The effect of previous coronary stenting on subsequent coronary artery bypass graft is inconclusive.
We used Taiwan's National Health Insurance Database to retrospectively evaluate patients with ...multivessel coronary artery bypass graft between January 2000 and December 2013. Overall, 32,335 patients who received coronary artery bypass graft were included, of whom 3028 had previous coronary stenting. Propensity-score matching yielded 2977 cases each for evaluation under the previous stenting and no stenting groups. The 30-day mortality and major adverse cardiac events, including all-cause mortality, acute myocardial infarction, and revascularization, were considered primary outcomes.
The number of coronary artery bypass grafts decreased per year. However, the percentage of patients who had previous coronary stent implantation before coronary artery bypass graft increased steadily (P for trend <.001), and the average number of stents implanted in a patient also increased per year (P for trend <.001). The previous stent group had a significantly greater 30-day mortality rate than did the no-stent group (7.2% vs 5.0%; odds ratio, 1.47; 95% confidence interval, 1.19-1.82). The previous stent group had a greater rate of revascularization (14.4% and 10.0%; subdistribution hazard ratio, 1.50; 95% confidence interval, 1.30-1.74) in the last follow-up at year 13.
Previous coronary stenting before coronary artery bypass graft for multivessel coronary artery disease significantly increased 30-day mortality but did not affect late survival. However, patients who had coronary stenting before coronary artery bypass graft experienced more revascularization events during late follow-up.
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Abstract
Mechanochemical synthesis of Si/Cu
3
Si-based composite as negative electrode materials for lithium ion battery is investigated. Results indicate that CuO is decomposed and alloyed with Si ...forming amorphous Cu-Si solid solution due to high energy impacting during high energy mechanical milling (HEMM). Upon carbonization at 800 °C, heating energy induces Cu
3
Si to crystallize in nanocrystalline/amorphous Si-rich matrix enhancing composite rigidity and conductivity. In addition, residual carbon formed on outside surface of composite powder as a buff space further alleviates volume change upon lithiation/delithiation. Thus, coin cell made of C-coated Si/Cu
3
Si-based composite as negative electrode (active materials loading, 2.3 mg cm
−2
) conducted at 100 mA g
−1
performs the initial charge capacity of 1812 mAh g
−1
(4.08 mAh cm
−2
) columbic efficiency of 83.7% and retained charge capacity of 1470 mAh g
−1
(3.31 mAh cm
−2
) at the end of the 100
th
cycle, opening a promised window as negative electrode materials for lithium ion batteries.
Since 2013, rabies cases have been reported among Formosan ferret badgers in Taiwan, and they have been shown to be the major reservoirs for Taiwanese enzootics. To control and eradicate rabies, the ...authorities plan to implement a vaccination programme. Before distributing live vaccines in the field, this study assessed the safety, efficacy, and immunogenicity of SAG2 vaccine on ferret badgers by direct oral instillation. After application of 109 TCID50/dose, no virus was excreted into the oral cavity 1-7 days post-application, and safety was also satisfactorily verified over a 266-day period. Moreover, despite the low level of rabies virus neutralising antibodies induced after vaccination of a 108 TCID50/dose, the efficacy assessment revealed a 100% survival rate (15/15) of vaccinees and an 87.5% fatality rate (7/8) in control animals after a challenge on the 198th day post-vaccination. The immunisation and protection rates obtained more than 6 months after a single vaccination dose demonstrated that SAG2 is an ideal vaccine candidate to protect Formosan ferret badgers against rabies in Taiwan.
14,14′‐Bidibenzoa,janthracenes (BDBAs) were prepared by iridium‐catalyzed annulation of 5,5′‐biterphenylene with alkynes. The molecular geometries of overcrowded BDBAs were verified by X‐ray ...crystallography. The two dibenzoa,janthryl moieties are connected through the sterically hindered 14 positions, resulting in highly distorted molecular halves. The conformation with a small twist angle between two molecular halves can minimize steric conflicts between the substituents at 1 and 13 positions and the carbon atoms of the central axis, as well as steric clashes between those substituents. One such example is octafluoro‐substituted BDBA, where the interplanar angle between two anthryl moieties is approximately 31° (currently the lowest reported value, cf. 81° in 9,9′‐bianthracene). The intramolecular interactions and electronic couplings between two molecular halves resulted in upfield 1H NMR signals, redshifted absorption and emission bands, and a reduced HOMO–LUMO gap. Photodynamic investigations on BDBAs indicated that the formation of the conventional symmetry‐breaking charge transfer (SBCT) state was suspended by restricted rocking around the central C−C bond. Such a mechanism associated with this highly constrained conformation was examined for the first time.
The overcrowded biaryl bears two highly distorted molecular halves and a small interplanar angle between two anthryl moieties (31°, currently the lowest reported value). The close contact between the two aryl fragments endows them with intramolecular interactions. Whereas the restricted rocking around the central C−C bond suspends the formation of the symmetry‐breaking charge transfer (SBCT) state.
Methylphenidate and atomoxetine are efficacious in reducing core symptoms of attention-deficit/hyperactivity disorder (ADHD), but little is known about their efficacy in improving ...emotional/behavioral problems among youths with ADHD.
One hundred sixty drug-naïve youths with DSM-IV-defined ADHD, aged 7-16 years, were recruited and randomly assigned to osmotic-release oral system methylphenidate (OROS-methylphenidate; n = 80) and atomoxetine (n = 80) in a 24-week, open-label, head-to-head clinical trial. The primary efficacy measure was parent-reported Child Behavior Checklist (CBCL), and the secondary efficacy measures included Youth Self Report (YSR) and Strengths and Difficulties Questionnaire (SDQ), which was based on the ratings of parents, teachers, and subjects.
For CBCL, both methylphenidate and atomoxetine groups showed significant improvement in all scores at weeks 8 and 24 except Somatic Complaints in the atomoxetine group. For SDQ, both treatment groups showed significant improvements in the Hyperactive and Conduct subscales for parent ratings, and the Externalizing subscale for teacher ratings at week 24. Methylphenidate was associated with greater improvements in Aggressive Behavior and Somatic Complaints of CBCL and in Conduct subscale of self-reported SDQ at week 24 compared with atomoxetine.
Our findings provide evidence to support that both methylphenidate and atomoxetine were effective in improving a wide range of emotional/behavioral problems in youths with ADHD after 24 weeks of treatment, with greater improvement in aggressive behavior, somatic complaints, and conduct problems in the methylphenidate group.
Methyl palmitate (MP) is a fatty acid methyl ester. Our recent study indicated that adrenergic nerve‐dependent functional sympathetic‐sensory nerve interactions were abolished by MP in mesenteric ...arteries. However, the effect of MP on perivascular nerves and cerebral blood flow remains unclear. In this study, the increase in basilar arterial blood flow (BABF) after the topical application of nicotinic acetylcholine receptor agonists was measured using laser Doppler flowmetry in anesthetized rats. The choline (a selective α7‐nicotinic acetylcholine receptor agonist)‐induced increase in BABF was abolished by tetrodotoxin (a neurotoxin), NG‐nitro‐L‐arginine (a nonselective NO synthase inhibitor), α‐bungarotoxin (a selective α7‐nicotinic acetylcholine receptor inhibitor), and chronic sympathetic denervation. In addition, the nicotine (a nicotinic acetylcholine receptor agonist)‐induced increase in BABF was inhibited by MP in a concentration‐dependent manner. The acetylcholine‐induced increase in BABF was not affected by MP. The myography results revealed that nicotine‐induced vasorelaxation was significantly inhibited by MP, but was reversed by chelerythrine (a protein kinase C inhibitor). MP‐induced vasodilation was significantly greater in BA rings without endothelium compared to those with endothelium. Meanwhile, MP did not affect baseline BABF. Our results indicate that MP acts as a neuromodulator in the cerebral circulation where it activates the PKC pathway and causes a diminished nicotine‐induced increase in blood flow in the brainstem, and that the vasorelaxation effect of MP may play a minor role.
This study evaluated the risk of major bleeding associated with concomitant use of direct oral anticoagulant (DOAC) and anticancer drugs (ACDs), which share metabolic pathways, in patients with ...atrial fibrillation (AF) and cancer. We performed a retrospective cohort study using Taiwan’s National Health Insurance database and included patients with AF and cancer who received DOAC prescriptions from 1 to 2012 to 31 December 2017. The incidence of major bleeding in person-quarters with concomitant use of DOAC and any of 15 ACDs with inhibitory or competitive effects of CYP3A4 or P-gp activity (docetaxel, vinorelbine, methotrexate, irinotecan, etoposide, doxorubicin, cyclophosphamide, imatinib, nilotinib, abiraterone, bicalutamide, tamoxifen, anastrozole, cyclosporine, tacrolimus) was compared with that in person-quarters with DOAC alone. Adjusted incidence-rate differences between DOAC use with and without concurrent ACDs were estimated using Poisson regression models weighted by the inverse probability of treatment. In 13,158 patients with AF and cancer (76.9 ± 8.9 years; male 60%), 1545 major bleeding events occurred during 90,540 DOAC-exposed person-quarters. Concurrent use of DOAC and any of 15 ACDs occurred in only 18% of patients. Compared with use of DOAC alone, concomitant use of DOAC and these ACDs was not associated with an increased risk of major bleeding. Co-medication with DOAC and ACDs with inhibitory or competitive effects on CYP3A4 or P-gp activity was not associated with a higher risk of major bleeding than DOAC alone. Our findings may provide clinicians with confidence regarding the safety of concurrent use of DOAC and ACDs in patients with AF and cancer.
Endothelial dysfunction plays an integral role in pulmonary hypertension (PH). AMPK (AMP-activated protein kinase) and ACE2 (angiotensin-converting enzyme 2) are crucial in endothelial homeostasis. ...The mechanism by which AMPK regulates ACE2 in the pulmonary endothelium and its protective role in PH remain elusive.
We investigated the role of AMPK phosphorylation of ACE2 Ser680 in ACE2 stability and deciphered the functional consequences of this post-translational modification of ACE2 in endothelial homeostasis and PH.
Bioinformatics prediction, kinase assay, and antibody against phospho-ACE2 Ser680 (p-ACE2 S680) were used to investigate AMPK phosphorylation of ACE2 Ser680 in endothelial cells. Using CRISPR-Cas9 genomic editing, we created gain-of-function ACE2 S680D knock-in and loss-of-function ACE2 knockout (ACE2
) mouse lines to address the involvement of p-ACE2 S680 and ACE2 in PH. The AMPK-p-ACE2 S680 axis was also validated in lung tissue from humans with idiopathic pulmonary arterial hypertension.
Phosphorylation of ACE2 by AMPK enhanced the stability of ACE2, which increased Ang (angiotensin) 1-7 and endothelial nitric oxide synthase-derived NO bioavailability. ACE2 S680D knock-in mice were resistant to PH as compared with wild-type littermates. In contrast, ACE2-knockout mice exacerbated PH, a similar phenotype found in mice with endothelial cell-specific deletion of AMPKα2. Consistently, the concentrations of phosphorylated AMPK, p-ACE2 S680, and ACE2 were decreased in human lungs with idiopathic pulmonary arterial hypertension.
Impaired phosphorylation of ACE2 Ser680 by AMPK in pulmonary endothelium leads to a labile ACE2 and hence is associated with the pathogenesis of PH. Thus, AMPK regulation of the vasoprotective ACE2 is a potential target for PH treatment.
Background
Whether four direct oral anticoagulants (DOACs) are superior to warfarin among Asians with non-valvular atrial fibrillation (NVAF) remains unclear in the real-world setting.
Methods
We ...searched PubMed and Medline + Journals@Ovid + EMBASE from September 17, 2009 to May 4, 2019 to perform a systematic review and meta-analysis of all observational real-world studies comparing four DOACs with warfarin specifically focused on Asian patients with NVAF.
Results
From the original 212 results retrieved, 18 studies were included in the meta-analysis. Overall, DOACs were associated with lower risks of thromboembolism (hazard ratio; 95% confidence interval, 0.70; 0.63–0.78), acute myocardial infarction (0.67; 0.57–0.79), all-cause mortality (0.62; 0.56–0.69), major bleeding (0.59; 0.50–0.69), intracranial hemorrhage (0.50; 0.40–0.62), gastrointestinal bleeding (0.66; 0.46–0.95), and any bleeding (0.82; 0.73–0.92) than warfarin. There was statistic heterogeneity between DOACs for the risks of thromboembolism (
P
interaction = 0.03) and acute myocardial infarction (
P
interaction = 0.007) when compared to warfarin. However, all DOACs showed lower risks of thromboembolism and acute myocardial infarction than warfarin when pooling studies that compared individual DOAC with warfarin. With regard to the other outcomes when compared to warfarin, there was no statistical heterogeneity between DOACs. In addition, the effectiveness and safety of four DOACs versus warfarin persisted in the subgroups of either standard-dose or low-dose DOACs.
Conclusions
The meta-analysis shows that the DOACs had greater effectiveness and safety compared to warfarin in real-world practice for stroke prevention, among Asian patients with NVAF.
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