Shih-Sheng Chang

An Intelligent Telecardiology System Using a Wearable and Wireless ECG to Detect Atrial Fibrillation

This study presents a novel wireless, ambulatory, real-time, and autoalarm intelligent telecardiology system to improve healthcare for cardiovascular disease, which is one of the most prevalent and costly health problems in the world. This system consists of a lightweight and power-saving wireless ECG device equipped with a built-in automatic warning expert system. This device is connected to a mobile and ubiquitous real-time display platform. The acquired ECG signals are instantaneously transmitted to mobile devices, such as netbooks or mobile phones through Bluetooth, and then, processed by the expert system. An alert signal is sent to the remote database server, which can be accessed by an Internet browser, once an abnormal ECG is detected. The current version of the expert system can identify five types of abnormal cardiac rhythms in real-time, including sinus tachycardia, sinus bradycardia, wide QRS complex, atrial fibrillation (AF), and cardiac asystole, which is very important for both the subjects who are being monitored and the healthcare personnel tracking cardiac-rhythm disorders. The proposed system also activates an emergency medical alarm system when problems occur. Clinical testing reveals that the proposed system is approximately 94% accurate, with high sensitivity, specificity, and positive prediction rates for ten normal subjects and 20 AF patients. We believe that in the future a business-card-like ECG device, accompanied with a mobile phone, can make universal cardiac protection service possible.

Viscolin reduces VCAM-1 expression in TNF-α-treated endothelial cells via the JNK/NF-κB and ROS pathway

Viscolin, a major active component in a chloroform extract of Viscum coloratum, has antioxidative and anti-inflammatory properties. We focused on its effects on the expression of vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-α (TNF-α)-treated human umbilical vein endothelial cells (HUVECs). The TNF-α-induced expression of VCAM-1 was significantly reduced by respectively 38±7 or 34±16% when HUVECs were pretreated with 10 or 30μM viscolin, as shown by Western blotting, and was also significantly reduced by pretreatment with the antioxidants N-acetylcysteine, diphenylene iodonium chloride, and apocynin. Viscolin also reduced TNF-α-induced VCAM-1 mRNA expression and promoter activity, decreased reactive oxygen species (ROS) production, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and significantly reduced the binding of monocytes to TNF-α-stimulated HUVECs. The attenuation of TNF-α-induced VCAM-1 expression and cell adhesion was partly mediated by a decrease in JNK phosphorylation. Furthermore, viscolin reduced VCAM-1 expression in the aorta of TNF-α-treated mice in vivo. Taken together, these data show that viscolin inhibits TNF-α-induced JNK phosphorylation, nuclear translocation of NF-κB p65, and ROS generation and thereby suppresses VCAM-1 expression, resulting in reduced adhesion of leukocytes. These results also suggest that viscolin may prevent the development of atherosclerosis and inflammatory responses.

The Role of False Lumen Size in Prediction of In-Hospital Complications After Acute Type B Aortic Dissection

OBJECTIVESnThe aim of this study was to determine whether false lumen size predicts in-hospital complications for acute type B aortic dissection.nnnBACKGROUNDnThe incidence of complications developing in patients with acute type B aortic dissection has been high. However, methods for recognizing high-risk patients have not been well-studied. We used quantitative analysis by computed tomography (CT) to predict the occurrence of in-hospital complications.nnnMETHODSnFifty-five consecutive patients with acute type B aortic dissection documented by CT imaging were analyzed. They were divided into groups, with and without in-hospital complications, and compared regarding maximal aortic diameter (MAD), maximal false lumen area (MFLA), minimal true lumen area (MTLA), branch-vessel involvement (BVI), and longitudinal length (LL) of aortic dissection.nnnRESULTSnThere were 31 patients with a stable course (group 1) and 24 patients who developed complications (group 2). The MFLA of group 2 was significantly larger than that of group 1 (group 1 vs. group 2=577.7+/-273.2 mm2 vs. 1,899.3+/-1,642.4 mm2, p<0.001). The BVI number was also higher in group 2 (group 1 vs. group 2=1.0+/-1.1 vs. 3.3+/-2.0, p<0.001). On multivariate analysis, only MFLA and BVI number were independent predictors of in-hospital complications. Patients with initial MFLA>or=922 mm2 or BVI number>or=2 showed a significantly higher incidence of in-hospital complications than the other patients (p<0.001).nnnCONCLUSIONSnA large MFLA and a higher BVI number are powerful predictors of in-hospital complications after acute type B aortic dissection.

MicroRNA-20a regulates autophagy related protein-ATG16L1 in hypoxia-induced osteoclast differentiation.

Autophagy and autophagy-related proteins (ATGs) play decisive roles in osteoclast differentiation. Emerging lines of evidence show the deregulation of miRNA in autophagic responses. However, the role of hypoxia and involvement of miRNA in osteoclast differentiation are unclear. In the present study, we demonstrate that hypoxia caused induction of autophagy and osteoclast differentiation markers in RAW264.7 cells stimulated with M-CSF and RANKL. In addition, miR-20a was significantly repressed during hypoxia and identified as the prime candidate involved in hypoxia-induced osteoclast differentiation. The results from dual luciferase reporter assay revealed that miR-20a directly targets Atg16l1 by binding to its 3UTR end. Further, miR-20a transfection studies showed significant down regulation of autophagic proteins (LC3-II and ATG16L1) and osteoclast differentiation markers (Nfatc1, Traf6, and Trap) thus confirming the functional role of miR-20a under hypoxic conditions. Results of chromatin immunoprecipitation assay showed that HIF-1α binds to miRNA-20a. From miRNA Q-PCR results, we confirmed that shRNA HIF-1α knockdown significantly downregulated both autophagy (LC3, p62, Atg5, Atg12, Atg16l1, Atg7, Becn1, Atg9a) and osteoclast markers (Traf6, Nfatc1, Ctsk, cFos, Mmp9, Trap) in RAW264.7 cells. Thus, our findings suggest that the regulatory axis of HIF-1α-miRNA-20a-Atg16l1 might be a critical mechanism for hypoxia-induced osteoclast differentiation.

MiR-20a-5p mediates hypoxia-induced autophagy by targeting ATG16L1 in ischemic kidney injury

AIMSnAutophagy is a cellular homeostatic mechanism activated under stress conditions and might act as protective response for cell survival in ischemic kidney injury. The micro RNA (miRNA) network may be critically involved in the regulation of autophagy. The aim of this study was to evaluate whether miRNA regulates autophagy in ischemic kidney injury and renal proximal tubular cells under hypoxic conditions.nnnMATERIALS AND METHODSnIschemic kidney injury was performed by clamping bilateral renal pedicles for 60min in male mice. Human kidney proximal tubular (HK-2) cells were exposed to in vitro hypoxic conditions. ATG16L1 is essential for autophagosome formation. Bioinformatics analyses were used to select the candidate miRNA, miR-20a-5p, which potentially targets ATG16L1. Gain-of-function and loss-of-function methods were employed to evaluate the effects of miRNA on autophagy. Chromatin immunoprecipitation analysis and promoter luciferase reporter assays were used to evaluate the interaction of transcriptional factors with miRNA.nnnKEY FINDINGSnIncreased expression of punctate LC3 and ATG16L1, autophagy-related proteins, and down-expression of miR-20a-5p were detected in kidneys after ischemic injury and in HK-2 cells under hypoxic conditions. 3-untranslated region luciferase reporter assays indicated that miR-20a-5p targeted ATG16L1 messenger RNA. Over-expression of miR-20a-5p reduced the expression of LC3-II and ATG16L1 in HK-2 cells under hypoxic conditions, whereas antagomiR-20a reversed the inhibition. Using RNAi against hypoxia-inducible factor-1α (HIF-1α) in HK-2 cells, we confirmed the inhibitory binding of HIF-1α to miR-20a-5p.nnnSIGNIFICANCEnThe signaling axis of HIF-1α, miR-20a-5p, and ATG16L1 in autophagic process might be a critical adapting mechanism for ischemic kidney injury.

Gallic Acid Attenuates Platelet Activation and Platelet-Leukocyte Aggregation: Involving Pathways of Akt and GSK3β

Platelet activation and its interaction with leukocytes play an important role in atherothrombosis. Cardiovascular diseases resulted from atherothrombosis remain the major causes of death worldwide. Gallic acid, a major constituent of red wine and tea, has been believed to have properties of cardiovascular protection, which is likely to be related to its antioxidant effects. Nonetheless, there were few and inconsistent data regarding the effects of gallic acid on platelet function. Therefore, we designed this in vitro study to determine whether gallic acid could inhibit platelet activation and the possible mechanisms. From our results, gallic acid could concentration-dependently inhibit platelet aggregation, P-selectin expression, and platelet-leukocyte aggregation. Gallic acid prevented the elevation of intracellular calcium and attenuated phosphorylation of PKCα/p38 MAPK and Akt/GSK3β on platelets stimulated by the stimulants ADP or U46619. This is the first mechanistic explanation for the inhibitory effects on platelets from gallic acid.

Increased LDL electronegativity in chronic kidney disease disrupts calcium homeostasis resulting in cardiac dysfunction

Chronic kidney disease (CKD), an independent risk factor for cardiovascular disease, is associated with abnormal lipoprotein metabolism. We examined whether electronegative low-density lipoprotein (LDL) is mechanistically linked to cardiac dysfunction in patients with early CKD. We compared echocardiographic parameters between patients with stage 2 CKD (n = 88) and normal controls (n = 89) and found that impaired relaxation was more common in CKD patients. Reduction in estimated glomerular filtration rate was an independent predictor of left ventricular relaxation dysfunction. We then examined cardiac function in a rat model of early CKD induced by unilateral nephrectomy (UNx) by analyzing pressure-volume loop data. The time constant of isovolumic pressure decay was longer and the maximal velocity of pressure fall was slower in UNx rats than in controls. When we investigated the mechanisms underlying relaxation dysfunction, we found that LDL from CKD patients and UNx rats was more electronegative than LDL from their respective controls and that LDL from UNx rats induced intracellular calcium overload in H9c2 cardiomyocytes in vitro. Furthermore, chronic administration of electronegative LDL, which signals through lectin-like oxidized LDL receptor-1 (LOX-1), induced relaxation dysfunction in wild-type but not LOX-1(-/-) mice. In in vitro and in vivo experiments, impaired cardiac relaxation was associated with increased calcium transient resulting from nitric oxide (NO)-dependent nitrosylation of SERCA2a due to increases in inducible NO synthase expression and endothelial NO synthase uncoupling. In conclusion, LDL becomes more electronegative in early CKD. This change disrupts SERCA2a-regulated calcium homeostasis, which may be the mechanism underlying cardiorenal syndrome.

Digoxin use is associated with increased risk of stroke in patients with non-valvular atrial fibrillation — a nationwide population-based cohort study

☆ This study has been presented in part at the AHA Sc 2011, Orlando, Florida, USA. ☆☆ Funding sources: This study was supported in part b Taiwan (NSC 100-2314-B-039-042, NSC 101-2314-B-03 039-019), Taiwan Department of Health Clinical Trial and (DOH 101-TD-B-111-004), China Medical University Hosp 006, and DMR-102-007). All the aforementioned funding study design; in the collection, analysis and interpretatio report; or in the decision to submit the paper for publicat ⁎ Corresponding author at: Division of Cardiology, D Medical University Hospital 2, Yuh-Der Road, Taichun 4 22052121x3483; fax: +886 4 22065593. E-mail address: kuancheng.chang@gmail.com (K.-C. C

Cataract increases the risk of peripheral artery occlusive disease: A nationwide population-based cohort study with propensity score

PURPOSEnWe conducted this study to evaluate the risk of peripheral artery occlusive disease (PAOD) among patients with cataracts.nnnMETHODSnWe analyzed the data from Taiwan National Health Insurance Research Database. Study participants were classified into the cataract group and the non-cataract group between 2000 and 2010. All patients were observed from the index year until PAOD diagnosis, loss to follow up, or the end of 2011. Both study groups were 1:1 matching based upon a propensity score. We used a cox proportional hazards regression model to assess the hazard ratio (HR) and 95% confidence interval (CI) of PAOD for the cataract cohort compared with the non-cataract cohort.nnnRESULTSnAfter adjustment for age, sex and comorbidities, the risk of PAOD was significantly higher in the cataract cohort [adjusted HR (aHR)=1.48, 95% CI=1.38-1.58] than the non-cataract cohort.nnnCONCLUSIONSnWe found that patients with cataracts had a 1.48-fold increased risk of developing PAOD compared to the non-cataract patients.

Amniotic fluid induces platelet-neutrophil aggregation and neutrophil activation

OBJECTIVEnAmniotic fluid embolism syndrome is a fatal disease in pregnant women. The exact role of platelets and neutrophils in amniotic fluid embolism syndrome is not clear. We examined whether amniotic fluid could affect platelet-neutrophil aggregation and activation and the possible mechanisms.nnnSTUDY DESIGNnBlood samples from the pregnant women were pretreated ex vivo with their own amniotic fluid. Flow cytometry was used to measure platelet-neutrophil aggregation and activation. Neutrophil-mediated activity of p38 mitogen-activated protein kinase and extracellular signal-regulated protein kinases 1 and 2 was analyzed by Western blotting.nnnRESULTSnAmniotic fluid significantly induced platelet-neutrophil aggregation, neutrophil CD11b expression, and reactive oxygen species production. Amniotic fluid induced minimal platelet P-selectin expression. The increase of intracellular calcium level of neutrophils and the activity of p38 mitogen-activated protein kinase were enhanced by amniotic fluid stimulation.nnnCONCLUSIONnAmniotic fluid was able to induce neutrophil activation and platelet-neutrophil aggregation with minimal effect on platelet activation. These findings may provide a new insight in the understanding of the pathophysiologic condition of amniotic fluid embolism syndrome.