Activation of sonic hedgehog signaling by a Smoothened agonist restores congenital defects in mouse models of endocrine-cerebro-osteodysplasia syndrome.

BACKGROUND: Endocrine-cerebro-osteodysplasia (ECO) syndrome is a genetic disorder associated with congenital defects of the endocrine, cerebral, and skeletal systems in humans. ECO syndrome is caused by mutations of the intestinal cell kinase (ICK) gene, which encodes a mitogen-activated protein (MAP) kinase-related kinase that plays a critical role in controlling the length of primary cilia. Lack of ICK function disrupts transduction of sonic hedgehog (SHH) signaling, which is important for development and homeostasis in humans and mice. Craniofacial structure abnormalities, such as cleft palate, are one of the most common defects observed in ECO syndrome patients, but the role of ICK in palatal development has not been studied. METHODS: Using Ick-mutant mice, we investigated the mechanisms by which ICK function loss causes cleft palate and examined pharmacological rescue of the congenital defects. FINDINGS: SHH signaling was compromised with abnormally elongated primary cilia in the developing palate of Ick-mutant mice. Cell proliferation was significantly decreased, resulting in failure of palatal outgrowth, although palatal adhesion and fusion occurred normally. We thus attempted to rescue the congenital palatal defects of Ick mutants by pharmacological activation of SHH signaling. Treatment of Ick-mutant mice with an agonist for Smoothened (SAG) rescued several congenital defects, including cleft palate. INTERPRETATIONS: The recovery of congenital defects by pharmacological intervention in the mouse models for ECO syndrome highlights prenatal SHH signaling modulation as a potential therapeutic measure to overcome congenital defects of ciliopathies.

Iron-doped ZnO as a support for Pt-based catalysts to improve activity and stability: enhancement of metal-support interaction by the doping effect.

In heterogeneous catalysis, the role of the interface between a metal and a metal oxide in deciding catalytic performance has remained a long-standing question. Out of many molecular-scale factors that affect the properties of metal-oxide interfaces, doping or impurities in the oxides can result in excess charge carriers or oxygen vacancies on the oxides, which lead to a change in catalytic activity. For a model system with a tunable dopant, we employed Pt nanoparticles with Fe doping. We synthesized a series of Fe-doped ZnO with different Fe loadings (i.e., 0, 1, and 4%) using the co-precipitation method, and then deposited Pt nanoparticles onto these supports. The Pt-based catalysts were employed to investigate the effect of the dopant to promote the catalytic performance for the CO oxidation reaction. The 4% Fe loading sample showed the highest catalytic activity among the catalysts, with a turnover frequency of 5.37 s-1 at 126 °C. The dopant was found to enhance the interaction between the Pt nanoparticles and the catalyst support, including the prevention of metal sintering, which resulted in an improvement of catalytic activity.

Uveitis as an important ocular sign to help early diagnosis in Kawasaki disease.

PURPOSE: Incomplete Kawasaki disease (KD) is frequently associated with delayed diagnosis and treatment. Delayed diagnosis leads to increasing risk of coronary artery aneurysm. Anterior uveitis is an important ocular sign of KD. The purpose of this study was to assess differences in laboratory findings, including echocardiographic measurements, clinical characteristics such as fever duration and treatment responses between KD patients with and those without uveitis. METHODS: We conducted a prospective study with 110 KD patients from January 2008 to June 2013. The study group (n=32, KD with uveitis) was compared with the control group (n=78, KD without uveitis). Laboratory data were obtained from each patient including complete blood count (CBC), erythrocyte sedimentation rate (ESR), platelet count, and level of alanine aminotransferase, aspartate aminotransferase, serum total protein, albumin, C-reactive protein (CRP), and N-terminal probrain natriuretic peptide (NT-pro BNP). Echocardiographic measurements and intravenous immunoglobulin responses were compared between the two groups. RESULTS: The incidence of uveitis was 29.0%. Neutrophil counts and patient age were higher in the uveitis group than in the control group. ESR and CRP level were slightly increased in the uveitis group compared with the control group, but the difference between the two groups was not significant. No significant differences in coronary arterial complication and treatment responses were observed between the two groups. CONCLUSION: Uveitis is an important ocular sign in the diagnosis of incomplete KD. It is significantly associated with patient age and neutrophil count.

Cardiac Function in Kawasaki Disease Patients with Respiratory Symptoms.

BACKGROUND AND OBJECTIVES: Respiratory symptoms are often observed in children with Kawasaki disease (KD) during the acute phase. The association of respiratory viruses in children with KD was investigated using multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) and tissue Doppler echocardiography. SUBJECTS AND METHODS: 138 KD patients were included from January 2010 to June 2013. We compared 3 groups (group 1: n=94, KD without respiratory symptoms; group 2: n=44, KD with respiratory symptoms; and group 3: n=50, febrile patients with respiratory symptoms). Laboratory data were obtained from each patient including N-terminal pro-brain natriuretic peptide (NT-proBNP). Echocardiographic measurements were compared between group 1 and group 2. RT-PCR was performed using nasopharyngeal secretion to screen for the presence of 14 viruses in groups 2 and 3. RESULTS: The incidence of KD with respiratory symptoms was 31.8%. The duration of fever was significantly longer, and coronary artery diameter was larger in group 2 than in group 1. Tei index was significantly higher and coronary artery diameter larger in group 2 than group 1. Coronary artery diameter, C-reactive protein levels, platelet count, alanine aminotransferase levels, and NT-pro BNP levels were significantly higher and albumin levels lower in group 2 compared with group 3. CONCLUSION: NT-pro BNP was a valuable diagnostic tool in differentiating KD from other febrile viral respiratory infections. Some viruses were more frequently observed in KD patients than in febrile controls. Tei index using tissue Doppler imaging was increased in KD patients with respiratory symptoms.

Cardiovascular screening in asymptomatic adolescents with metabolic syndrome.

BACKGROUND: In recent days, the prevalence of childhood metabolic syndrome (MS) has increased substantially due to the increasing rate of childhood obesity on a global scale. The aims of this study were to detect the important parameters and provide the screening system to prevent cardiovascular disease in adolescents with MS. METHODS: Ninety one male adolescents were divided into two groups based on the presence or absence of MS. Anthropometric measurement and laboratory study were studied. Intimal medial thickness and pulse wave velocity were estimated. Left ventricular mass index (LVMI), ejection fraction, myocardial velocity, strain and strain rate were measured by tissue Doppler imaging and strain rate imaging. RESULTS: The prevalence of MS was 7.7%. Weight, body mass index (BMI), waist circumference (WC), glucose, insulin, homeostasis model assessment of insulin resistance, triglyceride and LVMI were significantly increased in the MS group. High density lipoprotein-cholesterol (HDL-C), peak early diastolic myocardial velocity (e'), systolic myocardial velocity (s') and global longitudinal strain were significantly lower in the MS group. In univariant analysis, LVMI was significantly correlated with BMI, WC, fat %, fat mass, systolic blood pressure, alanine aminotransferase, total cholesterol (TC) and low density lipoprotein-cholesterol. e' was significantly correlated with BMI, fat %, fat mass, and HDL-C. Global circumferential strain had significant correlation with glucose and TC. Basal anterolateral strain rate was significantly correlated with weight, BMI, WC, fat %, and fat mass. CONCLUSION: LVMI, strain and strain rate are practical and accurate parameters for assessment of left ventricular function in adolescents with MS.