Quantitative analysis of α-Gal trisaccharide content and its contribution to degeneration of bioprosthetic heart valves

Background: Commercial bioprosthetic heart valves (BHVs) are generally produced from porcine aortic heart valves or sewn from bovine pericardium. BHVs are durable in older patients, but in younger patients they are subject to age-dependent structural valve degeneration (SVD). SVD involves tissue calcification, which our research suggests is due in part to an immune mediated BHV injury caused by high levels of xenogeneic antigen galactose-alpha-1,3-galactose (α-Gal) on commercial valves and anti-Gal antibody universally present in patients. This suggests that α-Gal-free BHVs, unaffected by anti-Gal antibody could resist calcification and show improved durability in younger patients. Aim: This research was to develop quantitative methods to measure α-Gal antigen on animal tissue and further characterize the role of α-Gal-specific immune injury in tissue calcification. Methodology: I tested an α-galactosidase based colorimetric enzymatic assay for detecting galactose liberated from tissue and an α-Gal-specific inhibition ELISA (GIE) to measure α-Gal on fixed porcine pericardium. The α-Gal levels on wild type (WT), and α-Gal-free (GTKO) porcine tissue after glutaraldehyde fixation and after treating with various anticalcification processes were measured. The effects of anti-Gal antibody on WT and GTKO tissue calcification were measured using subcutaneous implants in anti-Gal antibody producing GTKO mice. Results: The α-galactosidase based colorimetric assay showed low sensitivity and was not pursued. The GIE, using two different anti-Gal reagents, was sensitive and reliable. A-Gal antigen levels, measured by GIE were not reduced by anticalcification processing. Minimal tissue calcification was observed in GTKO mice for both WT and GTKO tissue. There was no clear anti-Gal immune response to WT implants. Conclusion: This research shows that the current BHVs remain susceptible to immune injury as α-Gal antigen is not eliminated by the current anticalcification treatments. In addition caution is required when choosing the appropriate animal model to address the immune response factor in tissue calcification studies

Social influence protects collective decision making from equality bias

A basic tenet of research on wisdom of the crowds – and key assumption of Condorcet’s Jury Theorem – is the independence of voters’ opinions before votes are aggregated. However, we often look for others’ opinions before casting our vote. Such social influence can push groups towards herding, leading to “madness of the crowds”. To investigate the role of social influence in joint decision making, we had dyads of participants perform a visual odd-ball search task together. In the Independent (IND) condition participants initially made a private decision. If disagreeing, discussion and collective decision ensued. In the Influence (INF) condition no private decisions were made and collective decision was immediately negotiated. Dyads that did not accrue collective benefit under IND condition improved with added social influence under INF condition. In Experiment 2, covertly, we added noise to one of the dyad members’ visual search display. The resulting increased heterogeneity in dyad members’ performances impaired the dyadic performance under IND condition (Bahrami et al., 2010). Importantly, dyadic performance improved with social influence under INF, replicating Experiment 1. Further analyses revealed that under IND condition, dyads exercised equality bias (Mahmoodi et al., 2015) by granting undue credit to the less reliable partner. Under INF condition, however, the more reliable partner (correctly) dominated the joint decisions. While social influence may impede collective success under ideal conditions, our results demonstrate how it can help the group members overcome factors such as equality bias, which could potentially lead to catastrophic failure

Efficient single-step rapeseed oleosome extraction using twin-screw press

Oil in seeds is encapsulated in oleosomes, which are small lipid droplets surrounded by a phospholipid-protein monolayer. The currently proposed method to extract intact oleosomes includes mixing seeds with alkaline media in a ratio 1:7, batch blending and filtering. In this work, we propose the use of a twin-screw press to perform the oleosome extraction at pH 7. The results show that similarly to blender extraction, twin-screw press recovers ⁓60% of the oleosomes; however the twin-screw press is able to achieve this yield even when just pure water is used. While in the blender extraction, the yield depends on ionic strength and pH of the extraction media, when using twin-screw press, the oleosome extraction yield predominantly depends on the mechanical forces. These shear forces are able to break the cell walls and release the cellular material while maintaining the integrity of oleosomes. The oleosomes extracted with twin-screw press have similar characteristics than those obtained by the blending process. Overall, twin-screw press seems a promising alternative to scale-up the oleosome aqueous extraction, especially as neutral pH can be used and the water usage is significantly reduced. Additionally, preliminary results showed that the yield can increase up to 90 wt%.</p

Physical equivalency of wild type and Galactose α 1,3 Galactose free porcine pericardium; a new source material for bioprosthetic heart valves

Humans make high levels of antibody to carbohydrates with terminal galactose α 1,3 galactose (Gal) modifications. This Gal antigen is widely expressed in other mammals and is present on an array of current animal derived biomedical devices including bioprosthetic heart valves. There is growing interest in using Gal-free animal tissues from Gal knockout pigs (GTKO) as these tissues would not be affected by anti-Gal antibody mediated injury. In this study we compare the composition and biophysical characteristics of glutaraldehyde fixed porcine pericardium from standard and GTKO pigs. We show that with the exception of the Gal antigen which is only present in standard pig tissue both GTKO and standard pig tissue have the same general morphology and collagen content. Moreover uniaxial stress testing and suture retention testing indicate the tissues are equivalent in tensile strength. These studies indicate that genetic disruption of the α-galactosyltransferase (GGTA-1) which blocks synthesis of the Gal antigen has no significant impact on the structural integrity of porcine pericardium and suggest that this tissue could be directly substituted for standard pig pericardium in biomedical devices such as bioprosthetic heart valves. STATEMENT OF SIGNIFICANCE: Surgical heart valve replacement is a proven life saving therapy to treat heart valve dysfunction due to birth defects, infection and the effects of aging. Bioprosthetic heart valves (BHV) made from glutaraldehyde fixed animal tissues are an effective durable therapy in older patients (> 60 years) but exhibit age-dependent structural valve degeneration (SVD) in younger patients (<60 years). SVD is principally caused by BHV calcification. Immune injury contributes to age-dependent SVD through the interaction of galactose α 1,3 galactose (Gal) a dominant xenogeneic antigen present on commercial BHVs and universally abundant human anti-Gal antibody. This study measures the tissue equivalency between standard pig pericardium and Gal-free pericardium from genetically modified pigs as a first step towards making Gal-free BHVs

smart sustainable islands vs smart sustainable cities

This paper has several aims: a) the presentation of a critical analysis of the terms "smart sustainable cities" and "smart sustainable islands" b) the presentation of a number of principles towards to the development methodological framework of concepts and actions, in a form of a manual and actions guide, for the smartification and sustainability of islands. This kind of master plan is divided in thematic sectors (key factors) which concern the insular municipalities c) the creation of an island's smartification and sustainability index d) the first steps towards the creation of a portal for the presentation of our smartification actions manual, together with relative resources, smart applications examples, and, in the near future the first results of our index application in a number of Greek islands and e) the presentation of some proposals of possible actions towards their sustainable development and smartification for the municipalities - islands of Paros and Antiparos in Greece, as case studies

Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort

Objectives:We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged-infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies.Methods: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries.Results: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT(&gt; MIC) (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving beta-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P=0.012]. Additionally, in patients with a SOFA score of &gt;= 9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P=0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P=0.025].Conclusions: Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections

The Developing Human Connectome Project Neonatal Data Release

The Developing Human Connectome Project has created a large open science resource which provides researchers with data for investigating typical and atypical brain development across the perinatal period. It has collected 1228 multimodal magnetic resonance imaging (MRI) brain datasets from 1173 fetal and/or neonatal participants, together with collateral demographic, clinical, family, neurocognitive and genomic data from 1173 participants, together with collateral demographic, clinical, family, neurocognitive and genomic data. All subjects were studied in utero and/or soon after birth on a single MRI scanner using specially developed scanning sequences which included novel motion-tolerant imaging methods. Imaging data are complemented by rich demographic, clinical, neurodevelopmental, and genomic information. The project is now releasing a large set of neonatal data; fetal data will be described and released separately. This release includes scans from 783 infants of whom: 583 were healthy infants born at term; as well as preterm infants; and infants at high risk of atypical neurocognitive development. Many infants were imaged more than once to provide longitudinal data, and the total number of datasets being released is 887. We now describe the dHCP image acquisition and processing protocols, summarize the available imaging and collateral data, and provide information on how the data can be accessed