An atomic scale comparison of the reaction of Bioglass® in two types of simulated body fluid

A class of melt quenched silicate glasses, containing calcium, phosphorus and alkali metals, and having the ability to promote bone regeneration and to fuse to living bone, is produced commercially as Bioglass. The changes in structure associated with reacting the bioglass with a body fluid simulant (a buffered Tris(hydroxymethyl)aminomethane growth medium solution or a blood plasma-like salt simulated body fluid) at 37°C have been studied using both high energy and grazing incidence x-ray diffraction. This has corroborated the generic conclusions of earlier studies based on the use of calcia–silica sol-gel glasses whilst highlighting the important differences associated with glass composition; the results also reveal the more subtle effects on reaction rates of the choice of body fluid simulant. The results also indicate the presence of tricalcium phosphate crystallites deposited onto the surface of the glass as a precursor to the growth of hydroxyapatite, and indicates that there is some preferred orientation to their growth

Population and Virulence Factor Analysis of Staphylococcus aureus from Bovine Mastitis.

End of Project ReportsStaphylococcus aureus is a major cause of bovine mastitis and the disease is responsible for substantial economic losses in the dairy industry world-wide. A large number of commonly accepted virulence factors are associated with S. aureus but it is yet to be elucidated which of these are important for infection of the bovine udder. A rational and effective strategy for the control of intramammary infections may need to be directed against clones of S. aureus that commonly cause disease. The objective of this study was to characterise the genetic variance of S. aureus isolate populations from infected udders in Ireland using RAPD-PCR, ribotyping and multilocus enzyme electrophoresis (MLEE). Similar S. aureus isolates collected in the USA were also typed in order to compare strain differences in staphylococcal populations in a different environment. Phenotypic diversity based on a number of presumed virulence factors together with antibiotic sensitivity was examined and correlations between phenotype and genotype were identified, if present. In addition, a pathogenicity island encoding multiple superantigens was completely sequenced and characterised. Knockout mutants of these superantigens were also constructed and in vitro functional analysis performed. Laboratory animal experiments (mice and rabbits) were used to study the relative pathogenicity of individual staphylococcal strains (mice) and also to measure the immunological responses after prolonged exposure to the predominant strains (rabbits)

Budget Perspectives 2013. RESEARCH SERIES NUMBER 28 September 2012

The annual Budget Perspectives Conference provides a forum for discussing key public policy issues of both immediate and longer term concern. In the context of the current fiscal and economic crisis, research insights are needed at both the macro and micro level. The former are central to understanding and managing the significant reductions in the budget deficit needed to put Ireland's public finances on a sustainable footing. The latter are essential because a successful budgetary adjustment requires restructuring of both public expenditure and taxation. This in turn requires that policy adjustments take full account of both efficiency and equity issue and are seen to do so. The research papers presented at this year's annual Budget Perspectives Conference continue in this tradition, providing an opportunity for policymakers, social partners and researchers to engage with some of the major current issues

Effects of intraduodenal or intragastric administration of a bitter hop extract (Humulus lupulus L.), on upper gut motility, gut hormone secretion and energy intake in healthy-weight men

Gastrointestinal functions, particularly pyloric motility and the gut hormones, cholecystokinin and peptide YY, contribute to the regulation of acute energy intake. Bitter tastants modulate these functions, but may, in higher doses, induce GI symptoms. The aim of this study was to evaluate the effects of both dose and delivery location of a bitter hop extract (BHE) on antropyloroduodenal pressures, plasma cholecystokinin and peptide YY, appetite perceptions, gastrointestinal symptoms and energy intake in healthy-weight men. The study consisted of two consecutive parts, with part A including n = 15, and part B n = 11, healthy, lean men (BMI 22.6 ± 1.1 kg/m2 , aged 25 ± 3 years). In randomised, double-blind fashion, participants received in part A, BHE in doses of either 100 mg (“ID-BHE-100”) or 250 mg (“ID-BHE-250”), or vehicle (canola oil; “ID-control”) intraduodenally, or in part B, 250 mg BHE (“IG-BHE-250”) or vehicle (“IG-control”) intragastrically. Antropyloroduodenal pressures, hormones, appetite and symptoms were measured for 180 min, energy intake from a standardised buffet-meal was quantified subsequently. ID-BHE-250, but not ID-BHE-100, had modest, and transient, effects to stimulate pyloric pressures during the first 90 min (P < 0.05), and peptide YY from t = 60 min (P < 0.05), but did not affect antral or duodenal pressures, cholecystokinin, appetite, gastrointestinal symptoms or energy intake. IG-BHE-250 had no detectable effects. In conclusion, BHE, when administered intraduodenally, in the selected higher dose, modestly affected some appetite-related gastrointestinal functions, but had no detectable effects when given in the lower dose or intragastrically. Thus, BHE, at none of the doses or routes of administration tested, has appetite- or energy intake-suppressant effects.Vida Bitarafan, Penelope C.E. Fitzgerald, Sally D. Poppitt, John R. Ingram, Christine Feinle-Bisse

Resonance strength in Ne22(p,γ)Na23 from depth profiling in aluminum

A novel method for extracting absolute resonance strengths has been investigated. By implanting Ne22 ions into a thick aluminum backing and simultaneously measuring the Ne22+p and Al27+p reactions, the strength of the Erlab=479 keV resonance in Ne22(p,γ)Na23 was determined to be ωγ=0.524(51) eV. This result has significantly reduced uncertainties compared to earlier work. Our results are important for the absolute normalizations of resonance strengths in the Ne22(p,γ)Na23 hydrogen-burning reaction and in the Ne22+α s-process neutron-source reactions

A genomic portrait of the emergence, evolution, and global spread of a methicillin-resistant staphylococcus aureus pandemic

The widespread use of antibiotics in association with high-density clinical care has driven the emergence of drug-resistant bacteria that are adapted to thrive in hospitalized patients. Of particular concern are globally disseminated methicillin-resistant Staphylococcus aureus (MRSA) clones that cause outbreaks and epidemics associated with health care. The most rapidly spreading and tenacious health-care-associated clone in Europe currently is EMRSA-15, which was first detected in the UK in the early 1990s and subsequently spread throughout Europe and beyond. Using phylogenomic methods to analyze the genome sequences for 193 S. aureus isolates, we were able to show that the current pandemic population of EMRSA-15 descends from a health-care-associated MRSA epidemic that spread throughout England in the 1980s, which had itself previously emerged from a primarily community-associated methicillin-sensitive population. The emergence of fluoroquinolone resistance in this EMRSA-15 subclone in the English Midlands during the mid-1980s appears to have played a key role in triggering pandemic spread, and occurred shortly after the first clinical trials of this drug. Genome-based coalescence analysis estimated that the population of this subclone over the last 20 yr has grown four times faster than its progenitor. Using comparative genomic analysis we identified the molecular genetic basis of 99.8% of the antimicrobial resistance phenotypes of the isolates, highlighting the potential of pathogen genome sequencing as a diagnostic tool. We document the genetic changes associated with adaptation to the hospital environment and with increasing drug resistance over time, and how MRSA evolution likely has been influenced by country-specific drug use regimens

Results of Prevention of REStenosis with Tranilast and its Outcomes (PRESTO) trial

BACKGROUND: Restenosis after percutaneous coronary intervention (PCI) is a major problem affecting 15% to 30% of patients after stent placement. No oral agent has shown a beneficial effect on restenosis or on associated major adverse cardiovascular events. In limited trials, the oral agent tranilast has been shown to decrease the frequency of angiographic restenosis after PCI. METHODS AND RESULTS: In this double-blind, randomized, placebo-controlled trial of tranilast (300 and 450 mg BID for 1 or 3 months), 11 484 patients were enrolled. Enrollment and drug were initiated within 4 hours after successful PCI of at least 1 vessel. The primary end point was the first occurrence of death, myocardial infarction, or ischemia-driven target vessel revascularization within 9 months and was 15.8% in the placebo group and 15.5% to 16.1% in the tranilast groups (P=0.77 to 0.81). Myocardial infarction was the only component of major adverse cardiovascular events to show some evidence of a reduction with tranilast (450 mg BID for 3 months): 1.1% versus 1.8% with placebo (P=0.061 for intent-to-treat population). The primary reason for not completing treatment was > or =1 hepatic laboratory test abnormality (11.4% versus 0.2% with placebo, P<0.01). In the angiographic substudy composed of 2018 patients, minimal lumen diameter (MLD) was measured by quantitative coronary angiography. At follow-up, MLD was 1.76+/-0.77 mm in the placebo group, which was not different from MLD in the tranilast groups (1.72 to 1.78+/-0.76 to 80 mm, P=0.49 to 0.89). In a subset of these patients (n=1107), intravascular ultrasound was performed at follow-up. Plaque volume was not different between the placebo and tranilast groups (39.3 versus 37.5 to 46.1 mm(3), respectively; P=0.16 to 0.72). CONCLUSIONS: Tranilast does not improve the quantitative measures of restenosis (angiographic and intravascular ultrasound) or its clinical sequelae

Higher-Order Assembly of BRCC36-KIAA0157 Is Required for DUB Activity and Biological Function

BRCC36 is a Zn²⁺-dependent deubiquitinating enzyme (DUB) that hydrolyzes lysine-63-linked ubiquitin chains as part of distinct macromolecular complexes that participate in either interferon signaling or DNA-damage recognition. The MPN⁺ domain protein BRCC36 associates with pseudo DUB MPN⁻ proteins KIAA0157 or Abraxas, which are essential for BRCC36 enzymatic activity. To understand the basis for BRCC36 regulation, we have solved the structure of an active BRCC36-KIAA0157 heterodimer and an inactive BRCC36 homodimer. Structural and functional characterizations show how BRCC36 is switched to an active conformation by contacts with KIAA0157. Higher-order association of BRCC36 and KIAA0157 into a dimer of heterodimers (super dimers) was required for DUB activity and interaction with targeting proteins SHMT2 and RAP80. These data provide an explanation of how an inactive pseudo DUB allosterically activates a cognate DUB partner and implicates super dimerization as a new regulatory mechanism underlying BRCC36 DUB activity, subcellular localization, and biological function

Acute respiratory failure and the kinetics of neutrophil recovery in pediatric hematopoietic cell transplantation: a multicenter study

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.In this multicenter study, we investigated the kinetics of neutrophil recovery in relation to acuity and survival among 125 children undergoing allogeneic hematopoietic cell transplantation (allo-HCT) who required invasive mechanical ventilation (IMV). Recovery of neutrophils, whether prior to or after initiation of IMV, was associated with a significantly decreased risk of death relative to never achieving neutrophil recovery. A transient increase in acuity (by oxygenation index and vasopressor requirements) occurred among a subset of the patients who achieved neutrophil recovery after initiation of IMV; 61.5% of these patients survived to discharge from the intensive care unit (ICU). Improved survival among patients who subsequently achieved neutrophil recovery on IMV was not limited to those with peri-engraftment respiratory distress syndrome. The presence of a respiratory pathogen did not affect the risk of death while on IMV but was associated with an increased length of IMV (p < 0.01). Among patients undergoing HCT who develop respiratory failure and require advanced therapeutic support, neutrophil recovery at time of IMV and/or presence of a respiratory pathogen should not be used as determining factors when counseling families about survival