPF3B patients, and partially compensates for the loss of UPF3B function. Interestingly, UPF3A protein, but not mRNA, was stabilised in a quantitative manner that inversely correlated with the severity of patients' phenotype. This suggested that the ability to stabilize the UPF3A protein is a crucial modifier of the neurological symptoms due to loss of UPF3B. We also identified ARHGAP24, which encodes a GTPase-activating protein, as a canonical target of NMD, and we provide evidence that deregulation of this gene inhibits axon and dendrite outgrowth and branching. Our results demonstrate that the UPF3B-dependent NMD pathway is a major regulator of the transcriptome and that its targets have important roles in neuronal cells.
Asunto(s)
Perfilación de la Expresión Génica/métodos , Discapacidad Intelectual/genética , Degradación de ARNm Mediada por Codón sin Sentido/genética , Proteínas de Unión al ARN/genética , Encéfalo/crecimiento & desarrollo , Línea Celular , Línea Celular Transformada , Células Cultivadas , Proteínas Activadoras de GTPasa/genética , Expresión Génica/genética , Hipocampo/anatomía & histología , Hipocampo/crecimiento & desarrollo , Humanos , Mutación , Neuronas/citología , Proteínas de Unión al ARN/metabolismo , Transducción de Señal/genéticaRESUMEN
ARX mutations cause a diverse spectrum of human disorders, ranging from severe brain and genital malformations to non-syndromic intellectual disability (ID). ARX is a transcription factor with multiple domains that include four polyalanine (pA) tracts, the first two of which are frequently expanded by mutations. We progressively screened DNA samples from 613 individuals with ID initially for the most frequent ARX mutations (c.304ins(GCG)(7)'expansion' of pA1 and c.429_452dup 'dup24bp' of pA2). Five hundred samples without pA1 or pA2 mutations had the entire ARX ORF screened by single stranded polymorphism conformation (SSCP) and/or denaturing high pressure liquid chromatography (dHPLC) analysis. Overall, eight families with six mutations in ARX were identified (1.31%): five duplication mutations in pA2 (0.82%) with three new clinical reports of families with the dup24bp and two duplications larger than the dup24bp mutation discovered (dup27bp, dup33bp); and three point mutations (0.6%), including one novel mutation in the homeodomain (c.1074G>T). Four ultraconserved regions distal to ARX (uc466-469) were also screened in a subset of 94 patients, with three unique nucleotide changes identified in two (uc466, uc467). The subcellular localization of full length ARX proteins was assessed for 11 variants. Protein mislocalization increased as a function of pA2 tract length and phenotypic severity, as has been previously suggested for pA1. Similarly, protein mislocalization of the homeodomain mutations also correlated with clinical severity, suggesting an emerging genotype vs cellular phenotype correlation.
Asunto(s)
Discapacidades del Desarrollo/genética , Pruebas Genéticas/métodos , Proteínas de Homeodominio/genética , Factores de Transcripción/genética , Trastorno Autístico/diagnóstico , Trastorno Autístico/genética , Secuencia de Bases , Niño , Preescolar , Duplicación Cromosómica , Estudios de Cohortes , Secuencia Conservada , Discapacidades del Desarrollo/diagnóstico , Femenino , Estudios de Asociación Genética , Células HEK293 , Proteínas de Homeodominio/metabolismo , Humanos , Lactante , Masculino , Mutación , Tasa de Mutación , Linaje , Polimorfismo Conformacional Retorcido-Simple , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: The prevalence of obesity in children has increased substantially in recent years and, paediatric obesity and poor fitness are risk factors for disease. The present study aimed to assess changes in body mass index (BMI), the prevalence of obesity and changes in aerobic endurance over time in 9-10-year-old schoolchildren. METHODS: Participants were recruited by the SportsLinx project from primary schools across Liverpool. Height and weight data were used to calculate BMI. The prevalence of obesity and overweight were estimated using age- and sex-specific cut-off points. Performance on the 20-m multi-stage shuttle runs test (20 mMST) was used as a marker of aerobic endurance. Data were available for 13,418 (6572 boys, 6846 girls) 9-10-year-old children. Analysis of covariance was completed to assess year-on-year changes in BMI controlling for deprivation (IMD) and 20 mMST performance, and 20 mMST performance controlling for IMD and BMI. RESULTS: No significant changes in BMI from baseline were observed (P > 0.05). Obesity prevalence reduced in girls (2005 = 10.3%, 2008 = 8.52% in 2008). The data for boys showed no reductions in prevalence (2005 = 6.77%, 2008 = 7.87%). The most recent cohort for boys and two most recent cohorts for girls had lower levels of aerobic endurance than baseline (2004-2005) (P Asunto(s)
Índice de Masa Corporal
, Ejercicio Físico
, Obesidad/epidemiología
, Sobrepeso/epidemiología
, Resistencia Física
, Aptitud Física
, Análisis de Varianza
, Niño
, Inglaterra/epidemiología
, Femenino
, Humanos
, Masculino
, Prevalencia
, Valores de Referencia
, Carrera
, Factores Sexuales
, Aumento de Peso
RESUMEN
OBJECTIVES: To demonstrate the feasibility and value of social marketing over a wide geographical footprint, and to improve the snacking habits of pre-school children. STUDY DESIGN: Two cross-sectional studies before and approximately 3 months after a social marketing intervention targeted into the least affluent areas using convenience sampling. METHODS: Based on market research and directed at the least affluent areas, a brand was created ('Snack Right') and an information leaflet was distributed, supported by a media launch and events at children's centres in targeted areas. This evaluation of some aspects of the project is based on a questionnaire delivered before and after the events. RESULTS: There were several differences in pre- and post-event responses consistent with the messages delivered, for example increased spending on fruit (but not vegetables) and more positive attitudes towards fruits and vegetables. Some ambiguities were exposed, for example towards snacking, which have implications for the nutritional knowledge of health professionals. The Snack Right brand was recalled by a very high proportion of respondents at follow-up. CONCLUSIONS: This project has shown that social marketing is a viable tool at a subregional level and has the potential to change attitudes, knowledge and behaviour.
Asunto(s)
Conducta Alimentaria , Evaluación de Programas y Proyectos de Salud , Mercadeo Social , Preescolar , Estudios Transversales , Disparidades en el Estado de Salud , Humanos , Obesidad/prevención & controlRESUMEN
BACKGROUND: Studies suggest that 50% of people may suffer from chronic radiation enteritis (CRE) (Andreyev, J., 2005. Gastrointestinal complications of pelvic radiotherapy: are they of any importance? Gut 54, 1051-1054). Gami et al. (Gami, B., Harrington, K., Blake, P., Dearnaley, D., Andreyev, H.J.N., 2003. How patients manage gastrointestinal symptoms after pelvic radiotherapy. Alimentary Pharmacology and Therapeutics 18, 987-994) argue that this is unimportant if quality of life is unaffected. The aim of this study was to identify how many women experience CRE following radiotherapy and to investigate whether women who have higher doses of radiotherapy or more advanced stage of cancer are more at risk. METHODS: Women (=117) who had completed radiotherapy for cervical or endometrial cancer were asked to complete a validated questionnaire exploring bowel problems and quality of life. Responses were scored and compared to scores for women with known faecal incontinence (Bugg, G.J., Kiff, E.S., Hosker, G., 2001. A new condition-specific health-related quality of life questionnaire for the assessment of women with anal incontinence. British Journal of Obstetrics and Gynaecology 108 (10), 1057-1067). RESULTS: Using a score of '0' to indicate no symptoms, 47% of women gained scores indicative of CRE (>0), range 20-85 (mean 34, SD 14.4). Younger women (p<0.001) and women with cervical cancer (p<0.05) were more likely to score for CRE. No significant relationship was observed between score and either radiotherapy dose or stage of cancer. CONCLUSIONS: Scoring suggests that about half of woman treated with radiotherapy develop CRE. Quality of life is affected, particularly regarding tiredness and coping behaviours due to lack of warning signs for CRE.
Asunto(s)
Actitud Frente a la Salud , Neoplasias Endometriales/radioterapia , Enteritis/epidemiología , Calidad de Vida/psicología , Traumatismos por Radiación/epidemiología , Neoplasias del Cuello Uterino/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Enfermedad Crónica , Costo de Enfermedad , Inglaterra/epidemiología , Enteritis/etiología , Enteritis/psicología , Incontinencia Fecal/epidemiología , Femenino , Humanos , Persona de Mediana Edad , Investigación Metodológica en Enfermería , Prevalencia , Traumatismos por Radiación/etiología , Traumatismos por Radiación/psicología , Dosificación Radioterapéutica , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
BACKGROUND: Approximately 12,000 individuals undergo pelvic radiotherapy in the UK every year and up to 50% may develop symptoms of chronic radiation enteritis (CRE). Health professionals often give inappropriate dietary advice to patients in an attempt to avoid CRE symptoms, such as avoiding fibre, despite a lack of evidence to support this. METHODS: The present study aimed to explore dietary advice and changes made to the diet by women treated with pelvic radiotherapy. A questionnaire was distributed to 117 women attending Liverpool Women's Hospital, exploring symptoms of CRE and asking questions about diet and medication advice received, as well as changes made to the diet. RESULTS: Ninety-five (87.2%) women completed the questionnaire and 47% had changed their diet. No significant relationship was observed between receiving dietary advice and making changes to the diet (P > 0.05), although those advised by a dietitian were more likely to be taking regular anti-diarrhoeal medication (P < 0.05) and those taking regular medication found that it helped most/all of the time (P < 0.001). CONCLUSIONS: CRE sufferers should be dissuaded from unnecessarily restricting their diet, which may result in malnutrition. Regular follow-up screening should lead to the identification of sufferers and the offer of individual advice if necessary.
Asunto(s)
Conducta de Elección , Diarrea/prevención & control , Gastroenteritis/dietoterapia , Neoplasias/radioterapia , Educación del Paciente como Asunto , Radioterapia/efectos adversos , Enfermedad Crónica , Diarrea/tratamiento farmacológico , Dieta , Encuestas sobre Dietas , Femenino , Gastroenteritis/tratamiento farmacológico , Gastroenteritis/etiología , Humanos , Neoplasias/complicaciones , AutocuidadoRESUMEN
BACKGROUND: Obesity and being underweight in pregnancy are related to an increased risk of maternal and foetal morbidity, yet their prevalence is often unknown. The present study aimed to identify neighbourhoods with a higher than average prevalence or 'hot spots' of obesity and/or being underweight among first trimester pregnant women. METHODS: A database was compiled consisting of postcode, height and weight for 7981 women who had booked-in for antenatal care between July 2004 and June 2005 at Liverpool Women's Hospital. Body mass index (BMI) was calculated and women were categorised accordingly. Postcodes for 6865 cases across Merseyside were converted to geolocations (pin-points on a map) using conversion software (http://www.census.ac.uk/cdu/). RESULTS: There was a very high prevalence of being overweight (27%) and obesity (17%); 3.8% of women were underweight and probably malnourished (BMI < 18.5 kg m(-2)); and a further 10.7% of women were possibly malnourished (BMI < 20.0 kg m(-2). Deriving case density from the geolocations allowed visualisation and identification of six neighbourhoods with above average levels of obesity and three neighbourhoods had marked concentrations of both being underweight and obesity. CONCLUSIONS: These neighbourhoods, particularly those identified as 'hot spots' for both being underweight and obesity, include some of the most deprived wards in the UK. As dietetic intervention may help to promote optimal weight gain during pregnancy and improve dietary intake for pregnant women and their families, primary health care providers should target these localities with a high prevalence of low and high BMI as a priority.
Asunto(s)
Obesidad/epidemiología , Complicaciones del Embarazo/epidemiología , Delgadez/epidemiología , Adulto , Índice de Masa Corporal , Inglaterra/epidemiología , Femenino , Humanos , Desnutrición/complicaciones , Desnutrición/epidemiología , Obesidad/complicaciones , Sobrepeso/epidemiología , Embarazo , Prevalencia , Características de la Residencia , Factores Socioeconómicos , Delgadez/complicaciones , Salud UrbanaRESUMEN
BACKGROUND: Food deserts are thought to be a barrier to making healthier food choices. This concept has been challenged. The interaction between the physical environment and children's food choice has received little attention. The present study used food intake data to generate hypotheses concerning the role of the physical environment in food choice. METHODS: A cross-sectional analysis was conducted of the dietary habits of Year 5 (9-10-year-old) children from 90 of Liverpool's 118 primary schools. Individuals with the 'best' and 'worst' food choices were mapped and two areas associated with these extreme choices located. RESULTS: One thousand five hundred and thirty-five children completed the dietary questionnaire and supplied a full and valid postcode. Two adjacent areas with relatively large numbers of children in the 'best' and 'worst' food choice groups were chosen. Both areas had very similar socio-economic profiles. The contrast in the physical environments was striking, even on visual inspection. CONCLUSIONS: Food deserts as a cause of poor food choice did not stand scrutiny; the area located by the worst food choices had a plethora of shops selling food (better termed a food prairie), whereas the area located by the best food choices had no shops in evidence but did have more 'space'.
Asunto(s)
Conducta Alimentaria , Preferencias Alimentarias , Niño , Estudios Transversales , Dieta , Inglaterra , Ambiente , Humanos , Encuestas y CuestionariosRESUMEN
BACKGROUND: The chromosome 17q21.31 microdeletion syndrome is a novel genomic disorder that has originally been identified using high resolution genome analyses in patients with unexplained mental retardation. AIM: We report the molecular and/or clinical characterisation of 22 individuals with the 17q21.31 microdeletion syndrome. RESULTS: We estimate the prevalence of the syndrome to be 1 in 16,000 and show that it is highly underdiagnosed. Extensive clinical examination reveals that developmental delay, hypotonia, facial dysmorphisms including a long face, a tubular or pear-shaped nose and a bulbous nasal tip, and a friendly/amiable behaviour are the most characteristic features. Other clinically important features include epilepsy, heart defects and kidney/urologic anomalies. Using high resolution oligonucleotide arrays we narrow the 17q21.31 critical region to a 424 kb genomic segment (chr17: 41046729-41470954, hg17) encompassing at least six genes, among which is the gene encoding microtubule associated protein tau (MAPT). Mutation screening of MAPT in 122 individuals with a phenotype suggestive of 17q21.31 deletion carriers, but who do not carry the recurrent deletion, failed to identify any disease associated variants. In five deletion carriers we identify a <500 bp rearrangement hotspot at the proximal breakpoint contained within an L2 LINE motif and show that in every case examined the parent originating the deletion carries a common 900 kb 17q21.31 inversion polymorphism, indicating that this inversion is a necessary factor for deletion to occur (p<10(-5)). CONCLUSION: Our data establish the 17q21.31 microdeletion syndrome as a clinically and molecularly well recognisable genomic disorder.
Asunto(s)
Anomalías Múltiples , Deleción Cromosómica , Cromosomas Humanos Par 17/genética , Discapacidades del Desarrollo , Anomalías Múltiples/epidemiología , Anomalías Múltiples/genética , Anomalías Múltiples/fisiopatología , Adolescente , Adulto , Niño , Preescolar , Inversión Cromosómica , Discapacidades del Desarrollo/epidemiología , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/fisiopatología , Cara/patología , Femenino , Humanos , Lactante , Masculino , Hipotonía Muscular/epidemiología , Hipotonía Muscular/genética , Hipotonía Muscular/fisiopatología , Análisis de Secuencia por Matrices de Oligonucleótidos , Polimorfismo de Nucleótido Simple , Prevalencia , Adulto Joven , Proteínas tauRESUMEN
Ornithine transcarbamylase deficiency (OTCD) is an X-linked disorder of the urea cycle. It is often fatal in affected males. Treatment for affected individuals includes dietary protein restriction, activation of alternative pathways of nitrogen excretion and L-arginine supplementation. Depending on the amount of X chromosome inactivation skewing, females show variable clinical manifestations, and sometimes the need for treatment, including medications, is unclear. We conducted an n of 1 randomized controlled trial on an obligate OTC carrier. The treating physician and patient were blinded to treatment. Either placebo capsules or L-arginine capsules were given for weekly periods. Weekly efficacy indicators included plasma arginine and glutamine levels and a quality of life/mood assessment questionnaire scale. Clear evidence of benefit with L-arginine compared to placebo was shown. This is the first time an n of 1 randomized controlled trial has been reported for an X-linked metabolic condition. Despite some logistic hurdles, we have demonstrated that this method was an effective tool for determining the value of treatment. We propose that other rare metabolic conditions may be amenable to such trials, if the benefit of treatment is in doubt.
Asunto(s)
Arginina/administración & dosificación , Heterocigoto , Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa/tratamiento farmacológico , Ornitina Carbamoiltransferasa/metabolismo , Afecto , Arginina/sangre , Arginina/uso terapéutico , Estudios Cruzados , Método Doble Ciego , Femenino , Enfermedades Genéticas Ligadas al Cromosoma X/tratamiento farmacológico , Glutamina/sangre , Humanos , Masculino , Persona de Mediana Edad , Ornitina Carbamoiltransferasa/genética , Calidad de Vida , Encuestas y Cuestionarios , Inactivación del Cromosoma XRESUMEN
BACKGROUND: It is important to promote the intake of fruit and vegetables but it is not clear how children interpret the term 'portion'. The aim of this study was to describe portion sizes of various fruits and vegetables selected by primary school children. METHODS: A cross-sectional study collected data on children's self-selected portions of fruits and vegetables. Forty-three boys and 52 girls aged 9-10 years attending after school food clubs in Liverpool took part. Children placed a 'portion' of each fruit and vegetable into an empty bowl which was weighed using digital scales accurate to 1 g. RESULTS: Mean portion sizes ranged from 126 g for satsumas to 61 g for peas but there were no significant differences between boys and girls. Portions of fruits were larger than portions of vegetables and although there were statistically significant correlations between the portion sizes selected by individual children they were not particularly strong. CONCLUSIONS: These children had all taken part in activities promoting '5-a-day' but their perception of 'a portion' varied enormously. It is recommended that children receive targeted activities to help them improve their understanding of what constitutes a 'portion'.
Asunto(s)
Encuestas sobre Dietas , Frutas , Conocimientos, Actitudes y Práctica en Salud , Percepción del Tamaño , Verduras , Niño , Estudios Transversales , Ingestión de Alimentos , Ingestión de Energía , Inglaterra , Femenino , Promoción de la Salud , Humanos , Masculino , Política Nutricional , Estadísticas no ParamétricasRESUMEN
The amount of sugars consumed by young adolescents was assessed in 1990 using the same methods as those employed in a similar survey in 1980. The children were the same age (mean 11 years 6 months) and from the same seven schools in both survey. In 1980, 405 children completed the study and 379 in 1990. Information was collected using two 3-day dietary diaries, each child being interviewed by a dietitian upon completion of a diary. The dietitian in this study was calibrated closely with the dietitian who undertook the 1980 study so as to ensure comparable diet evaluation methods. Total sugars consumption was unchanged (117 g/day in 1980, 118 g/day in 1990) but consumption of non-milk extrinsic sugars increased (83 g/day in 1980, 90 g/day in 1990) and milk and intrinsic sugars decreased (34 g/day in 1980, 28 g/day in 1990) between the two surveys. In 1990, non-milk extrinsic sugars contributed 17% to total dietary energy intake, while milk and intrinsic sugars contributed 5%. There was little difference in percent contributions between the sexes, but some social-class trends were apparent. Confectionery provided 33% and soft drinks provided 27% of non-milk extrinsic sugars, these two dietary sources providing 60% of non-milk extrinsic or 46% of total sugars intake. These levels of consumption are considerably higher than those currently recommended in the UK.
Asunto(s)
Fenómenos Fisiológicos Nutricionales Infantiles , Encuestas sobre Dietas , Dieta/tendencias , Sacarosa en la Dieta/administración & dosificación , Bebidas Gaseosas/análisis , Niño , Estudios Transversales , Productos Lácteos/análisis , Registros de Dieta , Sacarosa en la Dieta/clasificación , Ingestión de Energía/fisiología , Inglaterra , Femenino , Análisis de los Alimentos , Humanos , Entrevistas como Asunto , MasculinoRESUMEN
OBJECTIVE: Dietary surveys of 11- to 12-year-old Northumbrian children in 1980 and 1990 revealed that consumption of non-milk extrinsic sugars (NMES) was 16-17% of energy intake. This study reports dietary sugars consumption in 2000 and compares it with data collected in 1980 and 1990, using identical methods. DESIGN: A repeat cross-sectional dietary survey of children aged 1-12 years attending the same schools as in the 1980 and 1990 surveys. SETTING: Seven middle schools in south Northumberland. SUBJECTS: All children aged 11-12 years old attending the seven schools. METHOD: Food consumption was recorded using two 3-day diet diaries. Food composition tables were used to calculate energy and nutrient intakes. NMES, and milk and intrinsic sugars were calculated using previously described methods. RESULTS: The numbers of children completing the surveys in 1980, 1990 and 2000 were 405, 379 and 424, respectively; approximately 60-70% of eligible children. Total sugars provided 22% of energy consistently over the three surveys. NMES consumption in 2000 provided 16% of energy compared with 16% in 1980 and 17% in 1990. Sources of NMES changed over the three surveys. NMES from soft drinks doubled from 15 to 31 g day(-1), and from breakfast cereals increased from 2 to 7 g day(-1) over the 20 years. Confectionery and soft drinks provided 61% of NMES. Over 20 years, the proportion of energy from fat decreased by 5% and from starch increased by 4%, creating a welcome tilt in the fat-starch see-saw, without an adverse effect on sugars intake. CONCLUSIONS: Consumption of NMES in 2000 was substantially higher than recommended, and there has been little change over 20 years. Continued and coordinated efforts are required at a national, community and individual level to reduce the intake of NMES.