Amperometric enzyme sensor to check the total antioxidant capacity of several mixed berries. comparison with two other spectrophotometric and fluorimetric methods

The aim of this research was to test the correctness of response of a superoxide dismutase amperometric biosensor used for the purpose of measuring and ranking the total antioxidant capacity of several systematically analysed mixed berries. Several methods are described in the literature for determining antioxidant capacity, each culminating in the construction of an antioxidant capacity scale and each using its own unit of measurement. It was therefore endeavoured to correlate and compare the results obtained using the present amperometric biosensor method with those resulting from two other different methods for determining the total antioxidant capacity selected from among those more frequently cited in the literature. The purpose was to establish a methodological approach consisting in the simultaneous application of different methods that it would be possible to use to obtain an accurate estimation of the total antioxidant capacity of different mixed berries and the food product

Efficacy and safety of left atrial appendage closure with WATCHMAN in patients with or without contraindication to oral anticoagulation: 1-Year follow-up outcome data of the EWOLUTION trial

Background Left atrial appendage (LAA) occlusion with WATCHMAN has emerged as viable alternative to vitamin K antagonists in randomized controlled trials. Objective EWOLUTION was designed to provide data in routine practice from a prospective multicenter registry. Methods A total of 1025 patients scheduled for a WATCHMAN implant were prospectively and sequentially enrolled at 47 centers. Indication for LAA closure was based on European Society of Cardiology guidelines. Follow-up and transesophageal echocardiography (TEE) were performed per local practice. Results The baseline CHA 2 DS 2 -VASc score was 4.5 ± 1.6; the mean age was 73.4 ± 9 years; previous transient ischemic attack/ischemic stroke was present in 312 (30.5%), 155 (15.1%) had previous hemorrhagic stroke, and 320 (31.3%) had a history of major bleeding; and 750 (73%) were deemed unsuitable for oral anticoagulation therapy. WATCHMAN implant succeeded in 1005 (98.5%) of patients, without leaks >5 mm in 1002 (99.7%) with at least 1 TEE follow-up in 875 patients (87%). Antiplatelet therapy was used in 784 (83%), while vitamin K antagonists were used in only 75 (8%). At 1 year, mortality was 98 (9.8%), reflecting the advanced age and comorbidities in this population. Device thrombus was observed in 28 patients at routine TEE (3.7%) and was not correlated with the drug regimen ( P = .14). Ischemic stroke rate was 1.1% (relative risk 84% vs estimated historical data); the major bleeding rate was 2.6% and was predominantly (2.3%) nonprocedure/device related. Conclusion LAA closure with the WATCHMAN device has a high implant and sealing success. This method of stroke risk reduction appears to be safe and effective with an ischemic stroke rate as low as 1.1%, even though 73% of patients had a contraindication to and were not using oral anticoagulation

Incidence and predictors of 2-year mortality following percutaneous left atrial appendage occlusion in the EWOLUTION trial

Aims: Sufficient survival time following left atrial appendage occlusion (LAAO) is essential for ensuring the efficacy and cost-effectiveness of this strategy for stroke prevention. Understanding prognostic factors for early mortality after LAAO could optimize patient selection. In the current study, we perform an in-depth analysis of 2-year mortality after LAAO, focusing particularly on potential predictors. Methods and results: The EWOLUTION registry is a real-world cohort comprising 1020 patients that underwent LAAO. Endpoint definitions were pre-specified, and death was categorized as cardiovascular, non-cardiovascular, or unknown origin. Mortality rates were calculated from Kaplan–Meier estimates. Baseline characteristics significantly associated with death in univariate Cox regression analysis were incorporated into the multivariate analysis. All multivariate predictors were included in a risk model. Two-year mortality rate was 16.4% [confidence interval (CI): 14.0–18.7%], with 50% of patients dying from a non-cardiovascular cause. Multivariate baseline predictors of 2-year mortality included age [hazard ratio (HR) 1.05, CI: 1.03–1.08, per year increase], heart failure (HR 1.73, CI: 1.24–2.41), vascular disease (HR 1.47, CI: 1.05–2.05), valvular disease (HR 1.63, CI: 1.15–2.33), abnormal liver function (HR 1.80, CI: 1.02–3.17), and abnormal renal function (HR 1.58, CI: 1.10–2.27). Mortality rate exhibited a gradual rise as the number of risk factors increased, reaching 46.1% in patients presenting with five or six risk factors. Conclusion: One in six patients died within 2 years after LAAO. We identified six independent predictors of mortality. When combined, this model showed a gradual increase in mortality rate with a growing number of risk factors, which may guide appropriate patient selection for LAAO. Clinical trial registration: The original EWOLUTION registry was registered at clinicaltrials.gov under identifier NCT01972282

Candidate biomarkers from the integration of methylation and gene expression in discordant autistic sibling pairs

While the genetics of autism spectrum disorders (ASD) has been intensively studied, resulting in the identification of over 100 putative risk genes, the epigenetics of ASD has received less attention, and results have been inconsistent across studies. We aimed to investigate the contribution of DNA methylation (DNAm) to the risk of ASD and identify candidate biomarkers arising from the interaction of epigenetic mechanisms with genotype, gene expression, and cellular proportions. We performed DNAm differential analysis using whole blood samples from 75 discordant sibling pairs of the Italian Autism Network collection and estimated their cellular composition. We studied the correlation between DNAm and gene expression accounting for the potential effects of different genotypes on DNAm. We showed that the proportion of NK cells was significantly reduced in ASD siblings suggesting an imbalance in their immune system. We identified differentially methylated regions (DMRs) involved in neurogenesis and synaptic organization. Among candidate loci for ASD, we detected a DMR mapping to CLEC11A (neighboring SHANK1) where DNAm and gene expression were significantly and negatively correlated, independently from genotype effects. As reported in previous studies, we confirmed the involvement of immune functions in the pathophysiology of ASD. Notwithstanding the complexity of the disorder, suitable biomarkers such as CLEC11A and its neighbor SHANK1 can be discovered using integrative analyses even with peripheral tissues

The ICARUS Experiment, A Second-Generation Proton Decay Experiment and Neutrino Observatory at the Gran Sasso Laboratory

The final phase of the ICARUS physics program requires a sensitive mass of liquid Argon of 5000 tons or more. The T600 detector stands today as the first living proof that such large detector can be built and that liquid Argon imaging technology can be implemented on such large scales. After the successful completion of a series of technical tests to be performed at the assembly hall in Pavia, the T600 detector will be ready to be transported into the LNGS tunnel. The operation of the T600 at the LNGS will allow us (1) to develop the local infrastructure needed to operate our large detector (2) to start the handling of the underground liquid argon technology (3) to study the local background (4) to start the data taking with an initial liquid argon mass that will reach in a 5-6 year program the multi-kton goal. The T600 is to be considered as the first milestone on the road towards a total sensitive mass of 5000 tons: it is the first piece of the detector to be complemented by further modules of appropriate size and dimensions, in order to reach in a most efficient and rapid way the final design mass. In this document, we describe the physics program that will be accomplished within the first phase of the program

First Results of the 140^{140}Ce(n,γ)141^{141}Ce Cross-Section Measurement at n_TOF

An accurate measurement of the $^{140}$Ce(n,γ) energy-dependent cross-section was performed at the n_TOF facility at CERN. This cross-section is of great importance because it represents a bottleneck for the s-process nucleosynthesis and determines to a large extent the cerium abundance in stars. The measurement was motivated by the significant difference between the cerium abundance measured in globular clusters and the value predicted by theoretical stellar models. This discrepancy can be ascribed to an overestimation of the $^{140}$Ce capture cross-section due to a lack of accurate nuclear data. For this measurement, we used a sample of cerium oxide enriched in $^{140}$Ce to 99.4%. The experimental apparatus consisted of four deuterated benzene liquid scintillator detectors, which allowed us to overcome the difficulties present in the previous measurements, thanks to their very low neutron sensitivity. The accurate analysis of the p-wave resonances and the calculation of their average parameters are fundamental to improve the evaluation of the $^{140}$Ce Maxwellian-averaged cross-section

First Results of the 140^{140}Ce(n,γ)141^{141}Ce Cross-Section Measurement at n_TOF

An accurate measurement of the $^{140}$Ce(n,γ) energy-dependent cross-section was performed at the n_TOF facility at CERN. This cross-section is of great importance because it represents a bottleneck for the s-process nucleosynthesis and determines to a large extent the cerium abundance in stars. The measurement was motivated by the significant difference between the cerium abundance measured in globular clusters and the value predicted by theoretical stellar models. This discrepancy can be ascribed to an overestimation of the $^{140}$Ce capture cross-section due to a lack of accurate nuclear data. For this measurement, we used a sample of cerium oxide enriched in $^{140}$Ce to 99.4%. The experimental apparatus consisted of four deuterated benzene liquid scintillator detectors, which allowed us to overcome the difficulties present in the previous measurements, thanks to their very low neutron sensitivity. The accurate analysis of the p-wave resonances and the calculation of their average parameters are fundamental to improve the evaluation of the $^{140}$Ce Maxwellian-averaged cross-section

A superoxide dismutase biosensor for measuring the antioxidant capacity of blueberry based integrators

Numerous studies and experimental research have indicated the involvement of reactive oxygen species (ROS) in particular, as well as of all types of free radicals in general, in the genesis of numerous pathologies[1]. The antioxidant compounds contained in many foods and beverages are capable of reacting with the radicals and thus play an important role in the prevention and defence against oxidative diseases, representing a protective factor of fundamental importance for human health. Sometimes, however, in the case of incorrect food habits or physical deficiencies, food intake alone is not sufficient to provide enough antioxidant nutrients. Therefore, in such cases, the use of food integrators is recommended. This has become a widespread practice although the antioxidant properties of these compounds are often not fully quantified. It is thus of particular and topical interest to be able to come up with new analytical methods to assess the antioxidant capacity of the various ‘over the counter’ products available in drugstores and that may be purchase without medical prescription. The aim of the present work was to investigate the antioxidant capacity of capsules containing blueberry based products which are included among the group of integrators most widely sold in drugstores owing to this capacity and produced by various drug firms. The results of the investigation are compared in order to rank these products in the order of their antioxidant capacity. Blueberries contain a relatively large amount of acids (citric, malic, etc.), sugars, pectins, tannins, mirtilline (glucoside pigment), anthocyanin (which has a beneficial effect on retina capillaries), vitamins A and C and, to a lesser extent, Vitamin B. It is therefore recommended in treating eye disorders (myopia and retinopatina), in combating eye fatigue, as an antidiarrhoic and against diabetes. It is useful for combating the fragility and excessive permeability of blood vessels [2] by exerting a protective action on capillaries. It is a known fact that the dry extract of blueberry can improve night vision [3]. In particular, black blueberry leaves and berries are rich in active principle. They contain antioxidant compounds like tannins, flavonoids, anthocyanins, glucosides and anthocyanidins. It is therefore its antiradical action that is of fundamental importance: blueberry anthocyanosides strongly inhibit free radicals as they are able to react with practically all known species of radicals [4]. In order to measure antioxidant capacity, in addition to the various spectrophotometric, voltammetric and fluorimetric methods described in the literature, our laboratory has recently developed a special electrochemical method based on a superoxide dismutase (SOD) biosensor [5] to determine the superoxide radical. Previous investigations clearly demonstrated how the results obtained using this new biosensor are comparable to those obtained using established methods (ORAC, DMPD, etc.) [6,7] and have shown the method to be a valid, “robust”, sensitive, practical and economic method. The results obtained by applying the SOD biosensor method to various blueberry based integrators were compared with the results obtained with the spectrophotometric method based on N,N–dimethyl-p-phenylenediamine (DMPD- FeCl3). The same results are currently being compared with those obtained also using the ORAC fluorimetric method, the most frequently used to determine antioxidant activity in food matrices and adopted as reference method. It is also planned to compare the antioxidant capacity of these integrators sold in drugstores with that of fresh and/or deep-frozen blueberries