Efficient attenuation of Friedreich's ataxia (FRDA) cardiomyopathy by modulation of iron homeostasis-human induced pluripotent stem cell (hiPSC) as a drug screening platform for FRDA

Friedreich’s ataxia (FRDA), a recessive neurodegenerative disorder commonly associated with hypertrophic cardiomyopathy, is caused by silencing of the frataxin (FXN) gene encoding the mitochondrial protein involved in iron-sulfur cluster biosynthesis. We aimed to utilize our previously established FRDA human induced pluripotent stem cell (hiPSC) derived cardiomyocytes model as a platform to assess the efficacy of treatment with either the antioxidant coenzyme Q10 analog, idebenone (IDE) or the iron chelator, deferiprone (DFP), which are both under clinical trial. In fact, DFP was able to more significantly suppress synthesis of reactive oxygen species (ROS) than IDE at the dosages of 10 nM and 25 μM respectively which agreed with the reduced rate of intracellular accumulation of iron by DFP treatment from 25 to 50 µM. With regard to cardiac electrical-contraction (EC) coupling function, decay velocity of calcium handling kinetics in FRDA-hiPSC-cardiomyocytes was significantly improved by DFP treatment but not by IDE. Further mechanistic studies revealed DFP also modulated iron induced mitochondrial stress as reflected by mitochondria network disorganization and decline in level of respiratory chain protein. In addition, iron-response protein (IRP-1) regulatory loop was overridden by DFP as reflected by the attenuated transferrin receptor (TSFR) suppression thereby reducing further iron uptake.published_or_final_versio

Split-Drain Magnetic Field-Effect Transistor Channel Charge Trapping and Stress Induced Sensitivity Deterioration

Session EB: Materials for ApplicationsThis paper proposed an analytical model on the deterioration of magnetic sensitivity of sectorial split-drain magnetic field-effect transistors (SD-MAGFETs). The deterioration is governed by the trap fill rate at the channel boundary traps, which is geometric dependent. Experimental results are presented which show good consistency with the analytical derivation. The deterioration is the most severe at a sector angle of 54.6°, which shows a design tradeoff with sensing hysteresis. Design guidelines for sectorial SD-MAGFET to obtain high sensitivity hysteresis and slow sensitivity deterioration are also presented which provide important information for efficient design. © 2013 IEEE.published_or_final_versio

Prognosis and functional outcome after ischaemic stroke in Chinese

Oral PresentationINTRODUCTION: Ischaemic stroke (ISS) is a significant cause of disability and mortality worldwide. Here, we studied the subtypes and long-term prognosis of ISS in our locality. METHODS: A total of 1214 patients with ISS receiving rehabilitation at Tung Wah Hospital during 2004-2008 were prospectively followed-up for a mean of 76±18 months. Presence of recurrent stroke and all-cause mortality during the follow-up period was documented. The modified Rankin Score (mRS) at 1-year follow-up was delin…published_or_final_versio

Prognostic implications of surrogate markers of atherosclerosis in low-to-intermediate risk patients with type 2 diabetes

Poster PresentationINTRODUCTION: Type 2 diabetes mellitus (T2DM) patients are at increased risk of developing cardiovascular events. Unfortunately traditional risk assessment scores, including the Framingham Risk Score (FRS), have only modest accuracy in cardiovascular risk prediction in these patients. METHODS: We sought to determine the prognostic values of different non-invasive markers of atherosclerosis, including brachial artery endothelial function, carotid artery atheroma burden, ankle-brachial index, arterial stiffness and computed tomography coronary artery calcium score (CACS) in 151 T2DM Chinese patients who were identified low-intermediate risk from the FRS recalib…published_or_final_versio

Roles of the CHADS2 and CHA2DS2-VASc scores in post-myocardial infarction patients: risk of new occurrence of atrial fibrillation and ischaemic stroke

Poster PresentationINTRODUCTION: Patients with myocardial infarction are at risk of development of atrial fibrillation (AF) and ischaemic stroke. We sought to evaluate the prognostic performance of the CHADS2 and CHA2DS2-VASc scores in predicting new AF and/or ischaemic stroke in post-ST segment elevation myocardial infarction (STEMI) patients. METHODS: A total of 607 consecutive post-STEMI patients without previously documented AF were stud…published_or_final_versio

A Chinese mind-body exercise improves self-control of children with autism : a randomized controlled trial

Author name used in this publication: Mei-chun Cheungpublished_fina

Stroke Patients with a Past History of Cancer Are at Increased Risk of Recurrent Stroke and Cardiovascular Mortality

published_or_final_versio

Antenatal risk factors for postnatal depression: a prospective study of chinese women at maternal and child health centres

Background: Risk factors for postnatal depression (PND) are under-explored in the Chinese populations. There is increasing recognition of the importance of identifying predictive factors during the antenatal period for PND. The present study aimed to identify the risk factors for postnatal depression in a community cohort of Chinese women with special focus on the antenatal risk factors.Methods: Eight hundred and five Chinese women were interviewed during their third trimester of pregnancy and at around 2 months postnatally. Putative risk factors for PND were collected and the diagnosis of PND was confirmed by the Structured Clinical Interview for DSM-IV Axis I Disorders. The 2-month postnatal depression status was used as the dependent variable for univariate and multivariate analyses against putative risk factors.Results: Marital dissatisfaction (Relative Risk = 8.27), dissatisfied relationship with mother-in-law (Relative Risk = 3.93), antenatal depressive symptomatology (Relative Risk = 3.90), and anxiety-prone personality (Relative Risk = 2.14) predicted PND in Chinese women independently.Conclusions: Chinese women tend to keep their own feelings and emotions and it is important to monitor Chinese pregnant women with these predictive risk factors so that PND can be identified early. © 2012 Siu et al; licensee BioMed Central Ltd.published_or_final_versio

A single residue substitution in the receptor-binding domain of H5N1 hemagglutinin is critical for packaging into pseudotyped lentiviral particles

© 2012 Tang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Serological studies for influenza infection and vaccine response often involve microneutralization and hemagglutination inhibition assays to evaluate neutralizing antibodies against human and avian influenza viruses, including H5N1. We have previously characterized lentiviral particles pseudotyped with H5-HA (H5pp) and validated an H5pp-based assay as a safe alternative for high-throughput serological studies in BSL-2 facilities. Here we show that H5-HAs from different clades do not always give rise to efficient production of H5pp and the underlying mechanisms are addressed. Methodology/Findings: We have carried out mutational analysis to delineate the molecular determinants responsible for efficient packaging of HA from A/Cambodia/40808/2005 (H5Cam) and A/Anhui/1/2005 (H5Anh) into H5pp. Our results demonstrate that a single A134V mutation in the 130-loop of the receptor binding domain is sufficient to render H5Anh the ability to generate H5Anh-pp efficiently, whereas the reverse V134A mutation greatly hampers production of H5Cam-pp. Although protein expression in total cell lysates is similar for H5Anh and H5Cam, cell surface expression of H5Cam is detected at a significantly higher level than that of H5Anh. We further demonstrate by several independent lines of evidence that the behaviour of H5Anh can be explained by a stronger binding to sialic acid receptors implicating residue 134. Conclusions: We have identified a single A134V mutation as the molecular determinant in H5-HA for efficient incorporation into H5pp envelope and delineated the underlying mechanism. The reduced binding to sialic acid receptors as a result of the A134V mutation not only exerts a critical influence in pseudotyping efficiency of H5-HA, but has also an impact at the whole virus level. Because A134V substitution has been reported as a naturally occurring mutation in human host, our results may have implications for the understanding of human host adaptation of avian influenza H5N1 virusesThis work was supported by grants from the Research Fund for the Control of Infectious Diseases of Hong Kong (RFCID#08070972), the Area of Excellence Scheme of the University Grants Committee (grant AoE/M-12/-06 of the Hong Kong Special Administrative Region, China), the French Ministry of Health, and the RESPARI project of the Institut Pasteur International Network