Resveratrol and derivatives for the treatment of atrial fibrillation

Resveratrol is a bioactive polyphenol, found in grapes, red wine, and peanuts, and has recently garnered much media and scientific attention for its diverse beneficial health effects as a nutritional supplement or nutraceutical. Of particular interest are the well-documented cardioprotective effects of resveratrol that are mediated by diverse mechanisms, including its antioxidant and vascular effects. However, it is now becoming clear that resveratrol may also exhibit direct effects on cardiac function and rhythm through modulation of signaling pathways that regulate cardiac remodeling and ion channel activity that controls cardiac excitability. Resveratrol may therefore possess antiarrhythmic properties that contribute to the cardiovascular benefits of resveratrol. Atrial fibrillation (AF) is the most common cardiac arrhythmia, although current therapies are suboptimal. Our laboratory has been studying resveratrol's effects on cardiac ion channels and remodeling pathways, and we initiated a drug development program aimed at generating novel resveratrol derivatives with improved efficacy against AF when compared to currently available therapeutics. This review therefore focuses on the effects of resveratrol and new derivatives on a variety of cardiac ion channels and molecular pathways that contribute to the development and maintenance of atrial fibrillation

An association study of DRD2 and COMT polymorphisms with novelty seeking and harm avoidance scores, in two independent samples of depressed patients

BACKGROUND: It was recently reported that an interaction of the dopamine D2 receptor (DRD2) and catechol-O-methyltransferase (COMT) influences the behavioural approach system – as measured using Carver and White's Behavioural Inhibition and Behavioural Approach System (BIS/BAS) scales – in a sample of healthy German subjects. The Temperament and Character Inventory (TCI), in particular the novelty seeking (NS) and harm avoidance (HA) scales, correlates moderately with the BIS/BAS measure. This study aimed to examine support for an association of DRD2 and COMT with behavioural activation, using the TCI within two independent samples of depressed outpatients (for both samples n = 146). METHODS: Two clinical samples of depressed patients were ascertained to assess the efficacy of two different pharmacotherapy and psychotherapy treatments. Analysis of variance (ANOVA) was used to analyse NS and HA scale and subscale scores with respect to gene loci within each clinical sample. Analysis of covariance were undertaken to examine the association of age and gender with NS and HA scores. An association of age group or gender with gene loci were explored using chi-squared tests, in each sample. RESULTS: No significant effect of DRD2 or COMT, either independently or as an interaction, on NS or HA scores was observed, within either sample. Whilst age was significantly negatively associated with NS scores, including age in the two- and three-way interactions did not affect the significance of the association of personality with gene loci. CONCLUSION: This study suggests that the COMT-DRD2 Equilibrium Model of Positive Emotionality recently proposed by Reuter and his colleagues is not applicable amongst currently depressed individuals, whose behavioural approach and inhibition tendencies have been assessed using the TCI

Ferrocenylmethylphosphanes and the Alpha Process for Methoxycarbonylation: The Original Story

The Lucite Alpha process is the predominant technology for the preparation of acrylics. This two-stage process involves the palladium-catalysed formation of methyl propanoate from ethene, CO, and methanol, followed by the oxidative formylation of methyl propanoate into methyl methacrylate. A range of bis-1,2-disubstituted aminomethylferrocenes has been prepared and characterised. These complexes serve as precursors to a variety of bulky ferrocenylmethyldiphosphanes that, in turn, function as ligands in the palladium-catalysed process. We describe the crystal structures of five ligand precursors and provide a rationale for their design. In situ catalyst testing on palladium complexes derived from ferrocenylphosphanes demonstrates that these are highly selective (>99.5%) catalysts for the formation of methyl propanoate from ethene, CO, and methanol and have turnover numbers exceeding 50,000. This article credits those researchers who worked on this project in the early days, who received little or no credit for their achievements and endeavours

Evaluation Research and Institutional Pressures: Challenges in Public-Nonprofit Contracting

This article examines the connection between program evaluation research and decision-making by public managers. Drawing on neo-institutional theory, a framework is presented for diagnosing the pressures and conditions that lead alternatively toward or away the rational use of evaluation research. Three cases of public-nonprofit contracting for the delivery of major programs are presented to clarify the way coercive, mimetic, and normative pressures interfere with a sound connection being made between research and implementation. The article concludes by considering how public managers can respond to the isomorphic pressures in their environment that make it hard to act on data relating to program performance.This publication is Hauser Center Working Paper No. 23. The Hauser Center Working Paper Series was launched during the summer of 2000. The Series enables the Hauser Center to share with a broad audience important works-in-progress written by Hauser Center scholars and researchers

‘Re-reading Raphael Samuel: Politics, Personality and Performance’

For British historian Raphael Samuel, history and politics were inextricable. Best known as the founder of the history workshop movement, the controversial historian took his stance on the democratisation of history-making, becoming an outspoken advocate for public history. Despite making a significant contribution to contemporary historiography, he remains a neglected, even disparaged, figure. This paper contends that the most significant aspect of Samuel’s historical work was not one or other theory of history or argument about the past but his entire way of being an historian. Samuel embodied as much as expressed his ideas, consciously using his personality as a powerful political tool. It is further argued that conventional approaches to intellectual history, focusing on textual outputs, do not fully recognise the significance of performative modes of thinking. Theoretical approaches to performance as identity offer important insight here but can be too schematic in their view of applied and enacted thought. A biographical approach, by contrast, provides the intimate perspective necessary to fully appreciate the fluidity and complexity of such a personality. The paper first situates Samuel in the context of his earlier life, focusing on how and why he created such a public persona and how he adapted it in response to changing circumstances. It then considers the implications and effectiveness of this persona by assessing how it was perceived and narrated by others, acknowledging, in the process, why different groups engaged with and interpreted it differently

Importance of basophil activation testing in insect venom allergy

<p>Abstract</p> <p>Background</p> <p>Venom immunotherapy (VIT) is the only effective treatment for prevention of serious allergic reactions to bee and wasp stings in sensitized individuals. However, there are still many questions and controversies regarding immunotherapy, like selection of the appropriate allergen, safety and long term efficacy.</p> <p>Methods</p> <p>Literature review was performed to address the role of basophil activation test (BAT) in diagnosis of venom allergy.</p> <p>Results</p> <p>In patients with positive skin tests or specific IgE to both honeybee and wasp venom, IgE inhibition test can identify sensitizing allergen only in around 15% and basophil activation test increases the identification rate to around one third of double positive patients. BAT is also diagnostic in majority of patients with systemic reactions after insect stings and no detectable IgE. High basophil sensitivity to allergen is associated with a risk of side effects during VIT. Persistence of high basophil sensitivity also predicts a treatment failure of VIT.</p> <p>Conclusion</p> <p>BAT is a useful tool for better selection of allergen for immunotherapy, for identification of patients prone to side effects and patients who might be treatment failures. However, long term studies are needed to evaluate the accuracy of the test.</p

The Alberta Heart Failure Etiology and Analysis Research Team (HEART) study

Background Nationally, symptomatic heart failure affects 1.5-2% of Canadians, incurs $3 billion in hospital costs annually and the global burden is expected to double in the next 1–2 decades. The current one-year mortality rate after diagnosis of heart failure remains high at >25%. Consequently, new therapeutic strategies need to be developed for this debilitating condition. Methods/Design The objective of the Alberta HEART program (http://albertaheartresearch.ca) is to develop novel diagnostic, therapeutic and prognostic approaches to patients with heart failure with preserved ejection fraction. We hypothesize that novel imaging techniques and biomarkers will aid in describing heart failure with preserved ejection fraction. Furthermore, the development of new diagnostic criteria will allow us to: 1) better define risk factors associated with heart failure with preserved ejection fraction; 2) elucidate clinical, cellular and molecular mechanisms involved with the development and progression of heart failure with preserved ejection fraction; 3) design and test new therapeutic strategies for patients with heart failure with preserved ejection fraction. Additionally, Alberta HEART provides training and education for enhancing translational medicine, knowledge translation and clinical practice in heart failure. This is a prospective observational cohort study of patients with, or at risk for, heart failure. Patients will have sequential testing including quality of life and clinical outcomes over 12 months. After that time, study participants will be passively followed via linkage to external administrative databases. Clinical outcomes of interest include death, hospitalization, emergency department visits, physician resource use and/or heart transplant. Patients will be followed for a total of 5 years. Discussion Alberta HEART has the primary objective to define new diagnostic criteria for patients with heart failure with preserved ejection fraction. New criteria will allow for targeted therapies, diagnostic tests and further understanding of the patients, both at-risk for and with heart failure

The Dutch health insurance reform: switching between insurers, a comparison between the general population and the chronically ill and disabled

Background: On 1 January 2006 a number of far-reaching changes in the Dutch health insurance system came into effect. In the new system of managed competition consumer mobility plays an important role. Consumers are free to change their insurer and insurance plan every year. The idea is that consumers who are not satisfied with the premium or quality of care provided will opt for a different insurer. This would force insurers to strive for good prices and quality of care. Internationally, the Dutch changes are under the attention of both policy makers and researchers. Questions answered in this article relate to switching behaviour, reasons for switching, and differences between population categories. Methods: Postal questionnaires were sent to 1516 members of the Dutch Health Care Consumer Panel and to 3757 members of the National Panel of the Chronically ill and Disabled (NPCD) in April 2006. The questionnaire was returned by 1198 members of the Consumer Panel (response 79%) and by 3211 members of the NPCD (response 86%). Among other things, questions were asked about choices for a health insurer and insurance plan and the reasons for this choice. Results: Young and healthy people switch insurer more often than elderly or people in bad health. The chronically ill and disabled do not switch less often than the general population when both populations are comparable on age, sex and education. For the general population, premium is more important than content, while the chronically ill and disabled value content of the insurance package as well. However, quality of care is not important for either group as a reason for switching. Conclusion: There is increased mobility in the new system for both the general population and the chronically ill and disabled. This however is not based on quality of care. If reasons for switching are unrelated to the quality of care, it is hard to believe that switching influences the quality of care. As yet there are no signs of barriers to switch insurer for the chronically ill and disabled. This however could change in the future and it is therefore important to monitor changes.

Coastal groundwater discharge – an additional source of phosphorus for the oligotrophic wetlands of the Everglades

In this manuscript we define a new term we call coastal groundwater discharge (CGD), which is related to submarine groundwater discharge (SGD), but occurs when seawater intrudes inland to force brackish groundwater to discharge to the coastal wetlands. A hydrologic and geochemical investigation of both the groundwater and surface water in the southern Everglades was conducted to investigate the occurrence of CGD associated with seawater intrusion. During the wet season, the surface water chemistry remained fresh. Enhanced chloride, sodium, and calcium concentrations, indicative of brackish groundwater discharge, were observed in the surface water during the dry season. Brackish groundwaters of the southern Everglades contain 1–2.3μM concentrations of total phosphorus (TP). These concentrations exceed the expected values predicted by conservative mixing of local fresh groundwater and intruding seawater, which both have TPμM. The additional source of TP may be from seawater sediments or from the aquifer matrix as a result of water–rock interactions (such as carbonate mineral dissolution and ion exchange reactions) induced by mixing fresh groundwater with intruding seawater. We hypothesize that CGD maybe an additional source of phosphorus (a limiting nutrient) to the coastal wetlands of the southern Everglades

Chinese students in a UK business school: hearing the student voice in reflective teaching and learning practice.

This paper presents the outcomes of a study carried out in 2001-2002 with nine postgraduate students from China, enrolled on taught master's programmes in a UK university business school. The aims of the research were to explore the development of the students' orientations to learning during their year of study in the UK, and to explore how the researcher's interactions with the study group contributed to her professional reflections and influenced her academic practice. The main conclusions of the project were that participants' underlying approaches to learning did not change substantially over the year, owing to the culturally implicit nature of UK academic conventions and that they experienced high levels of emotional isolation and loneliness, which affected their academic confidence