More, More, More: Reducing Thrombosis in Acute Coronary Syndromes Beyond Dual Antiplatelet Therapy-Current Data and Future Directions.

© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.Common to the pathogenesis of acute coronary syndromes (ACS) is the formation of arterial thrombus, which results from platelet activation and triggering of the coagulation cascade.1 To attenuate the risk of future thrombotic events, patients with ACS are treated with dual antiplatelet therapy (DAPT), namely, the combination of aspirin with a P2Y12 inhibitor, such as clopidogrel, ticagrelor, or prasugrel. Despite DAPT, some ≈10% of ACS patients experience recurrent major adverse cardiovascular events over the subsequent 30 days,2 driving the quest for more effective inhibition of thrombotic pathways. In this review, we provide an overview of studies to date and those ongoing that aim to deliver more effective combinations of antithrombotic agents to patients with recent ACS. We have chosen to confine the review to ACS patients without atrial fibrillation because those with atrial fibrillation have a clear indication for combination therapy that includes oral anticoagulation and should, we feel, be treated as a separate cohort. In this article, we discuss the limitations of the currently available clinical trial data and future directions, with suggestions for how practice might change to reduce the risk of coronary thrombosis in those at greatest risk, with minimal impact on bleeding.Peer reviewedFinal Published versio

Noncommunicating Isolated Enteric Duplication Cyst in the Abdomen in Children: Report of One Case and Review of the Literature

Noncommunicating isolated enteric duplications in the abdomen are an extremely rare variant of enteric duplications with their own blood supply. We report a case of a noncommunicating isolated ileal duplication in a 10-month-old boy. He was admitted because of severe abdominal distension and developed irritability abruptly. Abdominal ultrasound and computed tomography scan revealed a closed loop of small bowel that was dilated severely. A large tubular cyst hanging on the narrow vascular pedicle arising from the base of the terminal ileum mesentery was found with torsion of the pedicle in the right upper quadrant of the abdomen. Laparoscopic excision was performed successfully. Here, we will also review the previously reported cases to raise awareness of noncommunicating isolated enteric duplications in the literature.Keywords: Abdomen, Children, Duplication, Isolated, Noncommunicatin

High capacity cathode materials for Li-S batteries

To enhance the stability of sulfur cathode for a high energy lithium-sulfur battery, sulfur-activated carbon (S-AC) composite was prepared by encapsulating sulfur into micropores of activated carbon using a solution-based processing technique. In the analysis using the prepared specimen of S-AC composite by the focused ion beam (FIB) technique, the elemental sulfur exists in a highly dispersed state inside the micropores of activated carbon, which has a large surface area and a narrow pore distribution. The S-AC composite was characterized through X-ray powder diffraction (XRD), transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET) method, selected area electron diffraction (SAED), energy dispersive X-ray spectrometry (EDX), Fourier transform infrared spectroscopy (FT-IR), thermogravimetry analysis (TGA), and field emission scanning electron microscopy (FESEM). A lithium-sulfur cell using the S-AC composite has a high first discharge capacity over 800 mA h g -1 S even at a high current density such as 2C (3200 mA g -1 S) and has good cycleability around 500 mA h g-1 S discharge capacity at the 50th cycle at the same current density. © 2013 The Royal Society of Chemistry

Iron content in forage sorghum (Sorghum bicolor (L.) Moench) measured on different slit widths with atomic absorption spectrometry

Our objective was to know the right slit width for iron (Fe) concentration of forage sorghum, sorghum hybrid (Sorghum bicolor (L.) Moench), and also to discern which water treatment sludge (WTS) were good for ruminant's health with the feeding sorghum on the present study. The present experiment was carried out on a randomized block design with four treatments; Control, alum sludge compost, alum sludge + NPK (nitrogen, phosphorus, potassium fertilizers), alum sludge compost + NPK (nitrogen, phosphorus, potassium fertilizers). Sorghum hybrid was harvested, and iron content of it was analyzed with an atomic absorption spectrophotometer on background correction (BGC) mode. In order to analyze the iron (Fe) content of the sorghum with the spectrophotometer, three different slit widths conditions were used; 0.15, 0.20 and 0.25 nm. Absorbance and background values were obtained during the Fe analyses with the apparatus. When the background value is small, it is preferred for some trace metals’ analyses. Both (AM/BS) ratio (mean of the absorbance values<AM> to the standard deviation of back ground values<BS>) and (AS<standard deviation of the absorbance values>/BS) ratio, were larger on 0.25 nm slit than those on 0.15 and 0.20 nm slit, and, from our experiment, the condition seemed better on the 0.25 nm slit for the iron analysis with the spectrophotometer. Therefore, the sorghum hybrid grown on (Alum+NPK) and on (Compost only) might be dangerous for ruminants because of their higher values than 200 mg Fe/kg DM (dry matter).Key words: Absorbance, alum sludge, atomic absorption spectrophotometer, background, forage sorghum hybrid, iron, slit

The 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE) trial: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Second-generation drug-eluting stents (DES) have raised the bar of clinical performance. These stents are mostly made from cobalt chromium alloy. A newer generation DES has been developed from platinum chromium alloy, but clinical data regarding the efficacy and safety of the platinum chromium-based everolimus-eluting stent (PtCr-EES) is limited, with no comparison data against the cobalt chromium-based zotarolimus-eluting stent (CoCr-ZES). In addition, an antiplatelet regimen is an integral component of medical therapy after percutaneous coronary intervention (PCI). A 1-week duration of doubling the dose of clopidogrel (double-dose antiplatelet therapy (DDAT)) was shown to improve outcome at 1 month compared with conventional dose in acute coronary syndrome (ACS) patients undergoing PCI. However in Asia, including Korea, the addition of cilostazol (triplet antiplatelet therapy (TAT)) is used more commonly than doubling the dose of clopidogrel in high-risk patients.</p> <p>Methods</p> <p>In the 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE) trial, approximately 3,750 patients are being prospectively and randomly assigned in a 2 × 2 factorial design according to the type of stent (PtCr-EES vs CoCr-ZES) and antiplatelet regimen (TAT vs DDAT). The first primary endpoint is target lesion failure at 1 year for the stent comparison, and the second primary endpoint is net clinical outcome at 1 month for comparison of antiplatelet therapy regimen.</p> <p>Discussion</p> <p>The HOST-ASSURE trial is the largest study yet performed to directly compare the efficacy and safety of the PtCr-EES versus CoCr-ZES in an 'all-comers' population. In addition, this study will also compare the clinical outcome of TAT versus DDAT for 1-month post PCI.</p> <p>Trial registration</p> <p>ClincalTrials.gov number <a href="http://www.clinicaltrials.gov/ct2/show/NCT01267734">NCT01267734</a>.</p

The relevance of outsourcing and leagile strategies in performance optimization of an integrated process planning and scheduling

Over the past few years growing global competition has forced the manufacturing industries to upgrade their old production strategies with the modern day approaches. As a result, recent interest has been developed towards finding an appropriate policy that could enable them to compete with others, and facilitate them to emerge as a market winner. Keeping in mind the abovementioned facts, in this paper the authors have proposed an integrated process planning and scheduling model inheriting the salient features of outsourcing, and leagile principles to compete in the existing market scenario. The paper also proposes a model based on leagile principles, where the integrated planning management has been practiced. In the present work a scheduling problem has been considered and overall minimization of makespan has been aimed. The paper shows the relevance of both the strategies in performance enhancement of the industries, in terms of their reduced makespan. The authors have also proposed a new hybrid Enhanced Swift Converging Simulated Annealing (ESCSA) algorithm, to solve the complex real-time scheduling problems. The proposed algorithm inherits the prominent features of the Genetic Algorithm (GA), Simulated Annealing (SA), and the Fuzzy Logic Controller (FLC). The ESCSA algorithm reduces the makespan significantly in less computational time and number of iterations. The efficacy of the proposed algorithm has been shown by comparing the results with GA, SA, Tabu, and hybrid Tabu-SA optimization methods

Grazing-incidence small-angle X-ray scattering studies on templating nanopores in networked polymer thin films with a multi-armed porogen

The mechanism of thermal pore generation in organosilicate thin films loaded with a six-armed star-shaped poly(epsilon-caprolactone) porogen was quantitatively investigated by using in-situ grazing-incidence small-angle X-ray scattering and thermogravimetry. These analyses found that the blend components have a limited miscibility that depends on the compositionfor porogen loadings up to only 20 wt%, molecularly miscible blend films were obtained. Even for the miscible blend films, heating the films produced a curing reaction of the precursor matrix component, leading to the phase separation of the porogen component. This phase separation was found to begin at 393 K for 10 wt% porogen loaded films and at 373 K for 20 wt% porogen loaded films, and to continue for temperatures up to 423 K. The porogen aggregates remained and were confined within the matrix film without any further growth or movement until complete thermal decomposition above 564 K.ope

Protein arginine methyltransferase 5 is a key regulator of the MYCN oncoprotein in neuroblastoma cells.

Approximately half of poor prognosis neuroblastomas (NBs) are characterized by pathognomonic MYCN gene amplification and MYCN over-expression. Here we present data showing that short-interfering RNA mediated depletion of the protein arginine methyltransferase 5 (PRMT5) in cell-lines representative of NBs with MYCN gene amplification leads to greatly impaired growth and apoptosis. Growth suppression is not apparent in the MYCN-negative SH-SY5Y NB cell-line, or in two immortalized human fibroblast cell-lines. Immunoblotting of NB cell-lines shows that high PRMT5 expression is strongly associated with MYCN-amplification (P < 0.004, Mann-Whitney U-test) and immunohistochemical analysis of primary NBs reveals that whilst PRMT5 protein is ubiquitously expressed in the cytoplasm of most cells, MYCN-amplified tumours exhibit pronounced nuclear PRMT5 staining. PRMT5 knockdown in MYCN-overexpressing cells, including the SHEP-21N cell-line with inducible MYCN expression leads to a dramatic decrease in MYCN protein and MYCN-associated cell-death in SHEP-21N cells. Quantitative gene expression analysis and cycloheximide chase experiments suggest that PRMT5 regulates MYCN at a post-transcriptional level. Reciprocal co-immunoprecipitation experiments demonstrated that endogenous PRMT5 and MYCN interact in both SK-N-BE(2)C and NGP cell lines. By using liquid chromatography - tandem mass spectrometry (LC-MS/MS) analysis of immunoprecipitated MYCN protein, we identified several potential sites of arginine dimethylation on the MYCN protein. Together our studies implicate PRMT5 in a novel mode of MYCN post-translational regulation and suggest PRMT5 plays a major role in NB tumorigenesis. Small-molecule inhibitors of PRMT5 may therefore represent a novel therapeutic strategy for neuroblastoma and other cancers driven by the MYCN oncogene

Clinical significance of amyloid β positivity in patients with probable cerebral amyloid angiopathy markers

Purpose: We investigated the frequency and clinical significance of amyloid β (Aβ) positivity on PET in patients with cerebral amyloid angiopathy (CAA). / Methods: We recruited 65 patients who met the modified Boston criteria for probable CAA. All underwent amyloid PET, MRI, APOE genotyping and neuropsychological testing, and we obtained information on MRI markers of CAA and ischemic cerebral small-vessel disease (CSVD). We investigated the CAA/ischemic CSVD burden and APOE genotypes in relation to Aβ positivity and investigated the effect of Aβ positivity on longitudinal cognitive decline. / Results: Among the 65 CAA patients, 43 (66.2%) showed Aβ PET positivity (Aβ+). Patients with Aβ+ CAA had more lobar microbleeds (median 9, interquartile range 2–41, vs. 3, 2–8; P = 0.045) and a higher frequency of cortical superficial siderosis (34.9% vs. 9.1%; P = 0.025), while patients with Aβ− CAA had more lacunes (1, 0–2, vs. 0, 0–1; P = 0.029) and a higher frequency of severe white matter hyperintensities (45.5% vs. 20.9%; P = 0.040). The frequency of ε4 carriers was higher in Aβ+ patients (57.1%) than in Aβ− patients (18.2%; P = 0.003), while the frequency of ε2 carriers did not differ between the two groups. Finally, Aβ positivity was associated with faster decline in multiple cognitive domains including language (P < 0.001), visuospatial function (P < 0.001), and verbal memory (P < 0.001) in linear mixed effects models. / Conclusion: Our findings suggest that a significant proportion of patients with probable CAA in a memory clinic are Aβ− on PET. Aβ positivity in CAA patients is associated with a distinct pattern of CSVD biomarker expression, and a worse cognitive trajectory. Aβ positivity has clinical relevance in CAA and might represent either advanced CAA or additional Alzheimer’s disease neuropathological changes