Pomegranate polyphenols lower lipid peroxidation in adults with type 2 diabetes but have no effects in healthy volunteers:a pilot study

Aims. To examine the antioxidant and anti-inflammatory effects of pomegranate polyphenols in obese patients with type 2 diabetes (T2DM) (n = 8) and in healthy nondiabetic controls (n = 9). Methods. Participants received 2 capsules of pomegranate polyphenols (POMx, 1 capsule = 753?mg polyphenols) daily for 4 weeks. Blood draws and anthropometrics were performed at baseline and at 4 weeks of the study. Results. Pomegranate polyphenols in healthy controls and in T2DM patients did not significantly affect body weight and blood pressure, glucose and lipids. Among clinical safety profiles, serum electrolytes, renal function tests, and hematological profiles were not significantly affected by POMx supplementation. However, aspartate aminotransferase (AST) showed a significant increase in healthy controls, while alanine aminotransferase (ALT) was significantly decreased in T2DM patients at 4 weeks (P <0.05), though values remained within the normal ranges. Among the biomarkers of lipid oxidation and inflammation, oxidized LDL and serum C-reactive protein (CRP) did not differ at 4 weeks in either group, while pomegranate polyphenols significantly decreased malondialdehyde (MDA) and hydroxynonenal (HNE) only in the diabetic group versus baseline (P <0.05). Conclusions. POMx reduces lipid peroxidation in patients with T2DM, but with no effects in healthy controls, and specifically modulates liver enzymes in diabetic and nondiabetic subjects. Larger clinical trials are merited.

Effect of isomalt consumption on faecal microflora and colonic metabolism in healthy volunteers

Due to its low digestibility in the small intestine, a major fraction of the polyol isomalt reaches the colon. However, little is known about effects on the intestinal microflora. During two 4-week periods in a double-blind, placebo-controlled, cross-over design, nineteen healthy volunteers consumed a controlled basal diet enriched with either 30 g isomalt or 30 g sucrose daily. Stools were collected at the end of each test phase and various microbiological and luminal markers were analysed. Fermentation characteristics of isomalt were also investigated in vitro. Microbiological analyses of faecal samples indicated a shift of the gut flora towards an increase of bifidobacteria following consumption of the isomalt diet compared with the sucrose diet (P

GPCR structure, function, drug discovery and crystallography: report from Academia-Industry International Conference (UK Royal Society) Chicheley Hall, 1-2 September 2014

G-protein coupled receptors (GPCRs) are the targets of over half of all prescribed drugs today. The UniProt database has records for about 800 proteins classified as GPCRs, but drugs have only been developed against 50 of these. Thus, there is huge potential in terms of the number of targets for new therapies to be designed. Several breakthroughs in GPCRs biased pharmacology, structural biology, modelling and scoring have resulted in a resurgence of interest in GPCRs as drug targets. Therefore, an international conference, sponsored by the Royal Society, with world-renowned researchers from industry and academia was recently held to discuss recent progress and highlight key areas of future research needed to accelerate GPCR drug discovery. Several key points emerged. Firstly, structures for all three major classes of GPCRs have now been solved and there is increasing coverage across the GPCR phylogenetic tree. This is likely to be substantially enhanced with data from x-ray free electron sources as they move beyond proof of concept. Secondly, the concept of biased signalling or functional selectivity is likely to be prevalent in many GPCRs, and this presents exciting new opportunities for selectivity and the control of side effects, especially when combined with increasing data regarding allosteric modulation. Thirdly, there will almost certainly be some GPCRs that will remain difficult targets because they exhibit complex ligand dependencies and have many metastable states rendering them difficult to resolve by crystallographic methods. Subtle effects within the packing of the transmembrane helices are likely to mask and contribute to this aspect, which may play a role in species dependent behaviour. This is particularly important because it has ramifications for how we interpret pre-clinical data. In summary, collaborative efforts between industry and academia have delivered significant progress in terms of structure and understanding of GPCRs and will be essential for resolving problems associated with the more difficult targets in the future.

Calvinist Absolutism: Archbishop James Ussher and Royal Power

Archbishop James Ussher's manuscript notebooks allow us to observe the making of a Calvinist absolutist and to orientate the archbishop's beliefs about royal power within European Reformed thought as a whole. By 1643, Ussher was preaching a polished and complete theory of absolute royal power, and it is possible to track the development of this political theory forward from his undergraduate days in the 1590s. Throughout his life Ussher engaged anxiously with Reformed theologians abroad, who generally favored limited rather than absolute monarchy. Nevertheless, Ussher shared with these Reformed colleagues both an antipathy to aspects of Aristotelian politics and a commitment to the divine institution of royal power. Finally, despite Ussher's hostility to Laudian innovations in the Irish Church, his heartfelt political beliefs made him a firm supporter of Stuart absolutism throughout the Three Kingdoms.

Exodus? The training paths and plans of postgraduate medical trainees, under the Royal College of Physicians of Ireland

Background: In 2006, the Buttimer report highlighted the paucity of demographic data on those applying for and entering postgraduate medical education and training (PGMET) in Ireland. Today, concerns that there is an "exodus" of graduates of Irish medical schools are at the forefront of national discussion, however, published data on PGMET remains inadequate.

Aims: The objectives of this study were to collate existing data relating to trainees and training programmes at three stages of training and to examine the career plans of junior trainees.

Methods: Data from application forms for training programmes, commencing July 2012, under the Royal College of Physicians of Ireland (n = 870), were integrated with data from other existing sources. Candidates entering basic specialist training were surveyed with regard to career plans. Descriptive and comparative analysis was performed in SPSS version 18.

Results: Graduates of Irish medical schools made up over 70 % of appointees. Over 80 % of BST trainees aspired to work as consultants in Ireland, but 92.5 % planned to spend time working abroad (response rate 77 %). Decisions to leave the Irish system were linked to lifestyle, but also to failure to be appointed to higher specialist training. Significant numbers of trainees return to Ireland after a period abroad.

Conclusions: The trainee "exodus" is more complex than is often portrayed. The desire to spend time working outside Ireland must be accounted for in workforce planning and configuration of training programmes. Expansion of HST is a potential solution to reduce the numbers of graduates leaving Ireland post-BST.

The Royal Dublin Society Concert Archive

This research project documents the occurrence of the Royal Dublin Society (RDS) classical music recitals which were established in 1886 for the promotion of chamber music. Some 120 years of recitals spanning from 1886 to 2006 are recorded in the archives extant in the RDS Library and Archives, Ballsbridge, Dublin. The year 1925 marked the opening of the current concert hall (The Members’ Hall) and the initial phase of this research project focuses on the period 1925 to 1950. The archive documents appearances in Dublin by internationally renowned musicians in addition to the first Dublin performances of several twentieth-century works. Examination of the archive contributes to knowledge of chamber music performance in Dublin from the late nineteenth to the early twenty-first century and facilitates analysis of networks, repertory and reception.

Plasma levels of intermedin (adrenomedullin-2) in healthy human volunteers and patients with heart failure

Intermedin/adrenomedullin-2 (IMD) is a member of the adrenomedullin/CGRP peptide family. Less is known about the distribution of IMD than for other family members within the mammalian cardiovascular system, particularly in humans. The aim was to evaluate plasma IMD levels in healthy subjects and patients with chronic heart failure. IMD and its precursor fragments, preproIMD25–56 and preproIMD57–92, were measured by radioimmunoassay in 75 healthy subjects and levels of IMD were also compared to those of adrenomedullin (AM) and mid-region proadrenomedullin45–92 (MRproAM45–92) in 19 patients with systolic heart failure (LVEF < 45%). In healthy subjects, plasma levels (mean + SE) of IMD (6.3 + 0.6 pg ml−1) were lower than, but correlated with those of AM (25.8 + 1.8 pg ml−1; r = 0.49, p < 0.001). Plasma preproIMD25–56 (39.6 + 3.1 pg ml−1), preproIMD57–92 (25.9 + 3.8 pg ml−1) and MRproAM45–92 (200.2 + 6.7 pg ml−1) were greater than their respective bioactive peptides. IMD levels correlated positively with BMI but not age, and were elevated in heart failure (9.8 + 1.3 pg ml−1, p < 0.05), similarly to MRproAM45–92 (329.5 + 41.9 pg ml−1, p < 0.001) and AM (56.8 + 10.9 pg ml−1, p < 0.01). IMD levels were greater in heart failure patients with concomitant renal impairment (11.3 + 1.8 pg ml−1) than those without (6.5 + 1.0 pg ml−1; p < 0.05). IMD and AM were greater in patients receiving submaximal compared with maximal heart failure drug therapy and were decreased after 6 months of cardiac resynchronization therapy. In conclusion, IMD is present in the plasma of healthy subjects less abundantly than AM, but is similarly correlated weakly with BMI. IMD levels are elevated in heart failure, especially with concomitant renal impairment, and tend to be reduced by high intensity drug or pacing therapy.

"No Encores" The Royal Dublin Society Concert Archive Recitals in Retrospect: 1925-50

A large archive of sources for the RDS classical music recitals is extant in the Society’s Library, Ballsbridge, Dublin. The recitals were established in 1886 for the promotion of chamber music and in order to expose Dublin audiences to the works of the great composers. Extant in the collection are minute books; autographed programmes; newspaper cuttings which include previews, reviews and advertisements; correspondences with artists and agents; promotional material; selections of photographs; records of attendance, artists fees and takings; and volumes of printed music.
This paper will document the organisation, management and occurrence of the RDS classical music recitals for the period 1925 to 1950 and will encompass the opening of the current concert hall (The Members’ Hall, 1925), the Society’s bi-centenary celebrations (1931) and the continuance of the recitals within the context of the Second World War (1939- 45). The paper will examine and analyse the following: networks, repertoire and reception.
The RDS music committee established significant links with many performers and UK-based classical music agents. Recitalists include musicians of international renown; Myra Hess, Isolde Menges, Lili Kraus, Joseph Szigeti, Leon Goossens, Sir Hamilton Harty and The Hallé Orchestra, The Catterall Quartet and many local, Dublin-based musicians; Raidió Éireann Orchestra, Dublin String Orchestra, Dublin Philharmonic Orchestra and Culwick Choral Society. The compromises and collaborations in evidence between the music committee, agents and performers resulted in the presentation of varied and well-balanced programmes featuring sonatas, quartets, trios, concerti, overtures, symphonies and songs by composers including Beethoven, Mozart, Haydn and Brahms. Works by contemporary composers including Bax, Dohnanyi, Szymanowski and Suk were also regularly performed, as were works with an Irish influence or flavour. Audiences mainly consisted of members of the Society, music students were encouraged to attend at a reduced rate and reviews were regularly published in the Irish Times, Irish Independent and Irish Press.