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Background: Brugada syndrome (BrS) is an inherited channelopathy characterized by right precordial ST-segment elevation. This study investigates the clinical and genetic characteristics of children with BrS in Hong Kong., Methods: A retrospective review was conducted at the only tertiary pediatric cardiology center in Hong Kong from 2002 to 2022, including all pediatric BrS patients under 18 years old. The diagnosis of BrS was established with a type 1 ECG pattern detected spontaneously or induced by flecainide, excluding secondary causes., Results: Eight probands of mean age 10 years old were identified. Male dominance was observed (6 boys vs. 2 girls). The mean follow-up duration was 4.6 years (Median 3.5 years). Patients had type 1 ECG pattern either spontaneously (n = 4) or provoked by flecainide (n = 4). Fever was present in seven patients at the initial presentation, and two patients experienced aborted cardiac arrest and one had symptomatic ventricular tachycardia. All symptomatic patients received implantable cardioverter-defibrillator placement. Five asymptomatic patients (62.5%) were diagnosed with BrS through ECG during febrile illness, and they remained asymptomatic following conservative management involving strict fever control and medication avoidance. Two patients with mixed phenotype (one with long QT syndrome and another with ectopic atrial tachycardia) required antiarrhythmics and one patient received transcatheter ablation for atrial tachycardia to achieve optimal arrhythmia control., Conclusion: Fever plays a significant role in unmasking BrS in children. Asymptomatic children with BrS managed conservatively have a favorable prognosis. Difficult arrhythmia control was found in patients with mixed phenotype., (© 2024 The Author(s). Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited arrhythmia disorder characterized by ventricular arrhythmia triggered by adrenergic stimulation., Case Presentation: A 9-year-old boy presented with convulsions following physical exertion. Bidirectional ventricular tachycardia (VT) during a treadmill test led to the diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT). Genetic testing revealed a pathogenic variant of RYR2:c.720G>A (p.ArG2401His) . Nadolol was initially started. However, he experienced aborted VT arrest three years later. Flecainide was thus added as dual therapy and he underwent left cardiac sympathetic denervation (LCSD). Subsequently, a transvenous implantable cardioverter-defibrillator (ICD) was implanted because he still had several episodes of bidirectional VT. Despite a good compliance to medication, the patient still had exercise induced VT episodes with new onset of atrial fibrillation. High dose nadolol was required and amiodarone was added. Despite maximizing the dosage of these three antiarrhythmics, the patient continued to experience multiple episodes of ventricular fibrillation with appropriate ICD shocks and persistent atrial arrhythmias. Right cardiac sympathetic denervation (RCSD) was performed as the last modality of treatment. Patient had a total elimination of VT post bilateral sympathectomy. He remained asymptomatic on follow up. A follow-up treadmill test showed no recurrence of exercise-induced PVCs and VT., Conclusion: We illustrated the challenges and the complex decision-making process encountered in managing refractory CPVT. In patients unresponsive to conventional therapies, RCSD in additional to LCSD is a safe and effective alternative treatment. A history of LCSD should not preclude physicians from considering RCSD in children with refractory CPVT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Leung, Kwok, Lau, Lee and Tsao.)

Inherited cardiovascular conditions are significant causes of sudden cardiac death in the young (SCDY), making their investigation using molecular autopsy and prevention a public health priority. However, the molecular autopsy data in Chinese population is lacking. The 5-year result (2017-2021) of molecular autopsy services provided for victims of SCDY (age 1-40 years) was reviewed. The outcome of family cascade genetic screening and clinical evaluation was reviewed. A literature review of case series reporting results of molecular autopsy on SCDY in 2016-2023 was conducted. Among the 41 decedents, 11 were found to carry 13 sudden cardiac death (SCD)-causative genetic variants. Likely pathogenic (LP) variants were identified in the DSP, TPM1, TTN, and SCN5A genes. Cascade genetic testing identified four family members with LP variants. One family member with familial TPM1 variant was found to have hypertrophic cardiomyopathy upon clinical evaluation. This study provided insight into the genetic profile of molecular autopsy in a Chinese cohort of SCDY. The detection of important SCD-causative variants through molecular autopsy has facilitated family cascade screening by targeted genetic testing and clinical evaluation of at-risk family members. A literature review of the current landscape of molecular autopsy in the investigation of SCDY was conducted., (© 2024 Wiley Periodicals LLC.)

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) may cause sudden cardiac death (SCD) despite medical therapy. Therefore, implantable cardioverter-defibrillators (ICDs) are commonly advised. However, there is limited data on the outcomes of ICD use in children., Objective: The purpose of this study was to compare the risk of arrhythmic events in pediatric patients with CPVT with and without an ICD., Methods: We compared the risk of SCD in patients with RYR2 (ryanodine receptor 2) variants and phenotype-positive symptomatic CPVT patients with and without an ICD who were younger than 19 years and had no history of sudden cardiac arrest at phenotype diagnosis. The primary outcome was SCD; secondary outcomes were composite end points of SCD, sudden cardiac arrest, or appropriate ICD shocks with or without arrhythmic syncope., Results: The study included 235 patients, 73 with an ICD (31.1%) and 162 without an ICD (68.9%). Over a median follow-up of 8.0 years (interquartile range 4.3-13.4 years), SCD occurred in 7 patients (3.0%), of whom 4 (57.1%) were noncompliant with medications and none had an ICD. Patients with ICD had a higher risk of both secondary composite outcomes (without syncope: hazard ratio 5.85; 95% confidence interval 3.40-10.09; P < .0001; with syncope: hazard ratio 2.55; 95% confidence interval 1.50-4.34; P = .0005). Thirty-one patients with ICD (42.5%) experienced appropriate shocks, 18 (24.7%) inappropriate shocks, and 21 (28.8%) device-related complications., Conclusion: SCD events occurred only in patients without an ICD and mostly in those not on optimal medical therapy. Patients with an ICD had a high risk of appropriate and inappropriate shocks, which may be reduced with appropriate device programming. Severe ICD complications were common, and risks vs benefits of ICDs need to be considered., Competing Interests: Disclosures All authors have no conflicts to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Congenital long QT syndrome (LQTS) is an inherited arrhythmia syndrome associated with sudden cardiac death. Accurate interpretation and classification of genetic variants in LQTS patients are crucial for effective management. All patients with LQTS with a positive genetic test over the past 18 years (2002-2020) in our single tertiary pediatric cardiac center were identified. Reevaluation of the reported variants in LQTS genes was conducted using the American College of Genetics and Genomics (ACMG) guideline after refinement by the US ClinGen SVI working group and guideline by Walsh et al. on genetic variant reclassification, under multidisciplinary input. Among the 59 variants identified. 18 variants (30.5%) were reclassified. A significant larger portion of variants of unknown significance (VUS) were reclassified compared to likely pathogenic (LP)/pathogenic (P) variants (57.7% vs 9.1%, p < 0.001). The rate of reclassification was significantly higher in the limited/disputed evidence group compared to the definite/moderate evidence group (p = 0.0006). All LP/P variants were downgraded in the limited/disputed evidence group (p = 0.0057). VUS upgrades are associated with VUS located in genes within the definite/moderate evidence group (p = 0.0403) and with VUS present in patients exhibiting higher corrected QT intervals (QTc) (p = 0.0445). A significant number of pediatric LQTS variants were reclassified, particularly for VUS. The strength of the gene-disease association of the genes influences the reclassification performance. The study provides important insights and guidance for pediatricians to seek for reclassification of "outdated variants" in order to facilitate contemporary precision medicine., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Precision medicine in paediatric cardiac channelopathy and cardiomyopathy has a rapid advancement over the past years. Compared to conventional gene panel and exome-based testing, whole genome sequencing (WGS) offers additional coverage at the promoter, intronic regions and the mitochondrial genome. However, the data on use of WGS to evaluate the genetic cause of these cardiovascular conditions in children and adolescents are limited., Methods: In a tertiary paediatric cardiology center, we recruited all patients diagnosed with cardiac channelopathy and cardiomyopathy between the ages of 0 and 18 years old, who had negative genetic findings with prior gene panel or exome-based testing. After genetic counselling, blood samples were collected from the subjects and both their parents for WGS analysis., Results: A total of 31 patients (11 cardiac channelopathy and 20 cardiomyopathy) were recruited. Four intronic splice-site variants were identified in three cardiomyopathy patients, which were not identified in previous whole exome sequencing. These included a pathogenic variant in TAFAZZIN:c.284+5G>A (Barth syndrome), a variant of unknown significance (VUS) in MYBPC3:c.1224-80G>A and 2 compound heterozygous LP variants in LZTR1 ( LZTR1:c.1943-256C>T and LZTR1:c1261-3C>G ) in a patient with clinical features of RASopathy. There was an additional diagnostic yield of 1.94% using WGS for identification of intronic variants, on top of conventional gene testing., Conclusion: WGS plays a role in identifying additional intronic splice-site variants in paediatric patients with isolated cardiomyopathy. With the demonstrated low extra yield of WGS albeit its ability to provide potential clinically important information, WGS should be considered in selected paediatric cases of cardiac channelopathy and cardiomyopathy in a cost-effective manner., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Kwok, Kwong, Shi, Shih, Lee, Mak, Chui, Tsao and Chung.)

Background: In severely affected patients with catecholaminergic polymorphic ventricular tachycardia, beta-blockers are often insufficiently protective. The purpose of this study was to evaluate whether flecainide is associated with a lower incidence of arrhythmic events (AEs) when added to beta-blockers in a large cohort of patients with catecholaminergic polymorphic ventricular tachycardia., Methods: From 2 international registries, this multicenter case cross-over study included patients with a clinical or genetic diagnosis of catecholaminergic polymorphic ventricular tachycardia in whom flecainide was added to beta-blocker therapy. The study period was defined as the period in which background therapy (ie, beta-blocker type [beta1-selective or nonselective]), left cardiac sympathetic denervation, and implantable cardioverter defibrillator treatment status, remained unchanged within individual patients and was divided into pre-flecainide and on-flecainide periods. The primary end point was AEs, defined as sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter defibrillator shock, and arrhythmic syncope. The association of flecainide with AE rates was assessed using a generalized linear mixed model assuming negative binomial distribution and random effects for patients., Results: A total of 247 patients (123 [50%] females; median age at start of flecainide, 18 years [interquartile range, 14-29]; median flecainide dose, 2.2 mg/kg per day [interquartile range, 1.7-3.1]) were included. At baseline, all patients used a beta-blocker, 70 (28%) had an implantable cardioverter defibrillator, and 21 (9%) had a left cardiac sympathetic denervation. During a median pre-flecainide follow-up of 2.1 years (interquartile range, 0.4-7.2), 41 patients (17%) experienced 58 AEs (annual event rate, 5.6%). During a median on-flecainide follow-up of 2.9 years (interquartile range, 1.0-6.0), 23 patients (9%) experienced 38 AEs (annual event rate, 4.0%). There were significantly fewer AEs after initiation of flecainide (incidence rate ratio, 0.55 [95% CI, 0.38-0.83]; P =0.007). Among patients who were symptomatic before diagnosis or during the pre-flecainide period (n=167), flecainide was associated with significantly fewer AEs (incidence rate ratio, 0.49 [95% CI, 0.31-0.77]; P =0.002). Among patients with ≥1 AE on beta-blocker therapy (n=41), adding flecainide was also associated with significantly fewer AEs (incidence rate ratio, 0.25 [95% CI, 0.14-0.45]; P <0.001)., Conclusions: For patients with catecholaminergic polymorphic ventricular tachycardia, adding flecainide to beta-blocker therapy was associated with a lower incidence of AEs in the overall cohort, in symptomatic patients, and particularly in patients with breakthrough AEs while on beta-blocker therapy., Competing Interests: Disclosures A.W. is a consultant for ARMGO and LQT Therapeutics. S.S. is a consultant for Cardurion. M.J.A. is a consultant for Abbott, Boston Scientific, Bristol Myers Squibb, Daiichi Sankyo, Invitae, Medtronic, Tenaya Therapeutics, and UpToDate. M.J.A. and the Mayo Clinic are involved in an equity/royalty relationship with AliveCor, Anumana, Thryv Therapeutics, and Pfizer. However, none of these entities were involved in this study. S.P.E. is a consultant for UptoDate and has a relationship with Pfizer. S.C.Y. is a consultant for Boston Scientific and has received research grants from Medtronic and Biotronik. The other authors report no conflicts.

Background: Apple watch-derived electrocardiogram (awECG) may help identify prolongation of corrected QT (QTc) interval. This study aimed to determine its usefulness for assessment of prolongation of QTc interval in children and adolescents with long QT syndrome (LQTS)., Methods: Children and adolescents with and without LQTS were recruited for measurement of QTc intervals based on standard 12-lead (sECG) and awECG lead I, II and V5 tracings. Bland-Altman analysis of reproducibility, concordance assessment of T wave morphologies, and receiver operating characteristic (ROC) analysis of sensitivity and specificity of awECG-derived QTc interval for detecting QTc prolongation were performed., Results: Forty-nine patients, 19 with and 30 without LQTS, aged 3-22 years were studied. The intraclass correlation coefficient was 1.00 for both intra- and inter-observer variability in the measurement of QTc interval. The awECG- and sECG-derived QTc intervals correlated strongly in all three leads (r = 0.90-0.93, all p < 0.001). Concordance between awECG and sECG in assessing T wave morphologies was 84% (16/19). For detection of QTc prolongation, awECG lead V5 had the best specificity (94.4% and 87.5%, respectively) and positive predictive value (87.5% and 80.0%, respectively), and for identification of patients with LQTS, awECG leads II and V5 had the greatest specificity (92.3%-94.1%) and positive predictive value (85.7% to 91.7%) in both males and females., Conclusions: Apple Watch leads II and V5 tracings can be used for reproducible and accurate measurement of QTc interval, ascertainment of abnormal T wave morphologies, and detection of prolonged QTc interval in children and adolescents with LQTS., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Palliation of the single ventricle (SV) circulation is associated with a burden of lifelong complications. Previous studies have identified that the need for a permanent ventricular pacing system (PPM v ) may be associated with additional adverse long-term outcomes., Objectives: The goal of this study was to quantify the attributable risk of PPM v in patients with SV, and to identify modifiable risk factors., Methods: This international study was sponsored by the Pediatric and Congenital Electrophysiology Society. Centers contributed baseline and longitudinal data for functionally SV patients with PPM v . Enrollment was at implantation. Controls were matched 1:1 to PPM v subjects by ventricular morphology and sex, identified within center, and enrolled at matched age. Primary outcome was transplantation or death., Results: In total, 236 PPM v subjects and 213 matched controls were identified (22 centers, 9 countries). Median age at enrollment was 5.3 years (quartiles: 1.5-13.2 years), follow-up 6.9 years (3.4-11.6 years). Median percent ventricular pacing (Vp) was 90.8% (25th-75th percentile: 4.3%-100%) in the PPM v cohort. Across 213 matched pairs, multivariable HR for death/transplant associated with PPM v was 3.8 (95% CI 1.9-7.6; P < 0.001). Within the PPM v population, higher Vp (HR: 1.009 per %; P = 0.009), higher QRS z-score (HR: 1.19; P = 0.009) and nonapical lead position (HR: 2.17; P = 0.042) were all associated with death/transplantation., Conclusions: PPM v in patients with SV is associated with increased risk of heart transplantation and death, despite controlling for increased associated morbidity of the PPM v cohort. Increased Vp, higher QRS z-score, and nonapical ventricular lead position are all associated with higher risk of adverse outcome and may be modifiable risk factors., Competing Interests: Funding Support and Author Disclosures Drs Janousek and Fumanelli were supported by the Ministry of Health, Czech Republic: conceptual development of research organization, Motol University Hospital, Prague, Czech Republic. Dr Balaji has been a medical advisor/consultant to “yoR labs” (stock options). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The author declares no financial interests nor personal relationships which may be considered as potential completing interests.

Background: Several medication choices are available for acute and prophylactic treatment of refractory supraventricular tachycardia (SVT) in infants. There are almost no controlled trials, and medication choices are not necessarily evidence based. Our objective was to report the effectiveness of management strategies for infant SVT., Methods: A registry of infants admitted to hospital with re-entrant SVT and no haemodynamically significant heart disease were prospectively followed at 11 international tertiary care centres. In addition, a systematic review of studies on infant re-entrant SVT in MEDLINE and EMBASE was conducted. Data on demographics, symptoms, acute and maintenance treatments, and outcomes were collected., Results: A total of 2534 infants were included: n = 108 from the registry (median age, 9 days [0-324 days], 70.8% male) and n = 2426 from the literature review (median age, 14 days; 62.3% male). Propranolol was the most prevalent acute (61.4%) and maintenance treatment (53.8%) in the Registry, whereas digoxin was used sparingly (4.0% and 3.8%, respectively). Propranolol and digoxin were used frequently in the literature acutely (31% and 33.2%) and for maintenance (17.8% and 10.1%) ( P < 0.001). No differences in acute or prophylactic effectiveness between medications were observed. Recurrence was higher in the Registry (25.0%) vs literature (13.4%) ( P  < 0.001), and 22 (0.9%) deaths were reported in the literature vs none in the Registry., Conclusion: This was the largest cohort of infants with SVT analysed to date. Digoxin monotherapy use was rare amongst contemporary paediatric cardiologists. There was limited evidence to support one medication over another. Overall, recurrence and mortality rates on antiarrhythmic treatment were low., (© 2021 The Author(s).)

Background: Children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for sudden death, and a risk stratification tool does not exist., Objective: The purpose of this study was to determine whether proband status, age at symptom onset, and/or sex are independent predictors of cardiac events., Methods: A multicenter, ambispective, cohort of pediatric CPVT patients was categorized by sex, proband status, and age at symptom onset (D1: first decade of life [symptom onset <10 years] or D2: second decade of life [symptom onset 10-18 years, inclusive]). Demographics, therapy, genetics, and outcomes were compared between groups., Results: A total of 133 patients were included and stratified into 58 D1 and 75 D2 patients (68 female and 65 male; 106 probands and 27 relatives). Localization of RYR2 variants to hotspots differed based on proband status and age at symptom onset. The cardiac event rate was 33% (n = 44/133), inclusive of a 3% (n = 4/133) mortality rate, over a median of 6 years (interquartile range 3-11) after time of symptom onset. Proband status, rather than age at of symptom onset or sex, was an independent predictor of time to first cardiac event (P = .008; hazard ratio = 4.4). The 5-, 10- and 15-year event-free survival rates for probands were 77%, 56%, and 46%, respectively, and for relatives were 96%, 91%, and 86%, respectively. Event risk after diagnosis was 48% (32/67) in patients on β-blocker or flecainide alone vs 10% (5/48) in patients on β-blocker plus flecainide and/or left cardiac sympathetic denervation (P <.001)., Conclusion: Proband status, but not age at symptom onset or male sex, independently predicted an earlier onset of cardiac events. A larger sample size would enable a comprehensive investigation of other risk factors., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Recent studies have revealed that targeting amino acid metabolic enzymes is a promising strategy in cancer therapy. Acute myeloid leukemia (AML) downregulates the expression of argininosuccinate synthase (ASS1), a recognized rate-limiting enzyme for arginine synthesis, and yet displays a critical dependence on extracellular arginine for survival and proliferation. This dependence on extracellular arginine, also known as arginine auxotrophy, suggests that arginine deprivation would be a treatment strategy for AML. NEI-01, a novel arginine-depleting enzyme, is capable of binding to serum albumin to extend its circulating half-life, leading to a potent anticancer activity. Here we reported the preclinical activity of NEI-01 in arginine auxotrophic AMLs. NEI-01 efficiently depleted arginine both in vitro and in vivo NEI-01-induced arginine deprivation was cytotoxic to arginine auxotrophic AML cells through induction of cell-cycle arrest and apoptosis. Furthermore, the potent anti-leukemia activities of NEI-01 were observed in three different types of mouse models including human cell line-derived xenograft, mouse cell line-derived homografts in syngeneic mice and patient-derived xenograft. This preclinical data provide strong evidence to support the potential use of NEI-01 as a therapeutic approach in AML treatment., (©2021 American Association for Cancer Research.)

Objectives: The primary goal of this study was to evaluate the implant experience and midterm results of subcutaneous implantable cardioverter-defibrillators (S-ICDs) in pediatric patients and those with congenital heart disease., Background: The S-ICD was developed to avoid the lead-related complications associated with transvenous systems. The absence of intravascular or intracardiac components offers potential advantages to pediatric patients and those with congenital heart disease., Methods: This international, multicenter, retrospective, standard-of-care study was conducted through the Pediatric & Congenital Electrophysiology Society. Complications at 30 and 360 days, inappropriate shocks, and delivery of appropriate therapy were assessed., Results: The study included 115 patients with a median follow-up of 32 (19 to 52) months. Median age was 16.7 years (14.8 to 19.3 years), 29% were female, and 55% had a primary prevention indication. Underlying disease substrate was cardiomyopathy (40%), structural heart disease (32%), idiopathic ventricular fibrillation (16%), and channelopathy (13%). The complication rate was 7.8% at 30 days and 14.7% at 360 days. Overall, inappropriate shocks occurred in 15.6% of patients, with no single clinical characteristic reaching statistical significance. At implant, 97.9% of patients had successful first shock conversion with 96% requiring ≤65 J. Appropriate therapy was delivered to 11.2% of patients with an annual incidence of 3.9% and an acute first shock conversion success rate of 92.5%., Conclusions: This study found that in a heterogeneous population of pediatric patients and those with congenital heart disease, the S-ICD had comparable rates of complications, inappropriate shocks, and conversion efficacy compared with previously published studies on transvenous systems in similar populations., Competing Interests: Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. All rights reserved.)

Objectives: Milrinone is an inodilator widely used in the postoperative management of children undergoing cardiac surgery. The literature supporting its inotropic effect is sparse. We sought to study the effect of milrinone on the vasculature and its effects on the ventricular function using wave intensity analysis. We also intended to evaluate the feasibility of using wave intensity analysis by the bedside., Design: prospective single-center observational study., Setting: PICU of a tertiary children's hospital., Patients: Children (< 18 yr) admitted to PICU following cardiac surgery who required to be commenced on a milrinone infusion., Interventions: Echocardiography and Doppler ultrasound assessments for wave intensity analysis were performed prior to commencing milrinone and 4-6 hours after milrinone infusion., Measurements and Main Results: Wave intensity analysis was successfully performed and analyzed in 15 of 16 patients (94%). We identified three waves-a forward compression wave, backward compression wave, and forward decompression wave. The waves were described with their cumulative intensity and wave-related pressure change. There was a 26% reduction in backward compression wave cumulative intensity following the introduction of milrinone. Other variables (backward compression wave cumulative intensity/forward compression wave cumulative intensity ratio, backward compression wave wave-related pressure change, backward compression wave wave-related pressure change/forward compression wave wave-related pressure change ratio) consistent with vasodilation also decreased after milrinone. It also decreased the vascular wavespeed by 7.1% and increased the distensibility of the vessels by 14.6%. However, it did not increase forward compression wave cumulative intensity, a variable indicating the systolic force generated by the ventricle. Forward decompression wave cumulative intensity indicating ventricular early diastolic relaxation also did not change., Conclusions: In a cohort of children recovering in PICU after having undergone cardiac surgery, we found that milrinone acted as a vasodilator but did not demonstrate an improvement in the contractility or an improved relaxation of the left ventricle as assessed by wave intensity analysis. We were able to demonstrate the feasibility and utility of wave intensity analysis to further understand ventriculo-vascular interactions in an intensive care setting.

WHAT IS KNOWN ON THE SUBJECT?: Many Western countries have abandoned the wearing of nurse uniforms on inpatient mental health wards. The adoption of a non-uniform policy in Hong Kong was recently introduced in select rehabilitation units to align with the philosophy of the recovery model. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: The findings suggest that nurses perceived wearing non-uniform might help to reduce the self-stigma of service users and develop better self-esteem. The perceived potential benefits of the introduction of a non-uniform policy seemed to outweigh the perceived drawbacks. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The results further acknowledge the potential positive effects of nurses wearing non-uniform on facilitating psychiatric service users' recovery process. However, further research on service users' perspectives is required. The wearing of non-uniform may be considered to be extended to other psychiatric wards in Hong Kong and other similar Asian settings in order to potentially help promote patient's recovery and to reduce emotional distance between staff and service users. ABSTRACT: Introduction A non-uniform policy was recently adopted in selected Hong Kong rehabilitation wards to align with the philosophy of the recovery model. The change in policy is relatively novel in Asia, where no previous studies have reported how this may influence nursing care and service users' recovery. Aim To explore Hong Kong Mental Health Nurses' views about wearing non-uniform within an inpatient rehabilitation unit in regard to facilitating service users' recovery process. Method A qualitative descriptive study was conducted, utilizing individual in-depth semi-structured research interviews. Results A total of 12 interviews were conducted with nurse participants. The analysis process identified 3 main themes and 9 subthemes. Main themes were "building up rapport with service users," "non-uniform helps deinstitutionalization" and "different approaches to maximize the benefit and to minimize the risk." Discussion Despite some concerns, the majority of nurse participants positively viewed the policy of wearing non-uniform and felt it was potentially beneficial to service users' recovery process. Implications for practice Nurses perceived that wearing non-uniform may facilitate meaningful therapeutic engagement, and may help to reduce the self-stigma and develop the self-esteem of service users. Other inpatient units in Hong Kong and similar Asian settings might consider adopting the policy., (© 2020 John Wiley & Sons Ltd.)

L-arginine (L-Arg) depletion induced by randomly PEGylated arginine deiminase (ADI-PEG20) can treat arginosuccinate synthase (ASS)-negative cancers, and ADI-PEG20 is undergoing phase III clinical trials. Unfortunately, ASS-positive cancers are resistant to ADI-PEG20. Moreover, the yield of ADI production is low because of the formation of inclusion bodies. Here, we report a thermostable arginine-depleting enzyme, Bacillus caldovelox arginase mutant (BCA-M: Ser 161 ->Cys 161 ). An abundant amount of BCA-M was easily obtained via high cell-density fermentation and heat treatment purification. Subsequently, we prepared BCA-M-PEG20, by conjugating a single 20 kDa PEG monomer onto the Cys 161 residue via thio-chemistry. Unlike ADI-PEG20, BCA-M-PEG20 significantly inhibited ASS-positive lung cancer cell growth. Pharmacodynamic studies showed that a single intraperitoneal injection (i.p). administration of 250 U/mouse of BCA-M-PEG20 induced low L-Arg level over 168 h. The mono-PEGylation of BCA-M prolonged its elimination half-life from 6.4 to 91.4 h (a 14-fold increase). In an A549 lung cancer xenograft model, a weekly administration of 250 U/mouse of BCA-M-PEG20 suppressed tumor growth significantly. We also observed that BCA-M-PEG20 did not cause any significant safety issue in mouse models. Overall, BCA-M-PEG20 showed excellent results in drug production, potency, and stability. Thereby, it has great potential to become a promising candidate for lung cancer therapy.

Arginine deprivation cancer therapy targets certain types of malignancies with positive result in many studies and clinical trials. NEI-01 was designed as a novel arginine-depleting enzyme comprising an albumin binding domain capable of binding to human serum albumin to lengthen its half-life. In the present work, NEI-01 is shown to bind to serum albumin from various species, including mice, rat and human. Single intraperitoneal administration of NEI-01 to mice reduced plasma arginine to undetectable level for at least 9 days. Treatment of NEI-01 specifically inhibited cell viability of MIA PaCa-2 and PANC-1 cancer cell lines, which were ASS1 negative. Using a human pancreatic mouse xenograft model, NEI-01 treatment significantly reduced tumor volume and weight. Our data provides proof of principle for a cancer treatment strategy using NEI-01., Competing Interests: All the authors (JPHC, YC, DTLC, SHKC, KCC, KYN, OML, RMHW, AWLL, YOL, SYK), except YCL, are employees of New Epsilon Innovation Limited. There are no related patents, products in development, or marketed products to declare. This does not alter the authors’ adherence to all PLOS ONE policies on sharing data and materials.

Background: The use of high-density electroanatomical mapping in the Chinese population for congenital heart disease (CHD) is not well reported., Methods: Retrospective review of consecutive transcatheter ablation of atrial tachyarrhythmia using high-density mapping for CHD patients (at least moderate complexity) in the only tertiary congenital heart center in the territory from January 2017 to January 2019 was conducted. Orion mapping catheter in Rhythmia system (Boston Scientific) was used to create activation and voltage maps. Parameters including mechanism of arrhythmia, acute success, and follow-up data were recorded., Results: Eight patients were identified (median age 35.5 years) who underwent transcatheter ablation of atrial arrhythmia. More than one reentry circuits of IART were identified in five patients. It took a median of 32.4 minutes with 15,952 (IQR 13,395-18,530) mapping points per map. Cavo-annulus isthmus-dependent mechanism was the predominant reentry mechanism. Acute success with the elimination of all inducible tachycardia was achieved in six patients (75%), and partial success in two patients. There was recurrence of atrial arrhythmia in four patients (50%), in which three patients could be maintained in sinus rhythm with low-dose antiarrhythmic medication. Targeted substrate ablation was performed in six patients with multiple IART circuits. Critical anatomical pouches were identified in three patients, which were missed in the initial mapping using Orion basket mapping catheter., Conclusions: High acute success rate of atrial arrhythmia ablation can be achieved using high-density anatomical mapping in CHD. Substrate ablation was required with multiple IART circuits identified. Vigilance should be sought to identify anatomical pouches., Competing Interests: Authors declare no conflict of interests for this article., (© 2019 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Heart Rhythm Society.)

In this article, we problematize the concept of "culture" in genetic counseling. With globalization and increased mobility of both genetic professionals and clients, there is an increased acknowledgement of the impact of "culture" on a counseling process. There is, however, little agreement on what "culture" is. The essentialist understanding that has long been dominant in the medical literature views culture as a set of shared beliefs, attitudes and practices among a group of people. Such an approach does not account for the individual differences and the dynamic nature of genetic counseling encounters. Following Zayts and Schnurr (2017), we use the distinction between two orders of culture: culture 1 that refers to the static, generalized understanding of culture that is external to the specific context, and culture 2 , an analytic concept that denotes dynamic enactments of culture, emerging in the interaction. We use empirical data from genetic counseling sessions to illustrate these different facets of culture and to consider how and why speakers draw on them. The clinical implications of the study include highlighting the importance of cultural awareness among counselors, including cultural self-awareness, and demonstrating how authentic interactional data could be used to enhance cultural training in genetic counseling., (© 2019 Wiley Periodicals, Inc.)

There is paucity of long-term data on adult survivors after biventricular repair of pulmonary atresia with intact ventricular septum (PAIVS) and pulmonary stenosis (PS). This study aimed to determine the cardiac and non-cardiac outcomes of adult survivors after biventricular repair of PAIVS and PS. The cardiac, neurodevelopmental and liver problems of 111 adults, 40 with PAIVS and 71 with PS, were reviewed. The median follow-up duration of our patients was 26.5 years (range 14.8-55 years). The freedom from reintervention at 30 years was 17.4% and 73.3% for PAIVS and PS patients (p < 0.001), respectively. Compared with PS patients, PAIVS patients had significantly greater prevalence of right atrial and right ventricular (RV) dilatation, and moderate to severe tricuspid and pulmonary regurgitation (all p < 0.05), and cardiac arrhythmias (22.5% vs. 8.5%, p = 0.047). The freedom from development of cardiac arrhythmias at 30 years of 68.4% and 91.6%, respectively, in PAIVS and PS patients (p = 0.03). Cox proportional hazards model identified PAIVS as an independent risk factor for reintervention (HR 4.0, 95% CI 2.1-7.6, p < 0.001) and development of arrhythmias (HR 4.1, 95% CI 1.1-14.4, p = 0.03). Neurodevelopmental problems were found in 17.5% of PAIVS patients and 7.0% of PS patients (p = 0.11). Liver problems occurred in 2 (5%) PAIVS patients, both of whom required conversion to 1.5 ventricular repair. In conclusion, long-term problems, including the need for reinterventions, cardiac arrhythmias, RV dilation, pulmonary regurgitation, and neurodevelopmental and liver issues are more prevalent in adult PAIVS than PS survivors.

Introduction: Congenital long QT syndrome (LQTS) is a genetically transmitted cardiac channelopathy that can lead to sudden cardiac death. This study aimed to report the clinical and genetic characteristics of all young patients diagnosed with LQTS in the only tertiary paediatric cardiology centre in Hong Kong., Methods: This is a retrospective review of all paediatric and young adult patients diagnosed at our centre with LQTS from January 1997 to December 2016. The diagnosis of LQTS was established with a corrected QT interval (QTc) ≥480 ms, Schwartz score of >3 points, or the presence of a pathogenic mutation., Results: Fifty-nine patients (33 males) from 52 families were included, with a mean age of 8.17 years (range, 0.00-16.95 years) at presentation. Five patients had concomitant congenital heart diseases. The mean follow-up duration was 5.33 ± 4.65 years. The mean QTc in the cohort was 504 ± 47 ms. They presented with syncope and convulsion (49%), cardiac arrest (10%), bradycardia and neonatal atrioventricular block (12%). Fifteen (25%) patients were asymptomatic at diagnosis. Thirty-eight (64.4%) patients were confirmed to have a pathogenic mutation for LQTS genes. Forty-five (76.3%) patients received beta blocker therapy. Thirteen (22.0%) patients required implantable cardioverter defibrillator. There was no mortality in the study period. The 1-, 5-, and 10-year breakthrough cardiac event-free rates were 93.0%, 80.7%, and 72.6%, respectively., Conclusion: Identification of the disorder, administration of beta blockers, and lifestyle modification can prevent subsequent cardiac events in LQTS. Genotyping in patients with LQTS is essential in guiding medical therapy and improving prognosis.

Aims: To clarify the clinical characteristics and outcomes of children with SCN5A-mediated disease and to improve their risk stratification., Methods and Results: A multicentre, international, retrospective cohort study was conducted in 25 tertiary hospitals in 13 countries between 1990 and 2015. All patients ≤16 years of age diagnosed with a genetically confirmed SCN5A mutation were included in the analysis. There was no restriction made based on their clinical diagnosis. A total of 442 children {55.7% boys, 40.3% probands, median age: 8.0 [interquartile range (IQR) 9.5] years} from 350 families were included; 67.9% were asymptomatic at diagnosis. Four main phenotypes were identified: isolated progressive cardiac conduction disorders (25.6%), overlap phenotype (15.6%), isolated long QT syndrome type 3 (10.6%), and isolated Brugada syndrome type 1 (1.8%); 44.3% had a negative electrocardiogram phenotype. During a median follow-up of 5.9 (IQR 5.9) years, 272 cardiac events (CEs) occurred in 139 (31.5%) patients. Patients whose mutation localized in the C-terminus had a lower risk. Compound genotype, both gain- and loss-of-function SCN5A mutation, age ≤1 year at diagnosis in probands and age ≤1 year at diagnosis in non-probands were independent predictors of CE., Conclusion: In this large paediatric cohort of SCN5A mutation-positive subjects, cardiac conduction disorders were the most prevalent phenotype; CEs occurred in about one-third of genotype-positive children, and several independent risk factors were identified, including age ≤1 year at diagnosis, compound mutation, and mutation with both gain- and loss-of-function.

Objective: In our previous study, the prevalence of childhood masked hypertension was 11%. This study aims to assess the left ventricular mass index of persistent masked hypertension and determine the factors of elevated left ventricular mass index in Hong Kong Chinese adolescents from a community cohort., Design: Community prospective cohort study, follow-up of a case-control study in community., Subjects: Patients with masked hypertension at baseline were invited to recheck ambulatory blood pressure for the persistence of masked hypertension., Results: A total of 144 out of 165 patients with masked hypertension in the 2011/2012 ambulatory blood pressure survey consented to participate in the study. In all, 48 patients were found to have persistent masked hypertension by ambulatory blood pressure rechecking and were matched with normotensive controls by sex, age, and body height. The left ventricular mass (117.3±39.9 g versus 87.0±28.2 g versus 102.0±28.2 g) and left ventricular mass index (30.1±8.4 g/m2.7 versus 23.9±6.3 g/m2.7 versus 25.1±5.7 g/m2.7) were significantly higher in the persistent masked hypertension group (p<0.0001) compared with the patients without persistent masked hypertension and controls. In multivariate linear regression analysis, left ventricular mass index was found to be higher in male gender (β=4.874, p<0.0001) and the patients with persistent masked hypertension (β=2.796, p=0.003). In addition, left ventricular mass index was positively associated with body mass index z-score (β=3.045, p<0.0001) and low-density lipoprotein cholesterol concentration (β=1.634, p=0.015)., Conclusions: Persistent masked hypertension in adolescents is associated with elevated left ventricular mass index.

Background: Emerging data suggest impaired biventricular function in adults late after repair of ventricular septal defect (VSD). We assessed and compared right (RV) and left ventricular (LV) mechanics in adolescents and adults after surgical closure of doubly committed subarterial and perimembranous VSDs., Methods: A total of 75 subjects were studied: 29 patients after subarterial VSD repair (group I), 17 patients after perimembranous VSD repair (group II) and 29 age-matched controls (group III). RV and LV mechanics were assessed using tissue Doppler and speckle-tracking echocardiography, while RV outflow systolic function was quantified by systolic excursion and fractional shortening (FS)., Results: Compared with group III, groups I and II had significantly reduced tricuspid annular systolic and diastolic velocities, isovolumic myocardial acceleration, RV global longitudinal systolic and diastolic deformation parameters and RV outflow systolic excursion (all P < .05). Group I, but not II, had reduced RV outflow FS (P = .008) and the lowest global LV longitudinal systolic strain (P = .008) and systolic strain rate (P = .014). In group I, postoperative aortic regurgitation was associated with lower LV longitudinal systolic strain (P = .009) and early diastolic strain rate (P = .002), while right bundle branch block was associated with lower RV systolic strain rate (P = .048). As a group, RV outflow excursion (P < .001) and FS (P = .001) were correlated with LV global systolic strain., Conclusion: Adolescents and adults late after repair of subarterial and perimembranous VSDs show impairment of RV systolic and diastolic myocardial deformation. The RV outflow function and LV systolic deformation appear to be worse after repair of subarterial defects., (© 2017 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Due to its availability, atenolol is the primary beta-blocker used in Australia for children with long QT syndrome. There is limited data on long-term follow-up of its use., Methods: A single-tertiary-center, retrospective, observational study investigating all children and adolescents who had genetically proven long QT syndrome type 1 (LQT1) and type 2 (LQT2) was conducted. Their pretreatment exercise tests were evaluated for QTc intervals into the recovery phase of exercise., Results: Eighty six patients were identified (LQT1, 67, and LQT2, 19) from 2004 to 2014. The majority (86%) of patients were initially referred for family screening. Atenolol was administered at a mean dose of 1.58 ± 0.51 mg/kg/day. During the median follow-up period of 4.29 years, only one proband developed ventricular arrhythmia whilst taking atenolol, No patient had cardiac arrest or aborted cardiac arrest. With respect to side effects of atenolol, only two patients had intolerable side effects necessitating changes of medication. Evaluation of exercise tests (pretreatment) demonstrated that corrected QT (QTc) intervals at 2-3 min into the recovery phase of exercise were significantly prolonged for LQT1 patients. LQT1 patients with transmembrane mutation had longer QTc intervals than their C-terminus mutation counterparts, reaching statistical significance at 3 min into the recovery phase of exercise., Conclusions: Atenolol is an effective treatment for genetically proven LQT1 and LQT2 children and adolescents, with good tolerability. In LQT1 patients, QTc intervals at 2-3 min into the recovery phase of exercise were significantly prolonged, particularly in patients with transmembrane mutations.

Background and Objective: Our previous study showed that liver graft injury not only promotes tumor recurrence, but also induces chemoresistance in recurrent HCC after liver transplantation. Recently, we found that the hemoglobin-based oxygen carrier"YQ23" significantly ameliorates hepatic IR injury and prevent tumor recurrence. Here, we intended to explore the novel therapeutic strategy using oxygen carrier "YQ23"to sensitize chemotherapy in HCC., Methods: To investigate the role of YQ23 combined with Cisplatin, the proliferation of HCC cells was examined under combined treatment by MTT and colony formation. To explore the effect of YQ23 on sensitization of Cisplatin based chemotherapy, the orthotopic liver cancer model was established. To characterize the delivery of YQ23 in tumor tissue, the intravital imaging system was applied for longitudinal observation in ectopic liver cancer model. The distribution of YQ23 was examined by IVIS spectrum., Results: YQ23 significantly suppressed the proliferation of HCC cells under Cisplatin treatment in a dose and time dependent manner. Moreover, YQ23 administration significantly sensitized Cisplatin based chemotherapy in orthotopic liver cancer model. Down-regulation of DHFR may be one of the reasons for YQ23 sensitizing Cisplatin based chemotherapy. Real-time intravital imaging showed that YQ23 accumulated in the tumor tissue and maintained as long as 3 days in ectopic liver cancer model. The IVIS spectrum examination showed that YQ23 distributed mainly at liver and bladder within the first 36 hours after administration in orthotopic liver cancer model., Conclusion: YQ23 treatment may be a potential therapeutic strategy to sensitize chemotherapy in HCC., Competing Interests: CONFLICTS OF INTEREST The YQ23 product is provided by New β Innovation Limited.

Introduction: Colonic stenting has evolved to be an alternative to emergency laparotomy in the management of acute left-sided malignant colonic obstruction. This retrospective comparative study aimed to review the outcomes of colonic stent as bridge to surgery with emergency operation in a regional hospital in Hong Kong., Method: Consecutive patients who were admitted from January 2006 to July 2014 with diagnosis of malignant left-sided colonic obstruction (from splenic flexure to rectosigmoid colon) were included. Patients with peritonitis or disseminated disease were excluded. Colonic stenting was attempted in all eligible patients when fluoroscopy was available in the endoscopy suite during office hour. Otherwise, emergency operation was performed. For patients with clinical success in colonic stenting, interval colectomies were performed. The postoperative outcomes, including the 30-days mortality, the stoma creation rate, the complication rate as well as the survival data were analyzed on an intention-to-treat (ITT) basis., Results: From January 2006 to July 2014, 62 patients underwent colonic stenting and 40 patients underwent emergency operations. The technical success rate and the clinical success rate of stenting were 95.2 and 83.9 %, respectively. Laparoscopic resection was achieved in 74.2 % in the stenting group. More primary anastomoses were performed in the stenting group (71.0 vs. 27.5 %, p = 0.000). The stenting group had a significantly lower permanent stoma rate (16.1 vs. 52.5 %, p < 0.000), fewer Dindo grade III to IV postoperative morbidity (16.1 vs. 40 %, p = 0.007), and the 30-day mortality rate was lower (3.2 vs. 17.5 %, p = 0.018), translating into a better overall 5-year survival rate. The disease-free survival was comparable between the two groups., Conclusions: Colonic self-expanding metal stent is effective in the management of acute left-sided colonic obstruction. It is associated with reduced stoma creation rate and postoperative morbidity. The oncological safety is not jeopardized by stenting and the interval operation.

Background: To overcome the problems of previously reported hemoglobin-based oxygen carriers, we developed a stabilized nonpolymeric cross-linked tetrameric hemoglobin solution (YQ23). The aims of this study were to investigate the oxygen carrying and releasing properties of this novel hemoglobin-based oxygen carrier and to determine whether it has beneficial effects for hemorrhagic shock., Methods: Using a hemorrhagic shock model in Sprague-Dawley rats and mini-pigs, we tested the effects of infusing 0.1, 0.3, and 0.5 g/kg YQ23 on animal survival, tissue oxygen delivery (DO 2 ) and consumption (VO 2 ), hemodynamics parameters, and liver, renal, and cardiac function., Results: YQ23 infusion increased the survival rate of rats and pigs with severe hemorrhagic shock in a dose-dependent manner. Moreover, it improved the hemodynamic parameters, cardiac output, DO 2 and VO 2 , and the mitochondrial respiratory function of vital organs. Among the three doses of YQ23, 0.5 gHb/kg YQ23 achieved a similar beneficial effect as whole blood., Conclusions: This study indicated that the novel cross-linked tetrameric hemoglobin YQ23 has good oxygen carrying and releasing properties and exhibits beneficial effects on hemorrhagic shock in rats and pigs by improving the oxygen carrying and delivery function of blood, which maintains organ function., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Using data collected over a 1-year period on a stratified random sample of 368 parents with children studying in nurseries (mean age=3.97years), this study assessed the predictive effects of parental corporal punishment, parental psychological aggression, preschoolers' altruism, and preschoolers' forgiveness on preschoolers' anxiety symptoms in Hong Kong, China. Results of hierarchical regression analyses showed that parental psychological aggression, preschoolers' altruism and preschoolers' forgiveness at Time 1 significantly predicted preschoolers' anxiety at Time 2, when controlling for the initial level of preschoolers' anxiety and important demographic variables that co-vary with preschoolers' anxiety. Moreover, preschoolers' altruism moderated the predictive effect of parental psychological aggression on preschoolers' anxiety symptoms. The study has several significant contributions. First, the study supports the predictive effect of parental aggressive discipline on preschoolers' anxiety. Second, we provide evidence that preschoolers' altruism and forgiveness negatively predict preschoolers' anxiety symptoms. Third, preschoolers' altruism and forgiveness are shown to protect them against parental psychological aggression. A dual-focus approach to intervention and prevention is proposed to reduce aggressive discipline by parents as well as to enhance altruism and forgiveness in children. Parent training programs could be provided to teach parents positive discipline strategies. Home-based or school-based interventions could be designed for preschool children to foster and enhance their altruism and forgiveness., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

This study tested the model of suicidal ideation, incorporating family and personal factors to predict suicidal ideation with hopelessness as a mediating factor in the Hong Kong sample, to a sample in Shanghai. Using MGSEM, the study aims to investigate the personal correlates and the family correlates of suicidal ideation in Hong Kong and Shanghai adolescents. We integrated the family ecological and diathesis-stress-hopelessness models of suicidal ideation in connecting the correlates. A cross-sectional design was used. The full model achieved metric invariance and partial path-loading invariance. Family functioning and social problem solving negatively predicted hopelessness or suicidal ideation in both the Hong Kong and Shanghai adolescents. The results supported an integrative approach in facilitating parent-adolescent communication and strengthening family functioning, and reducing the use of negative social problem-solving styles in adolescent suicide prevention.

Purpose: Adjunct chemoradiation is offered to unresectable esophageal squamous cell carcinoma (ESCC) patients, while its use is limited in tumors with strong resistance. Oxygen carriers or anti-hypoxic drugs belong to an emerging class of regulators that can alleviate tumor hypoxia., Methods: We investigate the potential use of a novel oxygen carrier YQ23 in sensitizing chemoresistant ESCC in a series of subcutaneous tumor xenograft models developed using ESCC cell lines with different strengths of chemosensitivities., Results: Tumor xenografts were developed using SLMT-1 and HKESC-2 ESCC cell lines with different strengths of resistance to two chemotherapeutic drugs, 5-fluorouracil and cisplatin. More resistant SLMT-1 xenografts responded better to YQ23 treatment than HKESC-2, as reflected by the induced tumor oxygen level. YQ23 sensitized SLMT-1 xenografts toward 5-fluorouracil via its effect on reducing the level of a hypoxic marker HIF-1α. Furthermore, a derangement of tumor microvessel density and integrity was demonstrated with a concurrent decrease in the level of a tumor mesenchymal marker vimentin. Similar to the 5-fluorouracil sensitizing effect, YQ23 also enhanced the response of SLMT-1 xenografts toward cisplatin by reducing the tumor size and the number of animals with invasive tumors. Chemosensitive HKESC-2 xenografts were irresponsive to combined YQ23 and cisplatin treatment., Conclusions: In all, YQ23 functions selectively on chemoresistant ESCC xenografts, which implicates its potential use as a chemosensitizing agent for ESCC patients.

The study investigated the relationship among physical abuse, positive psychological factors including emotional competence and social problem-solving, and suicidal ideation among adolescents in China. The possible moderating effects of emotional competence and social problem-solving in the association between physical abuse and adolescent suicidal ideation were also studied. A cross-sectional survey employing convenience sampling was conducted and self-administered questionnaires were collected from 527 adolescents with mean age of 14 years from the schools in Shanghai. Results showed that physical abuse was significantly and positively related to suicidal ideation in both male and female adolescents. Emotional competence was not found to be significantly associated with adolescent suicidal ideation, but rational problem-solving, a sub-scale of social problem-solving, was shown to be significantly and negatively associated with suicidal ideation for males, but not for females. However, emotional competence and rational problem-solving were shown to be a significant and a marginally significant moderator in the relationship between physical abuse and suicidal ideation in females respectively, but not in males. High rational problem-solving buffered the negative impact of physical abuse on suicidal ideation for females. Interestingly, females with higher empathy and who reported being physically abused by their parents have higher suicidal ideation. Findings are discussed and implications are stated. It is suggested to change the attitudes of parents on the concept of physical abuse, guide them on appropriate attitudes, knowledge and skills in parenting, and enhance adolescents' skills in rational problem-solving., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Previous research showed an association among perceived stigma, perceived caregiving burden and marital satisfaction of mothers. However, little is known about their relationship among mothers of young children with disabilities in the Chinese context. The mediating role of perceived caregiving burden between perceived stigma and marital satisfaction was seldom explored. Hence, the present study aims to investigate the relationship between perceived stigma, perceived caregiving burden and marital satisfaction of Chinese mothers of children with intellectual disabilities or autism spectrum disorders in Hong Kong., Methods: A cross-sectional survey using convenience sampling was conducted with mothers of pre-school children with disabilities aged from 2 to 6. A total of 160 completed questionnaires were collected from five special child care centres in Hong Kong., Results: The findings in the hierarchical regression analyses showed that perceived stigma and perceived caregiving burden were significant predictors of mothers' marital satisfaction. Perceived burden, including perceived social burden, emotional burden and developmental burden but excluding time-dependence and physical burden, were found to be significant mediators between perceived stigma and marital satisfaction., Conclusion: To address the negative consequences brought on by stigma, measures can be taken to prevent stigmatisation and minimise the harmful effects. To alleviate mothers' perceived burden, Acceptance and Commitment Therapy, mutual support groups and psycho-educational and skills training programmes can be conducted for the mothers., (© 2014 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

Techniques for introducing foreign molecules and materials into living cells are of great value in cell biology research. A major barrier for intracellular delivery is to cross the cell membrane. Here we demonstrate a novel platform utilizing diamond nanoneedle arrays to facilitate efficient vector-free cytosolic delivery. Using our technique, cellular membrane is deformed by an array of nanoneedles with a force on the order of a few nanonewtons. We show that this technique is applicable to deliver a broad range of molecules and materials into different types of cells, including primary neurons in adherent culture. Especially, for delivering plasmid DNAs into neurons, our technique produces at least eightfold improvement (~45% versus ~1-5%) in transfection efficiency with a dramatically shorter experimental protocol, when compared with the commonly used lipofection approach. It is anticipated that our technique will greatly benefit basic research in cell biology and also a wide variety of clinical applications.

Background: Surgical therapies are the first-line treatments for hepatocellular carcinoma (HCC) patients. However, the high incidence of tumor metastasis after liver surgery remains a severe problem. We aim to investigate the roles and the underlying mechanism of YQ23, stabilized non-polymeric diaspirin cross-linked tetrameric hemoglobin, in liver tumor metastasis after major hepatectomy and partial hepatic ischemia reperfusion (I/R) injury., Methods: An orthotopic liver tumor model in Buffalo rat was established using the hepatocellular carcinoma cell line McA-RH7777. Major hepatectomy for tumor-bearing lobe and partial hepatic I/R injury were performed at two weeks after orthotopic liver tumor implantation. YQ23 (0.2 g/kg) was administered at 1 hour before ischemia and immediately after reperfusion. Blood samples were collected at day 0, 1, 7, 14, 21 and 28 for detection of circulating endothelial progenitor cells (EPCs) and regulatory T cells (Tregs)., Results: Our results showed that YQ23 treatment effectively inhibited intrahepatic and lung metastases together with less tumor angiogenesis at 4 weeks after major hepatectomy and partial hepatic I/R injury. The levels of circulating EPCs and Tregs were significantly decreased in YQ23 treatment group. Furthermore, YQ23 treatment also increased liver tissue oxygenation during hepatic I/R injury. Up-regulation of HO1 and down-regulation of CXCR3, TNF-α and IL6 were detected after YQ23 treatment., Conclusions: YQ23 treatment suppressed liver tumor metastasis after major hepatectomy and partial hepatic I/R injury in a rat liver tumor model through increasing liver oxygen and reducing the populations of circulating EPCs and Tregs.

Aims: To explore the relationship among perceived family functioning, emotional competence and suicidal ideation and to examine the moderating role of emotional competence in suicidal ideation., Background: Previous studies have highlighted that poor family relationships and emotional symptoms are significant predictors of suicidal ideation. However, the roles of perceived family functioning and emotional competence in predicting suicidal ideation have not been given adequate attention., Design: A cross-sectional survey using convenience sampling., Method: A questionnaire was administered to 302 university students from February-April in 2011 in Hong Kong. The means, standard deviations and Cronbach's alphas of the variables were computed. Pearson correlation analyses and hierarchical regression analyses were performed., Results: Hierarchical regression analyses showed that perceived high family functioning and emotional competence were significant negative predictors of suicidal ideation. Further analyses showed that parental concern, parental control and creative use of emotions were significant predictors of suicidal ideation. Emotional competence, specifically creative use of emotions, was found to moderate the relationship between perceived family functioning and suicidal ideation., Conclusion: The findings support the family ecological framework and provide evidence for emotional competence as a resilience factor that buffers low family functioning on suicidal ideation. Suggested measures to decrease suicidal ideation include enhancing parental concern, lessening parental control, developing students' awareness, regulation and management of their own emotions, fostering empathy towards others' emotional expression, enhancing social skills in sharing and influencing others' emotions and increasing the positive use of emotions for the evaluation and generation of new ideas., (© 2013 John Wiley & Sons Ltd.)

Catecholamine-associated cardiomyopathies caused by neuroblastoma have rarely been reported. We are reporting 2 cases of neuroblastoma associated with hypertension and severe cardiomyopathic changes in different extremes. One case was dilated cardiomyopathy with heart failure, and the other showed echocardiographic features simulating hypertrophic obstructive cardiomyopathy. Both girls had high levels of urine catecholamines on presentation. Anthracycline group of chemotherapy was avoided. Chemotherapy and tumor resection resulted in successful normalization of blood pressure and regression of cardiomyopathic changes. Blood pressure and cardiomyopathic changes should be monitored not only at presentation, but also during the treatment for neuroblastoma.

The present study examined the relationship among physical abuse, psychological abuse, perceived family functioning and adolescent suicidal ideation in Shanghai, China. Perceived family functioning was investigated as a possible moderator between physical abuse, psychological abuse and suicidal ideation. A cross sectional survey using convenience sampling was conducted. A total of 560 valid self-administered questionnaires were completed by the students aged from 12 to 17 in Shanghai. Descriptive statistical analyses, Pearson correlations analyses, and hierarchical regression analyses were adopted as methods of data analyses. Results indicated that physical abuse was significantly associated with greater adolescent suicidal ideation, while a higher level of perceived family functioning was significantly associated with lower suicidal ideation. However, psychological abuse was not associated with suicidal ideation. Perceived family functioning was shown to be a moderator between physical abuse and suicidal ideation. Specifically, mutuality and family communication moderated the relationship between physical abuse and suicidal ideation. To decrease adolescent suicidal ideation, measures are suggested to prevent physical abuse and enhance family functioning. First, it is important to increase the parents' awareness of the meaning and boundaries of physical abuse, as well as the role it plays in contributing to adolescent suicidal ideation. Second, parents should be taught appropriate parenting skills and knowledge and be guided to treat the children as individuals with their unique personality, rights and privileges. Third, it is important to promote family harmony, effective communication as well as mutual trust, concern and understanding among family members., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: Resting heart rate (RHR) is increasingly recognised as a prognostic marker for long term cardiovascular outcomes in adults. This study assessed associations of RHR with blood pressure (BP), anthropometry and exercise in a large representative sample of Hong Kong children., Study Design, Setting and Subjects: A territory-wide growth survey carried out in 2005-2006 included students sampled from each of Hong Kong's 18 districts. RHR and BP were measured by validated oscillometric BP devices and anthropometric data and exercise frequency were recorded. Multiple linear regressions were used to test associations among RHR and BP, anthropometry and exercise frequency., Results: Data on 14 842 children aged 6-18 years were available. Multiple linear regression analyses showed that RHR was positively associated with BP, and negatively associated with age and exercise frequency (p<0.001). RHR was more positively linked to waist circumference among the anthropometric measurements, and positive independent association was only identified in boys (p<0.001)., Conclusions: Elevated RHR is independently associated with elevated BP in children, whereas increased structured exercise is related to lower RHR.

Aims: This paper tests the mediating effect of institutional peer support on the relationship between physical declines and depressive symptoms among nursing home residents., Background: As the number of older adults living in nursing homes increases, peer support received from other residents in the institutions is critical to the psychological well-being of residents who face physical declines and reduction in family support. This study tested whether institutional peer support would account for the detrimental effect of physical declines on depressive symptoms of Chinese older people residing in nursing homes., Design: A cross-sectional design was used., Method: The study was conducted between January-March 2009 by convenience sampling. The sample consisted of 187 nursing home residents, with 54 men and 133 women. Interviews were conducted by an experienced research assistant, and responses on physical abilities and institutional peer support were collected. Geriatric Depression Scale was used to assess depressive symptoms of each participant., Results: Participants with poor physical abilities reported more depressive symptoms. Institutional peer support was negatively correlated with physical declines and depressive symptoms. Results of the regression analysis showed that the effect of physical declines on depressive symptoms was no longer significant when the influence of institutional peer support was statistically controlled, indicating a full mediation of institutional peer support on depression of older people., Conclusion: Findings of this study reveal that institutional peer support positively contributes to the psychological well-being of nursing home residents., (© 2012 Blackwell Publishing Ltd.)