The novel roles of YULINK in the migration, proliferation and glycolysis of pulmonary arterial smooth muscle cells: implications for pulmonary arterial hypertension.

BACKGROUND: Abnormal remodeling of the pulmonary vasculature, characterized by the proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) along with dysregulated glycolysis, is a pathognomonic feature of pulmonary arterial hypertension (PAH). YULINK (MIOS, Entrez Gene: 54468), a newly identified gene, has been recently shown to possess pleiotropic physiologic functions. This study aims to determine novel roles of YULINK in the regulation of PAH-related pathogenesis, including PASMC migration, proliferation and glycolysis. RESULTS: Our results utilized two PAH-related cell models: PASMCs treated with platelet-derived growth factor (PDGF) and PASMCs harvested from monocrotaline (MCT)-induced PAH rats (PAH-PASMCs). YULINK modulation, either by knockdown or overexpression, was found to influence PASMC migration and proliferation in both models. Additionally, YULINK was implicated in glycolytic processes, impacting glucose uptake, glucose transporter 1 (GLUT1) expression, hexokinase II (HK-2) expression, and pyruvate production in PASMCs. Notably, YULINK and GLUT1 were observed to colocalize on PASMC membranes under PAH-related pathogenic conditions. Indeed, increased YULINK expression was also detected in the pulmonary artery of human PAH specimen. Furthermore, YULINK inhibition led to the suppression of platelet-derived growth factor receptor (PDGFR) and the phosphorylation of focal adhesion kinase (FAK), phosphoinositide 3-kinase (PI3K), and protein kinase B (AKT) in both cell models. These findings suggest that the effects of YULINK are potentially mediated through the PI3K-AKT signaling pathway. CONCLUSIONS: Our findings indicate that YULINK appears to play a crucial role in the migration, proliferation, and glycolysis in PASMCs and therefore positioning it as a novel promising therapeutic target for PAH.

Kawasaki disease in children with Bacillus Calmette-Guérin scar reactivity: Focus on coronary outcomes.

BACKGROUND: /Purpose: Reactivity at the Bacillus Calmette-Guérin (BCG) scar is a pathognomonic feature of Kawasaki disease (KD). However, its value in predicting KD outcomes has not been emphasized. This study explored the clinical significance of BCG scar redness with respect to coronary artery outcomes. METHODS: This retrospective study collected data on children with KD from 13 hospitals in Taiwan during 2019-2021. Children with KD were categorized into four groups based on the KD type and BCG scar reactivity. Risk factors of coronary artery abnormalities (CAA) were analyzed in all groups. RESULTS: BCG scar redness occurred in 49% of 388 children with KD. BCG scar redness was associated with younger age, early intravenous immunoglobulin (IVIG) treatment, hypoalbuminemia, and CAA at the first echocardiogram (p < 0.01). BCG scar redness (RR 0.56) and pyuria (RR 2.61) were independent predictors of any CAA within 1 month (p < 0.05). Moreover, pyuria (RR 5.85, p < 0.05) in children with complete KD plus BCG scar redness was associated with CAA at 2-3 months; first IVIG resistance (RR 15.2) and neutrophil levels ≥80% (RR 8.37) in children with complete KD plus BCG scar non-redness were associated with CAA at 2-3 months (p < 0.05). We failed to detect any significant risk factors of CAA at 2-3 months in children with incomplete KD. CONCLUSION: BCG scar reactivity contributes to diverse clinical features in KD. It can be effectively applied to determine the risk factors of any CAA within 1 month and CAA at 2-3 months.

Epicardial Adipose Tissue Was Highly Associated with Reduction in Left Ventricular Diastolic Function as Early as in Adolescence.

Background: Epicardial adipose tissue (EAT) is increased in adolescents with obesity and may play a role in early cardiovascular pathophysiological changes. There is a lack of evidence focusing on the association between EAT and cardiac function in adolescents. This study explored associations between EAT, left ventricle (LV) geometric, and LV functional changes in adolescents. Methods: Adolescent volunteers between 10 and 20 years of age were included. Body mass index (BMI) was presented as age- and sex-specific BMI z-scores. Blood samples for glucose metabolism, lipid profiles, and high-sensitivity C-reactive protein (hs-CRP) were obtained. EAT thickness, LV hypertrophy, and LV diastolic function were measured by echocardiography. Results: The mean age of the 276 adolescents was 13.51 ± 2.44 years. BMI z-score was strongly associated with EAT thickness (r = 0.77; p < 0.001). Multivariable analysis revealed that age, insulin resistance, total cholesterol to high-density lipoprotein cholesterol ratio, and hs-CRP were independent predictors of increased EAT thickness. After adjusting for sex, age, and BMI z-score by multivariable analysis, EAT thickness was a strong predictor of higher LV mass indexed to height2.7, higher relative wall thickness, lower mitral annulus e'/a', and higher E/e' of the mitral annulus. There was no association between EAT and LV ejection fraction. Conclusions: EAT was highly associated with LV hypertrophy and reduction in LV diastolic function, independent of BMI z-score in the enrolled adolescents. Of note, the negative impacts of EAT on LV geometry and diastolic function occurred as early as in adolescence. This highlights the importance of preventing obesity and EAT deposition early in life.

Ascending Aortic Aneurysm After Repair of Aortico-Left Ventricular Tunnel.

Ascending aortic aneurysm following aortico-left ventricular tunnel (ALVT) repair is an uncommon but life-threatening complication. A 27-year-old man had received patch closure for ALVT at infancy. Eighteen years later, aortic valve replacement for severe aortic regurgitation and direct suture for recurrent slit tunnel were performed. Another 9 years later, ascending aortic replacement was performed because of ascending aortic aneurysm. Thus we report an uncommon case of ascending aortic aneurysm 27 years after the repair of an ALVT.

B-type natriuretic peptide prevents postnatal closure of ductus arteriosus by both vasodilation and anti-remodeling in neonatal rats.

The physiologic process of postnatal ductus arteriosus (DA) closure consists of vasoconstriction followed by vascular remodeling. We have recently reported that B-type natriuretic peptide (BNP), a potent vasodilator, also has anti-remodeling effects in pulmonary vasculature. However, its effects on DA have not been elucidated. We investigated whether BNP can prevent DA closure, and if so, the underlying mechanisms. Using in vivo studies, we examined effects of BNP (10 mg/kg, ip at birth) on DA closure in neonatal rats within 4 h after birth. We found that in control rats, the DA spontaneously closed at 4 h with a decreased DA diameter, enhanced intimal thickening, and luminal occlusion. BNP prevented DA closure at 4 h with a preserved DA diameter, attenuated intimal thickening, and preserved luminal patency. Ex vivo, BNP attenuated oxygen-induced vasoconstriction of isolated DA rings of newborn rats. These vasodilating effects were blunted by Rp-8-Br-PET-cGMPS, a cGMP inhibitor. In vitro, BNP inhibited angiotensin II (Ang II)-induced proliferation and migration of DA smooth muscle cells (DASMCs). BNP inhibited Ang II-induced mitochondrial reactive oxygen species (ROS) production and calcium overload in DASMCs. Finally, BNP inhibited Ang II-induced ERK1/2 activation. These in vitro effects were antagonized by Rp-8-Br-PET-cGMPS. In conclusion, BNP prevents postnatal DA closure by both vasodilation and anti-remodeling through the cGMP pathway. The mechanisms underlying anti-remodeling effects include anti-poliferation and anti-migration, with attenuation of mitochondrial ROS production and intracellular calcium and ERK1/2 signaling. Therefore, the BNP/cGMP pathway can be a promising therapeutic target for clinical management of DA patency.

Xanthine-based KMUP-1 improves HDL via PPARγ/SR-B1, LDL via LDLRs, and HSL via PKA/PKG for hepatic fat loss.

The phosphodiesterase inhibitor (PDEI)/eNOS enhancer KMUP-1, targeting G-protein coupled receptors (GPCRs), improves dyslipidemia. We compared its lipid-lowering effects with simvastatin and explored hormone-sensitive lipase (HSL) translocation in hepatic fat loss. KMUP-1 HCl (1, 2.5, and 5 mg/kg/day) and simvastatin (5 mg/kg/day) were administered in C57BL/6J male mice fed a high-fat diet (HFD) by gavage for 8 weeks. KMUP-1 inhibited HFD-induced plasma/liver TG, total cholesterol, and LDL; increased HDL/3-hydroxy-3-methylglutaryl-CoA reductase (HMGR)/Rho kinase II (ROCK II)/PPARγ/ABCA1; and decreased liver and body weight. KMUP-1 HCl in drinking water (2.5 mg/200 ml tap water) for 1-14 or 8-14 weeks decreased HFD-induced liver and body weight and scavenger receptor class B type I expression and increased protein kinase A (PKA)/PKG/LDLRs/HSL expression and immunoreactivity. In HepG2 cells incubated with serum or exogenous mevalonate, KMUP-1 (10(-7)∼10(-5) M) reversed HMGR expression by feedback regulation, colocalized expression of ABCA1/apolipoprotein A-I/LXRα/PPARγ, and reduced exogenous geranylgeranyl pyrophosphate/farnesyl pyrophosphate (FPP)-induced RhoA/ROCK II expression. A guanosine 3',5'-cyclic monophosphate (cGMP) antagonist reversed KMUP-1-induced ROCK II reduction, indicating cGMP/eNOS involvement. KMUP-1 inceased PKG and LDLRs surrounded by LDL and restored oxidized LDL-induced PKA expresion. Unlike simvastatin, KMUP-1 could not inhibit (14)C mevalonate formation. KMUP-1 could, but simvastatin could not, decrease ROCK II expression by exogenous FPP/CGPP. KMUP-1 improves HDL via PPARγ/LXRα/ABCA1/Apo-I expression and increases LDLRs/PKA/PKG/HSL expression and immunoreactivity, leading to TG hydrolysis to lower hepatic fat and body weight.

Lung function in very preterm infants with patent ductus arteriosus under conservative management: an observational study.

BACKGROUND: Persistent patent ductus arteriosus (PDA) during hospitalization is thought to be associated with adverse pulmonary outcomes in very preterm infants. This observational study aimed to compare the lung function in very preterm infants with and without PDA at discharge. METHODS: Very preterm infants, admitted to our neonatal intensive unit, who required respiratory support soon after birth and had undergone a lung function test at discharge, were enrolled. Infants with a need for positive-pressure support (either an invasive ventilator, or nasal continuous positive airway pressure without oxygen) or supplemental oxygen at a postmenstrual age of 36 weeks were defined as having bronchopulmonary dysplasia (BPD). Echocardiography was performed weekly for each of the very preterm infants with PDA to confirm closure of the PDA. The data were collected retrospectively. RESULTS: Fifty-two very preterm infants received lung function tests before discharge during the study period, 28 of whom had PDA and received conservative management, and 20 who did not. The other 4 infants who were given active treatment for PDA were excluded. Gestational age was significantly smaller in the PDA group than in the no-PDA group (27.1 ± 2.0 vs. 28.6 ± 1.6 weeks, p = 0.009). Birth weight did not differ significantly in those with and those without PDA (0.98 ± 0.26 vs. 1.12 ± 0.26 kg, p = 0.074). Significantly more infants with PDA had BPD (p = 0.002) and required respiratory support for a longer period (p = 0.001) than those without PDA. However, functional residual capacity (ml/kg) at discharge was comparable between the two groups after adjusting for gestational age and postmenstrual age at testing (21.6 ± 8.4 vs. 21.5 ± 6.7 ml/kg, p = 0.894). Other lung function test parameters were also comparable. CONCLUSION: Under a definition of BPD (including infants needing CPAP but without oxygen) other than the conventional definition, the very preterm infants in our study who received conservative management for PDA had a higher percentage of BPD than the infants without PDA. The parameters of the lung function test and lung clearance index were comparable between these two groups at discharge.

Early Elevated B-Type Natriuretic Peptide Levels are Associated with Cardiac Dysfunction and Poor Clinical Outcome in Pediatric Septic Patients.

BACKGROUND: To determine the B-type natriuretic peptide (BNP) level in pediatric septic patients, and to investigate its association with cardiovascular dysfunction and clinical outcome. METHODS: Pediatric patients with sepsis or septic shock were prospectively enrolled in our pediatric intensive care unit (PICU). On day 1 of admission, plasma BNP levels were measured at the time-point of echocardiography. Myocardial dysfunction was defined as left ventricular fractional shortening (FS) < 30%. Inotropic support was quantified by inotropic scores and disease severity was assessed by Pediatric Risk of Mortality (PRISM) III scores. Therafter, associations between BNP levels and clinical parameters were analyzed. RESULTS: There were 94 patients (mean: 5.6 yr, range: 2 mo-17 yr) that were consecutively enrolled in this study. The median BNP level was 127 pg/ml (range: 5 to 4950 pg/ml). BNP levels were correlated with PRISM III (rho = 0.36, p = 0.001) and C-reactive protein level (r = 0.39, p = 0.001). The median BNP levels were not only higher in patients with septic shock (n = 34) than those with sepsis (n = 58) (213 vs. 54 pg/ml, p = 0.0004), but also higher in patients with myocardial dysfunction (n = 18) than those with preserved myocardial function (n = 66) (765 vs. 65 pg/ml, p < 0.001). We also found that BNP levels correlated negatively with FS (r = -0.56, p < 0.001) and positively with inotropic scores (r = 0.34, p = 0.04). Most importantly, the median BNP levels were higher in non-survivors (n = 13) than survivors (n = 81) (367 vs. 106 pg/ml, p = 0.003). CONCLUSIONS: BNP levels are elevated in pediatric septic patients early in the disease course, and increased levels are associated with cardiovascular dysfunction and worse clinical outcome. KEY WORDS: B-type natriuretic peptide; Cardiac function; Pediatric; Sepsis; Septic shock.

Temporal changes of urinary oxidative metabolites of di(2-ethylhexyl)phthalate after the 2011 phthalate incident in Taiwanese children: findings of a six month follow-up.

A major incident involving phthalates-contaminated foodstuffs occurred in Taiwan in May 2011, leading to the quick removal of tainted food items from store shelves. We investigated changes in urinary oxidative di(2-ethylhexyl)phthalate (DEHP) metabolites, our proxy for exposure to DEHP-tainted foodstuffs in children ≤10 years, during the six months following withdrawal of the tainted food. Our hospital screened 60 possibly exposed children between May and June 2011. The children's food intake information was collected, and they were administered one-spot urine samples at baseline and at the two and six month follow-ups. All three samples were measured for four oxidative DEHP metabolites, mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), mono-(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP), and mono-(2-carboxymethylhexyl) phthalate (2cx-MMHP) by triple quadrupole liquid chromatography tandem mass spectrometry. Fifty-two children had been exposed. After excluding those without a full set of urine samples or adequate food intake information, 23 exposed children were studied. We found significantly positive correlations between DEHP daily intake and urinary 5OH-MEHP, 5oxo-MEHP, and 5cx-MEPP (p < 0.05). At the six month follow-up, all four metabolite concentrations had significantly decreased compared to the baseline. In conclusion, urinary DEHP metabolites decreased progressively in children after tainted food withdrawal, indicating that the main sources of phthalate contamination for children had been successfully controlled.

Changing patterns of infectious diseases in children during the COVID-19 pandemic.

Each infectious disease has had its own epidemic pattern and seasonality for decades. However, public health mitigation measures during the coronavirus disease 2019 (COVID-19) pandemic have resulted in changing epidemic patterns of infectious diseases. Stringent measures resulted in low incidences of various infectious diseases during the outbreak of COVID-19, including influenza, respiratory syncytial virus, pneumococcus, enterovirus, and parainfluenza. Owing to the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and subsequent immunity development, decreasing virulence of SARS-CoV-2, and worldwide immunization against SARS-CoV-2 in children beyond 6 months of age, mitigation measures are lifted country by country. Consequently, the immunity debt to infectious respiratory viruses other than SARS-CoV-2 contributed to the "off-season," "see-saw," and "upsurge" patterns of various infectious diseases in children. Moreover, apart from the persistence of SARS-CoV-2, the coexistence of other circulating viruses or bacterial outbreaks may lead to twindemics or tripledemics during the following years. Therefore, it is necessary to maintain hand hygiene and immunization policies against various pathogens to alleviate the ongoing impact of infectious diseases on children.

Similarities and Differences Between COVID-19-Related Multisystem Inflammatory Syndrome in Children and Kawasaki Disease.

In December 2019, the first case of coronavirus disease (COVID-19) was first reported in Wuhan, China. As of March 2021, there were more than 120 million confirmed cases of COVID-19 and 2.7 million deaths. The COVID-19 mortality rate in adults is around 1-5%, and only a small proportion of children requires hospitalization and intensive care. Recently, an increasing number of COVID-19 cases in children have been associated with a new multisystem inflammatory syndrome. Its clinical features and laboratory characteristics are similar to those of Kawasaki disease (KD), KD shock syndrome, and toxic shock syndrome. However, this new disorder has some distinct clinical features and laboratory characteristics. This condition, also known as multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, has been observed mostly in Europe and the United States. This emerging phenomenon has raised the question of whether this disorder is KD triggered by SARS-CoV-2 or a syndrome characterized by multisystem inflammation that mimics KD. This narrative review is to discuss the differences between MIS-C and KD with the aim of increasing pediatricians' awareness of this new condition and guide them in the process of differential diagnosis.

A Rare Complication During Transcatheter Closure of Double Atrial Septal Defects With Incomplete Cor Triatriatum Dexter: A Case Report.

The cor triatiatum dexter is an embryologic remnant derived from the right atrium and totally separate from the right atrium. An incomplete cor triatiatum dexter (iCTD) means a partially obstructive remnant at the right atrium. It is usually formed by a remnant of the Eustachian valve (EV), Thebesian valve (ThV), or Chiari network (CN). This anatomic variant is usually asymptomatic but is often associated with other heart abnormalities including atrial septal defects (ASDs), and has the potential to hamper percutaneous heart procedures such as electrophysiological study or ASD closure. Herein, we report a rare complication, transient heart ischemia, in transcatheter closure of double ASDs in a 55-year-old woman with EV. This rare complication was thought to be caused by coronary sinus obstruction during device placement. The ischemic change was resolved spontaneously after we withdrew the device. For a second attempt, we adjusted the position of the device to avoid coronary sinus obstruction under transesophageal echocardiogram guidance and the device was smoothly deployed in a good position with a minimal residual shunt. This case suggests that anatomy details in percutaneous heart procedures are important, and this rare and dangerous complication, heart ischemia, should be identified immediately during the procedure.

B-type natriuretic peptide predicts responses to indomethacin in premature neonates with patent ductus arteriosus.

OBJECTIVES: To determine whether B-type natriuretic peptide (BNP) predicts indomethacin responsiveness in premature neonates with patent ductus arteriosus (PDA). STUDY DESIGN: Premature neonates receiving indomethacin for an echocardiograhically large (diameter>1.5 mm) and clinically significant PDA were prospectively studied. All neonates underwent paired echocardiography and BNP measurements at baseline and 24 hours after each dose of indomethacin. After treatment, neonates who responded (with closed or insignificant PDA) and neonates who did not respond (with persistent significant PDA requiring surgical ligation) were compared. RESULTS: Thirty-one premature neonates (mean gestational age, 30 weeks) underwent 119 paired echocardiography and BNP determinations. Mean BNP levels (1286+/-986 pg/mL) associated with significant PDA (n=96) were higher than those associated with closed or insignificant PDA (n=23; 118+/-124 pg/mL; P<.001). Twenty-three neonates responded and 8 neonates did not respond to indomethacin. Mean baseline BNP levels were higher in neonates who were non-responders (2234+/-991 pg/mL) than neonates who were responders (983+/-814 pg/mL; P=.001). A baseline BNP level>1805 pg/mL had a sensitivity rate of 88% and a specificity rate of 87% for predicting indomethacin non-responsiveness (P=.003). CONCLUSIONS: High baseline BNP levels predict poor responses to indomethacin and the need for surgery in premature neonates with PDA.

Initial Experience With Patent Ductus Arteriosus Ligation in Pre-term Infants With Bidirectional Shunt Pattern.

Background: Patent ductus arteriosus (PDA) with a bidirectional shunt reflects critical clinical conditions. The operability of PDA with a bidirectional shunt in pre-term infants is still not clearly clarified. This study aimed to investigate the feasibility and the outcomes of PDA ligation in pre-term infants with a bidirectional shunt PDA. Methods: All pre-term infants receiving PDA ligation between 2013 and 2019 were enrolled in this prospective study. Patients were allocated into two groups based on the shunting direction of PDA, which were the left-to-right group (group A) and the bidirectional group (group B). Clinical characteristics and pre-op comorbidities were analyzed. Intraoperative complications, post-op neurological sequelae, necrotizing enterocolitis, survival, and mortality were compared between these two groups. Results: Thirty-seven pre-term infants were enrolled (18 in group A, 19 in group B). The mean post-menstrual age at PDA surgery was 32.0 ± 1.3 and 32.8 ± 1.5 weeks, respectively. Before surgery, 44.4 and 89.5% (group A vs. B) of the patients were using invasive mechanical ventilator (p < 0.01). The requirement of high-frequency oscillatory ventilatory support was significantly higher in group B. PDA rupture-related bleeding during exposing PDA or ligating PDA occurred in four infants, and all were all in group B, including one with delayed hemothorax. Early surgical mortality within 30 days of surgery was higher in group B (0 vs. 21.1%, p < 0.05), but only one death could be attributed to the surgery, which was caused by a pain-induced pulmonary hypertension crisis. The 5-year survival was 100% in group A, and 73.7% in group B (p < 0.05). Conclusion: We did not recommend routine PDA ligation in pre-term infants with a bidirectional shunt. However, a bidirectional shunt should not be an absolute contraindication if they fulfill indications of PDA closure. Unexpected intraoperative PDA rupture and delayed hemothorax in a bidirectional shunt PDA should be carefully monitored. Aggressive post-op pain control is also warranted to avoid pulmonary hypertension crisis. The post-op early mortality rate was higher in the bidirectional group, which could be inherent to their poor pre-operative lung condition. Only one death was directly related to the surgery.

Septic arthritis as the initial manifestation of fatal Vibrio vulnificus septicemia in a patient with thalassemia and iron overload.

Vibrio vulnificus infection is an uncommon but potentially fatal disease in children such that prompt recognition has prognostic implications. We describe here the case of a 9-year-old female with thalassemia and iron overload who presented with septic arthritis as an atypical initial manifestation of fatal V. vulnificus septicemia. This report underscores the possibility of septic arthritis as an early manifestation of V. vulnificus septicemia. Pediatricians should be alert to this extremely invasive disease, especially in children with iron overload.

Montelukast as monotherapy in children with mild persistent asthma.

The cysteinyl leukotrienes cause bronchoconstriction, increased mucus production and airway inflammation, three major features of asthma. Several randomized controlled trials have shown the efficacy of leukotriene receptor antagonists for improving asthma outcomes. The drug is favored for treating childhood asthma, where poor compliance with inhalation therapy is a therapeutic challenge. To assess the effectiveness of Montelukast in asthmatic children under real-life conditions, a prospective, single-arm, multicenter, open-label observational study was performed on asthmatic children 2- to 14-years-old with a history of physician-diagnosed mild persistent asthma. Montelukast was given once daily for 12 consecutive weeks. By the end a significant improvement of the daytime asthma symptom score, nighttime asthma score, peak expiratory flow rate (PEFR) and mean score of the investigators' global evaluation was noted (p < 0.05). These results suggest that montelukast is an effective monotherapy controller in children with mild persistent asthma.

Serum apoptotic marker M30 is positively correlated with early diastolic dysfunction in adolescent obesity.

PURPOSE: Obesity in adolescence has been shown to be related to cardiac geometric and functional changes. Cardiac dysfunction in adults with obesity could be attributed to chronic low-grade inflammation, apoptosis of cardiomyocyte, and glucose metabolic disorder. The aforementioned association in adolescents with obesity have never been well studied. Our aim was to determine the types of cardiac dysfunction in adolescents with obesity and survey the association between cardiac dysfunction and chronic low-grade inflammation, apoptosis, and glucose dysregulation in adolescents with obesity. METHODS: Adolescents aged between 10 and 20 years were enrolled in this study. Body mass index, waist-to-hip ratio, blood pressure, glucose metabolism, and high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-a (TNF-α), and apoptosis marker M30 levels were measured. Echocardiographic indices were also measured. The association between serum biomarkers and echocardiographic function parameters was analyzed. RESULTS: Diastolic dysfunction was the major finding in the cardiac functional assessment. The main changes in glucose metabolism were elevated C-peptide level and insulin resistance. Hs-CRP, IL-6, and M30 levels also increased with adolescent obesity. M30 was the major biomarker that was highly correlated to diastolic dysfunction indices in adolescents with obesity. CONCLUSIONS: Diastolic dysfunction was the main change in adolescent obesity. Insulin resistance, apoptotic marker M30, hs-CRP, and IL-6 were all elevated in adolescents with obesity. Only M30 was related to indices of left ventricular diastolic dysfunction among adolescents with obesity, rather than inflammation or insulin resistance.

Isoeugenodilol inhibits smooth muscle cell proliferation and neointimal thickening after balloon injury via inactivation of ERK1/2 pathway.

The purpose of this study was to determine the efficacy and the possible mechanism of action of the synthesized drug isoeugenodilol (a new third-generation beta-adrenoceptor blocker) on the growth factor-induced proliferation of cultured rat vascular smooth muscle cells (VSMCs) and neointimal formation in a rat carotid arterial balloon injury model. Isoeugenodilol significantly inhibited 10% FBS, 20 ng/ml PDGF-BB, and 20 ng/ml vascular endothelial growth factor (VEGF)-induced proliferation. In accordance with these findings, isoeugenodilol revealed blocking of the FBS-inducible progression through the G(0)/G(1) to the S phase of the cell cycle in synchronized cells. Neointimal formation, measured 14 days after injury, was reduced by the oral administration of isoeugenodilol (10 mg/kg/day). In an in vitro assay, isoeugenodilol inhibited the migration of VSMCs stimulated by PDGF-BB. These findings indicate that isoeugenodilol shows an inhibitory potency on neointimal formation due to inhibition of both migration and proliferation of VSMCs. In addition, isoeugenodilol in concentration-dependent manner decreased the levels of phosphorylated ERK1/2 in both VSMCs and balloon-injured carotid arteries. The levels of phosphorylated MEK1/2 and Pyk2 as well as intracellular Ca(2+) and reactive oxygen species (ROS) were in concentration-dependent manner reduced by isoeugenodilol. Taken together, these results indicate that isoeugenodilol may suppress mitogen-stimulated proliferation and migration partially through inhibiting cellular ROS and calcium, and hence, through activation of the Pyk2-ERK1/2 signal pathway. This suggests that isoeugenodilol has potential for the prevention of atherosclerosis and restenosis.

Recent review of transcatheter closure of atrial septal defect.

Atrial septal defect (ASD) is one of the two most common congenital heart diseases in children and adult. After the application of catheter intervention for ASD, this became an alternative treatment other than surgery from late 1990. In 2001, the procedure was further approved by the US Food and Drug Administration (FDA), and become the first choice for most cases of secundum type of ASD worldwide. The success rate is more than 98% in literature reviews, with low complication rates in percutaneous ASD closure. Major complications are around 1%, including device embolization, cardiac erosions, new-onset atrial arrhythmia, and other comorbidities. We reviewed indications for percutaneous secundum type ASD closure, technique, successful rate and major complications in this article. To complete the catheter intervention with difficult ASD conditions, various procedural techniques have been developed recently. We also report a challenging case by a current balloon-assisted technique for huge ASD closure.