Search

Aim The safety concern of statins is still a major issue for Asians. The aim of this study is to compare the risk of statin-associated adverse events among potent statins. Methods We included patients from the Taiwan National Health Insurance Research Database who had been treated with atorvastatin, rosuvastatin, or pitavastatin and were without diabetes at baseline. They were classified into three groups: usual-dose statin (atorvastatin 10 mg/d or rosuvastatin 5-10 mg/d), high-dose statin (atorvastatin 20-40 mg/d and rosuvastatin 20 mg/d), and pitavastatin (2-4 mg/d). The primary endpoint is a composite of safety events, including hepatitis, myopathy, and new-onset diabetes mellitus (NODM). We matched age, sex, and year of recruitment among the three groups (n=50,935 in each group) and then used the multivariate Cox proportional hazards model to evaluate the relation between the safety endpoint and different statin groups. Results After a mean follow-up of 3.08±0.83 years, the safety events occurred in 9.84% in the pitavastatin group, 10.88% in the usual-dose statin group, and 10.49% in high-dose statin group. The multivariate Cox proportional hazards model indicated that usual-dose statin and high-dose statin were associated with a higher risk of the composite safety events compared with pitavastatin (adjusted hazard ratio [aHR]: 1.12, 95% confidence interval [CI]: 1.08-1.17 for usual-dose statin and aHR: 1.06, 95% CI: 1.02-1.10 for high-dose statin). The risks of hepatitis requiring hospitalization and NODM were especially lower in pitavastatin group. Conclusions Compared with atorvastatin and rosuvastatin, pitavastatin might be associated with a lower risk of safety events in Asians.

Venous thromboembolism (VTE) presenting as deep vein thrombosis and pulmonary embolism clinically is a potentially fatal cardiovascular diseases with short-term and long-term sequelae. Furthermore, there is high recurrent rate in VTE patients during follow-up. Anticoagulation with traditional anticoagulants or new generation of oral anticoagulants is the gold standard treatment in patients with VTE. On the other hand, there is remarkable progression in device-based or surgical thrombectomy in managements of VTE in recent years. Current evidence also demonstrates the efficacy and safety of these invasive procedures in selective VTE patients. The present article will illustrate recent advances of device-based or surgical thrombectomy in VTE treatment.

Background The 2013 American College of Cardiology/American Heart Association cholesterol guideline recommends high-intensity statin (HIS) in patients with atherosclerotic cardiovascular disease, but little is known about the efficacy and safety of HIS in Asian ethnicity. We assessed the effects of HIS in Taiwanese with acute myocardial infarction (AMI). Methods Consecutive patients admitted for new AMI between January 2010 and December 2013 without prior statin use were enrolled from the Taiwan National Health Insurance Research Database. Patients were grouped based on the intensity of statin they took after discharge. The primary endpoint was the composite outcome of all-cause mortality, recurrent myocardial infarction, and stroke. We also compared the incidences of severe hepatitis and myopathy that need admission between HIS and non-HIS groups. We used propensity score analysis to match covariates between groups and Cox proportional hazards models with adjustment to estimate the risks of clinical outcomes. Results After 1:4 propensity score match, there were 4402 patients in the HIS group and 17,608 patients in the non-HIS group. After follow-up for 3 years, 668 patients (15.2%) in the HIS group and 2749 (15.6%) in the non-HIS group had the primary composite endpoint. Cox proportional-hazards analyses showed that HIS did not further reduce composite endpoint (adjusted hazard ratio, 0.975; 95% confidence interval, 0.896-1.062); however, HIS patients had a lower risk of ischemic stroke at 3-year follow-up. Regarding safety, HIS did not increase hospitalization rates for severe hepatitis and myopathy. Conclusions Patients with AMI in Taiwan with HIS had similar clinical outcomes to those with non-HIS. Using HIS for the effective reduction of low-density lipoprotein cholesterol is safe in Taiwan.

This study delineated the characteristics of 24 (11.2%) culture-positive, influenza-associated pulmonary aspergillosis (IAPA) patients out of 215 patients with severe influenza during 2016–2019 in a medical center in southern Taiwan. Twenty (83.3%) patients did not have EORTC/MSG-defined host factors. The mean time from influenza diagnosis to Aspergillus growth was 4.4 days, and 20 (83.3%) developed IAPA within seven days after influenza diagnosis. All patients were treated in intensive care units and all but one (95.8%) received mechanical ventilation. Aspergillus tracheobronchitis was evident in 6 (31.6%) of 19 patients undergoing bronchoscopy. Positive galactomannan testing of either serum or bronchoalveolar lavage was noted in all patients. On computed tomography imaging, IAPA was characterized by peribronchial infiltrates, multiple nodules, and cavities superimposed on ground-glass opacities. Pure Aspergillus growth without bacterial co-isolation in culture was found in 17 (70.8%) patients. A. fumigatus (15, 62.5%), A. flavus (6, 25.0%), and A. terreus (4, 16.7%) were the major causative species. Three patients had mixed Aspergillus infections due to two species, and two had mixed azole-susceptible and azole-resistant A. fumigatus infection. All patients received voriconazole with an all-cause mortality of 41.6%. Of 14 survivors, the mean duration of antifungal use was 40.5 days. In conclusion, IAPA is an early and rapidly deteriorating complication following influenza that necessitates clinical vigilance and prompt diagnostic workup.

Background Statin associated adverse events (SAAEs), including hepatitis, myopathy and new onset diabetes mellitus (NODM), are major reasons that prevent the use of statins. We compared the risk of SAAEs among the commonly used statins to see if SAAEs were similar among the statins. Methods We retrieved data from the Taiwan National Health Insurance Research Database. From January 2013 to December 2017, all statin-treated patients without diabetes at baseline were enrolled. We classified eligible patients into pitavastatin (2–4mg/day), moderate-intensity statin (MIS [atorvastatin 10–20 mg/day or rosuvastatin 5–10 mg/day]), and high-intensity statin group (HIS [atorvastatin ≥40 mg/day and rosuvastatin ≥20mg/day]). The study endpoint is a composite of safety events, including hepatitis, myopathy, and NODM. All patients were followed-up for at least one year until December 2018. We used propensity score to balance the baseline differences between the 3 statin groups (N=50935 in each group). Results After a mean follow up time of 3.08 years, the safety events occurred in 5014 patients in pitavastatin group (9.84%), 5542 in MIS group (10.88%), and 5343 in HIS group (10.49%). Multivariate Cox proportional hazards model showed that MIS and HIS statins were associated with a higher risk of safety events compared with pitavastatin (adjusted hazard ratio [aHR] 1.122, 95% confidence interval [CI] 1.08–1.17 for MIS and aHR 1.056, 95% CI 1.02–1.10 for HIS). Most events were NODM, with 4818 events in pitavastatin (9.46%), 5284 in MIS (10.37%), and 5113 in HIS group (10.04%). Multivariate Cox proportional hazard analysis showed higher risk of NODM in MIS (adjusted HR 1.111, 95% CI 1.07–1.16) and HIS (aHR 1.050, 95% CI 1.01–1.10) compared with pitavastatin. Time-varying HR analysis showed increased risk of NODM with use of all these statins for more than 1 year compared with non-statin users. Conclusions Pitavastatin was associated with a lower risk of SAAEs, especially NODM, compared with atorvastatin and rosuvastatin. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Orient EuroPharma Co., Ltd.

Background and aims Thrombomodulin (TM) is an endothelial cell membrane-bound anticoagulant protein expressed in normal arteries. After vascular injury, medial and neointimal smooth muscle cells (SMCs) exhibit large amounts of TM. The purpose of this study was to investigate the physiological significance of vascular SMC-bound TM. Methods The morphology, expression of phenotype markers and cell behaviors of cultured aortic SMCs after knockdown of TM were observed. Transgenic mice with SMC-specific TM deletion were generated, and carotid neointima formation was induced by carotid ligation. Results Cultured human aortic SMCs displayed a synthetic phenotype with a rhomboid-shaped morphology and expressed TM. TM knockdown induced a spindle-shaped change in morphology with an increased expression of contractile phenotype marker and decreased expression of synthetic phenotype marker. TM knockdown not only attenuated the proliferation of SMCs but also reduced tumor necrosis factor-α-induced nuclear factor-κB activation and interlukin-6 production. In a carotid artery ligation model, transgenic mice with SMC-specific TM deletion (SM22-cretg/TMflox/flox) had significantly less cellular proliferation in arterial walls compared with wild type mice (SM22-cretg/TM+/+). The neointima area and neointima/media area ratio were smaller in SM22-cretg/TMflox/flox mice at 4 weeks after ligation. Conclusions Our results indicate that vascular SMC-bound TM plays a role in changes of the SMC phenotype. It also influences SMC cell behavior and injury-induced neointima formation.

In this study, fabrication of microfluidic paper based analytical devices (μPADs) by microembossing was proposed. Different from the embossing methods described in the literature, the filter paper was embossed such that a protruded structure was formed, which subsequently became the channel after heating the wax at the backside of the filter paper. It was found that, when using the Whatman No. 3 filter paper, the embossing pressure needed to be larger than 50 kg/cm2 in conjunction with using a minimal 2-mm wide channel, and the wax heating time ranged from 15 to 45 s in order to obtain a reliable μPAD with repetitive and consistent results. In addition, there was no need of a hydrophobic material as the backside support. The glucose detection was demonstrated using the μPADs as fabricated and a linear relationship was obtained between 5 and 50 mM glucose concentrations. With the proposed method, the processing time of fabricating μPADs can be reduced within approximately 1 min.

Background: Tumor endothelial marker 1 (TEM1), also known as endosialin or CD248, is a transmembrane protein that expresses in mesenchymal lineage-derived cells only during embryogenesis and becomes undetectable in normal tissues after birth. Re-expression of TEM1 is found on activated cells of mesenchymal lineage during pathological conditions, such as stroma cells in cancer, fibroblasts in organ fibrosis and wound healing, indicating its potential role in tissue remodeling and repair. The expression levels and physiological functions of TEM1 in heart are unknown. Methods and Results: All data were presented as mean ± standard error. In 2 explanted hearts from patients with heart failure (HF) received heart transplantation, immunofluorescence staining showed TEM1 was highly expressed in cardiomyocytes (CMs) and also in cardiac fibroblasts. In mouse HF models induced by intraperitoneal doxorubicin injection (5 mg/kg/wk for 4 wks) or coronary ligation, immunohistochemistry study showed TEM1 expression in hearts. Western blot showed 1.23±0.02 and 1.56±0.04-fold increase of cardiac TEM1 expression compared to controls, respectively. In vitro studies showed TEM1 expression increased in cultured CMs (H9C2 cells) treated with: (1) mechanical stretch (10% elongation at 60 cycles/min) (0 vs 0.5 vs 1 vs 3 hr, Western blot ratio: 1 vs 1.86±0.20 vs 1.87±0.20 vs 1.21±0.21, p Conclusions: Our study results indicate that TEM1 is upregulated in CMs after cardiac injury and influences the cell behaviors of CMs that related to cardiac remodeling.

A compact coupled-fed loop MIMO antennas with variable radiation patterns for 5G notebook PC applications has been proposed. It shows that good impedance matching and isolation can be achieved in the desired 3.5 GHz band. And from the analysis results, it shows that eight distinguishable diverse MIMO patterns can be generated successfully and controlled by changing different states of low-cost switches. The proposed MIIMO antennas are expected to have higher adaptive capability within different practical multipath channel environments.

Human genetics, biomarker, and animal studies implicate loss of function in bone morphogenetic protein (BMP) signaling and maladaptive transforming growth factor-β (TGFβ) signaling as drivers of pulmonary arterial hypertension (PAH). Although sharing common receptors and effectors with BMP/TGFβ, the function of activin and growth and differentiation factor (GDF) ligands in PAH are less well defined. Increased expression of GDF8, GDF11, and activin A was detected in lung lesions from humans with PAH and experimental rodent models of pulmonary hypertension (PH). ACTRIIA-Fc, a potent GDF8/11 and activin ligand trap, was used to test the roles of these ligands in animal and cellular models of PH. By blocking GDF8/11- and activin-mediated SMAD2/3 activation in vascular cells, ACTRIIA-Fc attenuated proliferation of pulmonary arterial smooth muscle cells and pulmonary microvascular endothelial cells. In several experimental models of PH, prophylactic administration of ACTRIIA-Fc markedly improved hemodynamics, right ventricular (RV) hypertrophy, RV function, and arteriolar remodeling. When administered after the establishment of hemodynamically severe PH in a vasculoproliferative model, ACTRIIA-Fc was more effective than vasodilator in attenuating PH and arteriolar remodeling. Potent antiremodeling effects of ACTRIIA-Fc were associated with inhibition of SMAD2/3 activation and downstream transcriptional activity, inhibition of proliferation, and enhancement of apoptosis in the vascular wall. ACTRIIA-Fc reveals an unexpectedly prominent role of GDF8, GDF11, and activin as drivers of pulmonary vascular disease and represents a therapeutic strategy for restoring the balance between SMAD1/5/9 and SMAD2/3 signaling in PAH.

Background In Asia, little information is available about contemporary real-world treatment patterns for venous thromboembolism (VTE).Methods and Results:Consecutive patients (n=11,414) from the Taiwan National Health Insurance Research Database with initial VTE and taking oral anticoagulants between May 1, 2014 and June 30, 2016 were included. The temporal trends of using oral anticoagulants and pharmacomechanical therapy during the study period were evaluated. The efficacy and safety of nonvitamin K antagonist oral anticoagulants (NOACs) vs. warfarin were compared. Propensity score analysis (NOACs n=3,647 vs. warfarin n=3,647) was used to balance covariates between groups, and Cox proportional hazards models with adjustment were used to estimate the risks of clinical outcomes. The use of NOACs increased from 0.3% to 60.2% for VTE treatment during the study period. Pharmacomechanical therapy was used in 9.60%, 8.22%, and 5.63% from 2014 through 2016. NOACs were associated with a 16% risk reduction (adjusted hazard ratio [aHR] 0.84, 95% confidence interval [CI] 0.77-0.93) in all-cause mortality and a 21% risk reduction (aHR 0.79, 95% CI 0.65-0.96) in recurrent VTE vs. warfarin. Overall, NOACs were associated with a lower risk of major bleeding compared with warfarin (aHR 0.804, 95% CI 0.648-0.998). Conclusions In real-world practice, NOACs have become the major anticoagulant used for Asians with VTE. Although NOACs had a lower risk of recurrent VTE and major bleeding compared with warfarin in Taiwan, we still need a large-scale randomized controlled trial to confirm the findings.

In this study, rapid and direct Raman analysis of microalgae was demonstrated through measurement of algal cells (or algal paste) prepared by microwell-assisted filtration using an anodic aluminum oxide (AAO) membrane. To obtain the algal paste, an array of polydimethylsiloxane (PDMS) microwells with through holes was placed on top of the AAO membrane, after which a vacuum was initiated and a droplet of algal solution dispensed inside the PDMS microwells for a 5-min filtration process. The results showed that the AAO membrane has the lowest background noise compared to other types of filter papers or membranes. Compared to the droplet evaporation method, the “coffee-ring” effect was effectively suppressed when applying our proposed filtration method. The algal cells became stacked inside the microwells, which led to relatively uniform and strong Raman signals across individual algal paste and consistency among different algal pastes.

Background Thrombomodulin (TM) is a cell membrane-bound anticoagulant protein that only expresses on endothelial cells in normal artery. Vascular smooth muscle cells (SMCs) start to exhibit TM after arterial injury. Our previous study demonstrated that vascular SMC-bound TM expression was associated with SMC synthetic phenotype. TM knockdown not only attenuated aortic SMCs proliferation but also reduced aortic SMC-mediated inflammation. In this study, we investigated the effect of vascular SMC-bound TM on arterial injury-induced neointima formation in mouse. Methods and results Because complete loss of TM in TM knockout transgenic mice causes embryonic lethality, we generated vascular SMC-specific TM-deficient mice (SM22-cretg/TMflox/flox) and their wild-type controls (SM22-cretg/TM+/+) using the Cre-loxP system to explore the role of vascular SMC membrane-bound TM in vivo. The blood pressure and body weight were similar between SM22-cretg/TMflox/flox mice and their wild-type controls. Carotid ligation caused neointima formation in mice. Immunofluorescence staining showed that there was large amount TM expression in the medial and neointimal cells at 4 weeks in SM22-cretg/TM+/+ mice after carotid ligation, but there was no TM staining could be found in SM22-cretg/TMflox/flox mice. There was a progressively increased neointima area from 2 to 4 weeks after carotid ligation both in SM22-cretg/TMflox/flox mice and SM22-cretg/TM+/+ mice, but the neointima area and neointima/media area ratio were significantly smaller in SM22-cretg/TMflox/flox mice than SM22-cretg/TM+/+ mice. Immunofluorescence staining showed that there were less Ki67-positive cells in the media and neointima in SM22-cretg/TMflox/flox mice indicating less proliferating cells in the arterial wall of TM-deficient mice. The α-smooth muscle actin-positive staining area was also larger in the SM22-cretg/TMflox/flox mice, suggesting TM deficiency of SMCs in medial lesion exhibited a more contractile status after carotid ligation. Conclusions Our results indicated that vascular SMC-bound TM not only mediated vascular SMC phenotype change and cell behavior but also significantly influenced arterial injury-induced neointima formation. Acknowledgement/Funding This study was sponsored by grants 104-2314-B-006-083-MY2 and 106-2314-B-006-045-MY3 from the Ministry of Science and Technology, Taipei, Taiwan.

In recent years, the paper-based microfluidics has been gaining attention because it is regarded as an inexpensive tool for detection and analysis in biomedical applications and clinical settings. This report, for the first time, describes a relatively simple and fast method, i.e. filtration-assisted screen printing (FASP) that can produce microfluidic paper-based analytical devices (μPAD) at ambient condition with time for constructing the channel wall of fluidic channel as less as 30 s. The channel walls are constructed by the polymer retained inside the filter paper at the designated locations through filtration. It is found that the flow behavior inside the channels was affected by the channel width while the influence of filtration time on the channel dimensions and porosity is minimal. Detection of glucose was demonstrated using the μPAD as fabricated. The proposed method provides a fast and reliable alternative to other state-of-the-art fabrication techniques, which can facilitate in extending the research and development in paper-based microfluidics.

Introduction: Therapies targeting the underlying mechanisms of pulmonary arterial hypertension (PAH) might modify the natural history of disease. The genetics of heritable PAH implicate deficient BMP signaling as a pathogenetic driver. Lung tissues from experimental and human PAH exhibit deficient BMP & excessive TGFβ signaling. While previous studies suggest agonism of BMP9 signaling or inhibition of TGFβ signaling may prevent experimental PH, the roles of activin and growth and differentiation factor (GDF) ligand signaling are unclear. ACTRIIA-Fc (sotatercept) is an activin- and GDF8/11-specific ligand trap currently in Phase 2 studies for anemia and multiple myeloma. Hypothesis: ACTRIIA-Fc inhibits activin and GDF8/11 signaling in vascular cells to attenuate experimental PH and pulmonary vascular remodeling. Methods: Impact of ACTRIIA-Fc on BMP & TGFβ signaling was examined in human pulmonary microvascular endothelial (PMVEC) and pulmonary arterial smooth muscle cells (PASMC). ACTRIIA-Fc (15 mg/kg s.c. 2x/week), sildenafil (30 mg/kg p.o. BID) or vehicle were given prophylactically for 4 weeks to rats developing PH following a single injection of MCT (40 mg/kg s.c.), or via single injection of SU5416 (200 mg/kg s.c.) combined with hypoxia (FIO2=0.10, SU-Hx). Alternately, rats were allowed to develop PH following SU-Hx treatment for 3 weeks or MCT treatment for 4 weeks, and then treated with ACTRIIA-Fc (1, 3, or 10 mg/kg s.c. 2x/week) or isotype-matched control antibody (3 weeks under normoxia following SU-Hx, or 2 weeks following MCT). Invasive hemodynamics, RV mass and vascular remodeling were assessed. Results: In PMVEC, ACTRIIA-Fc enhanced BMP9-induced SMAD1/5/8 activation and transcriptional activity, and reversed inhibition of BMP9 signaling by GDF11. ACTRIIA-Fc inhibited GDF8-, GDF11- and activin A-mediated SMAD2 phosphorylation and myogenic differentiation of PASMC. In vivo , a standard dose of ACTRIIA-Fc prevented PH, RV hypertrophy and PV remodeling in MCT- and SU-Hx-rats, with more potency than sildenafil. All doses of ACTRIIA-Fc attenuated PH and RV hypertrophy when given in a delayed fashion after MCT- and SU-Hx-treatment, with graded effects on PV remodeling. Conclusions: ACTRIIA-Fc rebalances GDF11 vs. BMP9 signaling, with distinct effects in vascular endothelium vs. media, and potently inhibits experimental PH in several rodent models. Given its well-defined tolerability, dosing, and efficacy in previous human studies, ACTRIIA-Fc is an attractive candidate for PAH as a novel, mechanism-targeted therapy.

BACKGROUND Statin therapy is beneficial for ischemic stroke patients, but little is known about whether statin adherence affects clinical outcome. We therefore evaluated the effect of statin adherence in patients with ischemic stroke or transient ischemic attack (TIA). METHODS AND RESULTS From Taiwan Bureau of National Health Insurance database, we enrolled patients with no prior statin therapy admitted for ischemic stroke or TIA between January 2002 and December 2005. Patients were grouped based on statin adherence according to medication possession ratio (MPR): good adherence (MPR >80%; n=2,274), intermittent adherence (MPR=40-80%; n=3,710), and poor adherence (MPR

Statin reduces low-density lipoprotein cholesterol and improves clinical outcomes in high risk patients. In general, statin is a safe and well-tolerated medication. However, varieties of adverse effects are reported in some patients and may interfere long-term drug compliance. Statin-associated muscle events and liver function change account for most of these adverse effects. Patients are regarded as statin intolerance if they need to discontinue statin therapy due to these adverse effects. To date, there is no universal standard definition of statin intolerance. But a pragmatic definition of statin intolerance is essential and helpful for clinicians in daily practice. In this article, after expert consensus meetings and literature review, criteria were recommended to identify patients with statin intolerance in Taiwan. The purpose of this statement is to help health care professionals in Taiwan to diagnose and manage individuals who develop muscular and hepatic side effects after statin therapy. KEYWORDS: Statin, Side effect, Consensus

Background: The aim of this study was to determine the validity of acute myocardial infarction (AMI) diagnosiscoding in the National Health Insurance Research Database (NHIRD) by cross-comparisons of discharge diagnoseslisted in the NHIRD with those in the medical records obtained from a medical center in Taiwan.Methods: This was a cross-sectional study comparing records in the NHIRD and discharge notes in one medicalcenter (DNMC) in the year 2008. Positive predictive values (PPVs) for AMI diagnoses were evaluated by reviewingthe relevant clinical and laboratory data recorded in the discharge notes of the medical center. Agreement incomorbidities, cardiac procedures, and antiplatelet agent (aspirin or clopidogrel) prescriptions between the twodatabases was evaluated.Results: We matched 341 cases of AMI hospitalizations from the two databases, and 338 cases underwent completechart review. Of these 338 AMI cases, 297 were confirmed with clinical and lab data, which yielded a PPVof 0.88.The consistency rate for coronary intervention, stenting, and antiplatelet prescription at admission was high, yieldinga PPVover 0.90. The percentage of consistency in comorbidity diagnoses was 95.9% (324/338) among matched AMIcases.Conclusions: The NHIRD appears to be a valid resource for population research in cardiovascular diseases.Key words: acute myocardial infarction; NHIRD; Taiwan; validity; pharmacoepidemiology

Stress-induced alteration in endothelial cells (ECs) integrity precedes the development of atherosclerosis. Previous studies showed that the soluble recombinant thrombomodulin (rTM) not only increases ECs proliferation but also exerts anti-apoptotic activity in ECs. However, the functional significance of soluble rTM on autophagy-related apoptosis in ECs is still undetermined. Implicating a cytoprotective role for rTM in persistent serum starvation (SS)-induced autophagy in cultured ECs, we found that treatment of rTM decreased the expression of SS-induced autophagy-related proteins, ATG5 and LC3, and the formation of autophagosomes through activation of AKT/mTOR pathway. In addition, treatment of rTM decreased SS-induced EC apoptosis, but this effect of rTM could not be recapitulated by co-treatment with a potent autophagy inducer, rapamycin and in ECs with ATG5 knockdown. In human atherosclerosis specimens, expression of autophagy markers, ATG13 and LC3, were more abundant in aortic intimal ECs with severe atherosclerosis than those without atherosclerosis. Moreover, compared to saline treatment group, administration of rTM reduced LC3 and ATG13 expression, intimal EC apoptosis, and atherosclerotic lesion severity in the aorta of apolipoprotein E deficient mice. In conclusion, treatment with rTM suppressed stress-induced autophagy overactivation in ECs, provided ECs protective effects, and decreased atherosclerosis in apolipoprotein E deficient mice.

Mono-aluminum, di-magnesium and tri-zinc complexes coordinated by a Biphen2- ligand (Biphen-H2 = 3,3′-di-tert-butyl-5,5′,6,6′-tetramethylbiphenyl-2,2′-diol) were synthesized and structurally characterized by X-ray single crystal determinations. The reaction of Biphen-H2 with AlMe3 (1.0 mol equiv.) in THF produced the tetra-coordinated monomeric aluminum complex [Al(Biphen)Me(THF)] (1), but treatment of Biphen-H2 with MgnBu2 under the same stoichiometric proportion in THF gave the dimeric magnesium complex [Mg(μ-Biphen)(THF)]2 (2). Tri-zinc [Zn3(μ, μ-Biphen)2Et2(THF)2] (3) resulted from treatment of Biphen-H2 with ZnEt2 (1.5 mol equiv) in THF; it consists of two different kinds of four-coordinated Zn centers. All of metal complexes are coordinated by at least one neutral THF coligand, indicating each metal center can behave as an active site to activate monomers during ring-opening polymerization (ROP). Catalysis for ROP of e-caprolactone (e-CL) or β-butyrolactone (β-BL) of complexes 1–3 are investigated, and the comparative studies of e-CL polymerization are also discussed.

Histopathological assays gain physiological insights into the mechanisms by which kumquat and calamondin are resistant to citrus canker caused by Xanthomonas citri subsp. citri (Xcc). Unlike Mexican lime, which is highly susceptible to Xcc, calamondin and kumquat leaves challenged with Xcc developed rapid necrosis, resembling a hypersensitive reaction. Fluorescent microscopy examination identified fluorescent materials around the necrotic lesions in kumquat and calamondin leaves challenged with Xcc, but not in Mexican lime. The resistant cultivars inoculated with Xcc exhibited lower antioxidant enzymatic activities and accumulated less H 2 O 2 . These modifications serve as physical barriers to ward off pathogen, thereby suppressing lesion development.

Background and purpose: Infection is a major medical problem in patients with acute stroke. Recent evidences suggest that statins reduce infection-associated complications. The purpose of this study was to examine the influence of statin treatment on mortality and functional outcomes in patients with stroke-associated infection. Methods: In this prospective observational cohort study, 514 patients with acute ischaemic stroke or transient ischaemic attack (mean age, 74 ± 11 years; men, 48%) with infection occurring in the first 7 days after admission were included. We examined the effect of in-hospital statin treatment on mortality and favorable functional outcome (modified Rankin Scale score ≤2) at 3 months follow-up. Results: Infection occurred at 0.93 ± 1.49 days after admission. All patients had not received statin treatment prior to admission, and 121 patients (24%) received statin at 1.71 ± 1.28 days after admission. Follow-up at 3 months was completed for 511 patients (99%). National Institutes of Health Stroke Scale score and Charlson index were the most important independent predictors of mortality and functional outcome. Univariate [hazard ratio (HR), 0.82; 95% confidence intervals (CI), 0.47–1.42] and multivariate (HR, 1.68; 95% CI, 0.79–3.56) Cox regression analysis showed that statin did not significantly decrease the morality. In propensity analysis, statin treatment still had no significant association with mortality (HR, 1.54; 95% CI, 0.68–3.47) in the multivariate analyses after adjusting for age, sex, and propensity score. Conclusions: Statin use was not associated with a better functional outcome or survival in patients with stroke-associated infection.

Penicillium digitatum causes green mold on citrus, resulting in severe postharvest fruit decay and economic losses in many citrus-producing areas of the world. Forty isolates of P . digitatum were cultured from citrus groves, packinghouses, and local markets in Taiwan, and assessed quantitatively for their sensitivity to thiabendazole (TBZ) fungicide. Sensitivity assays using a 96-well microtiter plate revealed that, of 40 isolates examined, only one isolate collected from fruit produced in Taiwan and two isolates from Florida-imported citrus fruit were sensitive to TBZ. The concentration of TBZ causing a 50% growth reduction (EC 50 ) was less than 1 μg/mL. The remaining 37 isolates could tolerate high concentrations of TBZ, with an EC 50 greater than 80 μg/mL. Overall, more than 97% of P . digitatum isolates tested in Taiwan were found to be resistant to TBZ. In vitro assays also revealed the ineffectiveness of TBZ for controlling a TBZ-resistant isolate on sweet oranges. A sequence analysis of β-tubulin genes revealed that all TBZ-resistant isolates displayed a single transversion point mutation, resulting in a change at either amino acid 198 (glutamic acid → glutamine) or 200 (phenylalanine → tyrosine). The repetitive use of a single fungicide over several decades has favored the selection and dominance of TBZ-resistant isolates of P . digitatum .

Two novel sulfonate phenol ligands—3,3′-di-tert-butyl-2′-hydroxy-5,5′,6,6′-tetramethyl-biphenyl-2-yl 4-X-benzenesulfonate (XCF3, LCF3-H, and XOCH3, LOMe-H)—were prepared through the sulfonylation of 3,3′-di-tert-butyl-5,5′,6,6′-tetramethylbiphenyl-2,2′-diol with the corresponding 4-substituted benzenesulfonyl chloride (1 equiv.) in the presence of excess triethylamine. Magnesium (Mg) complexes supported by sulfonate phenoxide ligands were synthesized and characterized structurally. The reaction of MgnBu2 with L-H (2 equiv.) produces the four-coordinated monomeric complexes (LCF3)2Mg (1) and (LOMe)2Mg (2). Complexes 1 and 2 are efficient catalysts for the ring-opening polymerization of e-caprolactone (e-CL) and trimethylene carbonate (TMC) in the presence of 9-anthracenemethanol; complex 1 catalyzes the polymerization of e-CL and TMC in a controlled manner, yielding polymers with the expected molecular weights and narrow polydispersity indices (PDIs). In e-CL polymerization, the activity of complex 1 is greater than that of complex 2, likely because of the greater Lewis acidity of Mg2+ metal caused by the electron-withdrawing substitute trifluoromethyl (CF3) at the 4-position of the benzenesulfonate group. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3564–3572, 2010

Endosialin is a highly sialylated type I transmembrane glycoprotein. It is found that upregulated endosialin participates in growth, progression, neoangiogenesis and metastasis of tumors and endosialin is regarded as one of therapeutic targets in cancers. Although endosialin expresses in normal

This paper presents a low-offset low-noise sigma-delta modulator with pseudorandom chopper-stabilization technique. The comparison of the noise-cancellation ability with the correlated double sampling and chopper-stabilization techniques is demonstrated; also, the noise performance of these cancellation techniques is observed and discussed. Using the proposed technique, the modulator achieves 92 dB of dynamic range and -135 dB of noise floor while consuming 950 ?W from a 3-V supply. Based on the experimental results, the pseudorandom chopper-stabilization technique has a DC offset voltage that is 6 dB lower than that of the chopper-stabilization technique, and retains a thermal noise floor that is 1.6 dB lower than that of the correlated double sampling technique.

Conventional echocardiography may not detect subtle cardiac dysfunction of septic patients. Two-dimensional left ventricular (LV) global peak systolic longitudinal strain (GLS) can detect early cardiac dysfunction. We sought to determine the prognostic value of GLS for septic shock patients admitted to intensive care units (ICUs). We prospectively included 111 ICU patients with septic shock. A full medical history was recorded for each patient, and LV systolic function, including GLS, was measured. Our endpoints were ICU and hospital mortality. The ICU and hospital mortalities were 31.5 % (n = 35) and 35.1 % (n = 39), respectively. There was no significant difference in LV ejection fraction of the non-survivors and the survivors; however, upon ICU admission, the non-survivors exhibited GLSs that were less negative than those of the survivors, which indicated worse LV systolic function. GLS of −13 % presented the best sensitivity and specificity in the prediction of mortality (area under the curve 0.79). The patients with GLS ≥ −13 % exhibited higher ICU and hospital mortality rates (hazard ratio 4.34, p

a Department of Neurology, Chi-Mei Medical Center, Tainan, Taiwan b Institute of Clinical Medicine, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan c Biostatistics Consulting Center, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan d Department of Internal Medicine, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan e Department of Occupational Safety and Health, Institute of Industrial Safety and Disaster Prevention, College of Sustainable Environment, Chia Nan University of Pharmacy and Science, Tainan, Taiwan

The main theme of this paper is to demonstrate the applications of the newly developed common-mode voltage reduction pulsewidth-modulation (PWM) technique, which restricts the common-mode voltage to one-third of DC-link voltage, to vector-controlled induction motor drives. As compared to previous common-mode voltage reduction techniques, the presented technique can be applied to the inverter with diode front end and has no adverse effect on the linear modulation range. Therefore, vector-controlled drives using the developed technique for inverter control have a wide speed range. Moreover, the effects of the common-mode voltage reduction PWM technique on speed response for vector-controlled induction motor drives will be fully investigated in this paper. It will be demonstrated by intensive experimental results that speed performance does not deteriorate significantly within the rated speed range.

Background and purpose Statin therapy is beneficial for primary and secondary prevention of ischaemic stroke, but its influence in patients with intracerebral hemorrhage (ICH) is unclear. An assessment was made of the effect of early statin therapy on patients with acute ICH. Methods Taiwan's National Health Insurance Research Database was screened for patients without prior statin therapy admitted from January to December 2008 for newly diagnosed ICH. Patients taking statins during hospitalization or within 3 months post-discharge were the early statin group (n = 749); patients who were not were the control group (n = 7583). The study end-points were recurrent ICH and all-cause mortality during follow-up. Results All eligible patients were followed up until 31 December 2010. During the follow-up, 69 (9.2%) patients in the early statin group and 677 (8.9%) control group patients had recurrent ICH. Cox proportional hazards analyses showed that early statin use did not increase the risk of recurrent ICH (adjusted hazard ratio 1.044; 95% confidence interval 0.812–1.341). During the same period, 90 (12.0%) of the early statin group and 1519 (20.0%) control group patients died. All-cause mortality was lower in the early statin group (adjusted hazard ratio 0.742; 95% confidence interval 0.598–0.919) than in the control group. Matched propensity score analyses were consistent with findings in Cox proportional hazards analyses. Conclusions Early statin group patients with acute ICH did not have a higher recurrent risk of ICH and might have lower all-cause mortality during follow-up. It is concluded that statin therapy might be beneficial for patients with ICH.

Although congenital defects of the diaphragm often occur in the period immediately following birth, 10–20% of these cases are diagnosed later. Diaphragmatic hernia with intrathoracic kidney is very rare. The radiographic appearance of diaphragmatic hernia with a thoracic kidney is similar to posterior mediastinal masses. Chest computed tomography (CT) is an important and efficient tool in confirming the diagnosis. We reported a 28-year-old man who suffered from nonspecific chest tightness for 1 month. He denied a history of traumatic chest injury. Transthoracic echocardiography revealed a left posterior reniform mass with central echo complex, which was finally confirmed by contrast-enhanced chest CT to be a congenital intrathoracic kidney.

Statin therapy has demonstrated clinical benefits in atherosclerotic diseases and statin adherence may influence clinical outcomes in patients with ischemic stroke. However, the potential effect of stain adherence in patients with hemorrhagic stroke (HS) is unknown. We screened patients who were

Analysis of short-term heart rate variability (HRV) may provide useful information about autonomic nervous control of heart rate recovery. We studied 495 individuals (273 men), age range 19–85 years, submitted to treadmill exercise tests and short-term HRV evaluations over time (standard deviation of the normal-to-normal interval [SDNN], the square root of the mean squared differences of successive normal-to-normal intervals [RMSSD], the number of interval differences of successive normal-to-normal intervals greater than 50 ms [NN50 count], the proportion derived by dividing NN50 count by the total number of normal-to-normal intervals [pNN50]) and frequency (low-frequency power [LF], high-frequency power [HF], total power) domains. Among 495 patients, 106 patients (68 men) were elderly (age ≥ 65 years). Male gender and hypertension were significantly higher in elderly patients. The young patients had higher HRR after exercise. HRR at 4 min (54 ± 13 vs 60 ± 12 beats/min; P = 0.003) was the most significant predictor for positive exercise test result. In the young group, both time domain measures (SDNN: correlation coefficient 0.34, P < 0.001; RMSSD: correlation coefficient 0.37, P < 0.001) and frequency domain measures (LF: correlation coefficient 0.21, P < 0.001; HF: correlation coefficient 0.13, P = 0.01; total power: correlation coefficient 0.22, P < 0.001) were significantly associated with HRR at 4 min. HRR at 4 min was significantly associated with short-term HRV of time and frequency domains in young individuals, but not elderly ones, receiving treadmill exercise test.

A low-profile surface-mount metal chip antenna with a symmetric planar inverted-F structure suitable for 2.4 GHz WLAN operation is presented. The proposed antenna is obtained by folding a single metal plate which includes several periodic slots and two-pairs of symmetric soldering strips as the feed and short pins. Due to the two-pairs of symmetric feed and short pins, it is more flexible to be integrated in the system circuit board. Besides, the two-pairs of symmetric pins are also the supporter of the proposed antenna, it leads that the proposed antenna doesn't need any base and has higher radiation efficiency due to the air substrate. The height of the proposed antenna is 3 mm only, and the bandwidth reaches 190 MHz. It can easily cover the 2.4 GHz band (2400-2484 MHz). Details of the antenna design and the experimental results for the proposed antenna are presented.