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BACKGROUND AND AIM: Hypertension (HTN) is common among obese children and adolescents and increases their cardiovascular risk later in adulthood. The aim of the study was to evaluate the prevalence of HTN identified by office blood pressure (BP) measurement and ambulatory BP monitoring (ABPM) in a cohort of obese children and adolescents and its association with anthropometric and glycometabolic indices. METHODS AND RESULTS: Seventy consecutive obese Caucasian children and adolescents aged 7-16 years were enrolled. Patients underwent ABPM, echocardiogram and carotid ultrasonography. Sex- and age-adjusted logistic multivariable analysis models were used to assess the association between HOMA-IR, HOMA-ß, QUICKI with HTN at ABPM. Receiver Operation Curve (ROC) analysis with Youden J statistics was used to identify the optimal HOMA-IR, HOMA-ß and QUICKI cut-off to predict HTN at ABPM. Hypertensive office BP was found in 25.7% of obese patients. ABPM diagnosed HTN in 34.9% of patients: 20.6% of obese patients had masked HTN (MHTN), and 12.7% had white coat HTN (WCH). Hypertensive obese patients (according to ABPM) had higher HOMA-IR and HOMA-ß, and a lower QUICKI than normotensive subjects. HOMA-IR, HOMA-ß and QUICKI predicted HTN at ABPM in obese patients in age- and sex-adjusted logistic multivariable models. Optimal cut-offs to predict HTN at ABPM in obese patients were: HOMA-IR ≥ 3.30, HOMA-ß ≥ 226.7 and QUICKI <0.33, with high sensitivity. CONCLUSIONS: A sequential testing strategy applying office BP and glycometabolic indices can identify hypertensive obese pediatric patients with high diagnostic accuracy and potentially reducing costs. This strategy needs validation in an external and larger cohort.

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AIM: Little is known about endothelial function in adolescents with type 1 diabetes, and we evaluated endothelial dysfunction, using reactive hyperaemia peripheral arterial tonometry (RH-PAT). METHODS: This prospective, observational, 1-year study focused on 73 adolescents with type 1 diabetes, using multiple daily injections or continuous subcutaneous insulin infusion. The subjects were assessed using RH-PAT, body mass index, blood pressure, fasting lipid profile, glycated haemoglobin, insulin requirements and hours of physical exercise per week. RESULTS: Endothelial dysfunction was observed in 56 patients (76.7%), with lower mean RH-PAT scores (1.26 ± 0.22 versus 2.24 ± 0.48, p < 0.0001) and higher glycated haemoglobin values at baseline (8.27 ± 1.24% versus 7.37 ± 0.54%, p = 0.006) and as a mean of the whole period since diagnosis (8.25 ± 1.22% versus 7.72 ± 0.82%, p = 0.034). A higher percentage of patients with endothelial dysfunction showed abnormal cardiac autonomic tests (p = 0.02) and were more sedentary, exercising <4 hours a week, than patients with normal endothelial function. After follow-up in 64/73 patients, we observed endothelial dysfunction in 81.8% of patients, despite a modest improvement in glycated haemoglobin. CONCLUSION: Adolescents with type 1 diabetes displayed evidence of endothelial dysfunction. Good metabolic control (glycated haemoglobin ≤7.5%, 58 mmol/mol) and regular physical activity of at least 4 h a week might be protective.

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During primary neurogenesis in Xenopus, a cascade of helix--loop--helix (HLH) transcription factors regulates neuronal determination and differentiation. While XNeuroD functions at a late step in this cascade to regulate neuronal differentiation, the factors that carry out terminal differentiation are still unknown. We have isolated a new Xenopus member of the Ebf/Olf-1 family of HLH transcription factors, Xebf3, and provide evidence that, during primary neurogenesis, it regulates neuronal differentiation downstream of XNeuroD. In developing Xenopus embryos, Xebf3 is turned on in the three stripes of primary neurons at stage 15.5, after XNeuroD. In vitro, XEBF3 binds the EBF/OLF-1 binding site and functions as a transcriptional activator. When overexpressed, Xebf3 is able to induce ectopic neurons at neural plate stages and directly convert ectodermal cells into neurons in animal cap explants. Expression of Xebf3 can be activated by XNeuroD both in whole embryos and in animal caps, indicating that this new HLH factor might be regulated by XNeuroD. Furthermore, in animal caps, XNeuroD can activate Xebf3 in the absence of protein synthesis, suggesting that, in vitro, this regulation is direct. Similar to XNeuroD, but unlike Xebf2/Xcoe2, Xebf3 expression and function are insensitive to Delta/Notch-mediated lateral inhibition. In summary, we conclude that Xebf3 functions downstream of XNeuroD and is a regulator of neuronal differentiation in Xenopus.

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Several genetic factors have been proven to contribute to the specification of the metencephalic-mesencephalic territory, a process that sets the developmental foundation for prospective morphogenesis of the cerebellum and mesencephalon. However, evidence stemming from genetic and developmental studies performed in man and various model organisms suggests the contribution of many additional factors in determining the fine subdivision and differentiation of these central nervous system regions. In man, the cerebellar ataxias/aplasias represent a large and heterogeneous family of genetic disorders. Here, we describe the identification by differential screening and the characterization of Mmot1, a new gene encoding a DNA-binding protein strikingly similar to the helix-loop-helix factor Ebf/Olf1. Throughout midgestation embryogenesis, Mmot1 is expressed at high levels in the metencephalon, mesencephalon, and sensory neurons of the nasal cavity. In vitro DNA binding data suggest some functional equivalence of Mmot1 and Ebf/Olf1, possibly accounting for the reported lack of olfactory or neural defects in Ebf-/- knockout mutants. The isolation of Mmot1 and of an additional homolog in the mouse genome defines a novel, phylogenetically conserved mammalian family of transcription factor genes of potential relevance in studies of neural development and its aberrations.

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To contribute to the isolation of genes within the q-24-qter region of the human X chromosome,we screened three cDNA libraries (human fetal brain, liver and skeletal muscle) with a cosmid clone containing a CpG island previously mapped in the q28 region. A full-length 2.1-kb cDNA clone was isolated (XIB); DNA databank searches revealed identity with an EST fragment (XAP-1), residing between the RCP/GCP and G6PD loci. The XIB coding region (909 bp) showed 44% amino acid (aa) identity to pig DNase I. Several conserved residues have been observed between these two genes including aa in the active site. XIB expressed a single transcript in adult heart and skeletal muscle, whereas, in some fetal tissues, two different-sized transcripts were seen. Zoo blot analysis showed a remarkable cross-species conservation. Expression and sequence of this novel gene are reported.

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