New Approaches on Japanese Knotweed (Fallopia japonica) Bioactive Compounds and Their Potential of Pharmacological and Beekeeping Activities: Challenges and Future Directions

Known especially for its negative ecological impact, Fallopia japonica (Japanese knotweed) is now considered one of the most invasive species. Nevertheless, its chemical composition has shown, beyond doubt, some high biological active compounds that can be a source of valuable pharmacological potential for the enhancement of human health. In this direction, resveratrol, emodin or polydatin, to name a few, have been extensively studied to demonstrate the beneficial effects on animals and humans. Thus, by taking into consideration the recent advances in the study of Japanese knotweed and its phytochemical constituents, the aim of this article is to provide an overview on the high therapeutic potential, underlining its antioxidant, antimicrobial, anti-inflammatory and anticancer effects, among the most important ones. Moreover, we describe some future directions for reducing the negative impact of Fallopia japonica by using the plant for its beekeeping properties in providing a distinct honey type that incorporates most of its bioactive compounds, with the same health-promoting properties

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Overview of IFMIF-DONES diagnostics: Requirements and techniques

The IFMIF-DONES Facility is a unique first-class scientific infrastructure whose construction is foreseen in Granada, Spain, in the coming years. Strong integration efforts are being made at the current project phase aiming at harmonizing the ongoing design of the different and complex Systems of the facility. The consolidation of the Diagnostics and Instrumentation, transversal across many of them, is a key element of this purpose. A top-down strategy is proposed for a systematic Diagnostics Review and Requirement definition, putting emphasis in the one-of-a-kind instruments necessary by the operational particularities of some of the Systems, as well as to the harsh environment that they shall survive. In addition, other transversal aspects such as the ones related to Safety and Machine Protection and their respective requirements shall be also considered. The goal is therefore to advance further and solidly in the respective designs, identify problems in advance, and steer the Diagnostics development and validation campaigns that will be required. The present work provides an overview of this integration strategy as well as a description of some of the most challenging Diagnostics and Instruments within the facility, including several proposed techniques currently under study

Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

<p>Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.</p> <p>Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.</p> <p>Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.</p&gt

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

FURTHER EXAMPLES OF A LIGAND FIELD CALCULATION FOR THE SIXFOLD COORDINATED COMPLEX Fe(H2O)2+6

Les ions paramagnétiques Fe2+ dans Fe(BF4)2. 6 H2O dans Co(BF4)2. 6 H2O et dans Co(ClO4)2. 6 H2O ont été observé à 4,2 K sous forme de poudre, par spectrométrie Mössbauer, avec un champ magnétique longitudinal appliqué allant jusque 50 kG. Le champ de symétrie du ligand aux sites de fer est principalement de type D3d. Tous les spectres peuvent être très bien interprétés dans le cadre de la théorie du champ de ligand réduit au sous-espace 5T2g des états de haut spin 5D, la symétrie réelle dans le sous-groupe C2h de D3d. Pour surmonter le grand nombre de paramètres concernés, la covalence, le couplage spin-orbite et les constantes hyperfines sont prises identiques pour tous les composés, ce qui est justifié par le fait que les liaisons du fer et par conséquent les molécules orbitales sont principalement déterminées par le complexe Fe(H2O)2+6. La distorsion identique de C2h dans ces composés, dans FeSiF6. 6 H2O et dans Fe(ClO4)2. 6 H2O donne lieu à un abaissement de la symétrie D3d.Mössbauer spectra of powder samples of the paramagnetic Fe2+ ion in Fe(BF4)2. 6 H2O and diluted in Co(BF4)2. 6 H2O and Co(ClO4)2. 6 H2O have been measured at 4.2 K in longitudinal external magnetic fields up to 50 kG. The ligand field symmetry at the Fe-site is mainly D3d. All spectra can be well reproduced within the ligand field theory restricted to the 5T2g subspace of the 5D high spin state and the effective symmetry at the iron site being C2h, the subgroup of D3d. To overcome the large number of parameters involved the covalency, the spin-orbit-coupling and the hyperfine constants are taken to be the same for all compounds due to the matter of fact that the binding to the iron ion and therefore the molecular orbitals are essentially determined by the Fe(H2O)2+6 complex. The similar C2h -distortions in these compounds and in FeSiF6. 6 H2O and Fe(ClO4)2. 6H2O are a hint at the Fe(H2O)2+6 complex itself giving rise to the lowering of the D3d symmetry rather than the environment in the crystal