Is clopidogrel better than aspirin following breakthrough strokes while on aspirin? A retrospective cohort study.

ObjectiveThere is insufficient evidence on which to base a recommendation for optimal antiplatelet therapy following a stroke while on aspirin. The objective was to compare clopidogrel initiation vs aspirin reinitiation for vascular risk reduction among patients with ischaemic stroke on aspirin at the time of their index stroke.DesignRetrospective.SettingWe conducted a nationwide cohort study by retrieving all hospitalised patients (≥18 years) with a primary diagnosis of ischaemic stroke between 2003 and 2009 from Taiwan National Health Insurance Research Database.ParticipantsAmong 3862 patients receiving aspirin before the index ischaemic stroke and receiving either aspirin or clopidogrel after index stroke during follow-up period, 1623 were excluded due to a medication possession ratio <80%. Also, 355 were excluded due to history of atrial fibrillation, valvular heart disease or coagulopathy. Therefore, 1884 patients were included in our final analysis.InterventionsPatients were categorised into two groups based on whether clopidogrel or aspirin was prescribed during the follow-up period. Follow-up was from time of the index stroke to admission for recurrent stroke or myocardial infarction, death or the end of 2010.Primary and secondary outcome measuresThe primary end point was hospitalisation due to a new-onset major adverse cardiovascular event (MACE: composite of any stroke or myocardial infarction). The leading secondary end point was any recurrent stroke.ResultsCompared to aspirin, clopidogrel was associated with a lower occurrence of future MACE (HR=0.54, 95% CI 0.43 to 0.68, p<0.001, number needed to treat: 8) and recurrent stroke (HR=0.54, 95% CI 0.42 to 0.69, p<0.001, number needed to treat: 9) after adjustment of relevant covariates.ConclusionsAmong patients with an ischaemic stroke while taking aspirin, clopidogrel initiation was associated with fewer recurrent vascular events than aspirin reinitiation

Efficacy of combined traditional Chinese medicine spray with premature ejaculation desensitization therapy for the treatment of primary premature ejaculation

Objectives: We recommend a new kind of spray made from eight kinds of traditional Chinese medicine, we aimed to investigate the safety and clinical efficacy of combined traditional Chinese medicine spray (TCMS) with premature ejaculation desensitization therapy (PEDT) for the treatment of primary premature ejaculation (PPE).Methods: A total of 90 patients with PPE were randomly assigned to receive TCMS, PEDT monotherapy or TCMS plus PEDT combination therapy for 6 weeks. Intravaginal ejaculation latency time (IELT) and Chinese index of sexual function for premature ejaculation (CIPE-5) were measured to evaluate the effect of each treatment.Results: Eighty six (86) participants completed the study voluntarily. Both IELT and CIPE-5 in these three groups increased after treatment when compared with baseline levels (p< 0.01). IELT and CIPE-5 after treatment in TCMS plus PEDT group were significantly higher than those in the other two groups (both p <0.05). Additionally, clinical efficacy in TCMS plus PEDT group (89.7%) was significantly higher than in TCMS (65.5%) and PEDT group (67.9%) (p< 0.01).Conclusion: The self-made TCMS was safe and effective for the treatment of PPE, a combination of TCMS and PEDT therapy was more effective than the TCMS or PEDT monotherapy.Keywords: Primary premature ejaculation (PPE); traditional Chinese mdicine spray (TCMS); premature ejaculation desensitization training therapy (PEDT); Intravaginal ejaculation latency time (IELT); Chinese index of sexual function for premature ejaculation (CIPE-5

Effect of Radiation Treatment Volume Reduction on Lymphopenia in Patients Receiving Chemoradiotherapy for Glioblastoma.

PURPOSE: To evaluate whether reduction in glioblastoma radiation treatment volume can reduce risk of acute severe lymphopenia (ASL). METHODS AND MATERIALS: A total of 210 patients with supratentorial/nonmetastatic glioblastoma were treated with radiation therapy (RT) plus temozolomide from 2007 to 2016 and had laboratory data on total lymphocyte counts. Before 2015, 164 patients were treated with standard-field RT (SFRT), and limited-field RT (LFRT) was implemented thereafter for 46 patients to reduce treatment volume. Total lymphocyte counts were evaluated at baseline, during RT, and at approximately week 12 from initiating RT. Acute severe lymphopenia was defined as any total lymphocyte count < 500 cells/μL within 3 months (by week 12) of initiating RT. Multivariate analysis for overall survival (OS) was performed with Cox regression and with logistic regression for ASL. Propensity score matching was performed to adjust for variability between cohorts. Acute severe lymphopenia, progression-free survival (PFS), and OS were compared using the Kaplan-Meier method. RESULTS: Limited-field RT patients had higher gross tumor volume than SFRT patients yet lower brain dose-volume parameters, including volume receiving 25 Gy (V25 Gy: 41% vs 53%, respectively, P < .01). Total lymphocyte count at week 12 was significantly higher for LFRT than for SFRT (median: 1100 cells/μL vs 900 cells/μL, respectively, P = .02). On multivariate analysis, ASL was an independent predictor of OS, and brain V25 Gy was an independent predictor of ASL. The ASL rate at 3 months was 15.5% for LFRT and 33.8% for SFRT (P = .12). In a propensity-matched comparison of 45 pairs of LFRT and SFRT patients, PFS (median: 5.9 vs 6.2 months, respectively, P = .58) and OS (median: 16.2 vs 13.9 months, respectively, P = .69) were not significantly different. CONCLUSIONS: Limited-field RT is associated with less lymphopenia after RT plus temozolomide and does not adversely affect PFS or OS. Brain V25 Gy is confirmed as an important dosimetric predictor for ASL

Antioxidative Characteristics of Anisomeles indica Extract and Inhibitory Effect of Ovatodiolide on Melanogenesis

The purpose of the study was to investigate the antioxidant characteristics of Anisomeles indica methanol extract and the inhibitory effect of ovatodiolide on melanogenesis. In the study, the antioxidant capacities of A. indica methanol extract such as DPPH assay, ABTS radical scavenging assay, reducing capacity and metal ion chelating capacity as well as total phenolic content of the extract were investigated. In addition, the inhibitory effects of ovatodiolide on mushroom tyrosinase, B16F10 intracellular tyrosinase and melanin content were determined spectrophotometrically. Our results revealed that the antioxidant capacities of A. indica methanol extract increased in a dose-dependent pattern. The purified ovatodiolide inhibited mushroom tyrosinase activity (IC50 = 0.253 mM), the compound also effectively suppressed intracellular tyrosinase activity (IC50 = 0.469 mM) and decreased the amount of melanin (IC50 = 0.435 mM) in a dose-dependent manner in B16F10 cells. Our results concluded that A. indica methanol extract displays antioxidant capacities and ovatodiolide purified from the extract inhibited melanogenesis in B16F10 cells. Hence, A. indica methanol extract and ovatodiolide could be applied as a type of dermatological whitening agent in skin care products

Efficacy of combined traditional Chinese medicine spray with premature ejaculation desensitization therapy for the treatment of primary premature ejaculation.

Objectives: We recommend a new kind of spray made from eight kinds of traditional Chinese medicine, we aimed to investigate the safety and clinical efficacy of combined traditional Chinese medicine spray (TCMS) with premature ejaculation desensitization therapy (PEDT) for the treatment of primary premature ejaculation (PPE). Methods: A total of 90 patients with PPE were randomly assigned to receive TCMS, PEDT monotherapy or TCMS plus PEDT combination therapy for 6 weeks. Intravaginal ejaculation latency time (IELT) and Chinese index of sexual function for premature ejaculation (CIPE-5) were measured to evaluate the effect of each treatment. Results: Eighty six (86) participants completed the study voluntarily. Both IELT and CIPE-5 in these three groups increased after treatment when compared with baseline levels (p< 0.01). IELT and CIPE-5 after treatment in TCMS plus PEDT group were significantly higher than those in the other two groups (both p <0.05). Additionally, clinical efficacy in TCMS plus PEDT group (89.7%) was significantly higher than in TCMS (65.5%) and PEDT group (67.9%) (p< 0.01). Conclusion: The self-made TCMS was safe and effective for the treatment of PPE, a combination of TCMS and PEDT therapy was more effective than the TCMS or PEDT monotherapy

Time-reversal symmetry breaking driven topological phase transition in EuB6_6

The interplay between time-reversal symmetry (TRS) and band topology plays a crucial role in topological states of quantum matter. In time-reversal-invariant (TRI) systems, the inversion of spin-degenerate bands with opposite parity leads to nontrivial topological states, such as topological insulators and Dirac semimetals. When the TRS is broken, the exchange field induces spin splitting of the bands. The inversion of a pair of spin-splitting subbands can generate more exotic topological states, such as quantum anomalous Hall insulators and magnetic Weyl semimetals. So far, such topological phase transitions driven by the TRS breaking have not been visualized. In this work, using angle-resolved photoemission spectroscopy, we have demonstrated that the TRS breaking induces a band inversion of a pair of spin-splitting subbands at the TRI points of Brillouin zone in EuB$_6$, when a long-range ferromagnetic order is developed. The dramatic changes in the electronic structure result in a topological phase transition from a TRI ordinary insulator state to a TRS-broken topological semimetal (TSM) state. Remarkably, the magnetic TSM state has an ideal electronic structure, in which the band crossings are located at the Fermi level without any interference from other bands. Our findings not only reveal the topological phase transition driven by the TRS breaking, but also provide an excellent platform to explore novel physical behavior in the magnetic topological states of quantum matter.Comment: 22 pages, 7 figures, accepted by Phys. Rev.

Fumarate Analogs Act as Allosteric Inhibitors of the Human Mitochondrial NAD(P)+-Dependent Malic Enzyme

Human mitochondrial NAD(P)+-dependent malic enzyme (m-NAD(P)-ME) is allosterically activated by the four-carbon trans dicarboxylic acid, fumarate. Previous studies have suggested that the dicarboxylic acid in a trans conformation around the carbon-carbon double bond is required for the allosteric activation of the enzyme. In this paper, the allosteric effects of fumarate analogs on m-NAD(P)-ME are investigated. Two fumarate-insensitive mutants, m-NAD(P)-ME_R67A/R91A and m-NAD(P)-ME_K57S/E59N/K73E/D102S, as well as c-NADP-ME, were used as the negative controls. Among these analogs, mesaconate, trans-aconitate, monomethyl fumarate and monoethyl fumarate were allosteric activators of the enzyme, while oxaloacetate, diethyl oxalacetate, and dimethyl fumarate were found to be allosteric inhibitors of human m-NAD(P)-ME. The IC50 value for diethyl oxalacetate was approximately 2.5 mM. This paper suggests that the allosteric inhibitors may impede the conformational change from open form to closed form and therefore inhibit m-NAD(P)-ME enzyme activity

Membrane curvature at a glance

Membrane curvature is an important parameter in defining the morphology of cells, organelles and local membrane subdomains. Transport intermediates have simpler shapes, being either spheres or tubules. The generation and maintenance of curvature is of central importance for maintaining trafficking and cellular functions. It is possible that local shapes in complex membranes could help to define local subregions. In this Cell Science at a Glance article and accompanying poster, we summarize how generating, sensing and maintaining high local membrane curvature is an active process that is mediated and controlled by specialized proteins using general mechanisms: (i) changes in lipid composition and asymmetry, (ii) partitioning of shaped transmembrane domains of integral membrane proteins or protein or domain crowding, (iii) reversible insertion of hydrophobic protein motifs, (iv) nanoscopic scaffolding by oligomerized hydrophilic protein domains and, finally, (v) macroscopic scaffolding by the cytoskeleton with forces generated by polymerization and by molecular motors. We also summarize some of the discoveries about the functions of membrane curvature, where in addition to providing cell or organelle shape, local curvature can affect processes like membrane scission and fusion as well as protein concentration and enzyme activation on membranes