The role of advanced glycation end products in retinal ageing and disease

The retina is exposed to a lifetime of potentially damaging environmental and physiological factors that make the component cells exquisitely sensitive to age-related processes. Retinal ageing is complex and a raft of abnormalities can accumulate in all layers of the retina. Some of this pathology serves as a sinister preamble to serious conditions such as age-related macular degeneration (AMD) which remains the leading cause of irreversible blindness in the Western world.

The formation of advanced glycation end products (AGEs) is a natural function of ageing but accumulation of these adducts also represents a key pathophysiological event in a range of important human diseases. AGEs act as mediators of neurodegeneration, induce irreversible changes in the extracellular matrix, vascular dysfunction and pro-inflammatory signalling. Since many cells and tissues of the eye are profoundly influenced by such processes, it is fitting that advanced glycation is now receiving considerable attention as a possible pathogenic factor in visual disorders.

This review presents the current evidence for a pathogenic role for AGEs and activation of the receptor for AGEs (RAGE) in initiation and progression of retinal disease. It draws upon the clinical and experimental literature and highlights the opportunities for further research that would definitively establish these adducts as important instigators of retinal disease. The therapeutic potential for novel agents that can ameliorate AGE formation of attenuate RAGE signalling in the retina is also discussed.

Campaigns Against Incineration in Ireland - North and South: Framing Networking and Political Opportunities

An analysis of community-based campaigns opposing waste incineration and advocating 'zero waste' policies in Ireland, North and South.

Synthesis of an analogue of the bisphosphonate drug Ibandronate for targeted drug-delivery therapeutic strategies

An analogue of the bisphosphonate drug Ibandronate was prepared and coupled via a cleavable ester function to a bromoacetyl linker with specific reactivity for thiol groups. This compound should find useful applications in therapeutic strategies aiming to deliver bisphosphonate drugs specifically to cancer cells making use of proteins as vectors. The specific delivery of bisphosphonates to cancer cells instead of bone, the usual site of accumulation of these cytotoxic drugs, could greatly widen their therapeutic applications.

Wholeness of healing: an innovative Student-Selected Component introducing United Kingdom medical students to the spiritual dimension in healthcare.

Objective: This Student Selected Component (SSC) was designed to equip United Kingdom (UK) medical students to engage in whole-person care. The aim was to explore students' reactions to experiences provided, and consider potential benefits for future clinical practice.

Methods: The SSC was delivered in the workplace. Active learning was encouraged through facilitated discussion with and observation of clinicians, the palliative team, counselling services, hospital chaplaincy and healing ministries; sharing of medical histories by patients; and training in therapeutic communication. Assessment involved reflective journals, literature appraisal, and role-play simulation of the doctor-patient consultation. Module impact was evaluated by analysis of student coursework and a questionnaire.

Results: Students agreed that the content was stimulating, relevant, and enjoyable and that learning outcomes were achieved. They reported greater awareness of the benefit of clinicians engaging in care of the "whole person" rather than "the disease." Contributions of other professions to the healing process were acknowledged, and students felt better equipped for discussion of spiritual issues with patients. Many identified examples of activities which could be incorporated into core teaching to benefit all medical students.

Conclusion: The SSC provided relevant active learning opportunities for medical students to receive training in a whole-person approach to patient care.

Future novel threats and opportunities facing UK biodiversity identified by horizon scanning

1. Horizon scanning is an essential tool for environmental scientists if they are to contribute to the evidence base for Government, its agencies and other decision makers to devise and implement environmental policies. The implication of not foreseeing issues that are foreseeable is illustrated by the contentious responses to genetically modified herbicide-tolerant crops in the UK, and by challenges surrounding biofuels, foot and mouth disease, avian influenza and climate change.

A Review of Demographic Ageing in the UK: Opportunities for Rural Research

Demographic ageing is a global phenomenon. UK policy and research have, until recently, focused on national trends and implications and largely viewed ageing as a 'pensions and care' problem. While other and more positive aspects are beginning to be acknowledged, regional, local, and rural impacts remain underinvestigated. This paper, by reviewing the literature from several disciplines and countries, introduces a series of research questions that could usefully inform future geographical inquiry. It argues that the nature, experiences, and consequences of demographic ageing will vary across space, stage in the life course and numerous aspects of our everyday lives. Our current knowledge and understanding are but the tip of the iceberg in terms of the research opportunities that lie ahead.

Promoting Civil Society Across the Borders of the EU Neighbourhood: Debates, Constraints and Opportunities

One of the aims of this article it to clarify the nature of the debate over 'civil society' and its relationship to the state. It begins by suggesting that the EU's borderland provides a context in which deep-rooted 'Western' and 'Eastern' understandings of state and civil society meet and overlap. The second section outlines the geo-political reshaping of the 'Neighbourhood'. It concentrates on the influence of non-EU actors, notably Russia, complementing the EU-focused literature on the subject. The third section elaborates the consensus in the literature on the weakness of civil society in the EU 'Neighbourhood'. This is followed by a discussion of 'Western' debates over the role and significance of civil society.

Emerging cardiovascular actions of the incretin hormone glucagon-like peptide-1: potential therapeutic benefits beyond glycaemic control?

Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted by the small intestine in response to nutrient ingestion. It has wide-ranging effects on glucose metabolism, including stimulation of insulin release, inhibition of glucagon secretion, reduction of gastric emptying and augmentation of satiety. Importantly, the insulinotropic actions of GLP-1 are uniquely dependent on ambient glucose concentrations, and it is this particular characteristic which has led to its recent emergence as a treatment for type 2 diabetes. Although the major physiological function of GLP-1 appears to be in relation to glycaemic control, there is growing evidence to suggest that it may also play an important role in the cardiovascular system. GLP-1 receptors (GLP-1Rs) are expressed in the heart and vasculature of both rodents and humans, and recent studies have demonstrated that GLP-1R agonists have wide-ranging cardiovascular actions, such as modulation of heart rate, blood pressure, vascular tone and myocardial contractility. Importantly, it appears that these agents may also have beneficial effects in the setting of cardiovascular disease (CVD). For example, GLP-1 has been found to exert cardioprotective actions in experimental models of dilated cardiomyopathy, hypertensive heart failure and myocardial infarction (MI). Preliminary clinical studies also indicate that GLP-1 infusion may improve cardiac contractile function in chronic heart failure patients with and without diabetes, and in MI patients after successful angioplasty. This review will discuss the current understanding of GLP-1 biology, examine its emerging cardiovascular actions in both health and disease and explore the potential use of GLP-1 as a novel treatment for CVD.