ABSTRACT
Introducción: La subunidad ácido-lábil (ALS) tiene un papel importante en los efectos endocrinos de los factores de crecimiento similares a la insulina (IGF) en tejidos diana. Históricamente ha recibido una atención limitada. El objetivo de nuestro estudio fue describir el rango normal de ALS en niños sanos y su relación con otros factores de crecimiento. Pacientes y métodos: Se diseñó un estudio descriptivo transversal. Se recopilaron datos sobre edad, altura, índice de masa corporal, edad gestacional, antropometría al nacer y niveles séricos de ALS, IGF1 e IGFBP3 de niños sanos de 2 a 15años con estatura estándar. Los niveles de ALS, IGF1 e IGFBP3 se midieron mediante ELISA. Se utilizaron modelos de normalización GAMLSS para la estandarización de variables. Resultados: Se recogieron muestras de 446 niños. En niños prepúberes, los niveles de ALS, IGF1 e IGFBP3 se correlacionaron de manera positiva en ambos sexos y con la edad (p<0,01). Los niveles de ALS, IGF1 e IGFBP3 y la relación molar IGF1/IGFBP3 fueron significativamente diferentes entre ambos sexos y más altos en los niños puberales (p<0,01). Se realizaron gráficas de normalidad por género para cada uno de los componentes del complejo ternario y para las relaciones molares IGF1/IGFBP3 e IGFBP3/ALS. Además, se construyeron fórmulas modelo para calcular el Z Score según la edad y el sexo. ConclusionesEste estudio podría determinar valores de referencia específicos por edad y sexo para IGF1, IGFBP3, ALS, IGF1/IGFBP3 e IGFBP3/ALS en niños españoles y parece establecer la relación entre edad, sexo y estadio puberal. (AU)
Introduction: The acid-labile subunit (ALS) plays an important role in the endocrine effects of insulin-like growth factors (IGFs) on target tissues. Historically, it has attracted limited attention. The aim of our study was to describe the normal range of ALS in healthy children and its association with other growth factors. Patients and methods: We designed a cross-sectional descriptive study. We collected data on age, height, body mass index, gestational age, anthropometry at birth and serum levels of ALS, IGF1 and IGFBP3 in healthy children aged 2-15years with a normal height. The levels of ALS, IGF1 and IGFBP3 were measured by ELISA. We fitted GAMLSS normalization models to standardize the variables. Results: Samples were collected from 446 children. In prepubertal children, the levels of ALS, IGF1 and IGFBP3 were positively correlated in both sexes and with age (P<.01). We found significant differences in the levels of ALS, IGF1 and IGFBP3 and the IGF1/IGFBP3 molar ratio between the sexes and higher levels in pubertal boys (P<.01). We generated normal probability plots for each sex for each of the components of the ternary complex and for the IGF1/IGFBP3 and IGFBP3/ALS molar ratios. In addition, we extracted equations from the models for the calculation of z-scores for age and sex. Conclusions: This study may contribute to age- and sex-specific reference values for IGF1, IGFBP3 and ALS levels and IGF1/IGFBP3 and IGFBP3/ALS ratios in Spanish children and suggests an association between age, sex and pubertal stage. (AU)
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Insulin-Like Growth Factor I , Insulin-Like Growth Factor Binding Protein 3 , Epidemiology, Descriptive , Cross-Sectional Studies , Spain , Body Mass IndexABSTRACT
INTRODUCTION: The acid-labile subunit (ALS) plays an important role in the endocrine effects of insulin-like growth factors (IGFs) on target tissues. Historically, it has attracted limited attention. The aim of our study was to describe the normal range of ALS in healthy children and its association with other growth factors. PATIENTS AND METHODS: We designed a cross-sectional descriptive study. We collected data on age, height, body mass index, gestational age, anthropometry at birth and serum levels of ALS, IGF1 and IGFBP3 in healthy children aged 2-15 years with a normal height. The levels of ALS, IGF1 and IGFBP3 were measured by ELISA. We fitted GAMLSS normalization models to standardize the variables. RESULTS: Samples were collected from 446 children. In prepubertal children, the levels of ALS, IGF1 and IGFBP3 were positively correlated in both sexes and with age (P < .01). We found significant differences in the levels of ALS, IGF1 and IGFBP3 and the IGF1/IGFBP3 molar ratio between the sexes and higher levels in pubertal boys (P < .01). We generated normal probability plots for each sex for each of the components of the ternary complex and for the IGF1/IGFBP3 and IGFBP3/ALS molar ratios. In addition, we extracted equations from the models for the calculation of z-scores for age and sex. CONCLUSIONS: This study may contribute age- and sex-specific reference values for IGF1, IGFBP3 and ALS levels and IGF1/IGFBP3 and IGFBP3/ALS ratios in Spanish children and suggests an association between age, sex, and pubertal stage.
Subject(s)
Reference Values , Male , Infant, Newborn , Female , Humans , Child , Child, Preschool , Adolescent , Spain , Cross-Sectional Studies , Gestational AgeABSTRACT
OBJECTIVES: The estimates of biological variation (BV) have traditionally been determined using direct methods, which present limitations. In response to this issue, two papers have been published addressing these limitations by employing indirect methods. Here, we present a new procedure, based on indirect methods that analyses data collected within a multicenter pilot study. Using this method, we obtain CVI estimates and calculate confidence intervals (CI), using the EFLM-BVD CVI estimates as gold standard for comparison. METHODS: Data were collected over a 18-month period for 7 measurands, from 3 Spanish hospitals; inclusion criteria: patients 18-75 years with more than two determinations. For each measurand, four different strategies were carried out based on the coefficient of variation ratio (rCoeV) and based on the use of the bootstrap method (OS1, RS2 and RS3). RS2 and RS3 use symmetry reference change value (RCV) to clean database. RESULTS: RS2 and RS3 had the best correlation for the CVI estimates with respect to EFLM-BVD. RS2 used the symmetric RCV value without eliminating outliers, while RS3 combined RCV and outliers. When using the rCoeV and OS1 strategies, an overestimation of the CVI value was obtained. CONCLUSIONS: Our study presents a new strategy for obtaining robust CVI estimates using an indirect method together with the value of symmetric RCV to select the target population. The CVI estimates obtained show a good correlation with those published in the EFLM-BVD database. Furthermore, our strategy can resolve some of the limitations encountered when using direct methods such as calculating confidence intervals.
Subject(s)
Data Mining , Databases, Factual , Humans , Pilot Projects , Reference ValuesABSTRACT
â¢OGM surgery is much more complex than a simple debate of "from above or from below" (transcranial vs endoscopic).â¢Lateral Sub-frontal and Superior Interhemispheric seem the most effective, superior and versatile approaches for OGM.â¢Minimally Invasive Transcranial approaches showed no inferiority in OGM sized <4 âcm.â¢Endoscopic Endonasal Approaches showed inferior results in surgical and in functional outcomes for OGM.
ABSTRACT
Diagnosis and classification of gliomas mostly relies on histopathology and a few genetic markers. Here we interrogated microarray gene expression profiles (GEP) of 268 diffuse astrocytic gliomas-33 diffuse astrocytomas (DA), 52 anaplastic astrocytomas (AA) and 183 primary glioblastoma (GBM)-based on multivariate analysis, to identify discriminatory GEP that might support precise histopathological tumor stratification, particularly among inconclusive cases with II-III grade diagnosed, which have different prognosis and treatment strategies. Microarrays based GEP was analyzed on 155 diffuse astrocytic gliomas (discovery cohort) and validated in another 113 tumors (validation set) via sequential univariate analysis (pairwise comparison) for discriminatory gene selection, followed by nonnegative matrix factorization and canonical biplot for identification of discriminatory GEP among the distinct histological tumor subtypes. GEP data analysis identified a set of 27 genes capable of differentiating among distinct subtypes of gliomas that might support current histological classification. DA + AA showed similar molecular profiles with only a few discriminatory genes overexpressed (FSTL5 and SFRP2) and underexpressed (XIST, TOP2A and SHOX2) in DA vs AA and GBM. Compared to DA + AA, GBM displayed underexpression of ETNPPL, SH3GL2, GABRG2, SPX, DPP10, GABRB2 and CNTN3 and overexpression of CHI3L1, IGFBP3, COL1A1 and VEGFA, among other differentially expressed genes.
Subject(s)
Astrocytoma/genetics , Brain Neoplasms/genetics , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Astrocytoma/diagnosis , Brain Neoplasms/diagnosis , Discriminant Analysis , Female , Humans , Linear Models , Male , Middle Aged , Multivariate Analysis , Mutation , Oligonucleotide Array Sequence Analysis , Signal Transduction , SoftwareABSTRACT
BACKGROUND: The prognostic impact of the expression profile of genes recurrently amplified in glioblastoma multiforme (GBM) remains controversial. METHODS: We investigated the RNA gene expression profile of epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 (CDK4), murine doble minute 4 (MDM4), and platelet derived growth factor receptor alpha (PDGFRA) in 83 primary GBM tumors vs. 42 normal brain tissue samples. Interphase FISH (iFISH) analysis for the four genes, together with analysis of intragenic deletions in EGFR and PDGFRA, were evaluated in parallel at the DNA level. As validation cohort, publicly available RNA gene expression data on 293 samples from 10 different GBM patient series were also studied. RESULTS: At the RNA level, CDK4 was the most frequently overexpressed gene (90%) followed by EGFR (58%) and PDGFRA (58%). Chromosome 7 copy number alterations, i.e., trisomy (49%) and polysomy (44%), showed no clear association with EGFR gene expression levels. In turn, intragenic EGFR deletions were found in 39 patients (47%), including EGFRvIII (46%) in association with EGFRvIVa (4%), EGFRvII (2%) or other EGFR deletions (3%) and PDGFRA deletion of exons 8-9 was found in only two tumors (2%). CONCLUSIONS: Overall, none of the gene expression profiles and/or intragenic EGFR deletions showed a significant impact on overall survival of GBM supporting the notion that other still unraveled features of the disease might play a more relevant prognostic role in GBM.
ABSTRACT
Great efforts focus on early detection of autism spectrum disorder, although some scientists and policy-makers have questioned early universal screening. The aim of this meta-analysis was to evaluate the diagnostic accuracy of the different screening tools. Several electronic databases were used to identify published studies. A Bayesian model was used to estimate the screening accuracy. The pooled sensitivity was 0.72 (95% CI 0.61-0.81), and the specificity was 0.98 (95% CI 0.97-0.99). Subgroup analyses to remove heterogeneity indicated sensitivity was 0.77 (95% CI 0.69-0.84), and specificity was 0.99 (95% CI 0.97-0.99; SD ≤ 0.01). Level 1 screening tools for ASD showed consistent statistically significant results and therefore are adequate to detect autism at 14-36 months.
