Molecular pathology of RUNX3 in human carcinogenesis

A major goal of molecular biology is to elucidate the mechanisms underlying cancer development and progression in order to achieve early detection, better diagnosis and staging and novel preventive and therapeutic strategies. We feel that an understanding of Runt-related transcription factor 3 (RUNX3)-regulated biological pathways will directly impact our knowledge of these areas of human carcinogenesis. The RUNX3 transcription factor is a downstream effector of the transforming growth factor-beta (TGF-beta) signaling pathway, and has a critical role in the regulation of cell proliferation and cell death by apoptosis, and in angiogenesis, cell adhesion and invasion. We previously identified RUNX3 as a major gastric tumor suppressor by establishing a causal relationship between loss of function and gastric carcinogenesis. More recently, we showed that RUNX3 functions as a bona fide initiator of colonic carcinogenesis by linking the Wnt oncogenic and TGF-beta tumor suppressive pathways. Apart from gastric and colorectal cancers. a multitude of epithelial cancers exhibit inactivation of RUNX3, thereby making it a putative tumor suppressor in human neoplasia. This review highlights our current understanding of the molecular mechanisms of RUNX3 inactivation in the context of cancer development and progression. (C) 2009 Elsevier B.V. All rights reserved.

Chernobyl: Living with Risk and Uncertainty

The nuclear accident in Chernobyl in 1986 is a dramatic example of the type of incidents that are characteristic of a risk society. The consequences of the incident are indeterminate, the causes complex and future developments unpredictable. Nothing can compensate for its effects and it affects a broad population indiscriminately. This paper examines the lived experience of those who experienced biographical disruption as residents of the region on the basis of qualitative case studies carried out in 2003 in the Chernobyl regions of Russia, Ukraine and Belarus. Our analysis indicates that informants tend to view their future as highly uncertain and unpredictable; they experience uncertainty about whether they are already contaminated, and they have to take hazardous decisions about where to go and what to eat. Fear, rumours and experts compete in supplying information to residents about the actual and potential consequences of the disaster, but there is little trust in, and only limited awareness of, the information that is provided. Most informants continue with their lives and do what they must or even what they like, even where the risks are known. They often describe their behaviour as being due to economic circumstances; where there is extreme poverty, even hazardous food sources are better than none. Unlike previous studies, we identify a pronounced tendency among informants not to separate the problems associated with the disaster from the hardships that have resulted from the break-up of the USSR, with both events creating a deep-seated sense of resignation and fatalism. Although most informants hold their governments to blame for lack of information, support and preventive measures, there is little or no collective action to have these put in place. This contrasts with previous research which has suggested that populations affected by disasters attribute crucial significance to that incident and, as a consequence, become increasingly politicized with regard to related policy agendas.

Engagement in cultural activities and cause-specific mortality: Prospective cohort study

Objective. To determine the relation between engagement in cultural activities and main causes of mortality among full-time employees.

Job strain and leisure-time physical activity in female and male public sector employees

Background. High work stress could decrease physical activity but the evidence of the relationship has remained equivocal, The present study examined the association between job strain and leisure-time physical activity in a large sample of employees.

Uptake of breast screening is influenced by current religion and religion of upbringing

Research has shown that individuals with a current religious affiliation are more likely to use preventive health services. The aim of this study was to determine whether breast screening uptake in Northern Ireland is higher amongst women with a current affiliation to an organised religion and, for those with no current affiliation, to examine whether their religion of upbringing is associated with uptake of breast screening. The Northern Ireland Longitudinal Study (NILS) was used to link Census and national breast screening data for 37,211 women invited for routine breast screening between 2001 and 2004. Current religious affiliation, religion of upbringing and other demographic and socio-economic characteristics were as defined on the Census form. Multivariate logistic regression was used to determine the relationship between religion affiliation and attendance. Uptake of breast screening is about 25% lower for those without a current religious affiliation. There are modest differences between Catholics and Protestants, with the latter about 11% more likely to attend for screening. For those with no current religion, the religion of upbringing appears to positively influence attendance rates. These differences remain after adjustment for all of the socio-demographic and socio-economic factors that have been shown to influence uptake rates of breast screening in the UK to date. Record linkage is an efficient way to examine equity across demographic characteristics that are not routinely available. The lower uptake amongst those with no religious affiliation may mean that screening services may find it difficult to maintain or improve uptake rate in an increasingly secularised society.

The effectiveness of physical activity interventions in socio-economically disadvantaged communities: A systematic review.

OBJECTIVE: Interventions to increase levels of physical activity (PA) in socio-economically disadvantaged communities are needed but little is known about their effectiveness. This review examines the effectiveness of interventions designed to increase PA in these communities and the theoretical frameworks and components used. METHODS: Five databases were searched for papers published in English between January 2000 and December 2010 that reported outcomes of PA interventions in socio-economically disadvantaged communities. Studies targeting individuals with pre-existing disease and not reporting a measure of free-living PA were excluded. Two reviewers independently extracted data and evaluated quality of evidence against pre-defined criteria. RESULTS: Of 478 publications identified, 27 were included. We found that group-based interventions were effective for adults but not for children; evidence for the effectiveness of interventions targeting individuals was insufficient; limited evidence suggested that community-wide interventions produced small changes in PA. Interventions underpinned by any theoretical framework, compared to none, were more likely to be effective. Several effective interventions included education, PA and social support components. CONCLUSION: Compared to other approaches, multi-component adult group-based interventions with theoretical frameworks are most effective in increasing PA in socio-economically disadvantaged communities. More robust evaluations of interventions targeting individuals in these 'hard-to-reach' communities are required. Copyright © 2012. Published by Elsevier Inc.

Modelling coronary heart disease mortality in Northern Ireland between 1987 and 2007: broader lessons for prevention

To quantify how much of the coronary heart disease (CHD) mortality decline in Northern Ireland between 1987 and 2007 could be attributed to medical and surgical treatments and how much to changes in population cardiovascular risk factors.

Secondary prevention in the clinical management of patients with cardiovascular diseases. Core components, standards and outcome measures for referral and delivery.

Despite major improvements in diagnostics and interventional therapies, cardiovascular diseases remain a major health care and socio-economic burden both in western and developing countries, in which this burden is increasing in close correlation to economic growth. Health authorities and the general population have started to recognize that the fight against these diseases can only be won if their burden is faced by increasing our investment on interventions in lifestyle changes and prevention. There is an overwhelming evidence of the efficacy of secondary prevention initiatives including cardiac rehabilitation in terms of reduction in morbidity and mortality. However, secondary prevention is still too poorly implemented in clinical practice, often only on selected populations and over a limited period of time. The development of systematic and full comprehensive preventive programmes is warranted, integrated in the organization of national health systems. Furthermore, systematic monitoring of the process of delivery and outcomes is a necessity. Cardiology and secondary prevention, including cardiac rehabilitation, have evolved almost independently of each other and although each makes a unique contribution it is now time to join forces under the banner of preventive cardiology and create a comprehensive model that optimizes long term outcomes for patients and reduces the future burden on health care services. These are the aims that the Cardiac Rehabilitation Section of the European Association for Cardiovascular Prevention & Rehabilitation has foreseen to promote secondary preventive cardiology in clinical practice.

Economic aspects of pharmacotherapy for chronic constipation

Constipation is one of the most common digestive complaints. It is a symptom, not a disease. The subjectivity that this involves means that assessments of clinical epidemiology, socioeconomic costs and pharmacotherapy are difficult, since there is no definition of 'normal' bowel habit. Although constipation can affect all ages, the problem increases with age, and is of particular concern for those who are frail and in long term care. Cultural influences may affect the prevalence in older people. Drug therapy of constipation cannot be considered in isolation, since there are issues in the prevention of constipation and the principles of good management that also apply. Furthermore, some consideration of the pathophysiology and diagnosis is important. This is because a number of remediable causes can be identified, and the diagnostic process involves patient education, which in turn may be effective in reducing costs. It is the complaint of constipation which leads either to self-medication or to consultation with the medical profession. Both of these courses of action have a significant influence on utilisation of laxatives (cathartics), obtained both over-the-counter and by prescription. Although there are a large number of laxative preparations available, therapy has changed little in half a century. Costs may vary considerably, and with such a significant problem there is a need for comparative studies. However, study methodologies are difficult, and a significant placebo response may be found. Education and preventive measures have been shown to reduce laxative use and costs in institutions. Unfortunately, there are few comparative studies of individual laxatives and even fewer cost-effectiveness studies. Those that there are have been based in institutions, and so extrapolation to other situations may be difficult. In general, little attention is given to constipation. It is, however, an area with significant resource implications in which education and preventive measures have been shown to be beneficial. Even so, there is still a need for good comparative studies, particularly where cost effectiveness is concerned.

A framework for designing robust food supply chains

After years of emphasis on leanness and responsiveness businesses are now experiencing their vulnerability to supply chain disturbances. Although more literature is appearing on this subject, there is a need for an integrated framework to support the analysis and design of robust food supply chains. In this chapter we present such a framework. We define the concept of robustness and classify supply chain disturbances, sources of food supply chain vulnerability, and adequate redesign principles and strategies to achieve robust supply chain performances. To test and illustrate its applicability, the research framework is applied to a meat supply chain.

Brisk walking, fitness, and cardiovascular risk:a randomized controlled trial in primary care

To examine the effects of 30 min of self-paced, non-supervised, brisk walking, 5 days per week on the health and fitness of people aged 50-65 years.

Infection systems biology:from reactive to proactive (P4) medicine

This short review establishes the conceptual bases and discusses the principal aspects of P4-shorthand for predictive, preventive, personalized and participatory medicine-medicine, in the framework of infectious diseases. P4 medicine is a new way to approach medical care; instead of acting when the patient is sick, physicians will be able to detect early warnings of disease to take early action. Furthermore, people might even be able to adjust their lifestyles to prevent disease. P4 medicine is fuelled by systems approaches to disease, including methods for personalized genome sequencing and new computational techniques for building dynamic disease predictive networks from massive amounts of data from a variety of OMICs. An excellent example of the effectiveness of the P4 medicine approach is the change in cancer treatments. Emphasis is placed on early detection, followed by genotyping of the patient to use the most adequate treatment according to the genetic background. Cardiovascular diseases and perhaps even neurodegenerative disorders will be the next targets for P4 medicine. The application of P4 medicine to infectious diseases is still in its infancy, but is a promising field that will provide much benefit to both the patients and the health-care system.