Calcium channel blockers reduce the antiplatelet effect of clopidogrel

ObjectivesBecause of the known CYP3A4 inhibition by calcium-channel blockers (CCBs), we hypothesized that there might be a drug-drug interaction between clopidogrel and dihydropyridines in patients with coronary artery disease.BackgroundClopidogrel is activated by CYP3A4, which also metabolizes CCBs of the dihydropyridine class.MethodsResponsiveness to clopidogrel was assessed by the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay and aggregometry in 200 patients with coronary artery disease undergoing percutaneous coronary intervention.ResultsThe platelet reactivity index (PRI) (in the VASP assay, normal range 69% to 100%) was higher in patients receiving both clopidogrel and CCBs (61%) as compared with patients receiving clopidogrel without CCBs (48%). The absolute difference was 13% (95% confidence interval: 6% to 20%; p = 0.001), and the relative difference approached 21%. A decreased platelet inhibition by clopidogrel (PRI >69%) was seen in 40% of patients with concomitant CCB treatment and in 20% of patients without concomitant treatment (chi-square test, p = 0.008). Intake of CCB remained an independent predictor of reduced platelet inhibition by clopidogrel after adjustment for cardiovascular risk factors. Adenosine diphosphate-induced platelet aggregation was 30% higher in patients on concomitant CCB treatment compared with patients without CCBs (p = 0.046). Moreover, intake of CCBs was associated with adverse clinical outcome. In vitro incubation with CCBs (nimodipine, verapamil, amlodipine, and diltiazem) did not alter the PRI or the adenosine diphosphate–induced platelet aggregation of patients taking clopidogrel. This finding indicates that the negative effect occurs in vivo, conceivably at the level of the CYP3A4 cytochrome.ConclusionsCoadministration of CCBs is associated with decreased platelet inhibition by clopidogrel

A New Kind of Graded Lie Algebra and Parastatistical Supersymmetry

In this paper the usual $Z_2$ graded Lie algebra is generalized to a new form, which may be called $Z_{2,2}$ graded Lie algebra. It is shown that there exists close connections between the $Z_{2,2}$ graded Lie algebra and parastatistics, so the $Z_{2,2}$ can be used to study and analyse various symmetries and supersymmetries of the paraparticle systems

Optimal duration and combination of antiplatelet therapies following percutaneous coronary intervention: a meta-analysis.

Abstract Introduction The ideal duration of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) is still unknown. In this meta-analysis, we aimed to compare very short-term (1–3 months), short-term (6 months), standard-term (12 months) and long-term (>12 months) DAPT durations for efficacy and safety. Methods Overall DAPT comparisons were classified as "any shorter-term"/"any longer-term" DAPT. The primary outcome was a composite of major adverse cardiovascular events (MACE: non-fatal myocardial infarction, non-fatal stroke and cardiovascular death). The primary safety outcome was major bleeding. Results Twenty-six studies comprising 103.394 patients were included. Compared with standard-term DAPT duration, very short-term DAPT duration with subsequent drop of aspirin (RR 1.06, 95% CI, 0.95–1.18, p = 0.26) or drop of the P2Y12 inhibitor (RR 0.92, 95% CI, 0.72-1.16, p = 0.47) was not associated with a higher risk of MACE. Any longer-term compared with any shorter-term DAPT durations led to a significantly lower risk of MACE (RR 0.88, 95% CI, 0.81–0.96, p = 0.002), but a significantly higher risk of BARC 3-5 major bleeding events (RR 1.63, 95% CI, 1.22–2.17, p = 0.001). In the ACS subgroup receiving prasugrel or ticagrelor but not clopidogrel, any longer-term DAPT duration was associated with a significantly lower risk of MACE compared to any shorter-term DAPT duration (RR 0.84, 95% CI, 0.77–0.92, p = 0.0001). Conclusion DAPT may be shortened to 1-3 months in patients with low ischemic but high bleeding risk followed by aspirin or P2Y12 monotherapy. Prasugrel or ticagrelor based DAPT may be extended to >12 months in case of high ischemic and low bleeding risk. PROSPERO registration no CRD42020163719

Planck LFI flight model feed horns

this paper is part of the Prelaunch status LFI papers published on JINST: http://www.iop.org/EJ/journal/-page=extra.proc5/jinst The Low Frequency Instrument is optically interfaced with the ESA Planck telescope through 11 corrugated feed horns each connected to the Radiometer Chain Assembly (RCA). This paper describes the design, the manufacturing and the testing of the flight model feed horns. They have been designed to optimize the LFI optical interfaces taking into account the tight mechanical requirements imposed by the Planck focal plane layout. All the eleven units have been successfully tested and integrated with the Ortho Mode transducers.Comment: This is an author-created, un-copyedited version of an article accepted for publication in JINST. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The definitive publisher authenticated version is available online at 10.1088/1748-0221/4/12/T1200

Sex and gender in cardiovascular medicine: presentation and outcomes of acute coronary syndrome.

Although health disparities in women presenting with acute coronary syndrome (ACS) have received growing attention in recent years, clinical outcomes from ACS are still worse for women than for men. Women continue to experience higher patient and system delays and receive less aggressive invasive treatment and pharmacotherapies. Gender- and sex-specific variables that contribute to ACS vulnerability remain largely unknown. Notwithstanding the sex differences in baseline coronary anatomy and function, women and men are treated the same based on guidelines that were established from experimental and clinical trial data over-representing the male population. Importantly, younger women have a particularly unfavourable prognosis and a plethora of unanswered questions remains in this younger population. The present review summarizes contemporary evidence for gender and sex differences in vascular biology, clinical presentation, and outcomes of ACS. We further discuss potential mechanisms and non-traditional risk conditions modulating the course of disease in women and men, such as unrecognized psychosocial factors, sex-specific vascular and neural stress responses, and the potential impact of epigenetic modifications

An Alternative Method to Deduce Bubble Dynamics in Single Bubble Sonoluminescence Experiments

In this paper we present an experimental approach that allows to deduce the important dynamical parameters of single sonoluminescing bubbles (pressure amplitude, ambient radius, radius-time curve) The technique is based on a few previously confirmed theoretical assumptions and requires the knowledge of quantities such as the amplitude of the electric excitation and the phase of the flashes in the acoustic period. These quantities are easily measurable by a digital oscilloscope, avoiding the cost of expensive lasers, or ultrafast cameras of previous methods. We show the technique on a particular example and compare the results with conventional Mie scattering. We find that within the experimental uncertainties these two techniques provide similar results.Comment: 8 pages, 5 figures, submitted to Phys. Rev.

UNA MIRADA A TRAVÉS DE LAS MACROALGAS: Una lupa sumergida bajo los mares antárticos, recopilando y compartiendo el conocimiento sobre las macroalgas.

Bajo el mar antártico se esconde una vida única adaptada a condiciones extremas de temperatura y luz. Las macroalgas antárticas desempeñan un papel fundamental en la producción de oxígeno y en la absorción de dióxido de carbono de la atmósfera, contribuyendo a regular el clima global. Estas importantes productoras primarias son auténticas ingenieras del ecosistema marino, crean y modifican los hábitats y proveen refugio y protección a una variedad de organismos marinos. Se presentan aquí las diferentes líneas de investigación desarrolladas en Caleta Potter, un ecosistema marino antártico costero seriamente afectado por los fenómenos asociados al cambio global

The Optimal Choice of Trap Type for the Recently Spreading Jewel Beetle Pests Lamprodila festiva and Agrilus sinuatus (Coleoptera, Buprestidae)

BACKGROUND: Two jewel beetle species native to Europe, the cypress jewel beetle, Lamprodila (Palmar, Ovalisia) festiva L. (Buprestidae, Coleoptera), and the sinuate pear tree borer, Agrilus sinuatus Olivier (Buprestidae, Coleoptera), are key pests of ornamental thuja and junipers and of orchard and ornamental rosaceous trees, respectively. Although chemical control measures are available, due to the beetles’ small size, agility, and cryptic lifestyle at the larval stage, efficient tools for their detection and monitoring are missing. Consequently, by the time emerging jewel beetle adults are noticed, the trees are typically significantly damaged. METHODS: Thus, the aim of this study was to initiate the development of monitoring traps. Transparent, light green, and purple sticky sheets and multifunnel traps were compared in field experiments in Hungary. RESULTS: Light green and transparent sticky traps caught more L. festiva and A. sinuatus jewel beetles than non-sticky multifunnel traps, regardless of the larger size of the colored surface of the funnel traps. CONCLUSIONS: Although light green sticky sheets turned out to be optimal for both species, using transparent sheets can reduce catches of non-target insects. The key to the effectiveness of sticky traps, despite their reduced suitability for quantitative comparisons, may lie in the behavioral responses of the beetles to the optical features of the traps

Catches of Euxoa tritici in pheromone traps for Anarsia lineatella are due to the presence of (Z)-5-decenyl acetate as an impurity

Traps baited with the synthetic pheromone of Anarsia lineatella Zeller (Lepidoptera: Gelechiidae) frequently captured also Euxoa tritici L. males (Lepidoptera: Noctuidae) in field tests in Hungary. As (E)-monounsaturated compounds are uncommon among sex attractants or pheromone components of Noctuidae, it was hypothesized that the Euxoa catches may have been due to impurities of the (Z) isomer in synthetic (E)-5-decenyl acetate, which is the major component in the pheromone lure of A. lineatella. Traps baited with synthetic (Z)-5-decenyl acetate captured large numbers of E. tritici, and the compound showed a clear dose–response effect. Reanalysis of the synthetic batch of (E)-5-decenyl acetate used in preparation of the A. lineatella lure showed the presence of 10% of the (Z) isomer. Traps baited with synthetic (Z)-5-decenyl acetate can be used in the future for detection and monitoring purposes of E. tritici, a widely distributed pest of cereals and other field crops. The compound also showed attraction of Euxoa seliginis Duponche

Investigation of transition frequencies of two acoustically coupled bubbles using a direct numerical simulation technique

The theoretical results regarding the ``transition frequencies'' of two acoustically interacting bubbles have been verified numerically. The theory provided by Ida [Phys. Lett. A 297 (2002) 210] predicted the existence of three transition frequencies per bubble, each of which has the phase difference of $\pi /2$ between a bubble's pulsation and the external sound field, while previous theories predicted only two natural frequencies which cause such phase shifts. Namely, two of the three transition frequencies correspond to the natural frequencies, while the remaining does not. In a subsequent paper [M. Ida, Phys. Rev. E 67 (2003) 056617], it was shown theoretically that transition frequencies other than the natural frequencies may cause the sign reversal of the secondary Bjerknes force acting between pulsating bubbles. In the present study, we employ a direct numerical simulation technique that uses the compressible Navier-Stokes equations with a surface-tension term as the governing equations to investigate the transition frequencies of two coupled bubbles by observing their pulsation amplitudes and directions of translational motion, both of which change as the driving frequency changes. The numerical results reproduce the recent theoretical predictions, validating the existence of the transition frequencies not corresponding to the natural frequency.Comment: 18 pages, 8 figures, in pres